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Objective: To evaluate the effectiveness and safety of the combination of granulocyte-monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC). Materials and methods: A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy. Results: Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique. Conclusions: Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.
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Eliminación de Componentes Sanguíneos/métodos , Colitis Ulcerosa/terapia , Terapia Combinada/métodos , Granulocitos/citología , Monocitos/citología , Adalimumab/uso terapéutico , Adulto , Anticuerpos Monoclonales/uso terapéutico , Femenino , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto JovenRESUMEN
Human colon lipid analysis by imaging mass spectrometry (IMS) demonstrates that the lipid fingerprint is highly sensitive to a cell's pathophysiological state. Along the colon crypt axis, and concomitant to the differentiation process, certain lipid species tightly linked to signaling (phosphatidylinositols and arachidonic acid (AA)-containing diacylglycerophospholipids), change following a rather simple mathematical expression. We extend here our observations to ethanolamine plasmalogens (PlsEtn), a unique type of glycerophospholipid presenting a vinyl ether linkage at sn-1 position. PlsEtn distribution was studied in healthy, adenomatous, and carcinomatous colon mucosa sections by IMS. In epithelium, 75% of PlsEtn changed in a highly regular manner along the crypt axis, in clear contrast with diacyl species (67% of which remained constant). Consistently, AA-containing PlsEtn species were more abundant at the base, where stem cells reside, and decreased while ascending the crypt. In turn, mono-/diunsaturated species experienced the opposite change. These gradients were accompanied by a gradual expression of ether lipid synthesis enzymes. In lamina propria, 90% of stromal PlsEtn remained unchanged despite the high content of AA and the gradient in AA-containing diacylglycerophospholipids. Finally, both lipid and protein gradients were severely affected in polyps and carcinoma. These results link PlsEtn species regulation to cell differentiation for the first time and confirm that diacyl and ether species are differently regulated. Furthermore, they reaffirm the observations on cell lipid fingerprint image sensitivity to predict cell pathophysiological status, reinforcing the translational impact both lipidome and IMS might have in clinical research.
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Desdiferenciación Celular/fisiología , Colon/fisiología , Células Epiteliales/fisiología , Mucosa Intestinal/fisiología , Plasmalógenos/metabolismo , Adenocarcinoma/patología , Pólipos Adenomatosos/patología , Adulto , Anciano , Biopsia , Colon/citología , Colon/patología , Neoplasias del Colon/patología , Colonoscopía , Células Epiteliales/patología , Femenino , Voluntarios Sanos , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Metabolismo de los Lípidos/fisiología , Masculino , Persona de Mediana Edad , Plasmalógenos/análisisRESUMEN
Membrane lipids are gaining increasing attention in the clinical biomarker field, as they are associated with different pathologic processes such as cancer or neurodegenerative diseases. Analyzing human colonoscopic sections by matrix assisted laser/desorption ionization (MALDI) mass spectrometry imaging techniques, we identified a defined number of lipid species changing concomitant to the colonocyte differentiation and according to a quite simple mathematical expression. These species felt into two lipid families tightly associated in signaling: phosphatidylinositols and arachidonic acid-containing lipids. On the other hand, an opposed pattern was observed in lamina propria for AA-containing lipids, coinciding with the physiological distribution of the immunological response cells in this tissue. Importantly, the lipid gradient was accompanied by a gradient in expression of enzymes involved in lipid mobilization. Finally, both lipid and protein gradients were lost in adenomatous polyps. The latter allowed us to assess how different a single lipid species is handled in a pathological context depending on the cell type. The strict patterns of distribution in lipid species and lipid enzymes described here unveil the existence of fine regulatory mechanisms orchestrating the lipidome according to the physiological state of the cell. In addition, these results provide solid evidence that the cell lipid fingerprint image can be used to predict precisely the physiological and pathological status of a cell, reinforcing its translational impact in clinical research.
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Biomarcadores/metabolismo , Colon/metabolismo , Colon/patología , Lípidos/fisiología , Humanos , Fosfatidilinositoles/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
INTRODUCTION: Randomized controlled trials provide the best scientific evidence for the efficacy of biological drugs in inflammatory bowel disease (IBD). However, findings obtained from these trials might not be reproducible in clinical practice. This study aimed to estimate the percentage of patients with IBD treated with biologics who would have been eligible for randomized controlled trials, and to compare the theoretical efficacy of biological drugs with their effectiveness in clinical practice. METHODS: We performed a retrospective multicenter study in 375 patients with IBD treated with anti-TNF agents and followed-up for 1 year. The eligibility criteria for the trial were taken from the ACCENT, SONIC, ACT, CLASSIC and CHARM trials. Eligible patients were included in a second analysis to compare results in clinical practice versus those hypothetically obtained if the patient had been included in a trial. RESULTS: Only 45.6% of 375 patients would have been eligible for pivotal trials. One-year clinical benefit (remission or response) was similar for eligible and non-eligible cohorts (68.4% vs. 68.6%, P=.608). The clinical benefit was greater for current clinical practice than for a hypothetical trial situation (68.4% vs. 44.4%, P<.001) in eligible patients. CONCLUSION: More than half of patients with IBD treated with biologic drugs would not be represented in pivotal trials. The effectiveness of anti-TNF drugs in clinical practice exceeds their theoretical efficacy.
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Adalimumab/uso terapéutico , Factores Biológicos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Muestreo , Resultado del Tratamiento , Adulto JovenRESUMEN
Imaging mass spectrometry is becoming a reference technique in the field of lipidomics, due to its ability to map the distribution of hundreds of species in a single run, along a tissue section. The next frontier is now achieving increasing resolution powers to offer cellular (or even sub-cellular) resolution. Thus, the new spectrometers are equipped with sophisticated optical systems to decrease the laser spot to <30 µm. Here, we demonstrate that by using the correct matrix (i.e., a matrix that maximizes ion detection and forms small crystals) and a careful preparation, it is possible to achieve resolutions of â¼5-10 µm, even with spectrometers equipped with non-optimal optics, which produces laser spots of 50 µm or even larger. As a proof of concept, we present images of distributions of lipids, both in positive and negative ion mode, over human colon endoscopic sections, recorded using 2-mercaptobenzothiazole for positive ion mode and 2,5-diaminonaphtalene for negative ion mode and an LTQ-Orbitrap XL, equipped with a matrix-assisted laser desorption ionization (MALDI) source that produces astigmatic laser spots. Graphical Abstract Imaging mass spectrometry is becoming an invaluable technique to complement traditional histology, but still higher resolutions are required. Here we deal with such issue.
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Benzotiazoles/metabolismo , Colon/metabolismo , Metabolismo de los Lípidos , Naftalenos/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Humanos , Microscopía Electrónica de RastreoRESUMEN
BACKGROUND: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. AIM: To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. DESIGN: Prospective multicenter study. PATIENTS: In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. INTERVENTION: Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. OUTCOME: Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). CONCLUSIONS: Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.
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Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Levofloxacino , Ofloxacino/uso terapéutico , Adulto , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Pruebas Respiratorias , Claritromicina/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/crecimiento & desarrollo , Humanos , Modelos Logísticos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Análisis Multivariante , Ofloxacino/administración & dosificación , Ofloxacino/efectos adversos , Omeprazol/uso terapéutico , Estudios Prospectivos , Inhibidores de la Bomba de Protones/uso terapéutico , Inducción de Remisión , España/epidemiología , Encuestas y Cuestionarios , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
Background: In patients with Crohn's disease (CD), endoscopic recurrence precedes clinical recurrence after ileocolonic resection. Guidelines recommend ileocolonoscopy within the first year after surgery. The study examined endoscopic monitoring and treatment decisions in CD patients in a real-world setting. Methods: The Practicrohn study involved adult patients from 26 Spanish hospitals who underwent ileocolonic resection with anastomosis from 2007 to 2010. Medical records data were collected retrospectively from diagnosis to index surgery and up to 5 years after surgery. Results: Of 314 analyzed patients, 262 (83%) underwent endoscopic evaluation, but only 30% (n = 95) had planned endoscopy as part of follow-up within the first year after surgery. An upward trend was observed in the proportion of endoscopies performed or planned within the first year after surgery across the selection period. More patients with than without endoscopic recurrence in the first year after surgery had a medication change, mainly for endoscopic activity in the absence of clinical symptoms (54 vs 13%; p = 0.02). Conclusions: Between 2007 and 2010, endoscopic monitoring of patients within the first year after CD-related surgery was less than adequate based on current standards, but showed improvement. Medication changes were in general agreement with current guideline recommendations. This work was presented as a poster (number P686) by M. Barreiro-de Acosta et al. at ECCO (European Crohn's and Colitis Organisation) '18 in Vienna, Austria, 14-17 February 2018.
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Colon/cirugía , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Íleon/cirugía , Adolescente , Adulto , Cuidados Posteriores , Anastomosis Quirúrgica , Colectomía , Enfermedad de Crohn/cirugía , Endoscopía Gastrointestinal , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , España , Adulto JovenRESUMEN
OBJECTIVE: To determine the diagnostic accuracy of computed tomography colonography (CTC) compared with conventional colonoscopy (CC). METHODS: Patients with an indication of CC were included. Fifty patients underwent CTC using multidetector CT before diagnostic colonoscopy was performed by an expert colonoscopist. Diagnostic accuracy was assessed individually both for each polyp and for each patient. RESULTS: Fifty patients were included and 40 polyps were analyzed. The by-polyp sensitivity of CTC was 15% for polyps 5 mm or less, 75% for polyps 5- 10 mm and 75% for polyps 10 mm or larger. By-patient specificity was 6% for polyps 5 mm or less, 75% for polyps 5-10 mm and 80% for polyps 10 mm or larger. The specificity of CTC was 94%. CTC was preferred over CC by 90% of the patients. The mean colonoscopy examination time was 30 minutes for CC and 35 minutes for CTC (p < 0.05). CONCLUSIONS: The sensitivity of CTC is moderate in detecting polyps larger than 10 mm, low in detecting 5-10 mm polyps and very low in detecting those less than 5 mm. The overall specificity of the procedure was 94%. Procedure time was lower with CC than with CTC but the latter was better tolerated by most patients.
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Pólipos del Colon/diagnóstico , Colonografía Tomográfica Computarizada , Colonoscopía , Pólipos/diagnóstico , Neoplasias del Recto/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Adherent-invasive Escherichia coli (AIEC) strains are genetically variable and virulence factors for AIEC are non-specific. FimH is the most studied pathogenicity-related protein, and there have been few studies on other proteins, such as Serine Protease Autotransporters of Enterobacteriacea (SPATEs). The goal of this study is to characterize E. coli strains isolated from patients with Crohn's disease (CD) in Chile and Spain, and identify genetic differences between strains associated with virulence markers and clonality. We characterized virulence factors and genetic variability by pulse field electrophoresis (PFGE) in 50 E. coli strains isolated from Chilean and Spanish patients with CD, and also determined which of these strains presented an AIEC phenotype. Twenty-six E. coli strains from control patients were also included. PFGE patterns were heterogeneous and we also observed a highly diverse profile of virulence genes among all E. coli strains obtained from patients with CD, including those strains defined as AIEC. Two iron transporter genes chuA, and irp2, were detected in various combinations in 68-84% of CD strains. We found that the most significant individual E. coli genetic marker associated with CD E. coli strains was chuA. In addition, patho-adaptative fimH mutations were absent in some of the highly adherent and invasive strains. The fimH adhesin, the iron transporter irp2, and Class-2 SPATEs did not show a significant association with CD strains. The V27A fimH mutation was detected in the most CD strains. This study highlights the genetic variability of E. coli CD strains from two distinct geographic origins, most of them affiliated with the B2 or D E. coli phylogroups and also reveals that nearly 40% of Chilean and Spanish CD patients are colonized with E.coli with a characteristic AIEC phenotype.
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BACKGROUND: Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. METHODS: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. RESULTS: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. CONCLUSIONS: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.
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Antiinflamatorios/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Fístula Cutánea/tratamiento farmacológico , Fístula Rectal/tratamiento farmacológico , Ustekinumab/uso terapéutico , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Enfermedad de Crohn/complicaciones , Fístula Cutánea/etiología , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Fístula Rectal/etiología , Retratamiento , Estudios Retrospectivos , España , Ustekinumab/administración & dosificación , Ustekinumab/efectos adversosRESUMEN
Next generation sequencing approaches allow the retrieval of several orders of magnitude larger numbers of amplified single sequences in 16S rRNA diversity surveys than classical methods. However, the sequences are only partial and thus lack sufficient resolution for a reliable identification. The OPU approach used here, based on a tandem combination of high quality 454 sequences (mean >500 nuc) applying strict OTU thresholds, and phylogenetic inference based on parsimony additions to preexisting trees, seemed to improve the identification yields at the species and genus levels. A total of thirteen biopsies of Crohn-diagnosed patients (CD) and seven healthy controls (HC) were studied. In most of the cases (73%), sequences were affiliated to known species or genera and distinct microbial patterns could be distinguished among the CD subjects, with a common depletion of Clostridia and either an increased presence of Bacteroidetes (CD1) or an anomalous overrepresentation of Proteobacteria (CD2). Faecalibacterium prausnitzii presence was undetectable in CD, whereas Bacteroides vulgatus-B. dorei characterized HC and some CD groups. Altogether, the results showed that a microbial composition with predominance of Clostridia followed by Bacteroidetes, with F. prausnitzii and B. vulgatus-B. dorei as major key bacteria, characterized what could be considered a balanced structure in HC. The depletion of Clostridia seemed to be a common trait in CD.
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Bacterias/clasificación , Bacterias/genética , Biota , Colon/microbiología , Enfermedad de Crohn/microbiología , Mucosa Intestinal/microbiología , Biopsia , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Humanos , Región Mediterránea , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
AIM: To perform a systematic review on the efficacy of pantoprazole based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of pantoprazole and other proton pump inhibitors (PPIs) when co-prescribed with antibiotics. METHODS: Studies evaluating pantoprazole combined with antibiotics were considered. Only randomized clinical trials comparing pantoprazole and other PPIs when co-prescribed with antibiotics, and differing only in the PPI (pantoprazole vs other), were eligible for inclusion in the meta-analysis. Bibliographical searches in several electronic databases, and manual search of abstracts from congresses, were conducted. The percentage (weighted mean) of patients with eradication success was calculated. Meta-analysis was performed combining the odds ratios (ORs) of the individual studies in a global OR. RESULTS: The mean eradication rate with pantoprazole plus clarithromycin for 14 days was 60%. Cure rates with 7 day pantoprazole based triple regimens were higher: pantoprazole, amoxicillin and clarithromycin (78%); pantoprazole, clarithromycin and nitroimidazole (84%); and pantoprazole, amoxicillin and nitroimidazole (74%). Twelve studies comparing pantoprazole and other PPIs were selected for the meta-analysis, including 534 and 603 patients, respectively. The mean eradication rate for H. pylori using pantoprazole plus antibiotics was 83%, and 81% when other PPIs were used (OR = 1; 95% confidence interval (CI) from 0.61 to 1.64). When sub-analysis was performed, including only studies comparing pantoprazole with omeprazole, or pantoprazole with lansoprazole, differences were also statistically non-significant. The meta-analysis of the six studies prescribing equivalent doses of all PPIs demonstrated similar results with pantoprazole and with other PPIs (OR = 1.07; 95% CI from 0.71 to 1.62), the results being statistically homogeneous. CONCLUSIONS: Pantoprazole achieves similar cure rates to those of omeprazole and lansoprazole when co-prescribed with antibiotics for the eradication of H. pylori infection.
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Antiinfecciosos/uso terapéutico , Bencimidazoles/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Sulfóxidos/uso terapéutico , 2-Piridinilmetilsulfinilbencimidazoles , Quimioterapia Combinada , Helicobacter pylori/efectos de los fármacos , Humanos , Omeprazol/análogos & derivados , Pantoprazol , Inhibidores de la Bomba de Protones , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIM: Lymphomagenesis is a multifactorial process in which genetic, environmental and infectious factors can be involved. The aim of the present study was to assess the prevalence of hepatitis C virus (HCV) infection among patients with non-Hodgkin's lymphoma (NHL), and to compare it with that of a control group of voluntary blood donors. METHODS: All consecutive patients with a histological diagnosis of NHL from January 1996 to December 2001 were included in this prospective study. As control group for HCV infection, voluntary blood donors recruited over the same time period from the same geographical area were considered. The presence of anti-HCV antibodies was investigated by ELISA-II and RIBA-II, and viraemia (HCV RNA) was tested by using a polymerase chain reaction (PCR). HCV genotyping was also performed. RESULTS: Ninety-nine patients (mean age 48 years) with NHL were diagnosed during the study period. Histological classification of NHL was high-intermediate grade (63 patients), and low grade (36 patients). Immunophenotype distribution was type B (86 patients) and type T (13 patients). Seven of the 99 NHL patients (7%) were infected with HCV (both using serology and PCR), five of them with immunophenotype B and two with immunophenotype T. The prevalence of HCV infection according to NHL phenotype was 5.8% in B-cell NHL and 15.4% in T-cell NHL. The HCV genotype was 1b in six cases, and 3a in one. In voluntary blood donors (mean age 45 years), HCV infection was detected in 517/55 587 (0.93%). Therefore, HCV infection was more frequent in NHL patients than in controls (odds ratio = 8.1; 95% CI = 3.7-17.6). The odds ratio for the association of HCV and B-cell NHL was 6.2 (95% CI = 2.5-15.3), and for T-cell NHL 16.4 (95% CI = 3.7-72.8). CONCLUSION: The prevalence of HCV infection in patients with NHL (both B- and T-type) is higher than that observed in controls, suggesting a role of HCV in lymphoma aetiopathogenesis.
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Hepatitis C/epidemiología , Linfoma no Hodgkin/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/análisis , Donantes de Sangre , Femenino , Genotipo , Hepatitis C/patología , Humanos , Inmunofenotipificación/métodos , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Prospectivos , Viremia/complicacionesRESUMEN
INTRODUCCIÓN: Los ensayos clínicos aleatorizados proporcionan la mejor evidencia científica de la eficacia de los fármacos biológicos en la enfermedad inflamatoria intestinal (EII). Sin embargo, los resultados pueden no ser reproducibles en la práctica clínica. Los objetivos de este estudio son analizar el porcentaje de pacientes con EII tratados con fármacos biológicos que habrían podido ser elegidos para un ensayo clínico aleatorizado y comparar la eficacia teórica de los fármacos biológicos con su efectividad en la práctica clínica. MÉTODOS: Realizamos un estudio retrospectivo multicéntrico en 375 pacientes con EII tratados con anti-TNF con un seguimiento de un año. Los criterios de elegibilidad para la condición de ensayo clínico fueron extraídos de los estudios pivotales ACCENT, SONIC, ACT, CLASSIC y CHARM. Los pacientes elegibles fueron incluidos en un segundo análisis para comparar los resultados en la práctica clínica con los obtenidos tras realizar una estimación teórica si el paciente hubiese sido incluido en un estudio pivotal. RESULTADOS: Solo el 45,6% de los 375 pacientes cumplían los criterios de selección para un estudio pivotal. El beneficio clínico al año fue similar entre los pacientes elegibles y no elegibles (68,4% vs 68,6%). El beneficio clínico en los pacientes elegibles fue mayor en la práctica clínica que en la condición hipotética de un ensayo clínico (68,4% vs 44,4%, p < 0,001). CONCLUSIÓN: Más de la mitad de los pacientes con EII tratados con fármacos biológicos no estarían representados en los ensayos pivotales. La efectividad de los fármacos anti-TNF en la práctica clínica es superior a su eficacia teórica
INTRODUCTION: Randomized controlled trials provide the best scientific evidence for the efficacy of biological drugs in inflammatory bowel disease (IBD). However, findings obtained from these trials might not be reproducible in clinical practice. This study aimed to estimate the percentage of patients with IBD treated with biologics who would have been eligible for randomized controlled trials, and to compare the theoretical efficacy of biological drugs with their effectiveness in clinical practice. METHODS: We performed a retrospective multicenter study in 375 patients with IBD treated with anti-TNF agents and followed-up for 1 year. The eligibility criteria for the trial were taken from the ACCENT, SONIC, ACT, CLASSIC and CHARM trials. Eligible patients were included in a second analysis to compare results in clinical practice versus those hypothetically obtained if the patient had been included in a trial. RESULTS: Only 45.6% of 375 patients would have been eligible for pivotal trials. One-year clinical benefit (remission or response) was similar for eligible and non-eligible cohorts (68.4% vs. 68.6%, P=.608). The clinical benefit was greater for current clinical practice than for a hypothetical trial situation (68.4% vs. 44.4%, P<.001) in eligible patients. CONCLUSION: More than half of patients with IBD treated with biologic drugs would not be represented in pivotal trials. The effectiveness of anti-TNF drugs in clinical practice exceeds their theoretical efficacy
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Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Terapia Biológica/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Estudios Retrospectivos , Resultado del Tratamiento , Infliximab/farmacocinética , Adalimumab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológicoRESUMEN
AIM: Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure. DESIGN: Prospective multicenter study. PATIENTS: in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. INTERVENTION: A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. OUTCOME: Eradication was confirmed with (13)C-urea breath test 4-8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS: Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77-86%) and 77% (73-82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe. CONCLUSION: Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Levofloxacino , Ofloxacino/uso terapéutico , Omeprazol/uso terapéutico , Pruebas Respiratorias , Claritromicina/uso terapéutico , Quimioterapia Combinada , Endoscopía Gastrointestinal , Femenino , Estudios de Seguimiento , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores de la Bomba de Protones/uso terapéutico , Insuficiencia del Tratamiento , Urea/análisisAsunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Arginina/efectos adversos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Gastroscopía , Ibuprofeno/efectos adversos , Combinación de Medicamentos , Humanos , Úlcera Péptica/inducido químicamente , Úlcera Péptica/diagnóstico , Estudios Prospectivos , Valores de Referencia , Índice de Severidad de la EnfermedadRESUMEN
OBJETIVO: Determinar la exactitud diagnóstica de la colonoscopia virtual (CV) comparada con la colonoscopia convencional (CC).MÉTODOS: Se incluyeron pacientes con indicación de CC. Seles realizó una CV y, posteriormente, se llevó a cabo la CC sin sedación por parte de un colonoscopista experto. El análisis del rendimiento diagnóstico se efectuó tanto individualmente para cada pólipo como por paciente.RESULTADOS: Se han incluido 50 pacientes, y se contabilizóun total de 40 pólipos. La CV tuvo una sensibilidad del 15% para pólipos menores de 5 mm, aumentó hasta el 75% para pólipos de entre 5 y 10 mm, y fue del 75% para los mayores de 10 mm. La sensibilidad respecto al diagnóstico de pacientes con lesiones fue del 6% para pólipos menores de 5 mm, del 75% para pólipos de 5-10 mm y del 80% para los mayores de 10 mm. La especificidad de la colonoscopia virtual fue del 94%. La CV fue la exploración preferida por el 90% de los pacientes. La duración media de la CC fue de 30 min, mientras que la de la CV fue de 35 min (p < 0,05).CONCLUSIONES: La CV es una técnica moderadamente sensiblepara la detección de pólipos mayores de 10 mm; dichasensibilidad desciende considerablemente en los pólipos de5-10 mm y es muy baja para los menores 5 mm. La especificidad global de la prueba ha sido del 94%. La duración de la CC fue menor que la de la CV, y esta última fue mejor tolerada por la mayoría de los pacientes
OBJECTIVE: To determine the diagnostic accuracy of computed tomography colonography (CTC) compared with conventional colonoscopy (CC).METHODS: Patients with an indication of CC were included.Fifty patients underwent CTC using multidetector CT beforediagnostic colonoscopy was performed by an expert colonoscopist.Diagnostic accuracy was assessed individuallyboth for each polyp and for each patient.RESULTS: Fifty patients were included and 40 polyps wereanalyzed. The by-polyp sensitivity of CTC was 15% forpolyps 5 mm or less, 75% for polyps 5- 10 mm and 75%for polyps 10 mm or larger. By-patient specificity was 6% for polyps 5 mm or less, 75% for polyps 5-10 mm and 80%for polyps 10 mm or larger. The specificity of CTC was94%. CTC was preferred over CC by 90% of the patients.The mean colonoscopy examination time was 30 minutesfor CC and 35 minutes for CTC (p < 0.05).CONCLUSIONS: The sensitivity of CTC is moderate in detecting polyps larger than 10 mm, low in detecting 5-10 mm polyps and very low in detecting those less than 5 mm. The overall specificity of the procedure was 94%. Procedure time was lower with CC than with CTC but the latter was better tolerated by most patients
Asunto(s)
Humanos , Pólipos del Colon/diagnóstico , Colonoscopía/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias Colorrectales/diagnóstico , Sensibilidad y EspecificidadRESUMEN
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