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OBJECTIVE: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy). DESIGN: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE). RESULTS: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively). CONCLUSION: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal. TRIAL REGISTRATION NUMBER: NCT00571337 and NCT02177071.
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BACKGROUND & AIMS: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.
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BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess. CLINICALTRIALS: gov, Number: NCT02856763.
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Absceso Abdominal , Productos Biológicos , Enfermedad de Crohn , Humanos , Masculino , Adulto , Femenino , Adalimumab/uso terapéutico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Estudios Prospectivos , Absceso/tratamiento farmacológico , Resultado del Tratamiento , Absceso Abdominal/tratamiento farmacológico , Recurrencia , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: EUS-guided radiofrequency ablation (EUS-RFA) has been described as a potentially curative option for solid and cystic pancreatic neoplasms. We aimed to assess the safety and efficacy of pancreatic EUS-RFA in a large study population. METHODS: A retrospective study retrieving all consecutive patients who underwent pancreatic EUS-RFA during 2019 and 2020 in France was conducted. Indication, procedural characteristics, early and late adverse events (AEs), and clinical outcomes were recorded. Risk factors for AEs and factors related to complete tumor ablation were assessed on univariate and multivariate analyses. RESULTS: One hundred patients (54% men, 64.8 ± 17.6 years old) affected by 104 neoplasms were included. Sixty-four neoplasms were neuroendocrine neoplasms (NENs), 23 were metastases, and 10 were intraductal papillary mucinous neoplasms with mural nodules. No procedure-related mortality was observed, and 22 AEs were reported. Proximity of pancreatic neoplasms (≤1 mm) to the main pancreatic duct was the only independent risk factor for AEs (odds ratio [OR), 4.10; 95% confidence interval [CI), 1.02-15.22; P = .04). Fifty-nine patients (60.2%) achieved a complete tumor response, 31 (31.6%) a partial response, and 9 (9.2%) achieved no response. On multivariate analysis, NENs (OR, 7.95; 95% CI, 1.66-51.79; P < .001) and neoplasm size <20 mm (OR, 5.26; 95% CI, 2.17-14.29; P < .001) were independently related to complete tumor ablation. CONCLUSIONS: The results of this large study confirm an overall acceptable safety profile for pancreatic EUS-RFA. Close proximity (≤1 mm) to the main pancreatic duct represents an independent risk factor for AEs. Good clinical outcomes in terms of tumor ablation were observed, especially for small NENs.
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Neoplasias Quísticas, Mucinosas y Serosas , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Ablación por Radiofrecuencia , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios Retrospectivos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Ablación por Radiofrecuencia/métodos , Tumores Neuroendocrinos/cirugía , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: We developed and validated a magnetic resonance imaging-based index to predict Crohn's disease (CD) postoperative recurrence (POR). METHODS: Patients with CD who underwent a postoperative evaluation for recurrence (with colonoscopy and MRI no longer than 105 days apart) were included between 2006 and 2016 in University Hospital of Nancy, France. MRI items with good levels of intra-rater and inter-rater agreement (Gwet's coefficient ≥0.5) were selected. The MRI in Crohn's Disease to Predict Postoperative Recurrence (MONITOR) index's performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and accuracy, by considering the Rutgeerts score as the gold standard. The MONITOR index was validated with a bootstrap method and an independent cohort. RESULTS: Seventy-three MRI datasets were interpreted by 2 radiologists. Seven items (bowel wall thickness, contrast enhancement, T2 signal increase, diffusion-weighted signal increase, edema, ulcers, and the length of the diseased segment) had a Gwet's coefficient ≥0.5 and were significantly associated with the Rutgeerts score, leading to their inclusion in the MONITOR index. All the items had a weighting of 1, except the "ulcers" item weighting 2.5, reflecting the higher adjusted odds ratio. The AUROC [95% confidence interval] for the prediction of endoscopic POR (Rutgeerts score >i1) was 0.80 [0.70-0.90]. The optimal threshold was a MONITOR index ≥1, giving a sensitivity of 79%, a specificity of 55%, a predictive positive value of 68%, and a predictive negative value of 68%. The bootstrap validation gave an AUROC of 0.85 [0.73-0.97]. In the validation cohort, a MONITOR index ≥1 gave a sensitivity of 87%, a specificity of 75%, a predictive positive value of 84.6%, and a predictive negative value of 75%. CONCLUSIONS: The MONITOR index is an efficient, reliable, easy-to-apply tool that can be used in clinical practice to predict the POR of CD.
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Enfermedad de Crohn , Colonoscopía , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Humanos , Imagen por Resonancia Magnética , Periodo Posoperatorio , Recurrencia , Índice de Severidad de la Enfermedad , ÚlceraRESUMEN
BACKGROUND & AIMS: Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting. METHODS: Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries. RESULTS: Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p < .001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p < .001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p < .001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year). CONCLUSIONS: Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting. CLINICALTRIALS: gov Identifier: NCT00903799.
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Terapia por Estimulación Eléctrica , Gastroparesia , Estimulación Eléctrica , Terapia por Estimulación Eléctrica/efectos adversos , Estrés Financiero , Vaciamiento Gástrico , Humanos , Náusea/etiología , Calidad de Vida , Resultado del Tratamiento , Vómitos/etiología , Vómitos/terapiaRESUMEN
INTRODUCTION: The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance. METHODS: We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index >150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of <150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic. RESULTS: At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26. DISCUSSION: In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.
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Enfermedad de Crohn , Adulto , Anticuerpos , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Humanos , Infliximab/uso terapéutico , Estudios Prospectivos , Retratamiento , Resultado del TratamientoRESUMEN
Background Assessment of the biliary origin of acute pancreatitis (AP) is crucial because it affects patient treatment to avoid recurrence. Although CT is systematically performed to determine severity in AP, its usefulness in assessing AP biliary origin has not been evaluated. Purpose To assess abdominal CT features associated with acute biliary pancreatitis (ABP) and to evaluate the predictive value of a combination of CT and clinical data for determining a biliary origin in a first episode of AP. Materials and Methods From December 2014 to May 2019, all consecutive patients who presented with a first episode of AP and with at least 6 months of follow-up were retrospectively reviewed. Evidence of gallstones was mandatory for a clinical diagnosis of ABP. Abdominal CT images were reviewed by two abdominal radiologists. Univariable and multivariable statistical analyses were performed, and a nomogram was constructed on the basis of the combination of clinical and CT features. This nomogram was validated in a further independent internal cohort of patients. Results A total of 271 patients (mean age ± standard deviation, 56 years ± 20; 160 men) were evaluated. Of these, 170 (63%) had ABP. At multivariable analysis, age (odds ratio [OR], 1.06; 95% CI: 1.03, 1.09; P < .001), alanine aminotransferase level (OR, 1.00; 95% CI: 1.00, 1.01; P = .009), gallbladder gallstone (OR, 15.59; 95% CI: 4.61, 68.62; P < .001), choledochal ring sign (OR, 5.73; 95% CI: 2.11, 17.05; P < .001), liver spontaneous attenuation (OR, 1.07; 95% CI: 1.04, 1.11; P < .001), and duodenal thickening (OR, 0.17; 95% CI: 0.03, 0.61; P = .01) were independently associated with ABP. The matching nomogram combining both clinical and CT features displayed an area under the curve of 0.94 (95% CI: 0.91, 0.97) in the study sample (n = 271) and 0.91 (95% CI: 0.84, 0.99) in the validation cohort (n = 51). Conclusion Abdominal CT provided useful features for diagnosis of acute biliary pancreatitis (ABP). Combining CT and clinical features in a nomogram showed good diagnostic performance for early diagnosis of ABP. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Chang in this issue.
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Sistema Biliar/diagnóstico por imagen , Pancreatitis/diagnóstico por imagen , Radiografía Abdominal/métodos , Tomografía Computarizada por Rayos X/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
OBJECTIVE: The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. METHODS: We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. RESULTS: Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4-15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19-56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). CONCLUSIONS: This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse.
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Antineoplásicos , Vasculitis por IgA , Enfermedades Inflamatorias del Intestino , Vasculitis , Antineoplásicos/uso terapéutico , Humanos , Inmunoglobulina A , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Recurrencia , Estudios Retrospectivos , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Factor de Necrosis Tumoral alfa , Vasculitis/inducido químicamenteRESUMEN
INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p = .21 and 0.94 [0.40-2.22], p = .89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.
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Colitis Ulcerosa , Ustekinumab , Humanos , Ustekinumab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Inhibidores del Factor de Necrosis Tumoral , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Cohortes , Fármacos Gastrointestinales/uso terapéutico , Inducción de RemisiónRESUMEN
Background: Anastomotic biliary stricture (ABS) remains the most frequent complication after liver transplantation (LT). This study aimed to identify new anastomotic biliary stricture risk factors, with a specific focus on postoperative events. Additionally, ABS management and impact on patient and graft survival were assessed. Methods: All consecutive patients who underwent LT with duct-to-duct anastomosis between 2010 and 2019 were included. All patients who died within 90 days after LT due to non-ABS-related causes were excluded. Results: Among 240 patients, 65 (27.1%) developed ABS after a median time of 142 days (range, 13-1265). Median follow-up was 49 months (7-126). Upon multivariable analysis, donor BMI (OR=0.509, p = 0.037), post-LT CMV primoinfection (OR = 5.244, p < 0.001) or reactivation (OR = 2.421, p = 0.015) and the occurrence of post-LT anastomotic biliary fistula (OR = 2.691, p = 0.021) were associated with ABS. Anastomotic technical difficulty did not independently impact the risk of ABS (OR = 1.923, p = 0.051). First-line ABS treatment was systematically endoscopic (100%), and required a median of 2 (range, 1-11) procedures per patient. Repeat LT was not required in patients developing ABS. The occurrence of ABS was not associated with overall patient survival (p = 0.912) nor graft survival (p = 0.521). Conclusion: The risk of developing ABS after LT seems driven by the occurrence of postoperative events such as CMV infection and anastomotic fistula. In this regard, the role of CMV prophylaxis warrants further investigations.
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Colestasis , Infecciones por Citomegalovirus , Trasplante de Hígado , Anastomosis Quirúrgica/efectos adversos , Colestasis/etiología , Colestasis/cirugía , Constricción Patológica/etiología , Constricción Patológica/terapia , Citomegalovirus , Infecciones por Citomegalovirus/complicaciones , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC). METHODS: We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC. RESULTS: A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor. CONCLUSION: This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients.
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Enfermedades Cardiovasculares , Colitis Ulcerosa , Tromboembolia Venosa , Adulto , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Estudios Transversales , Femenino , Humanos , Prevalencia , Factores de Riesgo , Autoinforme , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologíaRESUMEN
BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.
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Colitis Ulcerosa , Colitis Ulcerosa/tratamiento farmacológico , Ciclosporina/uso terapéutico , Humanos , Infliximab/uso terapéutico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Esteroides , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis. METHODS: For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (>12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 µs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes. RESULTS: During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P < .001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P < .01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life. CONCLUSIONS: In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.
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Terapia por Estimulación Eléctrica/métodos , Gastroparesia/complicaciones , Vómitos/terapia , Adulto , Estudios Cruzados , Método Doble Ciego , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados , Femenino , Vaciamiento Gástrico/fisiología , Gastroparesia/fisiopatología , Gastroparesia/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Vómitos/diagnóstico , Vómitos/etiologíaRESUMEN
INTRODUCTION: To identify factors associated with irreversible transmural necrosis (ITN) among critically ill patients experiencing nonocclusive mesenteric ischemia (NOMI) and to compare the predictive value regarding ITN risk stratification with that of the previously described Clichy score. METHODS: All consecutive patients admitted to the intensive care unit between 2009 and 2019 who underwent exploratory laparotomy for NOMI and who had an available contrast-enhanced computed tomography with at least 1 portal venous phase were evaluated for inclusion. Clinical, laboratory, and radiological variables were collected. ITN was assessed on pathological reports of surgical specimens and/or on laparotomy findings in cases of open-close surgery. Factors associated with ITN were identified by univariate and multivariate analysis to derive a NOMI-ITN score. This score was further compared with the Clichy score. RESULTS: We identified 4 factors associated with ITN in the context of NOMI: absence of bowel enhancement, bowel thinning, plasma bicarbonate concentration ≤15 mmol/L, and prothrombin rate <40%. These factors were included in a new NOMI-ITN score, with 1 point attributed for each variable. ITN was observed in 6%, 38%, 65%, 88%, and 100% of patients with NOMI-ITN score ranging from 0 to 4, respectively. The NOMI-ITN score outperformed the Clichy score for the prediction of ITN (area under the receiver operating characteristics curve 0.882 [95% confidence interval 0.826-0.938] vs 0.674 [95% confidence interval 0.582-0.766], respectively, P < 0.001). DISCUSSION: We propose a new 4-point score aimed at stratifying risk of ITN in patients with NOMI. The Clichy score should be applied to patients with occlusive acute mesenteric ischemia only.
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Intestino Delgado/patología , Isquemia Mesentérica/patología , Adulto , Anciano , Anciano de 80 o más Años , Bicarbonatos/sangre , Enfermedad Crítica , Femenino , Humanos , Intestino Delgado/irrigación sanguínea , Intestino Delgado/diagnóstico por imagen , Laparotomía , Masculino , Isquemia Mesentérica/sangre , Isquemia Mesentérica/complicaciones , Isquemia Mesentérica/diagnóstico por imagen , Persona de Mediana Edad , Análisis Multivariante , Necrosis , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/patología , Modelos de Riesgos Proporcionales , Tiempo de Protrombina , Medición de Riesgo , Sepsis/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.
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Algoritmos , Neoplasias del Ano/patología , Neoplasias del Ano/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Adulto , Anciano , Neoplasias del Ano/epidemiología , Carcinoma de Células Escamosas/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
Echinococcosis is a zoonosis caused by cestodes of the genus Echinococcus (family Taeniidae). This serious and near-cosmopolitan disease continues to be a significant public health issue, with western China being the area of highest endemicity for both the cystic (CE) and alveolar (AE) forms of echinococcosis. Considerable advances have been made in the 21st century on the genetics, genomics, and molecular epidemiology of the causative parasites, on diagnostic tools, and on treatment techniques and control strategies, including the development and deployment of vaccines. In terms of surgery, new procedures have superseded traditional techniques, and total cystectomy in CE, ex vivo resection with autotransplantation in AE, and percutaneous and perendoscopic procedures in both diseases have improved treatment efficacy and the quality of life of patients. In this review, we summarize recent progress on the biology, epidemiology, diagnosis, management, control, and prevention of CE and AE. Currently there is no alternative drug to albendazole to treat echinococcosis, and new compounds are required urgently. Recently acquired genomic and proteomic information can provide a platform for improving diagnosis and for finding new drug and vaccine targets, with direct impact in the future on the control of echinococcosis, which continues to be a global challenge.
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Equinococosis/epidemiología , Equinococosis/terapia , Zoonosis/parasitología , Albendazol/uso terapéutico , Animales , China/epidemiología , Ensayos Clínicos como Asunto , Cistectomía , Manejo de la Enfermedad , Humanos , Calidad de Vida , Trasplante Autólogo , Zoonosis/epidemiología , Zoonosis/terapiaRESUMEN
INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.
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Antiinflamatorios/uso terapéutico , Enfermedades del Ano/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fístula Rectal/tratamiento farmacológico , Ustekinumab/uso terapéutico , Absceso , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades del Ano/fisiopatología , Estudios de Cohortes , Enfermedad de Crohn/fisiopatología , Supervivencia sin Enfermedad , Femenino , Fármacos Gastrointestinales/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fístula Rectal/fisiopatología , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adulto JovenRESUMEN
The giant fibrovascular polyp of the esophagus is a rare, benign and typical entity described in 1957. This lesion is easily identifiable in its macroscopic and microscopic aspects. However, recent studies question the existence of the giant fibrovascular polyp of the esophagus. The demonstration of an amplification of the MDM2 gene poses the diagnosis of well-differentiated liposarcoma. We describe here a case of an esophagus polyp in a 67-year-old man. The diagnosis of giant fibrovascular polyp of the esophagus was initially retained. Secondly, the immunohistochemical and fluorescence in situ hybridization techniques showed amplification of the MDM2 gene and reclassified the lesion to a well-differentiated liposarcoma. The search for an undifferentiated contingent is essential to not ignore a dedifferentiated liposarcoma, which is a high-grade sarcoma with a poorer prognosis.
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Neoplasias Esofágicas/genética , Liposarcoma/genética , Pólipos/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Anciano , Diagnóstico Diferencial , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Amplificación de Genes , Humanos , Liposarcoma/diagnóstico , Liposarcoma/patología , Masculino , Pólipos/diagnóstico , Pólipos/patología , Tomografía Computarizada por Rayos XRESUMEN
The tumour-like growth of larval Echinococcus multilocularis tissue (causing alveolar echinococcosis, AE) is directly linked to the nature/orientation of the periparasitic host immune-mediated processes. Parasite-mediated immune suppression is a hallmark triggering infection outcome in both chronic human and murine AE. So far, little is known about secondary systemic immune effects of this pathogen on other concomitant diseases, e.g. endogenous gut inflammation. We examined the influence of E. multilocularis infection on murine dextran sodium sulphate (DSS) -induced colitis. At 3 months after E. multilocularis infection (chronic stage), the mice were challenged with 3% DSS in the drinking water for 5 days plus subsequently with tap water (alone) for another 4 days. After necropsy, fixed tissues/organs were sectioned and stained with haematoxylin & eosin for assessing inflammatory reactions. Cytokine levels were measured by flow cytometry and quantitative RT-PCR. Colitis severity was assessed (by board-certified veterinary pathologists) regarding (i) colon length, (ii) weight loss and (iii) a semi-quantitative score of morphological changes. The histopathological analysis of the colon showed a significant reduction of DSS-induced gut inflammation by concomitant E. multilocularis infection, which correlated with down-regulation of T helper type 1 (Th1)/Th17 T-cell responses in the colon tissue. Echinococcus multilocularis infection markedly reduced the severity of DSS-induced gut inflammation upon down-regulation of Th1/Th17 cytokine expression and attenuation of CD11b+ cell activation. In conclusion, E. multilocularis infection remarkably reduces DSS-induced colitis in mice by attenuating Th1/Th17-mediated immune reactions.