Prioritizing Sustainable Denim Fabric through Integrated Decision-Making Framework.

In this study, a combined multi-criteria decision-making (MCDM) approach that integrates the logarithm methodology of additive weights (LMAW) and the double normalization-based multiple aggregation (DNMA) methods has been utilized to determine the optimal fabric structures considering the performance characteristics of denim fabrics containing recycled cotton. This approach focuses on sustainability and performance criteria, applying advanced decision-making methodologies to provide in-depth analysis and guidance for denim fabric selection. In this research, 15 distinct criteria were taken into account. Alternatives were ranked based on outcomes obtained from these methods. Although it was not anticipated that the top-ranked alternatives would simultaneously fulfill the beneficial or non-beneficial orientation of all criteria, an examination of the top three alternatives (A12, A5, and A15) for both garment groups revealed that they indeed aligned with the pre-determined criterion orientation. This highlights the effectiveness of the multi-criteria decision-making approach in the context of this study.

Modeling transmission of avian influenza viruses at the human-animal-environment interface in Cuba.

Introduction: The increasing geographical spread of highly pathogenic avian influenza viruses (HPAIVs) is of global concern due to the underlying zoonotic and pandemic potential of the virus and its economic impact. An integrated One Health model was developed to estimate the likelihood of Avian Influenza (AI) introduction and transmission in Cuba, which will help inform and strengthen risk-based surveillance activities. Materials and methods: The spatial resolution used for the model was the smallest administrative district ("Consejo Popular"). The model was parameterised for transmission from wild birds to poultry and pigs (commercial and backyard) and then to humans. The model includes parameters such as risk factors for the introduction and transmission of AI into Cuba, animal and human population densities; contact intensity and a transmission parameter (ß). Results: Areas with a higher risk of AI transmission were identified for each species and type of production system. Some variability was observed in the distribution of areas estimated to have a higher probability of AI introduction and transmission. In particular, the south-western and eastern regions of Cuba were highlighted as areas with the highest risk of transmission. Discussion: These results are potentially useful for refining existing criteria for the selection of farms for active surveillance, which could improve the ability to detect positive cases. The model results could contribute to the design of an integrated One Health risk-based surveillance system for AI in Cuba. In addition, the model identified geographical regions of particular importance where resources could be targeted to strengthen biosecurity and early warning surveillance.

Stromal-Like Cells Are Found in Peripheral Blood of Patients With Inflammatory Bowel Disease and Correlate With Immune Activation State.

INTRODUCTION: Recent studies have identified a critical role of stromal-immune cell interactions in immunity and immune tolerance. Transcriptomic profiling has implicated stromal cells in immune-mediated disorders including the 2 common forms of inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). Stromal-immune interactions may edify inflammatory state and the development of IBD-related complications such as fibrosis, yet the lack of protein markers has hampered studying stromal-immune perturbation. METHODS: In this study, we designed a 40-color spectral flow cytometry assay to characterize hematopoietic and nonhematopoietic cells in intestinal biopsies and matched blood samples from patients with CD or UC. RESULTS: We identified circulating stromal-like cells that are significantly more abundant in IBD blood samples than in healthy controls. Those cells expressed podoplanin (PDPN), a commonly used marker for fibroblasts, and they were associated with activated and memory T and B cells and altered natural killer cell, monocyte, and macrophage populations. PDPN + cells in the blood correlated with PDPN + cells in the colon. Principal component analysis distinctly separated healthy blood samples from IBD blood samples, with stromal-like cells and B-cell subtypes dominating the IBD signature; Pearson correlation detected an association between PDPN + stromal-like cells and B-cell populations in IBD blood and gut biopsies. DISCUSSION: These observations suggest that PDPN + cells in the blood may serve as a biomarker of IBD. Understanding the relationship between stromal cells and immune cells in the intestine and the blood may provide a window into disease pathogenesis and insight into therapeutic targets for IBD.

The Effect of Etrasimod on Fecal Calprotectin and High-sensitivity C-reactive Protein: Results From the ELEVATE UC Clinical Program.

BACKGROUND: Biomarkers offer potential alternatives to endoscopies in monitoring ulcerative colitis (UC) progression and therapeutic response. This post hoc analysis of the ELEVATE UC clinical program assessed potential predictive values of fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) as biomarkers and associated responses to etrasimod, an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC, in 2 phase 3 clinical trials. METHODS: In ELEVATE UC 52 and ELEVATE UC 12, patients were randomized 2:1 to 2 mg of etrasimod once daily or placebo for 52 or 12 weeks, respectively. Fecal calprotectin/hsCRP differences between responders and nonresponders for efficacy end points (clinical remission, clinical response, endoscopic improvement-histologic remission [EIHR]) were assessed by Wilcoxon P-values. Sensitivity and specificity were presented as receiver operating characteristics (ROC) curves with area under the curve (AUC). RESULTS: In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 patients received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL/hsCRP concentrations were generally balanced. Both trials had lower week-12 median fCAL levels in week-12 responders vs nonresponders receiving etrasimod for clinical remission, clinical response, and EIHR (all P < .001), with similar trends for hsCRP levels (all P < .01). For etrasimod, AUCs for fCAL/hsCRP and EIHR were 0.85/0.74 (week 12; ELEVATE UC 52), 0.83/0.69 (week 52; ELEVATE UC 52), and 0.80/0.65 (week 12; ELEVATE UC 12). CONCLUSIONS: Fecal calprotectin/hsCRP levels decreased with etrasimod treatment; ROC analyses indicated a prognostic correlation between fCAL changes during induction and short-/long-term treatment response.

We show associations between fecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) levels with efficacy outcomes among patients receiving 2 mg of etrasimod once daily, and that fCAL levels may be an early indicator of the achievement of long-term efficacy end point achievement.

Early and Sustained Symptom Control with Mirikizumab in Patients with Ulcerative Colitis in the Phase 3 LUCENT Program.

BACKGROUND AND AIMS: Ulcerative colitis (UC), a chronic inflammatory bowel disease, may manifest with symptoms of increased stool frequency (SF), rectal bleeding (RB), bowel urgency (BU), abdominal pain (AP), and fatigue. Mirikizumab, an anti-IL-23p19 antibody, demonstrated efficacy and safety in patients with moderately to severely active UC in the LUCENT Phase 3 trials. We evaluated mirikizumab's efficacy in achieving symptom control and time to symptom improvement during induction, maintenance of sustained symptom control, "comprehensive symptom control", defined according to a combination of individual patient-reported outcomes, and prognostic baseline indicators of early symptomatic remission at week 4. METHODS: The results of LUCENT-1/-2 have previously been reported. Treatment differences for symptomatic endpoints were compared over 52 weeks versus placebo (PBO) and comprehensive symptomatic endpoints at 12 and 52 weeks of continuous treatment. Subgroup analyses were conducted for prior biologic or tofacitinib treatment failure. Prognostic analyses were run using regression analysis. RESULTS: By Week (W)2, mirikizumab-treated patients achieved greater reductions in SF, RB, BU, and fatigue versus PBO. At W4, there was a higher rate of AP improvement. At W12, a greater proportion of mirikizumab-treated patients achieved symptomatic remission, RB remission, SF remission, and BU remission/clinically meaningful improvement. Mirikizumab-treated patients sustained symptom control versus placebo patients in maintenance until W52. This treatment effect was shown in patients regardless of prior biologic or tofacitinib failure. Additionally, mirikizumab achieved comprehensive symptom control versus PBO at W12 and W52. CONCLUSIONS: Mirikizumab demonstrated efficacy in achieving and sustaining symptom control and comprehensive symptom control over 52 weeks. [NCT03518086; NCT03524092].

Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Events From the ELEVATE UC Clinical Program.

BACKGROUND AND AIMS: Infections are a safety concern in patients with ulcerative colitis (UC). Etrasimod is an oral, once-daily (QD), selective sphingosine 1phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. It leads to selective and reversible lymphocyte sequestration, and partial peripheral lymphocyte count decrease. We report infection events from the phase 3 ELEVATE program. METHODS: Proportions, incidence rates (IRs; per 100 patient-years) and descriptive analyses of all, serious, severe, herpes zoster, and opportunistic infections are reported in the Pivotal UC cohort (ELEVATE UC 52 and ELEVATE UC 12). Cox regression models evaluated potential baseline risk factors. RESULTS: In this analysis (n=787), proportions (IRs) of all infection events were similar for patients receiving etrasimod 2 mg QD (18.8% [41.1]) or placebo (17.7% [49.0]). Serious infections occurred in three (0.6%) and five (1.9%) patients receiving etrasimod and placebo, respectively. Two herpes zoster events were reported in each group (etrasimod: 0.4%; placebo: 0.8%); all localized and non-serious. One opportunistic infection event was reported in each group. No patient with an absolute lymphocyte count (ALC) <0.2 × 109/L reported serious/severe or opportunistic infections; no baseline risk factors were identified for such events. No deaths occurred. CONCLUSIONS: Patients receiving etrasimod demonstrated no increased risk of infection. The incidence of serious infections and herpes zoster was similar in each group. Among patients receiving etrasimod, no association between ALC <0.5 × 109/L and infection events was observed. Longer-term follow-up will further characterize the etrasimod safety profile.

Environmental Factors Associated with Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

BACKGROUND & AIMS: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy.

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti-IL-23 therapy. Experimental evidence generated from these investigations could establish a novel molecular ontology centered around IL-23-driven diseases, improve upon current approaches to treating IMIDs with IL-23 inhibition, and ultimately facilitate optimal identification of patients and, thereby, outcomes.

Extrachromosomal Circular DNA: An Emerging Potential Biomarker for Inflammatory Bowel Diseases?

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn's disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated.

Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

BACKGROUND: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104. METHODS: Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC). RESULTS: Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 76.6%, 89.0%, and 98.3% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 54.0%, 62.8%, and 70.1% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events. CONCLUSIONS: Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.

Long-term clinical response/remission, endoscopic, histologic, and symptomatic data from an open-label study in patients with moderately to severely active ulcerative colitis demonstrate that 2-year continuous mirikizumab treatment maintained clinical remission in a majority of induction clinical responders, regardless of previous biologic failure status.

The influence of exotic and native plants on illnesses with physical and spiritual causes in the semiarid region of Piauí, Northeast of Brazil.

BACKGROUND: Local medical systems (LMS) include native and exotic plants used for the treatment of diseases of physical and spiritual nature. The incorporation of exotic plants into these systems has been the subject of many studies. In this context, an analysis was conducted on the influence of the origin of plants on diseases of physical and spiritual nature in order to evaluate the therapeutic versatility of native and exotic species in these therapeutic targets, to investigate whether exotic plants mainly fill gaps not met by native plants (diversification hypothesis), and identify which species are prioritized in the redundant targets in these two therapeutic groups in the rural community of Morrinhos, Monsenhor Hipólito, Piauí. METHODS: Data collection took place in 2 stages. First, free lists and semi-structured interviews with local residents (n = 134) were conducted to survey plants used for therapeutic purposes and the associated illnesses. Then, another phase of interviews was carried out to evaluate the prioritization between native and exotic plants in redundant therapeutic targets. To test the diversification hypothesis (DH) in each group of illnesses, data were analyzed using generalized linear models (Poisson and Binomial GLMs); versatility was measured by the number of therapeutic indications and compared between resources using the Mann-Whitney test, and prioritization in each group was verified by comparing the proportions of native and exotic plants with the χ2 test. RESULTS: One hundred and thirty-two species of plants were surveyed, being 71 exotic and 61 native, with indications for physical and spiritual illnesses. The results revealed that the diversification hypothesis did not explain the inclusion of exotic plants in the local medical system to treat physical or spiritual illnesses and that the therapeutic versatility of exotic and native resources in the two groups was also similar (p > 0.05). However, exotic plants were prioritized in illnesses with physical causes and native plants in illnesses with spiritual causes. CONCLUSIONS: The local medical system presents similar and distinct patterns in the therapeutic targets, depending on the perspective evaluated. Therefore, it is necessary to investigate the patterns of use of medicinal plants in different sociocultural contexts in order to broaden the debate about the role of plant origin in the selection of treatments for illnesses with different causes.

Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.

BACKGROUND AND AIMS: Previously published long-term safety data reported a favourable ustekinumab safety profile for the treatment of inflammatory bowel disease [IBD]. We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn's disease [CD] and 4 years in ulcerative colitis [UC]. METHODS: In phase 3 studies, patients received a single intravenous placebo or ustekinumab [130 mg or ~6 mg/kg] induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab [90 mg q8w or q12w]. Analyses included all patients who received one dose of study treatment and included patients who were biologic-naïve and patients with a history of biologic failure. Safety outcomes are summarized and presented using number of events per 100 patient-years of follow-up and corresponding 95% confidence intervals. RESULTS: In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including major adverse cardiac events and malignancies, were similar between placebo and ustekinumab or not higher for ustekinumab. Opportunistic infections, including tuberculosis, and malignancies were reported infrequently. Rates of key safety events in the IBD group were no higher in the ustekinumab group than in the placebo group for both patients who were biologic-naïve or who had a history of biologic failure. No lymphomas or cases of posterior reversible encephalopathy syndrome [formerly known as reversible posterior leukoencephalopathy syndrome] were reported. CONCLUSION: The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo and continue to support the well-established safety profile across all approved indications. CLINICAL TRIALS.GOV NUMBERS: NCT00265122, NCT00771667, NCT01369329, NCT01369342, NCT01369355, NCT02407236.

Early Life and Childhood Environmental Exposures, More Than Genetic Predisposition, Influence Age of Diagnosis in a Diverse Cohort of 2952 Patients With IBD.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) develops from a combination of genetic and environmental factors. The aim of this study was to determine the contribution of established environmental risk factors and genetic risk on age of IBD diagnosis in a diverse cohort. METHODS: IBD patients in clinic completed detailed questionnaires. Blood was drawn for genetic analysis. Environmental risk factors and age of diagnosis were analyzed by ethnicity (Hispanic/Latinx or non-Hispanic White [NHW] individuals) and IBD subtype (ulcerative colitis or Crohn's disease [CD]). Weighted genetic risk scores and environmental risk scores were developed. We examined the relationship between environmental risk scores, genetic risk scores, and age of diagnosis. RESULTS: A total of 2952 patients were included: 58.9% had CD. A total of 46.83% were of Hispanic background. Early life exposures like cesarean delivery and being born in a developed country were associated with a younger age of IBD diagnosis. Childhood exposures such as frequent plastic water bottle use and having more than 1 bathroom at home were associated with a younger age of IBD. Hispanic and NHW individuals shared similar susceptibilities to environmental exposures. Environmental factors explained 21% of the variance in age of CD diagnosis and 39% in ulcerative colitis. In models incorporating genetic risk score and environmental risk score, the environment was the only significant factor associated with younger age of IBD diagnosis in all groups. CONCLUSIONS: Early life and childhood exposures impact IBD diagnosis and influence Hispanic and NHW individuals similarly. A cumulative environmental risk score contributes more to age of IBD diagnosis than genetic risk.

Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures.

BACKGROUND: One-third of veterans returning from the 1990-1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI. METHODS: Symptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using Analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups. RESULTS: GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both Healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F = 4.7, P = 0.01,) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F > 3.75, P < 0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms. CONCLUSION: We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.

Outcomes and Endpoints of Postoperative Recurrence in Crohn's Disease: Systematic Review and Consensus Conference.

BACKGROUND: Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries. METHODS: Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded. RESULTS: In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications. CONCLUSIONS: Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.

Epidemiologia de la Fluorosis Dental en adolescentes de 12 años: Revisión sistemática

La prevalencia de fluorosis dental presenta una gran variabilidad a nivel mundial. Es necesario su análisis como parte de la vigilancia epidemiológica. Objetivo: Conocer la literatura disponible sobre prevalencia de fluorosis dental a la edad de 12 años en relación con el método de fluoruración comunitario utilizado. Metodología: Dos investigadoras realizaron una revisión sistemática de la literatura sin límites temporales siguiendo las pautas PRISMA, utilizando las bases de datos Pubmed, Cochrane, Scopus, BVS y Google Schoolar en idioma inglés, español, portugués e italiano. Resultados: Fueron incluidos 19 artículos de diseño transversal, 16 pertenecientes a comunidades que utilizan agua fluorurada, uno que utiliza sal fluorurada y 2 que comparan resultados entre comunidades que utilizan agua o sal fluorurada. Conclusiones: existe gran variabilidad en los reportes de prevalencia de fluorosis dental. Independientemente del método de fluoruración comunitario utilizado las lesiones de fluorosis de severidad leve son las más prevalentes.

Os relatos sobre a prevalência de fluorose dentária aos 12 anos apresentam grande variabilidade, não havendo unificação quanto ao uso dos índices. Independentemente do meio comunitário de fluoretação e do índice utilizado, a fluorose dentária leve é ​​a mais prevalente. Objetivo: Conhecer a literatura disponível sobre prevalência de fluorose dentária aos 12 anos em relação ao método comunitário de fluoretação utilizado. Metodologia: Dois pesquisadores realizaram uma revisão sistemática da literatura sem limites de tempo seguindo as diretrizes PRISMA, utilizando as bases de dados Pubmed, Cochrane, Scopus, BVS e Google Schoolar em inglês, espanhol, português e italiano. Resultados: Foram incluídos 19 artigos transversais, sendo 16 pertencentes a comunidades que utilizam água fluoretada, un sal fluoretada e 2 que comparam resultados entre comunidades que utilizam água fluoretada ou salgada. Conclusões: Há grande variabilidade nos relatos de prevalência de fluorose dentária. Independentemente do método de fluoretação comunitária utilizado, as lesões de fluorose de gravidade leve são as mais prevalentes.

The prevalence of dental fluorosis presents great variability worldwide. Its analysis is necessary as part of epidemiological surveillance Objective: To know the available literature on the prevalence of dental fluorosis among 12 years-old in relation to the community fluoridation method used. Methodology: Two researchers carried out a systematic review of the literature without time limits following the PRISMA guidelines, using the Pubmed, Cochrane, Scopus, BVS and Google Schoolar databases in English, Spanish, Portuguese and Italian. Results: 19 cross-sectional articles were included, 16 belonging to communities that use fluoridated water, one that use fluoridated salt and 2 that compare results between communities that use fluoridated water or salt. Conclusions: there is great variability in the reports of prevalence of dental fluorosis. Regardless of the community fluoridation method used, fluorosis lesions of mild severity are the most prevalent.

Colorectal Cancer Immunotherapy: State of the Art and Future Directions.

Cancer immunotherapy has become an indispensable mode of treatment for a multitude of solid tumor cancers. Colorectal cancer (CRC) has been one of the many cancer types to benefit from immunotherapy, especially in advanced disease where standard treatment fails to prevent recurrence or results in poor survival. The efficacy of immunotherapy in CRC has not been without challenge, as early clinical trials observed dismal responses in unselected CRC patients treated with checkpoint inhibitors. Many studies and clinical trials have since refined immunotherapies available for CRC, solidifying immunotherapy as a powerful asset for CRC treatment. This review article examines CRC immunotherapies, from their foundation, through emerging avenues for improvement, to future directions.

Constituição psíquica e linguística de um sujeito com transtorno do espectro do autismo imerso em uma família vulnerável pela imigração no pós-guerra / Psychic and linguistic constitution of a subject with autism spectrum disorder immersed in a family vulnerable by post-war immigration / Constitución psíquica y lingüística de un sujeto con trastorno del espectro autismo inmerso en una familia vulnerable por inmigración de posguerra

Introdução: este artigo apresenta a constituição psíquica e linguística de um jovem autista, proveniente de uma família de imigrantes em situação de pós-guerra, em que entram em questão temas como o luto, a constituição psíquica transgeracional, e a presença de angústias no processo de desenvolvimento da criança em uma situação singular que é a presença do autismo. Objetivo: analisar os efeitos singulares da imigração e multiculturalismo em um caso de autismo e sua evolução terapêutica. Método: estudo de caso longitudinal, que utilizou diário clínico e filmagens de sessões com observações do desenvolvimento de Rafael, desde os dezoito meses até a idade adulta. Como abordagem terapêutica e análise dos resultados, foram utilizados aportes da constituição psíquica da teoria psicanalítica, e sobre o desenvolvimento linguístico em uma perspectiva enunciativa. Resultados: O multiculturalismo acarretava um desafio maior ao processo de aquisição da linguagem por parte da criança com autismo, enquanto o silêncio consequente da dor do luto, presente nos adultos, dificultava a troca verbal e atrasava sua constituição psíquica. O autismo, por sua vez, apresentou-se como transtornos qualitativos na comunicação, necessitando maior investimento por parte de seus cuidadores para que a aquisição da linguagem se desse, pois o paciente precisou ser fisgado para a nossa cultura. Conclusão: Diante de todo esse quadro, o caso clínico demonstra a importância do suporte terapêutico à família e do investimento contínuo na subjetivação, considerando e valorizando os diferentes códigos culturais que compõem o núcleo familiar. (AU)

Introduction: this article presents the psychic and linguistic constitution of an autistic young man, from a post-war immigrant family, in which themes such as mourning, the transgenerational psychic constitution, and the presence of anxieties in the process come into question of the child development in a unique situation that is the presence of autism. Objective: to analyze the unique effects of immigration and multiculturalism in a case of autism and its therapeutic evolution. Method: longitudinal case study, which used a clinical diary and footage of sessions with observations of the development of R. from eighteen months to adulthood. As a therapeutic approach and analysis of results, contributions from the psychic constitution of psychoanalytic theory, and on linguistic development in an enunciative perspective, were used. Results: Multiculturalism posed a greater challenge to the process of language acquisition by the child with autism, while the consequent silence of the pain of grief, present in adults, hindered verbal exchange and delayed their psychic constitution. Autism, in turn, presented itself as qualitative disorders in communication, requiring greater investment on the part of its caregivers for the acquisition of language to take place, as it needed to be hooked for our culture. Conclusion: Given this situation, this clinical case demonstrates the importance of therapeutic support to the family and the continuous investment in subjectivity, considering and valuing the different cultural codes that make up the family nucleus. (AU)

Introducción: este artículo presenta la constitución psíquica y lingüística de un joven autista, proveniente de una familia inmigrante de posguerra, en la que se cuestionan temas como el luto, la constitución psíquica transgeneracional y la presencia de ansiedades en el proceso del desarrollo del niño en una situación única que es la presencia del autismo. Objetivo: analizar los efectos singulares de la inmigración y la multiculturalidad en un caso de autismo y su evolución terapéutica. Método: estudio de caso longitudinal, que utilizó un diario clínico y metraje de sesiones con observaciones del desarrollo de R. desde los dieciocho meses hasta la edad adulta. Como abordaje terapéutico y análisis de resultados se utilizaron aportes desde la constitución psíquica de la teoría psicoanalítica y sobre el desarrollo lingüístico en perspectiva enunciativa. Resultados: El multiculturalismo supuso un mayor desafío al proceso de adquisición del lenguaje por parte del niño con autismo, mientras que el consiguiente silencio del dolor del duelo, presente en los adultos, dificultó el intercambio verbal y retrasó su constitución psíquica. El autismo, a su vez, se presentó como un trastorno cualitativo en la comunicación, requiriendo una mayor inversión por parte de sus cuidadores para que se produjera la adquisición del lenguaje, pues necesitaba engancharse a nuestra cultura. Conclusión: Ante esta situación, este caso clínico demuestra la importancia del apoyo terapéutico a la familia y la continua inversión en la subjetividad, considerando y valorando los diferentes códigos culturales que conforman el núcleo familiar. (AU)

Healthcare Utilization Patterns and Excessive Steroid Use in Late Adolescence Age and Young Adults With Crohn's Disease and Ulcerative Colitis.

Background and Aims: Late adolescents and young adults (AYA) with inflammatory bowel disease (IBD) are a vulnerable population as they transition to adult healthcare. We aim to provide a real-world data on their healthcare utilization patterns and medication use through a large database. Methods: We performed a retrospective cohort study from January 1, 2012, to June 30, 2020, using OneFlorida Data-Trust, an electronic health record-based data repository representing over half of the Florida population. Outcomes of interest included demographics, healthcare utilization, medications, and disease severity. Chi-square tests and logistic regression were used to compare the rates of medication use, healthcare utilization, and disease severity by age groups. Results: The number of patients who met our inclusion criteria was 10,578 with 2731 (25.8%) in the 17-25-year-old group. AYA patients had fewer ambulatory visits vs children (90% vs 95%; P value <.05). AYA patients were admitted more frequently from emergency facilities vs children (22.3% vs 10.9%; P value <.05). AYA patients received steroids more often than adults and younger patients (48.9% vs 45.3 vs 44.3% P value <.05, respectively). AYA patients received more narcotic (41.1% vs 22.3 % P value <.05) and antidepressant prescriptions (15.9% vs 9.5%; P value <.05) compared with children. With advancing age, a decrease in biologic use was noted (51% vs 40% vs 25.4% P value <.05, respectively). Conclusion: AYA patients with IBD have higher rates of hospital admissions from emergency department, fewer ambulatory health visits and they receive more steroids compared to children. Our study demonstrates the need for age-specific IBD programs for AYA patients.