Redox profile of silver catfish challenged with Aeromonas hydrophila and treated with hexane extract of Hesperozygis ringens (Benth.) Epling through immersion bath.

The growing increase in the fish farming sector has favored the establishment of bacterial outbreaks caused by Aeromonas hydrophila in several species. The hexane extract of Hesperozygis ringens (HEHR) (Lamiaceae) leaves increased the survival rate of silver catfish (Rhamdia quelen) experimentally infected by A. hydrophila. However, it is noteworthy that no reports have been found on the possible mechanisms of action of this extract in infected fish. This study aimed to evaluate the effect of the HEHR, administered through single immersion bath, on lipid peroxidation and antioxidant defenses in muscle and liver tissue of silver catfish challenged with A. hydrophila. The results showed that the oxidative status of silver catfish was altered, although oxidative stress was not triggered during the experiment. HEHR at 30 mg/L (HEHR30) was not characterized as a pro-oxidant agent in the presence of infection, unlike florfenicol and HEHR at 15 mg/L treatments in some cases. In short, HEHR30 provided an important increase in hepatic catalase activity, characterizing one of the possible mechanisms involved in the greater survival of fish experimentally infected by A. hydrophila. Additionally, HEHR30 did not induce lipid peroxidation, nor reduced antioxidant defenses of silver catfish infected or not by A. hydrophila.

The influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients.

BACKGROUND AND AIMS: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. METHODS: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. RESULTS: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. CONCLUSION: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.

Retrograde peripheral nerve regeneration from sensory to motor pathways in rats: a new experimental concept in nerve repair.

BACKGROUND: The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. METHODS: Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. RESULTS: Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. CONCLUSIONS: Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer.

Thiopurines have no impact on outcomes of Crohn's disease patients beyond 12 months of maintenance treatment with infliximab.

BACKGROUND: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. AIMS: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. METHODS: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure. RESULTS: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). CONCLUSION: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.

Erosion-inhibiting and enamel rehardening effects of different types of saliva.

OBJECTIVES: The objective of this study was to assess the effects of in situ saliva compared to in vitro human saliva, with or without mucin, on inhibiting erosion and promoting enamel rehardening. DESIGN: Bovine enamel blocks were randomly distributed into groups (n = 23): Gsitu (human saliva in situ), Gvitro (collected human saliva) and GvitroM (collected human saliva with mucin). The enamel blocks underwent a 2-hour period for the formation of salivary pellicle, based on the assigned groups. Subsequently, they were subjected to three erosive cycles, each of them consisting of an erosive challenge (immersion in 0.65 % citric acid, pH 3.5, 1 min) and saliva exposure (immersion in situ or in vitro saliva for 2 h). Microhardness measurements were performed at each cycle, after each experimental step (erosive challenge and exposure to saliva). RESULTS: After the first demineralization, in vitro saliva groups presented greater hardness loss, with no statistical difference between GVitroM and GVitro. After the third erosive demineralization the in situ saliva resulted in less hardness loss compared to the first demineralization. In relation to surface hardness recovery, there was no difference among types of saliva but there was a decrease in hardness as the cycles progressed. CONCLUSION: Saliva groups had different behaviors between the first and third demineralization, being similar after the third cycle in terms of hardness loss. Regarding hardness recovery, all saliva promoted enamel gain, but there was a gradual decrease with the progression of the cycles.

How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?-A prospective study.

BACKGROUND: Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD. OBJECTIVE: We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression. METHODS: Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices. RESULTS: The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 µg/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 µg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes. CONCLUSION: The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.

Inflammatory Bowel Disease Treatment in Cancer Patients-A Comprehensive Review.

Inflammatory bowel disease (IBD) is a chronic disease for which medical treatment with immunomodulating drugs is increasingly used earlier to prevent disability. Additionally, cancer occurrence in IBD patients is increased for several reasons, either IBD-related or therapy-associated. Doctors are therefore facing the challenge of managing patients with IBD and a past or current malignancy and the need to balance the risk of cancer recurrence associated with immunosuppressive drugs with the potential worsening of IBD activity if they are withdrawn. This review aims to explore the features of different subtypes of cancer occurring in IBD patients to present current evidence on malignancy recurrence risk associated with IBD medical therapy along with the effects of cancer treatment in IBD and finally to discuss current recommendations on the management of these patients. Due to sparse data, a case-by-case multidisciplinary discussion is advised, including inputs from the gastroenterologist, oncologist, and patient.

Early-onset colorectal cancer: A review of current knowledge.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Although most prevalent among older people, its incidence above 50 years old has been decreasing globally in the last decades, probably as a result of better screening. Paradoxically, its incidence in patients below 50 years old [early-onset CRC (EO-CRC)] has been increasing, for reasons not yet fully understood. EO-CRC's increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide. It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors. Its incidence is predicted to double until 2030, which makes EO-CRC a serious public health issue. Both modifiable and non-modifiable risk factors have been identified - some are potential targets for preventive measures. EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described. EO-CRC presents some distinctive features: Microsatellite in-stability is common, but another subtype of tumours, both microsatellite and chromosome stable also seems relevant. There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data. Due to the higher germline pathological mutations found in EO-CRC patients, an accurate genetic risk evaluation should be performed. In this review, we summarize the current evidence on epidemiological, clinical, histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors. We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.

Incidence and risk factors for neoplasia in inflammatory bowel disease.

INTRODUCTION: Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia. The aim was to evaluate the incidence of malignant neoplasia in IBD patients, associated risk factors and therapy adjustments. METHODS: Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological centre during 2015-2020 were included. RESULTS: 318 patients were included female 55.0%, age at diagnosis = 37.24(±15,28), Crohn's disease 52.5%, Primary Sclerosing Cholangitis n = 7, family history of cancer n = 12, previous diagnosis of neoplasia n = 23(7.2%). 42 cancers were diagnosed in 35 patients (11.0%) - median of 12.0(IQR = 7.5-21.0) years after IBD diagnosis. Most affected organs were the skin (n = 15 in 11 patients; melanoma = 1), colon/rectum (n = 8 in 6 patients), prostate (n = 4), breast (n = 3) and anal canal (n = 2). In those with non-melanoma skin cancer, 6 were under active treatment with azathioprine and 2 had stopped it for more than two years. In the univariate analysis, the occurrence of neoplasia was positively associated with tobacco exposure (p = 0.022), age at IBD diagnosis (p = 0.021), and negatively with infliximab exposure (p = 0.046). In 9 cases, cancer treatment was different because of the IBD, while IBD treatment was changed in 9 patients. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p = 0.004) and positively with salicylates use (p = 0.007). CONCLUSION: In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, tobacco exposure was a risk factor for the development of neoplasia.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

Endoscopic Approach to Duodenal Adenomas in Familial Adenomatous Polyposis: A Retrospective Cohort.

Introduction: Over 90% of the patients with familial adenomatous polyposis (FAP) will develop duodenal adenomas. Aim: The aim of this study was to evaluate the effectiveness and safety of endoscopic excision of large duodenal adenomas in FAP patients. Methods: All FAP patients from a familial risk clinic submitted to endoscopic therapy for duodenal adenomas ≥10 mm between January 2010 and February 2021 were included. Results: From 151 FAP families, 22 patients (50 lesions) were included: 54.5% female; median follow-up 8.5 (IQR: 5.8-12.3) years after the first endoscopy. First therapeutic endoscopy occurred at a median age of 41.0 years (IQR: 33.0-58.2). Repeat therapeutic endoscopy was required in 54.5% of patients. Median size of the largest adenoma was 15 mm (IQR: 10-18 mm); resection was piecemeal in 63.1% and en bloc in the remaining. In 2 cases, the resection was incomplete (fibrosis due to previous resection and difficult positioning). Complications occurred in 6.3% of the resected lesions (4 patients): 2 immediate (bleeding, perforation); 4 in the first week (1 bleeding, 2 mild pancreatitis, 1 perforation requiring surgery; the latter two after ampullectomy). Histology revealed low-grade dysplasia adenomas in 90.1%; no adenocarcinomas were found. One patient with Spigelman stage IV disease not amenable to endoscopic control underwent elective duodenopancreatectomy (without duodenal cancer). Conclusion: Endoscopic surveillance and treatment of duodenal adenomas in FAP patients was safe and effective in the prevention of duodenal cancer.

Introdução: Mais de 90% dos doentes com Polipose Adenomatosa Familiar (PAF) desenvolvem adenomas duodenais. Objetivo: Avaliar a eficacia e seguranca da excisao endoscopica de adenomas duodenais em doentes com PAF. Métodos: Incluidos todos os doentes com PAF submetidos a terapeutica endoscopica de adenomas duodenais ≥10 mm entre janeiro/2010-fevereiro/2021. Resultados: Em 151 familias com PAF, incluidos 22 doentes (50 lesoes): 54.5% mulheres; mediana do follow-up 12.3 (IQR: 6.0­19.0) anos. Primeira endoscopia terapeutica (ressecao de polipos duodenais ≥10 mm) ocorreu numa mediana de idades 41.0 (IQR: 33.0­58.2) anos. Em 54.5% dos casos, foi necessaria uma nova endoscopia terapeutica. Dimensao mediana do maior adenoma: 15 mm (IQR: 10­18 mm); ressecao realizada em piecemeal em 63.1% e em bloco nos restantes. Em dois casos, a ressecao endoscopica foi incompleta (fibrose em local de ressecao previa:1; posicionamento: 1). Complicacoes em 6.3% das lesoes ressecadas (4 doentes): 2 imediatas (hemorragia e perfuracao, manejadas endoscopicamente); 4 na primeira semana (1 hemorragia controlada endoscopicamente, 2 pancreatites ligeiras tratadas conservadoramente, 1 perfuracao com necessidade de cirurgia; as duas ultimas apos ampulectomia). A avaliacao histologica revelou adenomas com displasia de baixo grau em 90.1%; nenhum adenocarcinoma. Um doente com doenca Spigelman IV nao controlavel endoscopicamente realizou duodenopancreatectomia (sem cancro). Conclusão: A vigilancia e tratamento endoscopicos de adenomas duodenais em doentes com PAF revelaram-se seguros e eficazes na prevencao de cancro duodenal.

Direct Synthesis of HKUST-1 onto Cotton Fabrics and Properties.

Metal-organic frameworks are crystalline nanostructures formed by a metal interspersed by an organic binder. These metal-organic materials are examples of nanomaterials applied to textile material in search of new functionalized textiles. Cotton is a cellulosic fiber of great commercial importance, and has good absorption capacity and breathability; however, due to these characteristics, it is susceptible to the development of microorganisms on its surface. This work aims to analyze how the direct synthesis of HKUST-1 in cotton fabric modifies the chemical and physical properties. The material obtained was characterized by scanning electron microscopy to obtain its morphology, by spectrophotometry CIE L*a*b* to verify the color change, by a biological test to verify its resistance to microorganisms and, finally, by a unidirectional traction test to verify the change in its mechanical resistance. Thereby, it was possible to observe the formation of MOFs with the morphology of nanorods, and also, with regard to HKUST-1 in the cotton fabric, when applied, an elimination percentage higher than 99% was observed for both bacteria, E. coli and S. aureus. The presence of MOF was detected even after washing, however, the loss of 75% in the mechanical resistance of the material makes its potential for textile finishing unworkable.

Routine Immunohistochemical Analysis of Mismatch Repair Proteins in Colorectal Cancer-A Prospective Analysis.

Recognition of a hereditary colorectal cancer (CRC) syndrome is crucial and Lynch Syndrome (LS) is the most frequent immunohistochemistry (IHC)-screening for mismatch repair proteins (MMR) deficiency in CRC is therefore advocated. An unicentric cohort study was conducted in a central Oncological Hospital to assess its results. All patients under 70 years-old admitted between July 2017-June 2019 and submitted to surgery for CRC were included. Of 275 patients, 56.0% were male, median age 61.0 (IQR:54.5-65.0), with synchronous tumors in six. Histology revealed high grade adenocarcinoma in 8.4%; mucinous and/or signet ring differentiation in 11.3%; and lymphocytic infiltration in 29.8%. Amsterdam (AC) and Bethesda (BC) Criteria were fulfilled in 11 and 74 patients, respectively. IHC revealed loss of expression of MMR proteins in 24 (8.7%), mostly MLH1 and PMS2 (n = 15) and PMS2 (n = 4). Among these, no patients fulfilled AC and 13 fulfilled BC. BRAF mutation or MLH1 promoter hypermethylation was found in four patients with MLH1 loss of expression. Genetic diagnosis was performed in 51 patients, 11 of them with altered IHC. LS was diagnosed in four, and BC was present in three. One patient would not have been diagnosed without routine IHC screening. These results strengthen the important role of IHC screening for MMR proteins loss of expression in CRC.

Beliefs, knowledge, actions of nursing techniques in breastfeeding in pain management in immunization.

OBJECTIVE: Understand the beliefs, knowledge, and actions of nursing technicians on breastfeeding as a form of non-pharmacological intervention to relieve pain in newborns and infants during immunization. METHODS: Qualitative study carried out through semi-structured interviews with nine nursing technicians from three Basic Health Units in a city in the state of São Paulo. The theoretical approach of the Belief Model and the methodological framework of Thematic Analysis supported this study. RESULTS: Three themes originated: Beliefs, Knowledge, and Actions of nursing technicians. FINAL CONSIDERATIONS: Despite knowledge about the benefits of breastfeeding as the most effective method for relieving pain in newborns and infants during vaccination, their restrictive beliefs overrode the evidence, leading them to act in ways that discourage or prevent the mother from breastfeed during vaccination. Formal training is recommended to align with current evidence-based practices.

Colorectal cancer carcinogenesis: From bench to bedside.

Colorectal cancer (CRC) remains one of the main causes of cancer death in developed countries. Yet, it is potentially preventable, by removing the precursor lesions - adenomas or serrated lesions. Several studies proved that this intervention reduces CRC mortality and that the first colonoscopy's results can guide surveillance strategies. More recently, it became clear that several carcinogenesis pathways may lead to sporadic CRC. CRC is a heterogeneous disease, characterized by multiple molecular subtypes. Three main pathways have been implicated in the development of CRC: Chromosomal instability, microsatellite instability, and the "serrated" pathways, with overlapping features between them. This and other molecular and genetic based CRC classifications are known to have clinical implications, spanning from familial risk assessment to therapy choices. The authors review basic science data and provide insight on current implications for the management of patients with CRC.

Colorectal malignant polyps: a modern approach.

Colorectal malignant polyps (MP) are polyps with invasive cancer into the submucosa harboring a variable risk of lymph node involvement, which can be estimated through evaluation of morphological, endoscopic, and histologic features. The recent advances in imaging endoscopic techniques have led to the possibility of performing an optical diagnosis of T1 colorectal cancer, allowing the selection of the best therapeutic modality to optimize outcomes for the patient. When MP are diagnosed after endoscopic removal, their management can be challenging. Differentiating low- and high-risk histologic features that influence the possibility of residual tumor, the risk of recurrence and the risk of lymph node metastasis, is crucial to further optimize treatment and surveillance plans. While the presence of high-risk features indicates a need for surgery in the majority of cases, location, comorbidities and the patient's preference should be taken in account when making the final decision. This is a particularly important issue in the management of low rectal MP presenting with high-risk features, where chemoradiotherapy followed by a watch-and-wait strategy has demonstrated promising results. In this review we discuss the important prognostic features of MP and the most modern approaches regarding their management.

Subclinical Persistent Inflammation as Risk Factor for Crohn's Disease Progression: Findings From a Prospective Real-World Study of 2 Years.

BACKGROUND AND AIMS: Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers. METHODS: The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 µg/g, >250 µg/g, or >350 µg/g) or serum CRP (>3 µg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation. RESULTS: Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98-515] µg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80-6.00] µg/mL; P = .895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 µg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557-5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 µg/mL, FC >150 µg/g, FC >350 µg/g, double biomarkers (FC >250 µg/g and/or CRP >3 µg/mL), or more visits did not improve predictive ability. CONCLUSIONS: Persistent inflammation, defined simply and readily by FC >250 µg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients.

Beliefs, knowledge, actions of nursing techniques in breastfeeding in pain management in immunization / Creencias, conocimiento, acciones de técnicas de enfermería en la lactancia materna en el manejo del dolor en la inmunización / Crenças, conhecimento, ações de técnicas de enfermagem na amamentação no manejo da dor na imunização

ABSTRACT Objective: Understand the beliefs, knowledge, and actions of nursing technicians on breastfeeding as a form of non-pharmacological intervention to relieve pain in newborns and infants during immunization. Methods: Qualitative study carried out through semi-structured interviews with nine nursing technicians from three Basic Health Units in a city in the state of São Paulo. The theoretical approach of the Belief Model and the methodological framework of Thematic Analysis supported this study. Results: Three themes originated: Beliefs, Knowledge, and Actions of nursing technicians. Final considerations: Despite knowledge about the benefits of breastfeeding as the most effective method for relieving pain in newborns and infants during vaccination, their restrictive beliefs overrode the evidence, leading them to act in ways that discourage or prevent the mother from breastfeed during vaccination. Formal training is recommended to align with current evidence-based practices.

RESUMEN Objetivo: Comprender creencias, conocimiento y acciones de técnicas de enfermería sobre la lactancia materna como forma de intervención no farmacológica en el alivio del dolor en neonatos y en lactantes durante la inmunización. Métodos: Estudio cualitativo realizado mediante entrevistas semiestructuradas con nueve técnicas de enfermería de tres Unidades Básicas de Salud de una ciudad de São Paulo. El abordaje teórico del Modelo de Creencias y el referencial metodológico del Análisis Temático ampararon este estudio. Resultados: Originado tres temas: Creencias, Conocimiento y Acciones de las técnicas de enfermería. Consideraciones finales: Aunque del conocimiento sobre los beneficios de la lactancia materna como el método más eficaz para el alivio del dolor en neonatos y lactantes durante la vacunación, sus creencias restrictivas antepuestas a la evidencia, llevándolas a actuar de modo a desanimar o impedir la madre de amamantar durante la vacunación. Recomendado entrenamiento formal para alineamiento de prácticas actuales basadas en evidencias.

RESUMO Objetivo: Compreender as crenças, o conhecimento e as ações das técnicas de enfermagem sobre a amamentação como forma de intervenção não farmacológica no alívio da dor em recém-nascidos e em lactentes durante a imunização. Métodos: Estudo qualitativo realizado mediante entrevistas semiestruturadas com nove técnicas de enfermagem de três Unidades Básicas de Saúde de uma cidade do estado de São Paulo. A abordagem teórica do Modelo de Crenças e o referencial metodológico da Análise Temática ampararam este estudo. Resultados: Originaram-se três temas: Crenças, Conhecimento e Ações das técnicas de enfermagem. Considerações finais: Apesar do conhecimento sobre os benefícios da amamentação como o método mais eficaz para o alívio da dor em recém nascidos e lactentes durante a vacinação, suas crenças restritivas sobrepuseram-se à evidência, levando-as a agir de modo a desencorajar ou impedir a mãe de amamentar durante a vacinação. Recomenda-se treinamento formal para alinhamento de práticas atuais baseadas em evidências.

Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered.

Dysplasia Surveillance in Inflammatory Bowel Disease: A Cohort Study.

INTRODUCTION: Patients with colonic inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer (CRC), whereby surveillance colonoscopy is recommended. AIM: To study the clinical and endoscopic variables associated with dysplasia in IBD patients. METHODS: A cohort study was conducted on IBD patients who were part of a colonoscopy surveillance program between 2011 and 2016. RESULTS: A total of 342 colonoscopies were performed on 162 patients (105 with ulcerative colitis [UC] and 57 with Crohn's disease). Random biopsies were performed at least once on 81.5% of patients; 33.3% of the patients underwent chromoendoscopy (CE) at least once. Endoscopically resectable lesions were detected in 55 patients (34%), and visible lesions deemed unfit for endoscopic resection were found in 5 patients (3.1%). Overall, 62 dysplastic visible lesions (58 with low-grade dysplasia and 3 with high-grade dysplasia) and 1 adenocarcinoma were found in 34 patients. Dysplasia in random biopsies was present in 3 patients, the yield of random biopsies for dysplasia being 1.85%/patient (3/162), 1.75%/colonoscopy (6/342), and 0.25%/biopsy (9/3,637). Dysplasia detected in random biopsies was significantly associated with a personal history of visible dysplasia (p = 0.006). Upon univariate analysis, dysplasia was significantly associated with the type of IBD, the performance of random biopsies, and CE (p = 0.016/0.009/0.05, respectively). On multivariate analysis, dysplasia was associated with duration of disease. CONCLUSION: Our data confirm that patients with long-standing IBD, in particular UC, should be enrolled in dysplasia surveillance programs, and that performing CE and random biopsies seems to help in the detection of colonic neoplastic lesions.

INTRODUÇÃO: Nos doentes com doença inflamatória intestinal (DII) está recomendada vigilancia por colonoscopia para detetar e tratar lesões neoplásicas iniciais, dado o risco aumentado de cancro colo-rectal (CCR). O objetivo do trabalho foi estudar variáveis clínicas e endoscópicas associadas a displasia. MÉTODOS: Estudo coorte − doentes com DII integrados num programa de vigilância de displasia entre 2011­2016. RESULTADOS: Um total de 342 colonoscopias foi realizado em 162 doentes, 105 com colite ulcerosa (CU) e 57 com doença de Crohn (DC). Foram efetuadas biopsias aleatorias (BA) em 81,5% dos doentes (média: 27.5 ± 6.4 biopsias/colonoscopia) e 33.3% realizaram cromoendoscopia. 55 doentes apresentaram lesões endoscopicamente ressecáveis e 5 doentes lesões irressecáveis. No total, em 34 doentes, foram identificadas 6 lesões displásicas visíveis (58 com displasia de baixo grau e 3 com displasia de alto grau) e um adenocarcinoma. Foi detetada displasia em BA em 3 doentes sendo o rendimento das BA de 1.85% por doente (3/162), 1.75% por colonoscopia (6/342) e 0.25% por biopsia (9/3,637). A displasia em BA associou-se à historia pessoal de lesões displásicas (p = 0.006). A presença de displasia associouse, na análise univariada, com: tipo de DII (p = 0.016), realização de BA (p = 0.009) e cromoendoscopia (p = 0.05). Na anàlise multivariada, verificou-se associação com a duração da doença. CONCLUSÃO: Doentes com DII de longa duração deverão ser incluidos num programa de vigilància de displasia. A realizado de cromoendoscopia e BA é útil na deteção de lesões displásicas do cólon.