RESUMO
Tofacitinib is an oral small molecule JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). Its efficacy and safety have been demonstrated in phase III clinical trials and supported by real-life data. We report the case of an 18-year-old woman with a 1-year diagnosis of left-sided UC, with multiple admissions due to disease exacerbation or infections, refractory to infliximab (with azathioprine) and currently under treatment with vedolizumab and tacrolimus. She was admitted due to a severe disease exacerbation and, because of a previous history of neuropsychiatric side effects to corticotherapy, tofacitinib was initiated. In the following 6 days, there was no clinical improvement of UC, and serial blood work-up revealed moderate grade persistent peripheral eosinophilia (3000 cells/mm3) and acute kidney injury grade 1 KDIGO. Tofacitinib temporary suspension was decided, with a rapid normalization of renal function/eosinophil levels. Tofacitinib was restarted 2 days after its suspension. However, she developed moderate eosinophilia (2000 cells/mm3) again, which was considered an adverse effect (AE) to tofacitinib, leading to its suspension with eosinophilia resolution. Given the severity of the disease, after a multidisciplinary discussion, it was decided to start high-dose corticotherapy and ustekinumab with maintenance therapy every 4 weeks, and to add tacrolimus. Clinical and biochemical remission were achieved, and the patient was discharged. Three-month follow-up after tofacitinib suspension showed no recrudescence of eosinophilia. Tofacitinib represents a significant advance in the management of UC patients. The drug has a good safety profile with few related AE. This case aims to warn about an adverse reaction to tofacitinib not reported so far, including in a multicenter real-life setting recently published by Hernández et al where eosinophilia is also not described, thus emphasizing the rarity of this AE. To our knowledge this is the first case of tofacitinib-induced eosinophilia in the context of UC. .
Assuntos
Colite Ulcerativa , Eosinofilia , Feminino , Humanos , Adolescente , Tacrolimo/uso terapêutico , Resultado do Tratamento , Colite Ulcerativa/tratamento farmacológico , Eosinofilia/induzido quimicamente , Progressão da DoençaRESUMO
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.
Assuntos
Doença de Crohn , Adulto , Biomarcadores , Proteína C-Reativa , Progressão da Doença , Fezes , Humanos , Inflamação , Infliximab , Complexo Antígeno L1 Leucocitário , Estudos Prospectivos , Fatores de Risco , Inibidores do Fator de Necrose TumoralRESUMO
BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.
Assuntos
Colite Ulcerativa , Biomarcadores/análise , Biópsia , Colite Ulcerativa/diagnóstico , Colo , Colonoscopia , Fezes/química , Humanos , Mucosa Intestinal , Complexo Antígeno L1 Leucocitário , Índice de Gravidade de DoençaRESUMO
Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5-/-, MGAT5+/-) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.
Assuntos
Acetilglucosamina/farmacologia , Linfócitos T CD4-Positivos/imunologia , Colite Ulcerativa/imunologia , N-Acetilglucosaminiltransferases/fisiologia , Polissacarídeos/metabolismo , Imunidade Adaptativa , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Citocinas/metabolismo , Glicosilação , Humanos , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
BACKGROUND & AIMS: We performed a systematic review of changes in fecal and colon microbiomes of patients with inflammatory bowel diseases (IBDs) receiving treatment with monoclonal antibodies against tumor necrosis factor, integrins, or cytokines. We explored associations among microbiome composition and functions (at baseline and throughout the treatment) and therapy-related outcomes to determine whether colon or fecal microbiomes might be used as biomarkers of response to therapy. METHODS: We searched the PubMed, Web of Science, and Science Direct databases through February 2019 for studies of associations among the microbiomes of fecal or colon samples, biologic therapies, and IBDs. We used the critical appraisal skills program checklist to assess the quality of the study methods. RESULTS: From the 787 citations identified, 10 studies met the inclusion criteria. Changes in microbiomes of fecal or colon samples after treatment did not differ significantly among biologic agents; all produced decreases in relative abundances of Escherichia and Enterococcus and increases in genera that produce short-chain fatty acids. Fecal or colon microbiomes of patients who responded to therapy with antagonists of tumor necrosis factor or interleukins had higher α-diversity and increased relative abundances of different genera (Faecalibacterium, Roseburia, or Clostridium) from the Clostridiales order, either at baseline or during follow-up evaluation. Patients in remission after treatment with antibodies against integrins had decreased abundances of Roseburia. CONCLUSIONS: In a systematic review of 10 studies, we found evidence for consistent changes in microbiomes of fecal and colon samples from patients with IBD who responded to treatment with biologic agents. Prospective studies are needed to determine what changes are associated significantly with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.
Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Terapia Biológica , Colo , Fezes , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , InfliximabRESUMO
Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis.Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
Assuntos
Adenoma/genética , Colite Ulcerativa/genética , Colo/patologia , Neoplasias do Colo/genética , Metilação de DNA/genética , Mucosa Intestinal/patologia , Adenoma/patologia , Adulto , Biomarcadores Tumorais/genética , Carcinogênese/genética , Colite Ulcerativa/patologia , Neoplasias do Colo/patologia , Estudos Transversais , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Regiões Promotoras Genéticas/genéticaRESUMO
Inflammatory Bowel Disease and Psoriasis are chronic inflammatory diseases that share common genotype, clinical course, and immunological features, although its relationship is still unclear. We report a 34-year-old woman with ileal Crohn's disease diagnosed 14 years ago, with the development of extensive, exudative scalp lesions after adalimumab therapy. Biopsies from skin lesions were compatible with vulgar psoriasis. The patient reports no personal or family history of psoriasis. Due to persistence and further worsening of skin lesions, paradoxical etiology to adalimumab was presumed and the drug was stopped with complete resolution of skin lesions and intestinal disease in remission under methotrexate. Due to pregnancy-planification methotrexate was stopped and, 8 months-after, systemic steroid-therapy was introduced due to moderate-to-severe intestinal flare. Vedolizumab was started and at the second infusion patient reported hair loss with no other complaints. Twelve months after vedolizumab initiation the patient reported reappearance of the extensive scalp and peri-fistula psoriatic lesions. Topical therapy was started but unsuccessfully and given the progressive worsening of the lesions, vedolizumab was suspended, with skin improvement seen 1 month after discontinuation. There are few case-reports of vedolizumab acting as a trigger to some dermatological conditions in IBD-patients, including psoriasis. The molecular mechanism behind it isn't fully understood. We present and discuss, to our knowledge, the first case in the literature of psoriasis triggered by vedolizumab in Crohn's disease.
Assuntos
Doença de Crohn , Psoríase , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológicoRESUMO
In this paper, we address Zero-shot learning for sensor activity recognition using word embeddings. The goal of Zero-shot learning is to estimate an unknown activity class (i.e., an activity that does not exist in a given training dataset) by learning to recognize components of activities expressed in semantic vectors. The existing zero-shot methods use mainly 2 kinds of representation as semantic vectors, attribute vector and embedding word vector. However, few zero-shot activity recognition methods based on embedding vector have been studied; especially for sensor-based activity recognition, no such studies exist, to the best of our knowledge. In this paper, we compare and thoroughly evaluate the Zero-shot method with different semantic vectors: (1) attribute vector, (2) embedding vector, and (3) expanded embedding vector and analyze their correlation to performance. Our results indicate that the performance of the three spaces is similar but the use of word embedding leads to a more efficient method, since this type of semantic vector can be generated automatically. Moreover, our suggested method achieved higher accuracy than attribute-vector methods, in cases when there exist similar information in both the given sensor data and in the semantic vector; the results of this study help select suitable classes and sensor data to build a training dataset.
Assuntos
Atividades Humanas , Reconhecimento Automatizado de Padrão , Semântica , Bases de Dados como Assunto , HumanosRESUMO
The diversity of glycans expression within a cell or an organism is enormous and the amount of relevant biological information that each glycan structure encodes is far from being clarified. The importance of glycans in health and life sciences is highlighted by their multiple functional implications in different cellular and molecular biology processes with impact in homeostasis and diseases, such as cancer and inflammatory conditions. Glycans actively participate in the regulatory circuits that govern both innate and adaptive immune response. Changes in the glycans repertoire occur during the transition from normal to inflamed conditions and the aberrant expression of glycans dictates either pro-inflammatory or anti-inflammatory responses. This review summarizes how glycans integrate the regulatory networks of immune response with a focus on gut immunity.
Assuntos
Imunidade Adaptativa/imunologia , Homeostase/imunologia , Imunidade Inata/imunologia , Polissacarídeos/imunologia , Animais , Humanos , Inflamação/imunologiaRESUMO
The incidence of inflammatory bowel disease is increasing worldwide and the underlying molecular mechanisms are far from being fully elucidated. Herein, we evaluated the role of N-glycosylation dysregulation in T cells as a key mechanism in the ulcerative colitis (UC) pathogenesis. The evaluation of the branched N-glycosylation levels and profile of intestinal T cell receptor (TCR) were assessed in colonic biopsies from UC patients and healthy controls. Expression alterations of the glycosyltransferase gene MGAT5 were also evaluated. We demonstrated that UC patients exhibit a dysregulation of TCR branched N-glycosylation on lamina propria T lymphocytes. Patients with severe UC showed the most pronounced defect on N-glycan branching in T cells. Moreover, UC patients showed a significant reduction of MGAT5 gene transcription in T lymphocytes. In this study, we disclose for the first time that a deficiency in branched N-glycosylation on TCR due to a reduced MGAT5 gene expression is a new molecular mechanism underlying UC pathogenesis, being a potential novel biomarker with promising clinical and therapeutic applications.
Assuntos
Colite Ulcerativa/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/genética , Feminino , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Linfócitos T/metabolismoRESUMO
BACKGROUND: Anaemia is the most common complication in patients with inflammatory bowel disease (IBD). This study aims to assess the prevalence of anaemia in IBD patients and to know its characteristics with regard to the main IBD clinical features. METHODS: An observational cross-sectional multicentre study was conducted. We included all patients who had an appointment at the 15 participating centres during the period of 1 month, and who met the following selection criteria: age ≥18, diagnosis of IBD. Disease activity was evaluated by Harvey-Bradshaw Index (HBI) for Crohn's disease (CD), and by Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). RESULTS: One thousand three hundred and thirteen patients, were included: 54.8% female, mean age 42.8 (interquartile range (25th-75th): 31-53 years), 59% had a diagnosis of CD, 39% of UC and 2% IBD unclassified. The median follow-up since diagnosis was 7 years. The ongoing treatment was aminosalicylates (63.1%), corticosteroids (11.6%), immunomodulators (36.4%) and anti-tumour necrosis factor (27.3%). Anaemia was identified in 244 patients, representing a prevalence of 18.6% (95% CI 16.6-20.9). A majority of cases (90%) have mild/moderate anaemia (mean haemoglobin 11.3 ± 0.8 g/dl). Anaemia was significantly higher in females (p = 0.006), but there were no differences between CDs (19.1%) and UCs (17.7%; p = 0.688). Anaemia was more frequent in patients with active disease (HBI >4; SCCAI >2) than in those in clinical remission (33.6 vs. 15.6%, p < 0.001) and in patients on steroids (36.8%) vs. other treatments (p < 0.001). Only 47% of patients with anaemia were under any specific treatment (oral iron 67%; intravenous iron 41%). CONCLUSION: Anaemia was more frequent in patients with active disease and in those on corticosteroids. The treatment of anaemia still seems undervalued, whereas more than half of anaemic patients were not receiving any specific treatment and the use of oral iron prevails contrarily to current recommendations.
Assuntos
Corticosteroides/efeitos adversos , Anemia/epidemiologia , Anemia/terapia , Hemoglobinas/análise , Doenças Inflamatórias Intestinais/complicações , Ferro/uso terapêutico , Administração Oral , Corticosteroides/uso terapêutico , Adulto , Anemia/etiologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos Transversais , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ferro/administração & dosagem , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Prevalência , Índice de Gravidade de Doença , Oligoelementos/uso terapêuticoRESUMO
Preclinical Research The efficacy of anti-TNF agents in the treatment of multiple immune-mediated inflammatory diseases (IMIDs) has increased their daily use. However, concerns remain regarding their long-term safety profile. Using a literature-based review of the infectious and malignant complications of anti-TNF biologics in IMIDs including psoriasis, Rheumatoid Arthritis, and inflammatory bowel disease, this review presents current evidence relative to the safety of anti-TNF agents in the context infections and malignancy in adults with IMIDs. Treatment with anti-TNF biologics is an effective treatment option with known risks that can be mitigated by appreciating the safety aspects and via a thorough screening and continuous monitoring of the patient.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Doenças do Sistema Imunitário/tratamento farmacológico , Infecções/etiologia , Inflamação/tratamento farmacológico , Neoplasias/etiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Humanos , Infecções/induzido quimicamente , Infecções/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Neoplasias/induzido quimicamente , Neoplasias/imunologia , Infecções Oportunistas/induzido quimicamente , Infecções Oportunistas/etiologia , Infecções Oportunistas/imunologiaRESUMO
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 the majority of its 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.
Assuntos
Progressão da Doença , Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais , Infliximab , Complexo Antígeno L1 Leucocitário , Humanos , Masculino , Feminino , Infliximab/farmacocinética , Estudos Prospectivos , Adulto , Complexo Antígeno L1 Leucocitário/análise , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pessoa de Meia-Idade , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/sangue , Fezes/química , Peso Corporal , Colite Ulcerativa/tratamento farmacológicoRESUMO
Background and Aim: Aeromonas are Gram-negative rods known to cause a spectrum of diseases. Inflammatory bowel disease (IBD) is an idiopathic complex condition resulting from interaction of multiple factors. Aeromonas infection in association with IBD is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients. Methods: A retrospective observational analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a tertiary and university hospital. Results: Fifty patients were included, 56% male with a mean age of 42.1 years. Thirty-eight (76%) were non-IBD and 12 (24%) IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% developed mild, 44% moderate, and 16.7% severe infection. The main strains isolated were Aeromonas hydrophila/caviae. Bacterial co-isolation was found in 4 non-IBD and histological findings of cytomegalovirus in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in the IBD group. From IBD, 4 patients had the diagnosis of ulcerative colitis and 9 of Crohn's disease with colonic involvement. Of these patients, 5 received IBD diagnosis after the acute episode of Aeromonas infection. Conclusions: Clinical presentation of Aeromonas infection differs between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seems to greatly contribute to IBD manifestation.
Introdução: A etiologia da Doença Inflamatória Intestinal (DII) é complexa e resultante da interação de diversos fatores, nomeadamente microbiológicos. A infeção por Aeromonas caracteriza-se por um espectro alargado de manifestações clínicas. O papel da infeção por Aeromonas na DII não está caracterizado. Objetivos: Avaliar o significado da infeção por Aeromonas na DII e as diferenças com a infeção em doentes não-DII. Métodos: avaliação retrospetiva e observacional de todos os doentes com isolamento microbiológico de Aeromonas em amostras fecais num período de 10 anos, num hospital terciário. Resultados: foram avaliados 50 doentes, 56% do sexo masculino, com idade média de 42.1 anos. Doze (24%) com diagnóstico de DII e trinta e oito (76%) não-DII. Os doentes com DII encontravam-se mais frequentemente sob imunossupressão. Dois doentes foram assintomáticos, 44% desenvolveram doença ligeira, 44% moderada e 16.7% severa, havendo maior tendência para infeção severa nos DII. Os doentes não-DII apresentaram mais frequentemente febre e os DII diarreia sanguinolenta e dor abdominal. O uso de antimicrobianos foi superior no grupo DII e a utilização de corticoesteroides foi exclusiva nestes doentes. Isolamento concomitante de outros agentes microbiológicos ocorreu em 4 doentes não-DII e 2 com DII tinham histologia compatível com infeção por Citomegalovírus. Da população DII, 4 eram Colite Ulcerosa e 9 Doença de Crohn com envolvimento cólico. Destes, 5 receberam o diagnóstico após a infeção por Aeromonas. Conclusão: A apresentação clínica da infeção por Aeromonas foi distinta entre as populações DII e não-DII, sendo que os doentes DII apresentaram doença mais severa e maior utilização de antimicrobianos. A infeção na DII ocorreu essencialmente em doentes com envolvimento cólico.
RESUMO
Background: Inflammatory bowel diseases' (IBD) increasing incidence and prevalence place a heavy health and economic burden on society. Objectives: This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care. Methods: The burden of disease was expressed using disability-adjusted life years (DALY). Costs were estimated considering the societal perspective, using a prevalence-based model and prices established by law. An expert panel composed of 5 expert Portuguese gastroenterologists and a patient-reported study were conducted to support the cost analysis and fill in information gaps. Results: In Portugal, with a prevalence of 24,069 IBD patients and an incidence of 15/100,000, the burden of disease was estimated at 6,067 DALYs: 507 resulting from premature deaths and 5,560 from disability. Total cost was estimated at EUR 146 million per year, with direct costs representing 59%. Average yearly cost per IBD patient is EUR 6,075, where 60% is related to Crohn's disease and 40% to ulcerative colitis (UC). Conclusion: This study estimates the annual health burden and cost of IBD in Portugal, thus generating information with the intent to raise awareness of the need to advance health policies as well as better clinical and economic decisions in this pathology.
Contexto: A crescente incidência e prevalência das Doenças Inflamatórias Intestinais (DII) representam um pesado fardo para a saúde e economia na sociedade. Objetivos: Este estudo avalia o custo e a carga da DII em Portugal, com o objetivo de suportar a definição de políticas de saúde, alocação de recursos e cuidados com o doente. Métodos: A carga da doença foi calculada utilizando anos de vida ajustados à incapacidade (DALY). Os custos foram estimados tendo em conta a perspetiva da sociedade, utilizando um modelo baseado na prevalência e preços estabelecidos por lei. Foi realizado um painel de peritos, composto por 5 gastroenterologistas portugueses, assim como um estudo de mercado a doentes, de forma a suportar a análise de custos e colmatar lacunas de informação. Resultados: Em Portugal, com uma prevalência de 24,069 doentes e uma incidência de 15/100,000, o peso das DII foi estimado em 6.067 DALYs: 507 dos quais resultantes de mortes prematuras e 5.560 de incapacidade. O custo total foi estimado em 146 milhões de euros por ano, com os custos diretos a representarem 59% do total. O custo médio anual por doente de DII é de 6.075 EUR, onde 60% está relacionado com Doença de Crohn (DC) e 40% com Colite Ulcerosa. Conclusão: Este estudo estima os encargos anuais para a saúde e o custo da DII em Portugal, gerando informação relevante, com o intuito de alertar para a necessidade de uma evolução nas políticas de saúde, assim como como suportar melhores decisões clínicas e económicas nesta patologia.
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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.
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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.
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Doença de Crohn , Humanos , Infliximab/uso terapêutico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Estudos Prospectivos , Biomarcadores , Prognóstico , Progressão da DoençaRESUMO
INTRODUCTION: Inflammatory bowel disease (IBD) affects people from all age categories worldwide. Although the incidence of the disease is stabilizing or decreasing in most Western world countries, its prevalence is still increasing because of the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD incidence nationwide, analyzing regional, sex, and age distributions. METHODS: Data were provided by the Portuguese Shared Services of the Ministry of Health. This study consisted of a retrospective analysis of all first consultations coded for "Chronic enteritis/ulcerative colitis" (D94) in a primary healthcare setting, between 2017 and 2020, in Portugal. The primary outcome measure was the IBD incidence rate per 100,000 inhabitants. We also calculated the incidence rate per person-year and forecasted incidence until 2024. RESULTS: Between 2017 and 2019, the incidence rate of IBD in Portugal decreased from 54.9 to 48.6 per 100,000 inhabitants. The average incidence was 20 new cases of IBD per 1,000 person-year. It was predicted that, in December 2023, IBD incidence would reach 305.4 new cases (95% Prediction Interval 156.6-454.3), a similar result to the values forecasted for December 2021 (305.4, 95% Prediction Interval 197.3-413.6). DISCUSSION: The incidence of IBD slightly declined from 2017 to 2019, and it is posed to stabilize in the future. The presented data are of the utmost importance for the characterization of IBD in Southern European countries and the establishment of future health policies in the setting of compounding prevalence in the Western world.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Doença Crônica , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Humanos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Estudos Retrospectivos , OcidenteRESUMO
BACKGROUND: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal. METHODS: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY. RESULTS: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was 6295.28 (95% CI, 4660.55-8503.41). The pooled mean hospitalization cost PPY for CD patients was 2004.83 (95% CI, 1351.68-2973.59). The major contributors for the total health expenditure were biologics (5554.58) and medications (3096.53), followed by hospitalization (2004.83) and surgery (1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010. CONCLUSIONS: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.
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Produtos Biológicos , Doença de Crohn , Doenças Inflamatórias Intestinais , Produtos Biológicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Atenção à Saúde , Custos de Cuidados de Saúde , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Qualidade de VidaRESUMO
BACKGROUND: Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes. OBJECTIVE: This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes. METHODS: A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest. RESULTS: A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased. CONCLUSION: The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.