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INTRODUCTION: Identifying novel treatment strategies for patients with ulcerative colitis (UC) and at risk of relapse is critical. The objective of this study was to assess the efficacy of beclomethasone dipropionate (BDP) in lowering fecal calprotectin (FC) levels in UC patients in clinical remission and at risk of relapse. METHODS: This multicenter study comprised a double-blind, randomized, placebo-controlled phase (part I) and an open-label, non-randomized phase (part II). Eligible participants with UC in clinical remission, treated with 5-aminosalicylic acid and with FC levels ≥250 µg/g were randomized to receive 5 mg/day of BDP or placebo for 4 weeks (part I). At week 5, patients with FC ≥100 µg/g were treated with 5 mg/day of BDP for 4 weeks (part II), and FC levels were tested at week 9. RESULTS: Forty-three patients were randomized: 22 received BDP (group A) and 21 placebo (group B). At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 µg/g (p-value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p-value = 0.049). Both treatment groups showed a favorable safety profile, with most common adverse events being gastrointestinal disorders. CONCLUSION: In this multicenter, randomized clinical trial including patients with UC in clinical remission but with elevated FC, BDP was efficacious in reducing FC and well-tolerated.
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OBJECTIVE: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. PATIENTS AND METHODS: A retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS: Seventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35-61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5-7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. CONCLUSION: GMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.
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BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence [POR] after ileocaecal resection [ICR] for Crohn's disease [CD]. We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD patients undergoing first ICR were assigned to Cohort 1 if a biologic or immunomodulator was [re]started prophylactically after ICR, or to Cohort 2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR [Rutgeerts >i1]. Secondary endpoints were severe endoscopic POR [Rutgeerts i3/i4], clinical POR, surgical POR, and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment [proactive/Cohort 1] and 52.6% did not [reactive/Cohort 2]. Endoscopic POR [Rutgeertsâ >i1] rate was significantly higher in Cohort 2 [41.5% vs 53.8%, OR 1.81, pâ =â 0.039] at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found [OR 1.29, pâ =â 0.517]. Cohort 2 had significantly higher clinical POR rates [17.7% vs 35.7%, OR 3.05, pâ =â 0.002] and numerically higher surgical recurrence rates [6.7% vs 13.2%, OR 2.59, pâ =â 0.051]. Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach [HR 2.50, pâ =â 0.057]. Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in Cohort 2 [mean ratio 0.53, pâ =â 0.002], but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared with expectant management after first ileocaecal resection for Crohn's disease.
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Enfermedad de Crohn , Prevención Secundaria , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/prevención & control , Femenino , Estudios Retrospectivos , Masculino , Adulto , Prevención Secundaria/métodos , Prevención Secundaria/estadística & datos numéricos , Íleon/cirugía , Recurrencia , Persona de Mediana Edad , Factores Inmunológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Europa (Continente) , Ciego/cirugía , Colonoscopía/estadística & datos numéricos , Colonoscopía/métodosRESUMEN
OBJECTIVE: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.
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Antiinflamatorios no Esteroideos , Vacunas contra la COVID-19 , COVID-19 , Enfermedades Inflamatorias del Intestino , Mesalamina , Humanos , Mesalamina/uso terapéutico , Femenino , Estudios Prospectivos , Masculino , Vacunas contra la COVID-19/inmunología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Antivirales/sangre , Vacunación , Anciano , Seroconversión , Eficacia de las Vacunas , SARS-CoV-2/inmunologíaRESUMEN
BACKGROUND: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. METHODS: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. RESULTS: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. CONCLUSIONS: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.
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BACKGROUND: The response to SARS-CoV-2 vaccination decreases in inflammatory bowel disease (IBD) patients, specially under anti-TNF treatment. However, data on medium-term effectiveness are limited, specially using new recommended seroconversion rate (>260BAU/mL). Our aim was to evaluate the 6-month>260 BAU-seroconversion rate after full vaccination and after booster-dose. METHODS: VACOVEII is a Spanish multicenter, prospective study promoted by GETECCU. IBD patients full vaccinated against SARS-CoV-2 and without previous COVID-19 infection, treated or not with immunosuppressants, were included. The booster dose was administered 6 months after the full vaccination. Seroconversion was set at 260BAU/mL, according to most recent recommendations and was assessed 6 months after the full vaccination and 6 months after booster-dose. RESULTS: Between October 2021 and March 2022, 313 patients were included (124 no treatment or mesalazine; 55 immunomodulators; 87 anti-TNF; 19 anti-integrin; and 28 ustekinumab). Most patients received mRNA-vaccines (86%). Six months after full vaccination, overall seroconversion rate was 44.1%, being significantly lower among patients on anti-TNF (19.5%, p<0.001) and ustekinumab (35.7%, p=0.031). The seroconversion rate after booster was 92%. Again, anti-TNF patients had a significantly lower seroconversion rate (67%, p<0.001). mRNA-vaccine improved seroconversion rate (OR 11.720 [95% CI 2.26-60.512]). CONCLUSION: The full vaccination regimen achieves suboptimal response in IBD patients, specially among those anti-TNF or ustekinumab. The booster dose improves seroconversion rate in all patients, although it remains limited in those treated with anti-TNF. These results reinforce the need to prioritize future booster doses in patients on immunosuppressants therapy, specially under anti-TNF, and using mRNA-vaccines.
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BACKGROUND: Schizophrenia (SCZ) is caused by an interplay of polygenic risk and environmental factors, which may alter regulators of gene expression leading to pathogenic misexpression of SCZ risk genes. The CPEB family of RNA-binding proteins (CPEB1-4) regulates translation of target RNAs (approximately 40% of overall genes). We previously identified CPEB4 as a key dysregulated translational regulator in autism spectrum disorder (ASD) because its neuronal-specific microexon (exon 4) is mis-spliced in ASD brains, causing underexpression of numerous ASD risk genes. The genetic factors and pathogenic mechanisms shared between SCZ and ASD led us to hypothesize CPEB4 mis-splicing in SCZ leading to underexpression of multiple SCZ-related genes. METHODS: We performed MAGMA-enrichment analysis on Psychiatric Genomics Consortium genome-wide association study data and analyzed RNA sequencing data from the PsychENCODE Consortium. Reverse transcriptase polymerase chain reaction and Western blot were performed on postmortem brain tissue, and the presence/absence of antipsychotics was assessed through toxicological analysis. Finally, mice with mild overexpression of exon 4-lacking CPEB4 (CPEB4Δ4) were generated and analyzed biochemically and behaviorally. RESULTS: First, we found enrichment of SCZ-associated genes for CPEB4-binder transcripts. We also found decreased usage of CPEB4 microexon in SCZ probands, which was correlated with decreased protein levels of CPEB4-target SCZ-associated genes only in antipsychotic-free individuals. Interestingly, differentially expressed genes fit those reported for SCZ, specifically in the SCZ probands with decreased CPEB4-microexon inclusion. Finally, we demonstrated that mice with mild overexpression of CPEB4Δ4 showed decreased protein levels of CPEB4-target SCZ genes and SCZ-linked behaviors. CONCLUSIONS: We identified aberrant CPEB4 splicing and downstream misexpression of SCZ risk genes as a novel etiological mechanism in SCZ.
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Antipsicóticos , Trastorno del Espectro Autista , Esquizofrenia , Animales , Ratones , Antipsicóticos/uso terapéutico , Trastorno del Espectro Autista/genética , Encéfalo/metabolismo , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Esquizofrenia/genética , Esquizofrenia/tratamiento farmacológicoRESUMEN
INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.
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Enfermedad de Crohn , Fístula , Fístula Rectal , Adulto , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Ustekinumab/uso terapéutico , Resultado del Tratamiento , Terapia Biológica , Necrosis , Estudios Retrospectivos , Fístula Rectal/etiología , Fístula Rectal/terapiaRESUMEN
BACKGROUND AND AIMS: Extra-intestinal manifestations are frequently reported in inflammatory bowel diseases. However, data comparing the effect of vedolizumab and ustekinumab on articular extra-intestinal manifestations are limited. The aim here was to evaluate differences in new-onset and the evolution of pre-existing joint extra-intestinal manifestations during both treatments. METHODS: An international multicentre retrospective study was performed on inflammatory bowel disease patients who started vedolizumab or ustekinumab between May 2010 and December 2020. Extra-intestinal manifestations were assessed at baseline and joint extra-intestinal manifestations were evaluated throughout the 2-year follow-up. Arthropathy was defined by joint inflammation [arthritis/sacroiliitis], diagnosed by a rheumatologist, and arthralgia as articular pain without confirmed inflammation. Additionally, skin, ocular and hepatic extra-intestinal manifestations were assessed at baseline. Uni- and multivariate analyses were performed. RESULTS: In total, 911 patients [vedolizumab: 584; ustekinumab: 327] were included. Deterioration of pre-existing arthropathy and rate of new-onset arthropathy were not significantly associated with vedolizumab over ustekinumab. Arthropathy was used as reason to stop treatment in six vedolizumab and two ustekinumab patients. The odds of developing new arthralgia within 6 months was higher in patients who took vedolizumab compared to ustekinumab (adjusted odds ratio [aOR]: 2.28 [1.01-5.15], p = 0.047). However, this effect was not sustained during the 2-year follow-up (aOR: 1.35 [0.80-2.29], p = 0.259). Deterioration of pre-existing arthralgia was comparable between ustekinumab and vedolizumab-treated patients. In two vedolizumab-treated patients arthralgia was given as the reason to stop treatment. CONCLUSIONS: Vedolizumab and ustekinumab can be used safely in patients with articular extra-intestinal manifestations. Only a temporary increased risk for developing arthralgia has been observed under vedolizumab.
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Artritis , Enfermedades Inflamatorias del Intestino , Humanos , Ustekinumab/efectos adversos , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios de Cohortes , Artritis/complicaciones , Inflamación/complicaciones , Artralgia/inducido químicamenteRESUMEN
BACKGROUND AND AIMS: Crohn's disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. METHODS: Clinical information from all adult patients with CD and at least one ECF-excluding perianal fistulae-were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. RESULTS: A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, pâ =â 0.001, and HR 1.49, 95% CI 1.07-2.06, pâ =â 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. CONCLUSIONS: ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.
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Enfermedad de Crohn , Fístula Intestinal , Fístula Rectal , Adulto , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Fístula Intestinal/etiología , Fístula Intestinal/cirugía , Calidad de Vida , Fístula Rectal/etiología , Fístula Rectal/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Huntington's disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophylinked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamineresponsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD.
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Enfermedad de Huntington , Poliadenilación , Factores de Transcripción/genética , Factores de Escisión y Poliadenilación de ARNm/genética , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/terapia , Proteínas de Transporte de Membrana , TranscriptomaRESUMEN
Correction of mis-splicing events is a growing therapeutic approach for neurological diseases such as spinal muscular atrophy or neuronal ceroid lipofuscinosis 7, which are caused by splicing-affecting mutations. Mis-spliced effector genes that do not harbour mutations are also good candidate therapeutic targets in diseases with more complex aetiologies such as cancer, autism, muscular dystrophies or neurodegenerative diseases. Next-generation RNA sequencing (RNA-seq) has boosted investigation of global mis-splicing in diseased tissue to identify such key pathogenic mis-spliced genes. Nevertheless, while analysis of tumour or dystrophic muscle biopsies can be informative on early stage pathogenic mis-splicing, for neurodegenerative diseases, these analyses are intrinsically hampered by neuronal loss and neuroinflammation in post-mortem brains. To infer splicing alterations relevant to Huntington's disease pathogenesis, here we performed intersect-RNA-seq analyses of human post-mortem striatal tissue and of an early symptomatic mouse model in which neuronal loss and gliosis are not yet present. Together with a human/mouse parallel motif scan analysis, this approach allowed us to identify the shared mis-splicing signature triggered by the Huntington's disease-causing mutation in both species and to infer upstream deregulated splicing factors. Moreover, we identified a plethora of downstream neurodegeneration-linked mis-spliced effector genes that-together with the deregulated splicing factors-become new possible therapeutic targets. In summary, here we report pathogenic global mis-splicing in Huntington's disease striatum captured by our new intersect-RNA-seq approach that can be readily applied to other neurodegenerative diseases for which bona fide animal models are available.
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Empalme Alternativo/genética , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Factores de Empalme de ARN/genética , Animales , Cuerpo Estriado/patología , Humanos , Enfermedad de Huntington/patología , Ratones , Análisis de Secuencia de ARN/métodosRESUMEN
INTRODUCCIÓN: Las Aeromonas son la causa de múltiples enfermedades en humanos, siendo la gastroenteritis la más frecuente. El papel de Aeromonas como patógeno en las enterocolitis y su relación con la enfermedad inflamatoria intestinal siguen siendo controvertidos. OBJETIVO: Determinar la incidencia de la infección por Aeromonas en nuestro entorno y su posible relación con la enfermedad inflamatoria intestinal. PACIENTES Y MÉTODOS: Estudio retrospectivo y observacional de todos los pacientes adultos con al menos un aislamiento de Aeromonas en el cultivo de heces entre enero de 2015 y diciembre de 2017 en el Hospital Galdakao-Usansolo (Vizcaya). RESULTADOS: Se identificaron 98 pacientes con un cultivo de heces positivo para Aeromonas (edad media 62 años, 51% mujeres), estimando una incidencia de 32 casos/105 habitantes-año. El 11% tenía un diagnóstico previo de enfermedad inflamatoria intestinal (4 colitis ulcerosa y 7 enfermedad de Crohn). Estos pacientes se encontraban en tratamiento inmunosupresor con más frecuencia, aunque tenían menos comorbilidades que el grupo sin esta patología. También observamos que la comorbilidad era el factor que más se asociaba a la infección por Aeromonas. CONCLUSIONES: La infección por Aeromonas tiene una incidencia de 32 casos/105 habitantes-año, y afecta tanto a pacientes inmunocompetentes como a inmunodeprimidos. La incidencia está influida por la inmunosupresión en pacientes con enfermedad inflamatoria intestinal, mientras que la comorbilidad parece conferir un mayor riesgo en pacientes sin esta patología
INTRODUCTION: Aeromonas can cause several diseases in humans, with gastroenteritis accounting for most cases. The role of Aeromonas as a pathogen in human enterocolitis has been questioned in recent years. OBJECTIVE: To determine the incidence of gastrointestinal infection caused by Aeromonas in our area and its possible relationship to inflammatory bowel disease. PATIENTS AND METHODS: This was a retrospective observational study. All adult patients with a positive stool culture for Aeromonas were identified between January 2015 and December 2017 at Hospital Galdakao-Usansolo (Vizcaya, Spain). RESULTS: Ninety-eight patients were identified (median age 62 years; 51% women). Therefore, the incidence in our area was 32 cases per 105 inhabitants per year. Eleven per cent of them had been previously diagnosed with inflammatory bowel disease (four with ulcerative colitis and seven with Crohn's disease). Patients with inflammatory bowel disease more often received immunosuppressive therapy. Conversely, patients without inflammatory bowel disease suffered from more comorbidities. We also found comorbidity to be the risk factor most associated with Aeromonas infection. CONCLUSION: Aeromonas infection is a common gastrointestinal infection that may occur in both immunocompetent and immunocompromised patients. Immunosuppression is a significant factor in inflammatory bowel disease patients, while comorbidity seems to confer a higher risk on patients without this disease
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Gastrointestinales/epidemiología , Enfermedades Transmisibles/epidemiología , Infecciones por Bacterias Gramnegativas/etiología , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Gastrointestinales/complicaciones , Estudios Retrospectivos , Heces , Aeromonas/aislamiento & purificación , Dolor Abdominal/etiología , Factores de RiesgoRESUMEN
Huntington's disease (HD) is a fatal degenerative disorder affecting the nervous system. It is characterized by motor, cognitive, and psychiatric dysfunctions, with a late onset and an autosomal dominant pattern of inheritance. HD-causing mutation consists in an expansion of repeated CAG triplets in the huntingtin gene (HTT), encoding for an expanded polyglutamine (polyQ) stretch in the huntingtin protein (htt). The mutation causes neuronal dysfunction and loss through multiple mechanisms, affecting both the nucleus and cytoplasm. P2X7 receptor (P2X7R) emerged as a major player in neuroinflammation, since ATP - its endogenous ligand - is massively released under this condition. Indeed, P2X7R stimulation in the central nervous system (CNS) is known to enhance the release of pro-inflammatory cytokines from microglia and of neurotransmitters from neuronal presynaptic terminals, as well as to promote apoptosis. Previous experiments performed with neurons expressing the mutant huntingtin and exploiting HD mouse models demonstrated a role of P2X7R in HD. On the basis of those results, here, we explore for the first time the status of P2X7R in HD patients' brain. We report that in HD postmortem striatum, as earlier observed in HD mice, the protein levels of the full-length form of P2X7R, also named P2X7R-A, are upregulated. In addition, the exclusively human naturally occurring variant lacking the C-terminus region, P2X7R-B, is upregulated as well. As we show here, this augmented protein levels can be explained by elevated mRNA levels. Furthermore, in HD patients' striatum, P2X7R shows not only an augmented total transcript level but also an alteration of its splicing. Remarkably, P2X7R introns 10 and 11 are more retained in HD patients when compared with controls. Taken together, our data confirm that P2X7R is altered in brains of HD subjects and strengthen the notion that P2X7R may represent a potential therapeutic target for HD.
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OBJECTIVE: To evaluate the impact of magnetic resonance enterography (MRE) diagnosis on clinical decision-making regarding treatment choice and maintenance of treatment over time in patients with inflammatory bowel disease (IBD). METHODS: A cohort of patients who underwent MRE for IBD assessment between 2011 and 2014 was analyzed. From clinical records, we retrospectively retrieved their demographic data and clinical data on their IBD at the time of MRE, the results of MRE and the patient's clinical course. Medical management decisions made during the three months following MRE and at the 15-month follow-up were assessed. RESULTS: In total, 474 MREs were reviewed. In the first three-month period, MRE results led to changes in the medical management of 266 patients (56.1%). Of those, maintenance therapy was altered in 140 patients (68.3%) (90.7% step-up and 9.3% top-down strategy), 65 (24.4%) were prescribed a course of steroids and 61 (22.9%) underwent surgery. MRE confirmed a CD diagnosis in 14/41 patients (34.1%) previously diagnosed with indeterminate colitis or ulcerative colitis and in 4/18 patients (22.2%) with suspected IBD. At the 15-month follow-up, treatment remained unchanged in 289 patients (65.8%). CONCLUSIONS: These results suggest that MRE is a diagnostic tool that provides valid information for the clinical-decision making process for patients with CD
OBJETIVO: Evaluar el impacto del diagnóstico de la enterografía por resonancia magnética (ERM) en la toma de decisiones clínicas con respecto a la elección del tratamiento y el mantenimiento del mismo a lo largo del tiempo en pacientes con enfermedad inflamatoria intestinal (EII). MÉTODOS: Se analizó una cohorte de pacientes que se sometieron a ERM para la evaluación de EII entre 2011 y 2014. De los registros clínicos recuperamos retrospectivamente sus datos demográficos y datos clínicos sobre su EII en el momento de la ERM, los resultados de la ERM y la evolución clínica del paciente. Se evaluaron las decisiones de manejo médico tomadas durante los 3 meses posteriores a la ERM y a los 15 meses de seguimiento. RESULTADOS: Se revisaron 474 ERM. En el primer período de 3 meses, los resultados de la ERM llevaron a cambios en el manejo médico en 266 pacientes (56,1%). De ellos, se modificó el tratamiento de mantenimiento en 140 (68,3%) pacientes (se escaló en el 90,7% y top-down en el 9,3%), 65 (24,4%) recibieron un curso de esteroides y 61 (22,9%) se sometieron a cirugía. La ERM confirmó un diagnóstico de enfermedad de Crohn (EC) en 14/41 pacientes (34,1%) diagnosticados previamente con colitis indeterminada o colitis ulcerosa y en 4/18 pacientes (22,2%) con sospecha de EII. A los 15 meses de seguimiento, el tratamiento se mantuvo sin cambios en 289 (65,8%) pacientes. CONCLUSIONES: Estos resultados sugieren que la ERM es una herramienta de diagnóstico que proporciona información válida para el proceso de toma de decisiones clínicas para pacientes con EC
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Humanos , Masculino , Adulto Joven , Adulto , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Toma de Decisiones , Estudios de Cohortes , Imagen por Resonancia Magnética/métodos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Enfermedad de Crohn/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
INTRODUCTION: Aeromonas can cause several diseases in humans, with gastroenteritis accounting for most cases. The role of Aeromonas as a pathogen in human enterocolitis has been questioned in recent years. OBJECTIVE: To determine the incidence of gastrointestinal infection caused by Aeromonas in our area and its possible relationship to inflammatory bowel disease. PATIENTS AND METHODS: This was a retrospective observational study. All adult patients with a positive stool culture for Aeromonas were identified between January 2015 and December 2017 at Hospital Galdakao-Usansolo (Vizcaya, Spain). RESULTS: Ninety-eight patients were identified (median age 62 years; 51% women). Therefore, the incidence in our area was 32 cases per 105 inhabitants per year. Eleven per cent of them had been previously diagnosed with inflammatory bowel disease (four with ulcerative colitis and seven with Crohn's disease). Patients with inflammatory bowel disease more often received immunosuppressive therapy. Conversely, patients without inflammatory bowel disease suffered from more comorbidities. We also found comorbidity to be the risk factor most associated with Aeromonas infection. CONCLUSION: Aeromonas infection is a common gastrointestinal infection that may occur in both immunocompetent and immunocompromised patients. Immunosuppression is a significant factor in inflammatory bowel disease patients, while comorbidity seems to confer a higher risk on patients without this disease.
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Aeromonas , Infecciones por Bacterias Gramnegativas/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Coinfección/microbiología , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/microbiología , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/microbiología , Femenino , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Huésped Inmunocomprometido , Terapia de Inmunosupresión , Incidencia , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.
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Factores Biológicos/uso terapéutico , Enfermedad de Crohn/terapia , Endoscopía Gastrointestinal/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Tiempo de Tratamiento , Adalimumab/farmacología , Adalimumab/uso terapéutico , Adulto , Factores de Edad , Factores Biológicos/farmacología , Constricción Patológica/diagnóstico , Constricción Patológica/inmunología , Constricción Patológica/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Endoscopía Gastrointestinal/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Infliximab/farmacología , Infliximab/uso terapéutico , Intestinos/efectos de los fármacos , Intestinos/inmunología , Intestinos/cirugía , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the impact of magnetic resonance enterography (MRE) diagnosis on clinical decision-making regarding treatment choice and maintenance of treatment over time in patients with inflammatory bowel disease (IBD). METHODS: A cohort of patients who underwent MRE for IBD assessment between 2011 and 2014 was analyzed. From clinical records, we retrospectively retrieved their demographic data and clinical data on their IBD at the time of MRE, the results of MRE and the patient's clinical course. Medical management decisions made during the three months following MRE and at the 15-month follow-up were assessed. RESULTS: In total, 474 MREs were reviewed. In the first three-month period, MRE results led to changes in the medical management of 266 patients (56.1%). Of those, maintenance therapy was altered in 140 patients (68.3%) (90.7% step-up and 9.3% top-down strategy), 65 (24.4%) were prescribed a course of steroids and 61 (22.9%) underwent surgery. MRE confirmed a CD diagnosis in 14/41 patients (34.1%) previously diagnosed with indeterminate colitis or ulcerative colitis and in 4/18 patients (22.2%) with suspected IBD. At the 15-month follow-up, treatment remained unchanged in 289 patients (65.8%). CONCLUSIONS: These results suggest that MRE is a diagnostic tool that provides valid information for the clinical-decision making process for patients with CD.
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Toma de Decisiones Clínicas/métodos , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Imagen por Resonancia Magnética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/mortalidad , Enfermedades Inflamatorias del Intestino/mortalidad , Enfermedades Inflamatorias del Intestino/virología , Neumonía Viral/complicaciones , Neumonía Viral/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Femenino , Fármacos Gastrointestinales/uso terapéutico , Hospitalización/estadística & datos numéricos , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pandemias , Pronóstico , SARS-CoV-2 , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Tacrolimus is a calcineurin inhibitor commonly used for prophylaxis of rejection in renal and liver transplantation. There are limited but favourable data regarding its possible use in patients with inflammatory bowel disease (IBD). AIMS: To evaluate the efficacy and safety of tacrolimus in patients with IBD in clinical practice. METHODS: We performed a retrospective, multicentre study in 22 centres in Spain. All adult patients who received oral tacrolimus for luminal or perianal IBD were included. Clinical response was assessed by Harvey-Bradshaw index and partial Mayo score after 3 months. Perianal disease was evaluated by fistula drainage assessment. RESULTS: One hundred and forty-three patients were included (mean age 38 years; 51% male; median disease duration 110 months). In ulcerative colitis (UC) (n = 58), the partial Mayo score decreased after 3 months from median 6 to 3 (P = 0.0001), whereas in Crohn's disease (CD) (n = 85), the Harvey-Bradshaw index decreased after 3 months from median 9 to 7 (P = 0.011). In CD patients, blood tacrolimus concentrations during induction (>10 ng/mL vs <10 ng/mL; odds ratio 0.23, 95% CI 0.05-0.87) and the concomitant use of thiopurines (odds ratio 0.18, 95% CI 0.04-0.81) were associated with lower clinical disease activity at 3 months. Of 62 patients with perianal disease, complete closure was observed in 8% (n = 5) of patients with perianal fistulas, with 34% (n = 21) showing partial response. Treatment was maintained for a median of 6 months (IQR, 2-16). After a median clinical follow-up of 24 months (IQR, 15-57), the rate of treatment-related adverse events was 34%, correlating with blood drug concentrations (P = 0.021). Finally, 120 patients (84%) discontinued tacrolimus, usually due to absence or loss of response. Three patients (2%) were subsequently diagnosed with cancer. The overall rate of surgery was 39%, with a 33% colectomy rate in UC. CONCLUSIONS: Tacrolimus shows a clinical benefit in both CD and UC after 3 months of treatment, but its long-term effectiveness and frequent adverse events remain relevant issues in clinical practice.