The degree of bowel remission predicts phenotype progression in Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) are at risk of progressing from inflammatory to stricturing and penetrating phenotypes. The influence of the depth of remission on the risk of progression has not been adequately evaluated. METHODS: A retrospective cohort study including surgically naïve CD patients with inflammatory phenotype evaluated concomitantly by magnetic resonance enterography and colonoscopy. The degree of remission was correlated with the risk of progressing to stricturing and penetrating phenotypes. RESULTS: Three hundred nineteen CD patients were included: 27.0% with transmural remission, 16.0% with isolated endoscopic remission, 14.4% with isolated radiologic remission, and 42.6% without remission. Patients with transmural remission presented the lowest rates of phenotype progression (1.2%), with a significant difference compared to isolated radiologic remission (10.9%, p = 0.019), to isolated endoscopic remission (19.6%, p ≤ 0.001), and to no remission (46.3%, p ≤ 0.001). In multivariate regression analysis, transmural remission (OR 0.017 95% CI 0.002-0.135, p < 0.001), isolated radiologic remission (OR 0.139 95% CI 0.049-0.396, p < 0.001), and isolated endoscopic remission (OR 0.301 95% CI 0.123-0.736, p = 0.008) resulted in lower rates of phenotype progression compared to no remission. No patient with transmural or isolated radiologic remission progressed to penetrating phenotypes. CONCLUSION: The degree of bowel remission correlates with the risk of phenotype progression. Patients with transmural remission are at the lowest risk of progressing to stricturing and penetrating phenotypes.

Tight control using fecal calprotectin and early disease intervention increase the rates of transmural remission in Crohn's disease.

BACKGROUND: Increasing evidence supports the use of transmural remission as a treatment target in Crohn's disease (CD), but it is seldom achieved in clinical practice. Tight monitoring of inflammation using fecal calprotectin with reactive treatment escalation may potentially improve these results. AIMS: To evaluate if treatment escalation based on fecal calprotectin can improve the rates of transmural remission in CD. The influence of the timing of intervention on this strategy was also evaluated. METHODS: Retrospective cohort study including 256 CD patients with 2 consecutive assessments by MRI-enterography and colonoscopy and with regular monitoring using fecal calprotectin. For each occurrence of an elevated fecal calprotectin (≥250 µg/g), we evaluated whether a reactive adjustment of medical treatment was performed. The ratio of treatment escalation/elevated fecal calprotectin was correlated with the chances of reaching transmural remission. Early disease was defined as disease duration <18 months without previous exposure to immunomodulators and biologics. RESULTS: After a median follow-up of 2 years (IQR 1-4), 61 patients (23.8%) reached transmural remission. Ratios of escalation ≥50% resulted in higher rates of transmural remission (34.2% vs. 15.1%, p < 0.001). The effect was more pronounced in patients with early disease (50.0% vs. 12.0%, p = 0.003). In multivariate analysis, a treatment escalation ratio ≥50% (OR 3.46, 95% CI 1.67-7.17, p = 0.001) and early disease intervention (OR 3.24, 95% CI 1.12-9.34, p = 0.030) were independent predictors of achieving transmural remission. CONCLUSION: Tight-monitoring and reactive treatment escalation increase the rates of transmural remission in CD. Intervention in early disease further improves these results.

Proactive Infliximab Monitoring Improves the Rates of Transmural Remission in Crohn's Disease: A Propensity Score-Matched Analysis.

BACKGROUND: Few patients can reach transmural remission in Crohn's disease (CD) with currently available therapies. Proactive optimization of infliximab (IFX) based on trough levels may potentially improve these results. METHODS: Retrospective cohort study including consecutive CD patients starting treatment with IFX. Rates of transmural remission were compared between patients with and without therapeutic drug monitoring (target level: 5-7 µg/mL). A propensity score-matched analysis was performed to adjust for potential confounders. RESULTS: A total of 195 CD patients were included, 57.9% receiving proactive therapeutic drug monitoring. The rates of transmural remission were higher in patients under proactive therapeutic drug monitoring (37.2% vs 18.3%; P = .004) with similar results in the propensity score-matched analysis (34.2% vs 17.1%; P = .025). In multivariate analysis, proactive therapeutic drug monitoring was independently associated with transmural remission (odds ratio, 2.95; 95% confidence interval, 1.44-6.06; P = .003). CONCLUSIONS: Proactive optimization of IFX based on trough levels increases the rates of transmural remission in CD.

In the following study, we demonstrate that proactive optimization of infliximab using a trough level protocol (aim 5-7 µg/mL) results in higher rates of transmural remission compared with conventional infliximab treatment. These results remained significant in a propensity score­matched analysis.

Primary Diffuse Large B-Cell Lymphoma of the Rectum in a Non-Immunosuppressed Patient with Ulcerative Colitis.

Introduction: The incidence of primary colorectal lymphoma in the gastrointestinal tract is very low, the rectum being infrequently affected. The development of this entity in inflammatory bowel disease patients usually occurs in a context of immunosuppression-based therapy, with only a few case reports describing its development in patients presenting no known risk factors. Moreover, the clinical presentation of primary colorectal lymphomas may be difficult to distinguish from an acute flare of ulcerative colitis (UC). Case Presentation: We present a case of non-Hodgkin lymphoma of the rectum in a 42-year-old male with a 7-year history of UC and no previous exposure to immunomodulatory agents. He presented with a history of mucous diarrhoea, tenesmus, proctalgia and weight loss, refractory to optimized therapy. A lower gastrointestinal endoscopy was performed revealing a circumferential ulcerated lesion of the rectum, from which histopathological analysis established the diagnosis of a non-Hodgkin diffuse large B-cell lymphoma (DLBCL). Discussion/Conclusion: The present case suggests the existence of alternative mechanisms for the development of DLBCL in UC patients. The clinical presentation mimicking an acute flare of UC posed a diagnostic challenge, highlighting the complexity behind the management of UC patients.

Introdução: O linfoma não Hodgkin (LNH) difuso de grandes células B (DGCB) colorretal primário é uma entidade rara, estando a sua associação com a colite ulcerosa (CU) relacionada com a exposição a imunomoduladores. Apresentamos uma forma particularmente rara de LN-HDGCB primário, com atingimento do reto em doente com proctite ulcerosa sem história de imunossupressores, cuja apresentação simula agudização da CU. Descrição do caso clínico: Homem de 42 anos, com diagnóstico de proctite ulcerosa desde 2014, e sem história de terapêutica imunossupressora. Inicia quadro de diarreia com muco, proctalgia intensa, tenesmo e perda ponderal (10% em 2 meses), sem melhoria após otimização da terapêutica. Realiza colonoscopia que revela lesão ulcerada e circunferencial a nível do reto, condicionando estenose luminal, cujas biopsias revelaram LNHDGCB. Discussão/Conclusão: O presente caso sugere a existência de mecanismos fisiopatológicos alternativos à terapêutica imunossupressora para o desenvolvimento de LNH em doentes com CU. A apresentação clínica sugestiva de agudização da CU, constituiu um verdadeiro desafio diagnóstico, fazendo realçar a complexidade da abordagem destes doentes.

Proactive infliximab is more effective than vedolizumab in inducing fecal calprotectin remission in inflammatory bowel disease.

BACKGROUND: Current evidence suggests vedolizumab (VDZ) may be as effective as Infliximab (IFX) in inflammatory bowel disease. It is unknown if proactive therapeutic drug monitoring (PTDM) of IFX may improve these results. METHODS: Case-control study including consecutive patients with primary response to conventional IFX (n = 70), proactive IFX (n = 148), and VDZ (n = 95). PTDM was performed at week 14 and every other infusion, aiming at a trough level between 5 and 10 µg/ml. The primary outcome was fecal calprotectin (Fc) remission (<250 µg/g) at 1 year of treatment. Secondary outcomes included Fc remission at week 14 (proactive IFX/VDZ), clinical remission, treatment discontinuation, hospitalization, and surgery at 1-year of follow-up. RESULTS: Proactive IFX was superior to conventional IFX and VDZ in inducing Fc remission at 1-year (69.4% vs 47.1% vs 37.9%, p = .003 and p < .001). Results remained significant in biologic naïve patients (70.8% vs 44.4% vs 51.4%, p = .001 and p = .043) but comparisons between conventional IFX and VDZ were not significant (p = .265 and p = .664). In multivariate analysis correcting for prior biologic exposure, proactive IFX was more effective than conventional IFX (OR 2.480 95%CI [1.367-4.499], p = .003) and VDZ (OR 3.467 95%CI [1.578-7.617], p = .002) in inducing Fc remission. Amongst secondary outcomes, only clinical remission was significant between proactive IFX and VDZ in the overall cohort (80.4% vs 55.8%, p < .001) and in biologic naïve patients (80.2% vs 62.9%, p = .043). Fc remission at 1-year was associated with better results in most secondary outcomes. CONCLUSION: Proactive IFX was superior to VDZ in inducing Fc remission at 1-year, which was associated with improved clinical outcomes.SUMMARYCurrent evidence suggests that vedolizumab may be as effective as Infliximab in the treatment of patients with inflammatory bowel disease.There have been no studies comparing vedolizumab with proactively optimized Infliximab based on trough levels.We confirm that conventional IFX is as effective as vedolizumab but proactive IFX appears superior to vedolizumab in inducing fecal calprotectin remission.Fecal calprotectin remission associates with better clinical outcomes.

Outcomes of excessive alcohol drinkers without baseline evidence of chronic liver disease after 15 years follow-up: Heavy burden of cancer and liver disease mortality.

BACKGROUND: Most long-term heavy drinkers do not have clinically evident chronic liver disease (CLD). However, at any time-point, their risk of developing CLD remains unknown. We aimed to evaluate the long-term outcomes of a group of heavy drinkers, without evidence of CLD at baseline. METHODS: A cohort of 123 long-term heavy drinkers without CLD were prospectively recruited in 2002 and retrospectively followed until 2018. RESULTS: At baseline (2002), median alcohol consumption was 271±203g/day during 21.5±20 years, 65% being abstinent during the previous 1.75±5 months. Patients were followed for 14±3 years. During follow-up, 53% reported any alcohol intake. Alcohol consumption during follow-up associated weakly with either 1- or 6-months previous abstinence at baseline. Until 2018, progression to CLD occurred in 6%, associating with years of alcohol intake during follow-up (OR 1.15 [1.01-1.31]) and baseline alkaline-phosphatase (OR 1.05 [1.01-1.10]). During follow-up, being abstinent for at least 1 year positively associated with CLD-free survival. 27% died (55% of cancer-mostly oropharyngeal cancer, 27% of cardiovascular disease, and 9% of liver disease), with a mean age of 71 years [69-74] (10 years less than the expected in the Portuguese population). Achieving abstinence for at least 1 year positively associated with overall survival, while smoking, and hepatic steatosis at baseline associated negatively. CONCLUSION: Long-term heavy drinkers seemed to have a decreased life expectancy compared with the overall Portuguese population. Cancer was the main cause of death. Our results suggest that progression to CLD depends mostly on continued alcohol intake. Alcohol abstinence, even if temporary, seems to decrease the risks of CLD and mortality.

Proactive therapeutic drug monitoring is more effective than conventional management in inducing fecal calprotectin remission in inflammatory bowel disease.

BACKGROUND: Proactive therapeutic drug monitoring (pTDM) may improve treatment outcomes in inflammatory bowel disease. AIMS AND METHODS: We compared 135 patients following a prospective pTDM protocol aiming at an infliximab trough level (IFXTL) between 5 and 10 µg/ml with sequential measurements of Fc, with 108 patients from a retrospective group under conventional management. We evaluated the rates of Fc remission (<250 µg/g) and other clinical outcomes at 2-year of follow-up. RESULTS: pTDM associated with higher rates of Fc remission (69.6% vs. 50.0%; P = 0.002), and steroid-free clinical remission (78.4% vs. 55.2%, P = 0.028) with a trend for clinical remission (79.3% vs. 68.5%, P = 0.075). There was no difference in treatment discontinuation (P = 0.195), hospitalization (P = 0.156), and surgery (P = 0.110). Higher IFXTL associated with Fc remission at week 14 (6.59 vs. 2.96 µg/ml, P < 0.001), and at the end of follow-up (8.10 vs. 5.03 µg/ml, P = 0.001). In patients reaching Fc remission after week 14, IFXTL increased from week 14 to the end of follow-up (2.71 vs. 8.54 µg/ml, P < 0.001). Fc remission associated with higher rates of clinical (85.8% vs. 56.8% P < 0.001) and steroid-free clinical remission (86.9% vs. 50.0% P < 0.001), lower IFX discontinuation (8.8% vs. 36.8%, P < 0.001), and hospitalization (13.5% vs. 33.7%, P < 0.001), without significance for surgery (6.1% vs. 12.6%, P = 0.101). CONCLUSION: pTDM was more effective than conventional management in inducing Fc remission which was associated with improved outcomes.

Age at Diagnosis Is Determinant for the Outcome of Inflammatory Bowel Disease: Is It a Myth?

INTRODUCTION: Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: This cohort study included patients with CD and UC followed in 6 secondary and tertiary care centers in mainland Portugal. Patients were divided into a derivation (80%) cohort and a validation (20%) cohort. The primary outcome was progressive disease. Logistic regression analysis, receiver operating characteristic curves, and the areas under the curve (AUC) were performed. Odds ratios with 95% confidence intervals (CIs) were estimated. RESULTS: The derivation cohorts included 1245 patients with CD (68% with progressive disease) and 1210 patients with UC (37% with progressive disease), whereas the validation cohorts included 302 patients with CD and 271 patients with UC, respectively, with similar outcome proportions. In our final model, age at diagnosis older than 60 years was significantly associated with a lower risk of developing progressive disease (odds ratio 0.390, 95% CI 0.164-0.923, P = 0.032), with a high discriminative power (AUC 0.724, 95% CI 0.693-754) in patients with CD. However, according to this model, no significant associations were found between age at diagnosis and the risk of developing progressive disease in patients with UC. No differences were observed in the AUC values between the validation and the derivation cohorts. DISCUSSION: Patients with elderly-onset CD, but not patients with UC, were associated with a less progressive course of the disease.

Proactive Infliximab Drug Monitoring Is Superior to Conventional Management in Inflammatory Bowel Disease.

BACKGROUND: Increasing evidence supports the use of reactive therapeutic drug monitoring (TDM) in Crohn's disease (CD) and ulcerative colitis (UC) following secondary loss of response. It is still unknown if proactive TDM can improve clinical outcomes. METHODS: Consecutive patients completing infliximab (IFX) induction therapy were prospectively allocated into a proactive TDM protocol (pTDM). Before the fourth infusion and every 2 infusions, IFX trough levels and antidrug antibodies were measured using a drug-sensitive assay (Theradiag, Lisa Tracker). Treatment was proactively escalated aiming at an IFX trough level between 3 and 7 ug/mL (CD) and 5 and 10 ug/mL (UC). A retrospective cohort treated with IFX but without TDM served as the reference group. End points included the need for surgery, hospitalization, treatment discontinuation, and mucosal healing at 2 years of follow-up. RESULTS: Two hundred five patients were included, 56 in the proactive regimen. Treatment escalation was more common in pTDM patients (76.8% vs 25.5%; P < 0.001), who also required less surgery (8.9% vs 20.8%; P = 0.032) and presented higher rates of mucosal healing (73.2% vs 38.9%; P < 0.0001). Proactive TDM significantly decreased the odds of reaching any unfavorable outcome (odds ratio, 0.358; 95% confidence interval, 0.188-0.683; P = 0.002). CONCLUSIONS: Proactive TDM is associated with fewer surgeries and higher rates of mucosal healing than conventional non-TDM-based management.

Treat to target in inflammatory bowel disease: a survey of treatment strategies amongst Portuguese doctors.

BACKGROUND: treatment goals in inflammatory bowel disease have changed over the last few years and have shifted from a mainly symptom-based management to objective endpoints, such as mucosal healing and deep remission. A treat-to-target strategy to achieve these goals has been proposed by several experts, although the real-life clinical data is still lacking. This study aimed to investigate the current practices among Portuguese gastroenterologists who treat inflammatory bowel disease patients. METHODS: Portuguese gastroenterologists were asked to participate in an anonymous online survey. The questions focused on opinions and current practice with regard to treatment targets in inflammatory bowel disease. RESULTS: sixty-two physicians agreed to participate in the survey, 40 were gastroenterology specialists and 22 (35.5%) were fellows. Deep remission was considered as the main treatment goal for Crohn's disease and ulcerative colitis by 82% and 83.9% of the participants, respectively. Mucosal healing as a treatment target was used by 95% and 80% of participants in ulcerative colitis and Crohn's disease, respectively; 71% intensified the treatment to achieve mucosal healing after clinical remission. The most common definition of mucosal healing in Crohn's disease and ulcerative colitis was the absence of mucosal ulceration (32.3%) and a Mayo endoscopic sub-score of 0 (41.9%). Only 3.2% escalated treatment with the aim to achieve histologic remission in ulcerative colitis. CONCLUSION: a treat-to-target strategy to achieve mucosal healing and deep remission is currently accepted by a substantial number of Portuguese gastroenterologists.

Miniprobe endoscopic ultrasonography for the diagnosis of colon hemangiolymphangioma.

Hemangiolymphangioma is a very rare benign vascular tumor that affects the gastrointestinal tract in less than 1% of cases. We present the case of an asymptomatic 52-year-old female referred for endoscopic colorectal cancer screening. A sub-epithelial pediculated polypoid lesion in the splenic angle of the colon was identified. An endoscopic ultrasonography with a miniprobe was performed, which identified an anechoic lesion in the submucosal layer. Surgery was performed and the histologic findings were compatible with two hemangiolymphangioma lesions. This is one of the few cases reported in the literature of hemangiolymphangioma diagnosed by miniprobe endoscopic ultrasonography and the first to describe two lesions in the same patient.

Predicting the Course of Disease in Hospitalized Patients With Acute Severe Ulcerative Colitis.

BACKGROUND: Up to one-third of patients with acute severe ulcerative colitis (ASUC) will fail intravenous steroid (IVS) treatment, requiring rescue therapy with cyclosporin (Cys), infliximab (IFX), or colectomy. Although several scores for predicting response to IVS exist, formal comparison is lacking. METHODS: We performed a single-center retrospective analysis including 489 patients with ulcerative colitis. In patients with ASUC, the Mayo endoscopic subscore and the Oxford, Edinburgh, and Lindgren scores were assessed. Outcomes included IVS failure, need for rescue medical therapy, and surgery. RESULTS: One hundred twelve patients presented with ASUC. Forty-two percent showed an incomplete or absent response to IVS, 28.6% received rescue therapy (22 with IFX, 10 with Cys, and 1 with sequential treatment), and 26.8% required surgery. The Lindgren score showed the highest performance in predicting IVS failure (are under the curve [AUC], 0.856; 95% confidence interval [CI], 0.784-0.928), need for medical rescue therapy (AUC, 0.826; 95% CI, 0.749-0.902), and surgery (AUC, 0.836; 95% CI, 0.712-0.960; all P < 0.01). CONCLUSIONS: In our series, the Lindgren score was superior to the Mayo, Oxford, and Edinburgh scores in predicting major clinical outcomes in ASUC.

Development and Validation of Risk Matrices Concerning Ulcerative Colitis Outcomes-Bayesian Network Analysis.

BACKGROUND: Ulcerative colitis [UC] is a chronic inflammatory disease often accompanied by severe and distressing symptoms that, in some patients, might require a surgical intervention [colectomy]. This study aimed at determining the risk of experiencing progressive disease or requiring colectomy. MATERIAL AND METHODS: This was a multicentre study: patients' data [n = 1481] were retrieved from the Portuguese database of inflammatory bowel disease patients. Bayesian networks and logistic regression were used to build risk matrices concerning the outcomes of interest. RESULTS: The derivation cohort included a total of 1210 patients, of whom 6% required a colectomy and 37% had progressive disease [over a median follow-up period of 12 syears]. The risk matrices show that previously hospitalised patients with extensive disease, who are not on immunomodulators and who are refractory to corticosteroid treatment, are the ones at the highest risk of undergoing a colectomy [88%]; whereas male patients, with extensive disease and less than 40 years old at diagnosis, are the ones at the highest risk of experiencing progressive disease [72%]. These results were internally and externally validated, and the AUC [area under the curve] of the ROC [receiver operating characteristic] analysis for the derivation cohort yielded a high discriminative power [92% for colectomy and 72% for progressive disease]. CONCLUSIONS: This study allowed the construction of risk matrices that can be used to accurately predict a UC patient's likelihood of requiring a colectomy or of facing progressive disease, and can be used to individualise therapeutic strategies.

Systemic sclerosis and sarcoidosis: a rare case of chronic intestinal pseudo-obstruction.

The coexistence of systemic sclerosis (SSc) and sarcoidosis is an extremely rare phenomenon; some studies question its existence. We report the case of a male with a diagnosis of sarcoidosis that was admitted due to abdominal distension and pain. After a thorough investigation, he was diagnosed with severe chronic intestinal pseudo-obstruction as a manifestation of SSc.

A rare cause of acute liver failure- a case report.

BACKGROUND: Acute liver failure (ALF) induced by diffuse metastatic disease has rarely been reported. CASE PRESENTATION: We present a 51-years-old woman with relevant clinical history for breast cancer. The patient was admitted in the emergency department with jaundice, dark urine and pale stools. She was on the 10th day of hormonotherapy for recurrence of breast cancer, diagnosed 7 years previously. Usual causes of acute liver failure were excluded, all drugs were stopped and the imaging studies performed were positive only for steatosis. Nonetheless, ALF progressed and the patient died 4 days later. Autopsy demonstrated a massive intrasinusoidal infiltration of the liver by breast cancer cells. CONCLUSION: We highlight a rare cause of ALF. Although uncommon, physicians should be alert for this situation as the diagnosis can be challenging and the imaging studies can remain normal.

Transmural Healing Is Associated with Improved Long-term Outcomes of Patients with Crohn's Disease.

BACKGROUND: Mucosal healing (MH) is currently accepted as one of the best treatment targets in Crohn's disease. However, even in patients with sustained MH, residual bowel wall inflammation can still be detected by cross-sectional imaging. The long-term benefits of obtaining transmural healing (TH) have not been previously assessed. METHODS: We performed an observational study including 214 patients with Crohn's disease with a magnetic resonance enterography (MRE) and colonoscopy performed within a 6-month interval. Patients were classified as having TH (inactive MRE and colonoscopy), MH (active MRE with inactive colonoscopy), or no healing (active colonoscopy). Need for surgery, hospital admission, and therapy escalation were evaluated at 12 months of follow-up. RESULTS: Patients with TH presented lower rates of hospital admission, therapy escalation, and surgery than patients with MH or no healing. In logistic regression analysis, endoscopic remission (odds ratio 0.331 95% confidence interval [0.178-0.614], P < 0.001) and MRE remission (odds ratio 0.270 95% confidence interval [0.130-0.564], P < 0.001) were independently associated with a lower likelihood of reaching any unfavorable outcome. CONCLUSIONS: TH is associated with improved long-term outcomes in Crohn's disease and may be a more suitable target than MH.