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Despite the institution of an interdisciplinary Inflammatory Bowel Disease (IBD) centre is encouraged, how it may improve patient care is still unknown. In a 5-year period following organisation of an IBD centre, hospitalisations per patient/year decreased (0.41-0.17) and patients on biologics increased (7.7%-26.7%). Total number of hospitalisations (-18.4%) and length of hospitalisation (-29.4%) improved compared with a preceding 5-year period. These findings suggest that institution of an interdisciplinary IBD centre is associated with improved healthcare utilisation.
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Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.
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INTRODUCTION: The use of ustekinumab and vedolizumab as second-line therapies in patients with Crohn's disease (CD) in which tumour necrosis factor alpha inhibitors (TNFi) failed is still debated. The aim of this study was to compare, in a large multicenter observational retrospective cohort, the effectiveness of ustekinumab and vedolizumab as second-line therapies, as assessed by clinical and objective outcomes including endoscopy and gastrointestinal imaging. METHODS: Clinical response, remission, and steroid-free remission at weeks 26 and 52 were evaluated in a retrospective propensity score-weighted and propensity score-matched cohort of patients in which TNFi failed. Objective response and remission were evaluated by 1 or more techniques among endoscopy, magnetic resonance/computed tomography enteroclysis, and small bowel ultrasound. RESULTS: A total of 470 patients with CD (239 treated with ustekinumab and 231 treated with vedolizumab) were included in the study. At week 26, clinical outcomes were similar between the 2 groups. At week 52, clinical remission (ustekinumab 42.5% vs vedolizumab 55.5%, P = 0.01) and steroid-free remission (ustekinumab 40.6% vs vedolizumab 51.1%, P = 0.038) rates were significantly higher in vedolizumab-treated patients. Three hundred two patients (hundred thirty-five treated with ustekinumab and hundred sixty-seven treated with vedolizumab) had an objective evaluation of disease activity at baseline and week 52. At week 52, objective response and remission rates were similar between the 2 groups. Clinical response at week 26 predicted steroid-free remission at week 52 in both ustekinumab-treated and vedolizumab-treated patients. Safety profiles were similar between the 2 groups. DISCUSSION: In patients with CD in which TNFi failed, both ustekinumab and vedolizumab showed similar clinical effectiveness after 26 weeks of treatment. At 1 year, vedolizumab was associated with a higher rate of clinical remission when compared with ustekinumab. However, no difference was observed between the 2 groups when objective outcomes were investigated at this time point.
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Anticorpos Monoclonais Humanizados , Doença de Crohn , Ustekinumab , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêuticoRESUMO
BACKGROUND & AIMS: Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins. METHODS: We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤2 and ≤1 in each segment, or a total CD endoscopic index of severity score <3) was assessed by using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin. RESULTS: The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% confidence interval, 0.619-0.767), regardless of CD location or phenotype. A cutoff value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cutoff value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P < .001 in validation cohort 1 and 0.624, P = .109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC; P = .147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC; P = .298 in validation cohort 2). CONCLUSIONS: We developed an index called the EHI to identify patients with CD in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice to assess endoscopic activity in patients with CD.
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Colonoscopia , Doença de Crohn/diagnóstico , Fármacos Gastrointestinais/administração & dosagem , Infliximab/administração & dosagem , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Fezes/química , Feminino , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Recidiva , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG). It results from a pathergy response to trauma from effluent from the ostomy or secondary to trauma caused by removal of the ostomy appliance adhesive in contact with the skin. Currently, no evidence-based guidelines for the management of PPG exist. This case study reports a dramatic response to crushed corticosteroid tablets in a patient who proved refractory to first- and second-line treatments of her PPG and several surgeries. CASE: Ms T. was a 39-year-old woman with Crohn's disease who underwent several ileostomies, developed PPG, and failed treatment with adalimumab. Her PPG was successfully treated topically with crushed prednisone tablets. CONCLUSION: We found that crushed corticosteroid tablets were an effective treatment of PPG, due to the ability to reduce pain and allow adhesion of the ostomy appliance.
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Estomia , Pioderma Gangrenoso , Corticosteroides , Adulto , Feminino , Humanos , Ileostomia/efeitos adversos , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/etiologia , ComprimidosRESUMO
BACKGROUND: In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS: Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS: Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS: In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.
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Antivirais/uso terapêutico , Varizes Esofágicas e Gástricas/patologia , Hepatite C Crônica/tratamento farmacológico , Hipertensão Portal/fisiopatologia , Cirrose Hepática/fisiopatologia , Idoso , Progressão da Doença , Técnicas de Imagem por Elasticidade , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Feminino , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Contagem de Plaquetas , Índice de Gravidade de Doença , Baço/patologia , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
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.
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Corticosteroides/uso terapêutico , Colectomia/estatística & dados numéricos , Colite Ulcerativa/tratamento farmacológico , Progressão da Doença , Adulto , Colite Ulcerativa/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To help identify adverse events (AEs) in new biologic therapies and to spread the culture of pharmaceutical surveillance among patients affected by psoriasis or inflammatory bowel disease (IBD). MATERIALS AND METHODS: This active pharmacovigilance program provided all patients with telephone follow-ups (FU), carried out by a clinical pharmacologist for a total duration of 1 year. Collected AEs were classified according to the MedDRA dictionary. RESULTS: 21 patients with psoriasis and 10 patients with IBD were enrolled. In our sample, the AEs reported were frequent but mild, underlining the crucial role of active pharmacovigilance in detecting minor AEs rarely spontaneously reported by the patients. CONCLUSION: According to our experience, a multidisciplinary team is recommended to manage complex therapies improving AE reporting and promoting greater therapeutic adherence.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Terapia Biológica/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Farmacovigilância , Psoríase/tratamento farmacológico , HumanosRESUMO
Chronic hepatitis C virus (HCV) infection and autoimmune disorders show a complex interplay, with HCV often being identified as the trigger of autoimmune phenomena or diseases. While there is evidence of successful HCV treatment with direct-acting antivirals (DAA) in patients with concomitant HCV and autoimmune hepatitis (AIH), there are also sparse reports of AIH developing during, or following, DAA treatment. Here we report a case of a patient with suspected concomitant HCV and AIH who underwent liver biopsy but showed no histological hallmarks of autoimmunity. The patient later developed a hepatitic flare following DAA-induced viral clearance, and a second liver biopsy showed features compatible with AIH. Response to corticosteroid and azathioprine treatment was seen. This reports demonstrates that patients with features of auto-reactivity and HCV after DAA-induced viral clearance require careful follow-up.
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Hepatite C Crônica/complicações , Hepatite Autoimune/complicações , Actinas/imunologia , Idoso , Anticorpos Antinucleares/imunologia , Antivirais/uso terapêutico , Azatioprina/uso terapêutico , Biópsia , Carbamatos/uso terapêutico , Combinação de Medicamentos , Glucocorticoides/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Prednisolona/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The outcome of patients with chronic hepatitis C virus infection (HCV) and advanced, compensated liver disease after sustained virological response (SVR) to direct-acting antivirals (DAAs) has not yet been completely depicted. We aimed to assess the clinical, biochemical and instrumental outcome of patients with advanced, compensated chronic HCV-related liver disease with DAA-induced SVR to DAAs and who had at least 1-year follow-up. MATERIALS AND METHODS: Fifty-two patients with cirrhosis (n = 27) and fibrosis stage F3 (n = 25) followed up for a median of 60 weeks after successful DAA treatment were included. Laboratory work-up, including APRI and FIB-4 scores, liver transient elastography and measurement of the spleen bi-polar diameter were carried out before treatment and at the end of follow-up. RESULTS: Liver stiffness decreased (P < 0.0001) from a median baseline of 15.2 kPa (12.0-20.0) to 9.3 kPa (7.5-12.0) at follow-up. A liver stiffness value suggestive of the presence (ie, ≥21.0 kPa) of clinically significant portal hypertension was found in 13 patients (25.0%) at baseline and in seven patients (13.5%) at follow-up (P = 0.037). Both APRI (P < 0.0001) and FIB-4 score (P = 0.025) progressively decreased, while platelet count increased (143 × 109 /L [117-176] to 153 × 109 /L [139-186], P = 0.003), and spleen bi-polar diameter decreased (120 mm [112-123] to 110 mm [102-116], P = 0.0009) from baseline to the end of follow-up. CONCLUSIONS: In patients advanced, compensated chronic liver disease, liver stiffness significantly improves in the long-term after SVR, and this improvement is accompanied by an amelioration of indirect indices of liver fibrosis and function, and by a decrease in parameters of portal hypertension.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Idoso , Doença Crônica , Elasticidade/fisiologia , Técnicas de Imagem por Elasticidade/métodos , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Estudos Prospectivos , Resultado do TratamentoRESUMO
Objectives: Up to 40% of inflammatory bowel disease (IBD) patients treated with anti-TNF drugs lose response within 1 year of treatment, therefore requiring drug optimization. Although higher drug trough levels (TLs) are associated with sustained clinical outcomes, there are concerns that they may be associated with a higher risk of adverse events (AEs). The aim was to evaluate the presence of a possible association between drug TLs and the occurrence of AEs in IBD patients treated with anti-TNF drugs.Methods: We retrospectively studied a cohort of 113 IBD patients treated with adalimumab or infliximab, of whom 27 were in combination therapy with immunosuppressants. TLs were measured using a homogeneous mobility shift assay.Results: During a median follow-up of 16 months (range 1-144), we observed 103 AEs occurring in 58 patients. We found no statistically significant difference (p = .21) in median TLs between patients who did 6.7 mcg/mL; range 0.0-36.2) or did not (7.7 mcg/mL; range 0.0-20.7) experience an AE. No difference was observed in the rate of AEs between patients in mono- or combination therapy (p = .38), as well as between elderly (i.e., >65 years) and younger patients (p = .32). Considering a TL cutoff of 7 mcg/mL for infliximab and 12 mcg/mL for adalimumab, or even double these TL values, we observed no statistically significant difference in the rate of AEs occurrence.Conclusion: Our study suggests that, when clinically required, anti-TNF drug dosage may be increased without particular concerns regarding the risk of AEs occurrence in IBD patients, even in patients on combination therapy and elderly ones.
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Adalimumab/efeitos adversos , Adalimumab/farmacocinética , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Infliximab/farmacocinética , Adalimumab/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/sangue , Infliximab/sangue , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Growing evidence indicates tissue inhibitors of matrix metalloproteinases (TIMPs) as potential players in inflammatory bowel disease (IBD), but, no prospective data are available in IBD remission/relapse. MATERIAL & METHODS: In this prospective pilot study, a cohort of IBD patients (n = 32) was enrolled and treated with monoclonal anti-TNF-α antibodies. Patients were clinically followed up for a median period of 54 weeks. Serum circulating levels of C-reactive protein (CRP), TIMP-1 and -2, matrix metalloproteinase (MMP)-9 and -8, myeloperoxidase (MPO) and neutrophil elastase (NE) were assessed by ELISA at enrolment and at the end of the treatment. RESULTS: The percentage (%) TIMP-2 reduction from baseline to end of treatment was independently associated with IBD remission at the end of treatment and follow-up as well. ROC curve analysis further confirmed the good prognostic accuracy of % TIMP-2 reduction over the treatment period. Conversely, no other change in inflammatory molecule concentrations was able to predict short- or long-term IBD remission. CONCLUSIONS: This study indicates TIMP-2 reduction during IBD treatment with monoclonal anti-TNF-α antibodies as a potential prognostic parameter of short and long term remission. To understand if TIMP-2 is an innocent biomarker or an active pathophysiological factor in IBD remains to be clarified.
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Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Adulto , Anticorpos Monoclonais/uso terapêutico , Área Sob a Curva , Biomarcadores/metabolismo , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/sangue , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Indução de Remissão , Adulto JovemRESUMO
INTRODUCTION AND AIM: EVBL is a procedure frequently performed in cirrhotic patients for primary prophylaxis of bleeding. Patients with cirrhosis display various degrees of alteration of common coagulation parameters, and it is not known whether these alterations may predict post-EVBL bleeding. To evaluate factors predictive of post-endoscopic variceal band ligation (EVBL) bleeding in cirrhotic patients with thrombocytopenia. METHODS: We included 109 patients with cirrhosis undergoing EVBL for primary prophylaxis of variceal bleeding. Common coagulation parameters (INR, fibrinogen levels) and complete haemogram were obtained in all patients and evaluated subdividing patients in bleeders and non bleeders following EVBL. RESULTS: The incidence of post-EVBL bleeding was 5.5% (6 patients). INR and platelet counts, considered as continuous or dichotomous variables according to common cut-offs (i.e., INR>1.5, platelet count <50x109/L) were not predictors of post-EVBL bleeding. Patients who bled had significantly lower fibrinogen levels [146 mg/dL (98 - 262) versus 230 mg/dL (104 - 638), P=0.009], and no other biochemical or clinical predictors of bleeding were identified. A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding. CONCLUSION: low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients, and might be used to stratify patients' risk. However, due to their preliminary nature, these findings need to be confirmed in larger populations.
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Endoscopia/efeitos adversos , Varizes Esofágicas e Gástricas/cirurgia , Fibrinogênio/metabolismo , Hemorragia Gastrointestinal/prevenção & controle , Cirrose Hepática/complicações , Hemorragia Pós-Operatória/etiologia , Trombocitopenia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Coagulação Sanguínea , Regulação para Baixo , Endoscopia/métodos , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/sangue , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Coeficiente Internacional Normatizado , Ligadura/efeitos adversos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/diagnóstico , Medição de Risco , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
Granulocyte and monocyte apheresis has been used in different immune-mediated disorders, mainly inflammatory bowel diseases. The removal of activated leukocytes and several additional immunomodulatory mechanisms have been so far suggested to explain the anti-inflammatory effects of the treatment. Recent data indicate that, during centrifugation based apheresis, sHLA-I adsorbed to plastic circuits is able to induce TGFß1 production in activated leukocytes. On these bases, the present study was aimed at analyzing if this model could be applied to a noncentrifugation based apheresis, such as granulocyte and monocyte apheresis. Ten patients with ulcerative colitis were enrolled. Every patient received 5 weekly apheresis treatments. Cellulose acetate beads removed from the column post-GMA were stained by fluorescent anticlass I mAb and examined by fluorescent microscope. Moreover, sFasL plasma concentration, TGFß1 plasma levels, and the percentage of TGFß1 positive neutrophils were evaluated before and immediately after each single apheresis. Immunofluorescent images revealed a homogeneous layer of a sHLA-I adsorbed to the surface of the beads recovered following the procedure. sFasL plasma concentration progressively increased both following the procedures and during inter-procedure periods. Consistently, also TGFß1 plasma levels and the percentage of TGFß1 positive neutrophils increased during the procedures with a meaningful relationship with sFasL plasma levels. Taken together, these findings suggest that the immunosuppressive effects attributed to granulocyte and monocyte apheresis might depend, at least in part, on the sensitivity of activated leucocytes to the bioactivity of sHLA-I molecules. J. Clin. Apheresis 32:49-55, 2017. © 2016 Wiley Periodicals, Inc.
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Remoção de Componentes Sanguíneos/métodos , Colite Ulcerativa/terapia , Fator de Crescimento Transformador beta1/análise , Centrifugação , Granulócitos/citologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/fisiologia , Humanos , Técnicas de Imunoadsorção , Terapia de Imunossupressão/métodos , Leucaférese , Microesferas , Monócitos/citologia , Solubilidade , Fator de Crescimento Transformador beta1/genética , Regulação para CimaRESUMO
OBJECTIVES: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. METHODS: Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. RESULTS: Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE). CONCLUSIONS: IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.
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Ansiedade/epidemiologia , Depressão/epidemiologia , Refluxo Gastroesofágico/epidemiologia , Azia/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Adulto , Colonoscopia , Doenças do Esôfago/epidemiologia , Doenças do Esôfago/fisiopatologia , Monitoramento do pH Esofágico , Esofagoscopia , Fezes/química , Feminino , Refluxo Gastroesofágico/fisiopatologia , Azia/fisiopatologia , Humanos , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/fisiopatologia , Complexo Antígeno L1 Leucocitário/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Few data are available on the relevance of adalimumab (ADA) trough serum levels and anti-ADA antibodies (AAA) during long-term follow-up of patients with Crohn's Disease (CD), and their association with disease outcome. In this study, our aim was to assess ADA trough serum levels and the presence of AAA according to disease activity and clinical response during long-term follow-up in a series of patients with CD treated with ADA monotherapy. MATERIAL AND METHODS: We prospectively evaluated 23 consecutive, infliximab-naïve CD patients who achieved clinical remission/response after induction and were in maintenance treatment with ADA, and who were followed-up for at least 72 weeks. Blood samples were drawn at standardized time points to assess ADA through levels, AAA. RESULTS: At week 48, we found significantly (p = 0.027) different ADA trough serum levels in patients in remission (10.1 mcg/mL), mild (7.4 mcg/mL), and moderate/severe disease (4.5 mcg/mL). Median ADA trough levels were significantly lower in patients with AAA (3.7 mcg/mL versus 9.3 mcg/mL, p = 0.006). At the end of follow-up (median 102 weeks, range 73-112 weeks), ADA trough serum concentrations were significantly higher (11.9 mcg/mL) as compared to patients with mild and moderate/severe disease (5.5 mcg/mL, p = 0.0002). Furthermore, median ADA trough concentrations showed a trend towards lower levels in AAA positive patients (5.2 mcg/mL versus 7.2 mcg/mL, p = 0.371). CONCLUSIONS: Our results emphasize the relevance of therapeutic drug monitoring in CD patients on biologic treatment. ADA trough serum levels and the presence of AAA are important features in the management of patients on ADA treatment.