Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and ...different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.
After having received serious consideration in the 1990s, the hypothesis that biomechanics is phonologized into probabilistic phonotactics subsided for methodological difficulties, while related ...child language studies gained ground.
This paper aims at restoring the original adult language orientation of the discussion of biomechanically driven consonant–vowel co-occurrence. It presents new, detailed evidence on two languages, British English and Brazilian Portuguese, where there is clear lexical support for two CV co-occurrence biases attributable to biomechanics: a trend for the combination of coronal consonants with front vowels, and a trend against the combination of dorsal consonants with front vowels. It also shows that such biases are stronger under conditions that complicate speech planning.
The analysis uses log-linear modeling in conjunction with other statistical techniques to assure comparability with previous studies and reliability of multiple comparisons.
Low overall effect sizes indicate that biomechanically driven CV biases only weakly affect free combination. However, under such complicating conditions as repetition or lack of stress combined with occlusion/obstruence in initial position, effect sizes grow and significant factor interactions emerge, suggesting that such biases help simplify speech planning.
Revisiting the phonologization of biomechanics hypothesis with today׳s tools supports it sufficiently to justify further pursuit and search for explanations.
•New tools can now clarify long-pending issues on CV co-occurrence in lexicons.•They were applied to large databases of British English and Brazilian Portuguese.•Coronals and dorsals show consistent biomechanically driven biases.•Such biases interact with conditions that complicate speech planning.•Likely causes are synergy, co-articulation resistance and complexity of initiation.
This editorial to the Special Collection Laboratory Approaches to Portuguese Phonology aims at contextualizing the articles against the background of a two-century old scholarly tradition in the ...study of the Portuguese sound pattern. As foreseen in the Call for Papers, all the submissions received used laboratory methods to address long-standing issues raised by this tradition. Regardless of their publication order, the articles can be grouped into four topics: vowel variability, stress/stress-grouping, nasality, and fricative variability. Brief highlights on the works that paved the way for the state-of-the art in such topics are followed by comments on the gains introduced by the laboratory approach. Hopefully, this overview will help authors and readers evaluate the opportunities for further research along the lines indicated by the current results.
Background
Ulcerative colitis is a chronic relapsing disease usually treated with mesalamine. The need of steroid therapy at diagnosis is generally considered as a poor prognostic factor.
Aims
The ...aim of our study was to assess whether patients treated with corticosteroids at diagnosis have more clinical relapses, disease progression, or an increased risk of colectomy during a 5-year follow-up.
Methods
We retrospectively evaluated patients who had received diagnosis of ulcerative colitis with a 5-year follow-up. Relapse was defined as a worsening of symptoms requiring an increase in medical treatment. Progression of disease was defined as a proximal extension of mucosal involvement, comparing the colonoscopy performed 5 years after diagnosis with the first one. The need of corticosteroid treatment at diagnosis was correlated to number of relapses, disease progression, and colectomy rate.
Results
We included 230 patients, 116 of them (50%) treated with steroids at diagnosis. Multivariate analysis demonstrated that there is a strong correlation between corticosteroid use and number of relapses (
p
< 0.01), as well as with disease progression (
p
< 0.05). Seventeen patients (7.4%) underwent colectomy, but the correlation with steroids was not statistically significant.
Conclusions
These data provide evidence that the need of corticosteroids at diagnosis is associated with a worse clinical outcome.
Biological therapies are widely used for the treatment of ulcerative colitis. However, only a low proportion of patients achieve clinical remission and even less mucosal healing. There is currently ...scarce knowledge about the early markers of therapeutic response, with particular regard to mucosal healing. The aim of this prospective study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing.
A prospective observational study was conducted on patients with ulcerative colitis, who started biological therapy with infliximab, adalimumab, golimumab, or vedolizumab at our center. All patients underwent colonoscopy, performed by 2 blinded operators, at baseline and week 54 or in case of therapy discontinuation because of loss of response. FC was assessed at baseline and week 8 and evaluated as putative predictor of mucosal healing at week 54.
We enrolled 109 patients, and 97 were included in the analysis. Twenty-six patients (27%) experienced loss of response. Over 71 patients (73%) with clinical response at week 54, clinical remission was obtained in 60 patients (61.9%) and mucosal healing in 45 patients (46.4%). After 8 weeks of treatment, FC predicted mucosal healing at week 54 (P < 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value were estimated to be 75%, 88.9%, 86.6%, and 75.5%, respectively, based on a cutoff of 157.5 mg/kg.
The present study suggests that FC assessment after 8 weeks of treatment with all the biological drugs could represent a promising early marker of response to therapy in terms of mucosal healing.
Background
Data from trials of vedolizumab for inflammatory bowel disease and from real-world studies suggest an exposure-response relationship, such that vedolizumab trough levels may predict ...clinical and endoscopic outcomes.
Objective
The purpose of this study was to evaluate in a prospective observational study the utility of an early vedolizumab trough level assay for predicting the first-year vedolizumab therapy outcome.
Methods
This prospective observational study included consecutive inflammatory bowel disease patients. We measured vedolizumab trough levels and anti-vedolizumab antibodies at weeks 6 and 14. Clinical outcome was assessed at weeks 6, 14, 22 and 54. The primary endpoint was the correlation between early vedolizumab trough levels and vedolizumab persistence over the first year of treatment, defined as the maintenance of vedolizumab therapy due to sustained clinical benefit.
Results
We included 101 patients initiating vedolizumab. A cut-off vedolizumab trough level of 16.55 µg/ml at week 14 predicted vedolizumab persistence within the first year of therapy, with 73.3% sensitivity and 59.4% specificity (p = 0.0009). Week 14 vedolizumab trough level was significantly higher in patients with clinical remission at weeks 14, 22 and 54; and in patients achieving mucosal healing within 54 weeks.
Conclusion
High vedolizumab trough level at week 14 was associated with a higher probability of maintaining vedolizumab therapy over the first year due to sustained clinical benefit.
Irritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS.
Thirty IBS and 30 healthy ...volunteers were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid, plasma serotonin (5-hydroxytryptamine, 5-HT), endothelin, and neuropeptide Y (NPY), and plasma and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA).
Prevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 43.7 vs 14.8 18.1 pmol/L,
= 0.006), 5-HT (214.9 182.6 vs 141.0 45.5 pg/mL,
= 0.010), and endothelin 1.1 1.4 vs 2.1 8.1 pg/mL,
= 0.054, compared to healthy volunteers. Moreover, plasma NPY, endothelin, cortisol and 5-HT, and urinary 5-hydroxyindoleacetic acid were associated with some psychological disorders (
≤ 0.05). Despite a similar resting MSNA, after cold pressor test, IBS showed a blunted increase in MSNA burst frequency (+4.1 vs +7.8 bursts/min,
= 0.048; +30.1% vs +78.1%,
= 0.023). Baseline MSNA tended to be associated with urinary cortisol (
= 0.557,
= 0.059). Moreover, changes in heart rate after mental stress were associated with urinary cortisol (
= 0.682,
= 0.021) and changes in MSNA after mental stress were associated with plasma cortisol (
= 0.671,
= 0.024)."
Higher concentrations of endothelin, NPY, and 5-HT were found to be associated with some psychological disorders in IBS patients together with an altered cardiovascular autonomic reactivity to acute stressors compared to healthy volunteers.
Este artigo busca inspiração no ensaio de Chomsky (1967) sobre a responsabilidade dos intelectuais nas guerras imperialistas dos EUA para conclamar os linguistas a denunciar o uso das tecnologias de ...fala e linguagem nos mecanismos de controle da opinião pública do capitalismo atual. Para tanto, analisa a expansão e popularização dessa tecnologia como passo decisivo na consolidação do capitalismo digital do século XXI. Aponta, ainda, a sua mercantilização como fonte de mudanças no mercado de trabalho global conducentes à precarização em todos os campos, inclusive a ciência. Expõe, por fim, a exploração da mão de obra científica precarizada pelas gigantes da tecnologia digital como um dos principais meios da captura de dados pessoais via internet – um negócio ainda à espera de regulamentação.
Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic ...findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remissionmoreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.
Aims
Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and ...during VDZ treatment, and to investigate their association with mucosal healing and clinical remission.
Methods
We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log‐linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression.
Results
Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)‐8 values at baseline and with significant decrease in IL‐6 and IL‐8 levels over the first 6 weeks. A significant reduction of IL‐6 and IL‐8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL‐6 and IL‐8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission.
Conclusion
In UC patients, the serum patterns of IL‐6 and IL‐8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome.
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