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OBJECTIVE: Despite a growing armamentarium of medical therapies for ulcerative colitis (UC), colectomy remains an important therapeutic option. To better inform shared decision-making about surgery, we estimated the contemporary risk of mortality post-colectomy. METHODS: Mortality rates were estimated using the National Inpatient Sample (2016-2020). Factors associated with post-colectomy death were evaluated in multivariable regression. RESULTS: Post-colectomy mortality occurred in 1.2% [95% CI: 0.8%, 1.9%] of hospitalizations. Comorbidity burden, emergent laparotomy, and delays to surgery >5 days after admission were associated with mortality. CONCLUSIONS: Colectomy may be associated with mortality; however, this risk is heterogeneous based on patient- and procedural-related factors.
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OBJECTIVES: To investigate how psychological and behavioural factors change from the first to the last half of pregnancy. METHODS: In this prospective cohort study, we assessed the changes in psychological and behavioural factors across 10 domains among 445 women (mean age = 30.9 years) in Ontario, Canada. We collected data using 2 standardized questionnaires administered at <21 and 32-36 weeks of gestation. We computed intraclass correlation coefficients, percentages of no change, decrease, and increase, and mean differences between the 2 surveys. RESULTS: Most psychological and behavioural factors had intraclass correlation coefficients < 0.50 between the first and the second half of pregnancy, suggesting remarkable changes over the course of pregnancy. We observed significant decreases in self-efficacy, compensatory health beliefs, guilt regarding binge eating, emotional eating, dietary restriction, pregnancy-related nausea and food cravings, sleep duration, and physical activity. We also found increases in anxious and depressive symptoms and the tendency to accept friends' and family's beliefs regarding pregnancy. CONCLUSIONS: In the first prospective analysis, we found that many psychological and behavioural factors changed significantly over pregnancy.
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Ansiedade , Emoções , Gravidez , Humanos , Feminino , Adulto , Estudos Prospectivos , Inquéritos e Questionários , Ontário/epidemiologiaRESUMO
BACKGROUND AND AIMS: Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. METHODS: We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). RESULTS: Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. CONCLUSIONS: There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
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Doença de Crohn , Obstrução Intestinal , MicroRNAs , Biomarcadores , Proteína de Matriz Oligomérica de Cartilagem , Constrição Patológica/etiologia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Humanos , Obstrução Intestinal/etiologia , Serina EndopeptidasesRESUMO
BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.
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Doença de Crohn , Inibidores do Fator de Necrose Tumoral , Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Necrose , Recidiva , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) frequently experience chronic pain. Patients will often seek out care in the emergency department (ED) where short-term opioid use may be associated with potential treatment-related complications. We aimed to assess the rate and factors associated with opioid prescription in IBD patients discharged from the ED. METHODS: We conducted a cross-sectional analysis of data collected in the US National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2006-2017. We determined the proportion of adult patients (≥18 years) with IBD prescribed an opioid in ED or at ED discharge. Logistic regression was used to evaluate predictors of opioid prescription. Time-trend analysis was performed to evaluate temporal patterns in opioid use. All analyses were adjusted for complex survey design. RESULTS: We identified â¼965,000 weighted discharges from the ED for patients with IBD. In total, 51.9% [95% CI: 42.2% -61.6%] of visits resulted in opioid administration in ED and 35.3% [95% CI: 26.5% -45.2%] of IBD-related ED discharges were associated with an opioid prescription. IBD patients with moderate/severe pain (adjusted odds ratio aOR 5.06 [95% CI: 1.72 -14.90], p < 0.01) were more likely to receive opioids whereas older age (aOR 0.73 per decade [95% CI: 0.55 -0.98], p = 0.04) were less likely. In temporal analysis, a trend towards decreasing opioid use in ED and opioid prescriptions at discharge was observed in 2015-2017. CONCLUSIONS: More than one third of IBD patients are prescribed an opioid at discharge from ED, highlighting a potential gap in care for accessing effective pain management solutions in this population.
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Analgésicos Opioides , Doenças Inflamatórias Intestinais , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Serviço Hospitalar de Emergência , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Alta do Paciente , Padrões de Prática Médica , PrescriçõesRESUMO
BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs) require repeated health care encounters, although the focus of care differs when patients are seen in ambulatory, emergency department (ED), or inpatient settings. We examined contemporary trends and disparities in IBD-related health care visits. METHODS: We used data from the National Ambulatory Medical Care Survey, the Nationwide Emergency Department Sample, and the National Inpatient Sample to estimate the total number of annual IBD-related visits from 2005 through 2016. We performed logistic regression analyses to test temporal linear trends. Slope and differences in distributions of patient demographics were compared across time and treatment settings. RESULTS: From 2005 through 2016, approximately 2.2 million IBD-related ambulatory visits (95 CI, 1.9-2.5) occurred annually on average, increasing by 70.3% from the time period of 2005 to 2007 through the time period of 2008 to 2010, and decreasing by 19.8% from the time period of 2011 to 2013 through the time period of 2014 to 2016. An average of 115,934 IBD-related ED visits (95% CI, 113,758-118,111) and 89,111 IBD-related hospital discharges (95% CI, 87,416-90,807) occurred annually. Significant increases in the rate of IBD-related ED visits (3.2 visits/10,000 encounters; P < .0001) and hospital discharges (6.0 discharges/10,000 encounters; P < .0001) were observed from 2005 through 2016. The proportion of patients paying with private insurance decreased from 2005 through 2016, among all care settings. A greater proportion of young patients, patients with Crohn's disease, non-white patients, and patients with Medicare or Medicaid used hospital-based vs ambulatory services. CONCLUSIONS: In an analysis of data from 3 large databases, we found that although IBD-related ambulatory visits stabilized to decreased from 2005 through 2016, rates of ED use and admission to the hospital have continued to increase with changes in patient demographics, over time and among care settings.
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Doenças Inflamatórias Intestinais , Pacientes Internados , Idoso , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Medicare , Estados Unidos/epidemiologiaRESUMO
Bowel ultrasound (US) is accurate for assessing bowel inflammation and complications in Crohn disease. Additionally, contrast-enhanced US provides a quantitative, objective measurement of inflammatory activity in inflammatory bowel disease, and shear wave elastography predicts the stiffness of bowel, an increase of which suggests less response to medical therapy, often necessitating surgery. Overall, bowel US is an excellent, safe, and repeatable choice for routine surveillance and for urgent imaging. We describe an approach to evaluating inflammatory bowel disease and review its features on standard grayscale US with Doppler imaging and show how contrast-enhanced US and shear wave elastography can distinguish between inflammatory and fibrostenotic bowel.
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Meios de Contraste , Doença de Crohn/diagnóstico por imagem , Aumento da Imagem/métodos , Intestinos/diagnóstico por imagem , Ultrassonografia/métodos , Doença de Crohn/patologia , Técnicas de Imagem por Elasticidade , Humanos , Intestinos/patologiaRESUMO
BACKGROUND AND AIM: Contemporary techniques to assess disease activity or bowel damage in patients with inflammatory bowel disease (IBD), such as endoscopy and imaging, are either invasive or lack accuracy. Non-invasive biomarkers for this purpose remain an unmet medical need. Herein, we provide a comprehensive systematic review of studies evaluating blood extracellular matrix (ECM) biomarkers and their relevance in IBD. METHODS: We conducted a systematic review of PubMed, EMBASE, Web of Science, and Scopus to identify citations pertaining ECM biomarkers of IBD up to March 1, 2024. Studies were categorized based on marker subtype and clinical use. RESULTS: Thirty-one ECM markers were identified, 28 of these demonstrated the ability to differentiate IBD disease activity. Collagen III emerged as the most extensively investigated (1212 IBD patients), with the degradation marker C3M and deposition marker PRO-C3 being associated with IBD and subtypes. Collagen V markers C5M and PRO-C5 emerged as the most accurate single markers for diagnosis of IBD, with an area under the curves of 0.91 and 0.93, respectively. Overall, studies were characterized by variable endpoints. None of the studies included histological grading of intestinal damage, repair, or fibrosis formation as the primary outcome in relation to the ECM blood markers. CONCLUSIONS: Multiple ECM markers are linked with IBD and its phenotypes. However, more rigorous study designs and clearly defined endpoints are needed to ensure reproducibility and develop reliable and accurate biomarkers. ECM markers hold promise as they provide a 'window' into transmural tissue remodeling and fibrosis burden, warranting further investigation.
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Fibrostenosis of the small bowel is common in patients with Crohn's disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn's disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn's disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn's disease.
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Consenso , Doença de Crohn , Intestino Delgado , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Humanos , Intestino Delgado/patologia , FibroseRESUMO
BACKGROUND: Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri-enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. AIMS: To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. METHODS: We searched four databases up to 6 January 2024. Two-stage screening was done in duplicate. We assessed risk of bias using QUADAS-2. RESULTS: There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. CONCLUSIONS: This systematic review is the first step for a structured program to develop a stricture IUS index for CD.
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Doença de Crohn , Obstrução Intestinal , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/diagnóstico por imagem , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/patologia , Reprodutibilidade dos Testes , Intestinos/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
Alopecia areata is a non-scarring, autoimmune hair loss disorder that is associated with inflammatory bowel disease. Alopecia areata and inflammatory bowel disease may have a common pathogenic mechanism that involves the Janus kinase/STAT pathway. In addition, there are previous case reports of patients who developed alopecia areata while on biologic therapies for inflammatory bowel disease. JAK1 inhibitors are currently undergoing investigation as potential therapies for Crohn's disease. Upadacitinib, an oral JAK1 inhibitor, has demonstrated efficacy in treating Crohn's disease during phase III clinical trials. In this case report, we present a 23-year-old man with Crohn's disease who previously developed alopecia areata while on adalimumab. He had near-complete resolution of his alopecia universalis after 7 months of treatment with upadacitinib while on concurrent ustekinumab for Crohn's disease, which he had been taking for 16 months prior to starting upadacitinib. Upadacitinib may be a beneficial therapy for treating concomitant alopecia areata and Crohn's disease.
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BACKGROUND: Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials. AIMS: The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC. METHODS: EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo-controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random-effects models. Stratified analyses based on disease- and trial-level characteristics, leave-one-out meta-analysis, and cumulative meta-analysis were performed. RESULTS: Twelve RCTs enrolling a total of 391 patients (placebo n = 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%-38.4%), I2 = 60.8%, p < 0.01, and 19.9% (95% CI: 5.3%-39.0%), I2 = 66.4%, p = 0.01 (tests for heterogeneity), respectively. Clinical response to placebo was numerically higher in patients with lymphocytic compared to collagenous colitis (39.9% vs. 19.8%, p = 0.08). Heterogeneity in clinical response to placebo was significantly reduced when the Miehlke 2014 RCT was excluded in the leave-one-out meta-analysis or when a more stringent secondary definition of response based on the Hjortswang criteria was applied. CONCLUSIONS: Approximately one-quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo.
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Colite Colagenosa , Colite Microscópica , Adulto , Humanos , Budesonida/uso terapêutico , Colite Microscópica/tratamento farmacológico , Colite Colagenosa/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Management of Crohn's disease (CD) using dietary interventions has become an area of increased research interest. There is a lack of specific research exploring if diet and nutrition interventions are beneficial in patients with strictures, as current dietary recommendations in fibrostenotic CD are often based on clinical judgment. The aim of this systematic review was to assess the impact of dietary interventions in fibrostenotic CD on medical and surgical outcomes. Methods: A systematic search of MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), and Cochrane Central Register of Controlled Trials (Ovid) was conducted. Studies reporting dietary interventions or nutritional factors in fibrostenotic CD were included. Outcomes for studies assessing dietary interventions such as enteral nutrition were evaluated as changes in (1) CD symptoms (CD Activity Index), (2) stricture parameters on diagnostic imaging, and (3) rates of surgical or medical intervention following dietary interventions. Results: Five studies were included in this review. Three studies assessed exclusive enteral nutrition (EEN), one evaluated total parenteral nutrition (TPN), and one studied a liquid diet. All included studies evaluated symptoms as an outcome, while diagnostic imaging parameters and surgical outcomes in the studies were either absent or too heterogeneous to appraise improvement post dietary intervention. Included EEN studies displayed similar efficacy, with approximately 60% of patients having symptom improvement. The included TPN study also reported 75% of patients with symptom improvement, while the liquid diet did not. Conclusion: Exclusive enteral nutrition and total parental nutrition may provide benefit for use as a dietary intervention for fibrostenotic CD. There remains a need for high-quality controlled trials which utilize standardized definitions of strictures.
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Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods: We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results: A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn's disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion: Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.
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Background: Patients with inflammatory bowel disease (IBD) require accessible, timely, and noninvasive strategies to monitor disease. The aim was to assess the integration of intestinal ultrasound (IUS) on decision-making and endoscopy utilization in a standardized care pathway. Methods: This prospective, multicenter, international, observational cohort study included patients seen within a centralized model for IBD care was conducted during the COVID pandemic. Patients were evaluated with IUS alone or in combination with an in-clinic, unsedated sigmoidoscopy. Demographic, clinical, laboratory, and imaging data, clinical decisions, and need for urgent endoscopy, hospitalization, and surgeries were recorded. Results: Of the 158 patients included, the majority had an established diagnosis of Crohn's disease (nâ =â 123, 78%), and 47% (nâ =â 75) of patients were on biologic therapy. IUS identified active inflammation in 65% (nâ =â 102) of patients, and strictures in 14% (nâ =â 22). Fecal calprotectin levels correlated with inflammation detected on IUS (median of 50 µg/g [Q1-Q3: 26-107 µg/g] without inflammation and 270 µg/g [Q1-Q3: 61-556 µg/g] with inflammation; pâ =â 0.0271). In the majority of patients, clinical assessment with IUS led to an acute change in IBD-specific medications (57%, nâ =â 90) and avoided or delayed the need for urgent endoscopy (85%, nâ =â 134). Four patients were referred for urgent surgical consultation. Conclusions: Point-of-care IUS used in a flare clinic pathway is a useful strategy to improve effective IBD care delivery and to assist in therapeutic management decisions, in many cases avoiding the acute need for endoscopy.
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BACKGROUND: Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis. METHODS: Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals. RESULTS: The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively. CONCLUSIONS: Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.
Primary sclerosing cholangitis is a chronic liver disease with complications such as cirrhosis, cancer, and death. This study summarizes the incidence (0.87 per 100 000) and prevalence (13.53 per 100 000) of PSC and highlight needs in research to study the epidemiology of PSC.
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BACKGROUND: Skin prick test (SPT) and fluorescence enzyme immunoassay (FEIA) are widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic disease. Basophil activation test (BAT) could obviate disadvantages of SPT and FEIA. However, it is not known whether BAT gives similar results as SPT or FEIA for aeroallergens. OBJECTIVES: In this study, we compared the results of SPT, BAT and FEIA for different aeroallergens. METHODS: We performed BAT, SPT and FEIA in 41 atopic subjects (symptomatic and with positive SPT for at least 1 of 9 common aeroallergens) and 31 non-atopic subjects (asymptomatic and with negative SPT). RESULTS: Correlations between SPT and BAT, SPT and FEIA, and BAT and FEIA results were statistically significant but imperfect. Using SPT as the "gold standard", BAT and FEIA were similar in sensitivity. However, BAT had lower specificity than FEIA. False positive (BATposSPTneg) results were frequent in those atopic subjects who were allergic by SPT to a different allergen and rare in non-atopic subjects. The false positivity in atopic subjects was due in part to high levels of serum Total-IgE (T-IgE) levels in atopic individuals that lead to basophil activation upon staining with fluorochrome-labeled anti-IgE. CONCLUSION: As an alternative to SPT in persons allergic to aeroallergens, BAT in its present form is useful for distinguishing atopic from non-atopic persons. However, BAT in its present form is less specific than FEIA when determining the allergen which a patient is allergic to. This is due to IgE staining-induced activation of atopic person's basophils and/or nonspecific hyperreactivity of atopic person's basophils.
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Nitro-functionality, with a large deficit of negative charge, embraces biological importance and has proven its therapeutic essence even in chemotherapy. Functionally, with its strong electron-withdrawing capability, nitro can manipulate the electron density of organic moieties and regulates cellular-biochemical reactions. However, the chemistry of nitro-functionality to introduce physiologically relevant macroscopic properties from the molecular skeleton is unknown. Therefore, herein, a neurotransmitter moiety, dopamine, was chemically modified with a nitro-group to explore its influence on synthesizing a multifunctional biomaterial for therapeutic applications. Chemically, while the nitro-group perturbed the aromatic electron density of nitrocatecholic domain, it facilitated the suturing of nitrocatechol moieties to regain its aromaticity through a radical transfer mechanism, forming a novel macromolecular structure. Incorporation of the sutured-nitrocatecholic strand (S-nCAT) in a gelatin-based hydrogel introduced an electroconductive microenvironment through the delocalization of π-electrons in S-nCAT, while maintaining its catechol-mediated adhesive property for tissue repairing/sealing. Meanwhile, the engineered hydrogel enriched with noncovalent interactions, demonstrated excellent mechano-physical properties to support tissue functions. Cytocompatibility of the bioadhesive was assessed with in vitro and in vivo studies, confirming its potential usage for biomedical applications. In conclusion, this novel chemical approach enabled designing a multifunctional biomaterial by manipulating the electronic properties of small bioactive molecules for various biomedical applications.
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Strictures in Crohn's disease (CD) are a hallmark of long-standing intestinal damage, brought about by inflammatory and non-inflammatory pathways. Understanding the complex pathophysiology related to inflammatory infiltrates, extracellular matrix deposition, as well as muscular hyperplasia is crucial to produce high-quality scoring indices for assessing CD strictures. In addition, cross-sectional imaging modalities are the primary tool for diagnosis and follow-up of strictures, especially with the initiation of anti-fibrotic therapy clinical trials. This in turn requires such modalities to both diagnose strictures with high accuracy, as well as be able to delineate the impact of each histomorphologic component on the individual stricture. We discuss the current knowledge on cross-sectional imaging modalities used for stricturing CD, with an emphasis on histomorphologic correlates, novel imaging parameters which may improve segregation between inflammatory, muscular, and fibrotic stricture components, as well as a future outlook on the role of artificial intelligence in this field of gastroenterology.