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.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

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.

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.

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.

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.

Disagreement Among Gastroenterologists Using the Mayo and Rutgeerts Endoscopic Scores.

Background: Endoscopy is routinely performed in patients with inflammatory bowel disease to evaluate disease severity and guide important clinical decisions. However, variability in the interpretation of endoscopic findings can significantly impact patient management. Methods: Fifty-eight gastroenterologists were invited to participate in an online survey including pictures and video recordings of colonoscopies performed in patients with ulcerative colitis (UC) and Crohn's disease (CD). Participants were asked to rate the colorectal mucosa in patients with UC using the Mayo endoscopic subscore (MES), and the neo-terminal ileum and anastomosis in operated patients with CD using the Rutgeerts score (RS). Overall interrater agreement (IRA) and for several key end points was assessed using Krippendorff's alpha test. Results: The IRAs for the MES and RS were 0.47 (95% confidence interval [CI], 0.41-0.54) and 0.33 (95% CI, 0.28-0.38). The IRAs for UC mucosal healing (MES ≤ 1) and complete mucosal healing (MES = 0) were 0.57 (95% CI, 0.40-0.72) and 0.89 (95% CI, 0.73-1) and for CD postoperative recurrence (RS ≥ i2), and IRAs for severe postoperative recurrence (RS ≥ 3) were 0.44 (95% CI, 0.24-0.62) and 0.54 (95% CI, 0.36-0.71), respectively. Unexpectedly, although clinical information significantly influenced the IRA, participant expertise and consultation of scores did not produce significant changes in the IRA. Conclusions: A high rate of disagreement in endoscopic scoring was found in this study, even among experienced physicians. The variability in the assessment of mucosal healing and postoperative recurrence may translate into relevant differences in patient management.

Association Between Weekend and Holiday Admission with Pneumonia and Mortality in a Tertiary Center in Portugal: A Cross-Sectional Study.

INTRODUCTION: Acute bacterial pneumonia is a common and potentially fatal disease where early recognition and treatment are crucial. Increasing medical literature suggests worse outcomes in patients admitted for medical and surgical conditions during the weekend. Little is known about this effect in patients with acute bacterial pneumonia. Obective: The aim of this study was to evaluate the impact of weekend and holiday hospital admission on the outcomes of acute bacterial pneumonia. MATERIAL AND METHODS: Retrospective analysis of adult patients (> 18 years) with acute bacterial pneumonia collected from a tertiary referral center database. Length of stay, total cost, admission to intensive care unit, development of sepsis and organ failure, and mortality were compared between patients admitted on a weekday and patients admitted during a weekend or holiday. RESULTS: We analyzed 53 854 hospital admissions from 42 512 patients (median age 84.0 years, range 18 - 118 years), corresponding to 30 554 admissions during weekdays, 21 222 at weekends and 2078 during public holidays. Weekend and holiday admission was not associated with increased costs, length of stay, intensive care unit admission, development of sepsis, organ failure, and mortality. CONCLUSION: A weekend/holiday effect in acute bacterial pneumonia was not evident in our series.

Introdução: A pneumonia aguda bacteriana é uma entidade comum e potencialmente fatal em que o diagnóstico e tratamento precoces são cruciais. A literatura médica, de forma crescente, reporta piores resultados clínicos em doentes admitidos por doenças médicas e cirúrgicas durante o fim-de-semana. Pouco se sabe deste efeito em doentes com pneumonia aguda bacteriana. Objetivo: O objetivo deste estudo foi avaliar o impacto das admissões durante o fim-de-semana e feriados nos resultados clínicos de doentes admitidos com pneumonia aguda. Material e Métodos: Análise retrospetiva de doentes adultos (> 18 anos) com pneumonia aguda bacteriana recolhidos de uma base de dados de um centro hospitalar terciário. A duração do internamento, custos, admissão em unidade de cuidados intensivos, desenvolvimento de sépsis ou lesão de órgão alvo e mortalidade foram comparados entre doentes admitidos durante a semana e doentes admitidos durante o fim-de-semana ou feriados. Resultados: Verificaram-se 53 854 admissões hospitalares correspondendo a 42 512 doentes (idade mediana 84,0 anos, 18 - 118 anos). Um total de 30 554 admissões ocorreram durante os dias da semana, 21 222 durante o fim-de-semana e 2078 durante feriados. A admissão durante o fim-de-semana ou feriado não se associou a custos mais elevados, internamentos mais prolongados, maior admissão em unidade de cuidados intensivos, desenvolvimento de sépsis ou lesão de órgão alvo e mortalidade. Conclusão: A hipótese dos internamentos durante o fim-de-semana e feriados se associarem a piores resultados clínicos não se verificou no nosso estudo.

An unusual cause of Boerhaave’s syndrome in a young patient

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Intrahepatic clear cell cholangiocarcinoma - An uncommon histologic subtype: case report and literature review

Clear-cell cholangiocarcinoma is a very uncommon variant of cholangiocarcinoma with a largely unknown natural history and prognosis. We report a case of a 51-year-old previously healthy woman presenting with a large liver nodule found on routine imaging. Needle biopsy of the lesion suggested a non-hepatocellular carcinoma. After extensive workup for other primary neoplasms, the patient underwent a partial hepatectomy. Histopathology was compatible with a moderately differentiated clear-cell cholangiocarcinoma. There was no evidence of liver disease in the remaining tissue. The patient underwent chemotherapy and remains in clinical remission after two years (AU)

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Intrahepatic clear cell cholangiocarcinoma - An uncommon histologic subtype: case report and literature review.

Clear-cell cholangiocarcinoma is a very uncommon variant of cholangiocarcinoma with a largely unknown natural history and prognosis. We report a case of a 51-year-old previously healthy woman presenting with a large liver nodule found on routine imaging. Needle biopsy of the lesion suggested a non-hepatocellular carcinoma. After extensive workup for other primary neoplasms, the patient underwent a partial hepatectomy. Histopathology was compatible with a moderately differentiated clear-cell cholangiocarcinoma. There was no evidence of liver disease in the remaining tissue. The patient underwent chemotherapy and remains in clinical remission after two years.

The use of a segmental endoscopic score may improve the prediction of clinical outcomes in acute severe ulcerative colitis

Background: Acute severe colitis (ASC) remains a challenging complication of ulcerative colitis. The early identification of patients who will not respond to optimal therapy is warranted. Increasing evidence suggests that endoscopy may play a role in predicting important outcomes in acute severe colitis. Methods: The endoscopic activity of consecutive patients with acute severe colitis was evaluated using the Mayo endoscopic sub-score (Mayo) and the ulcerative colitis endoscopic index of severity (UCEIS). Two segmental indexes were also produced by summing the scores of the rectum and sigmoid (seg-Mayo and seg-UCEIS, respectively). Endpoints included the need for salvage therapy with infliximab or cyclosporine, refractoriness to corticosteroids, and colectomy. Results: Of one hundred and eight patients enrolled in the study, 60 (55.6%) were male; with a median age of 34.5 years (range 15-80). All patients received intravenous steroids. Fifty-nine patients (55.6%) showed an incomplete or absent response to steroids, 35 patients (34.3%) received salvage therapy with infliximab or cyclosporine and 38 patients (33.3%) were colectomized during the ndex hospitalization or within the first year of follow-up. All scores were able to predict the need for surgery, but only the seg-UCEIS significantly predicted refractoriness to steroids. Conclusions: There was a strong correlation between endoscopic severity and unfavorable outcomes. The UCEIS outperformed the Mayo endoscopic sub-score in all important outcomes. Segmental scoring further improved the performance of the UCEIS (AU)

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The use of a segmental endoscopic score may improve the prediction of clinical outcomes in acute severe ulcerative colitis.

BACKGROUND: Acute severe colitis (ASC) remains a challenging complication of ulcerative colitis. The early identification of patients who will not respond to optimal therapy is warranted. Increasing evidence suggests that endoscopy may play a role in predicting important outcomes in acute severe colitis. METHODS: The endoscopic activity of consecutive patients with acute severe colitis was evaluated using the Mayo endoscopic sub-score (Mayo) and the ulcerative colitis endoscopic index of severity (UCEIS). Two segmental indexes were also produced by summing the scores of the rectum and sigmoid (seg-Mayo and seg-UCEIS, respectively). Endpoints included the need for salvage therapy with infliximab or cyclosporine, refractoriness to corticosteroids, and colectomy. RESULTS: Of one hundred and eight patients enrolled in the study, 60 (55.6%) were male; with a median age of 34.5 years (range 15-80). All patients received intravenous steroids. Fifty-nine patients (55.6%) showed an incomplete or absent response to steroids, 35 patients (34.3%) received salvage therapy with infliximab or cyclosporine and 38 patients (33.3%) were colectomized during the index hospitalization or within the first year of follow-up. All scores were able to predict the need for surgery, but only the seg-UCEIS significantly predicted refractoriness to steroids. CONCLUSIONS: There was a strong correlation between endoscopic severity and unfavorable outcomes. The UCEIS outperformed the Mayo endoscopic sub-score in all important outcomes. Segmental scoring further improved the performance of the UCEIS.

Haemophilus parainfluenzae endocarditis with systemic embolisation following maxillary sinusitis.

The authors present a case of a man with Haemophilus parainfluenzae endocarditis complicated with embolisation to the central nervous system. The patient had no evidence of endocarditis by transoesophageal and transthoracic echocardiograms at baseline, but shortly after developed large mitral valve vegetations with valve rupture. The case highlights how rapidly structural valve damage can ensue despite good clinical and laboratorial antibiotic response.

Primary liposarcoma of the sigmoid presenting as colonic intussusception - A case report

Liposarcomas are malignant soft tissue neoplasms usually located in the retroperitoneum, head, neck and extremities. Although secondary invasion of the gastrointestinal tract by retroperitoneal sarcomas is frequent, primary involvement is uncommon. We report a young patient with Crohn’s disease in remission presenting with intussusception of the colon due to a primary liposarcoma of the sigmoid. Emergency resection confirmed the diagnosis. The patient remains in remission after five years. This represents the youngest diagnosis of liposarcoma to date and the first occurring in the sigmoid. We also highlight the concomitant diagnosis of Crohn´s disease (AU)

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Severe ischemic colitis following olanzapine use - A case report

Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics (AU)

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