Assessment of D-Dimers for the Early Prediction of Complications in Acute Pancreatitis.

OBJECTIVES: Severe acute pancreatitis (AP) is characterized by early microcirculation defects causing hypercoagulability. The purpose of this study was to evaluate the early predictive value of D-dimers in complicated AP. METHODS: This was a prospective single-center study conducted between September 2010 and April 2012. All patients had AP for less than 48 hours duration at admission. The plasma D-dimer level was determined at admission and every 12 hours over 3 days and compared to other validated severity criteria. RESULTS: Of 71 patients admitted with AP, 36 (53.1%) developed complicated AP. A threshold D-dimer level greater than 1474 ng/mL at 48 hours after pain onset was predictive of complications with an area under the curve (AUC) of 0.76. Combining D-dimers and C-reactive protein levels at 48 hours increased the prediction of complications (AUC of 0.83). At 36 hours, D-dimers greater than 1474 ng/mL predicted the occurrence of complications with an AUC of 0.75. CONCLUSIONS: D-Dimer levels were predictive of complications of AP as early as 36 hours after the onset of pain. This simple and reproducible marker might be useful in clinical practice to improve the early management of complicated AP.

Anti-TNF Monotherapy for Crohn's Disease: a 13-year Multicentre Experience.

BACKGROUND: Anti-tumour necrosis factor [TNF] therapy in combination with thiopurine is the most effective strategy for Crohn's disease, but raises safety concerns. METHODS: In a retrospective multicentre study, we investigated long-term outcome of patients starting anti-TNF monotherapy for Crohn's disease and investigated whether introducing an immunomodulator in patients losing response to anti-TNF monotherapy is effective for resetting immunogenicity. RESULTS: A total of 350 adult patients with Crohn's disease received either infliximab [n = 178, 51%] or adalimumab [n = 172, 49%] monotherapy. Mean duration of follow-up was 42 months. An immunomodulator was initiated in 53 patients [15%]. At last follow-up, 73.1% [n = 38] were in clinical remission [one patient with missing data]. Multivariate analysis identified anti-TNF type [higher need for starting immunomodulator for infliximab than for adalimumab; p = 0.0058] and first- vs second-/third-/fourth-line anti-TNF therapy [p = 0.014] as predictors of immunomodulator initiation. Among the 18 patients with available data, introduction of an immunomodulator was able to restore infliximab trough level within the therapeutic range and to induce clinical remission in 10 patients [55%]. Cumulative probability of remaining on anti-TNF therapy was 57.9% at 5 years among the 297 patients not starting an immunomodulator during follow-up. CONCLUSION: An immunomodulator was initiated in 15% of patients with Crohn's disease starting anti-TNF monotherapy. Independent predictors of immunomodulator initiation were infliximab use and second-/third-/fourth-line anti-TNF therapy. Resetting immunogenicity with an immunomodulator was effective in half of patients in a sub-study. Persistence of anti-TNF treatment at 5 years was observed in half of the 297 patients not starting an immumodulator in a real-life setting.

Treatment algorithms in Crohn's - up, down or something else?

Crohn's disease is a chronic, progressive and disabling condition. New therapeutic goals have emerged in Crohn's disease such as the need to look beyond symptoms by achieving mucosal healing that is known to be associated with better outcomes. Anti-TNF (Tumour Necrosis Factor) therapy is the most potent drug class to induce and maintain mucosal healing in Crohn's disease. Recent evidence indicates that the efficacy profile of thiopurines has been overestimated while the increased risk of malignancies (lymphoma, non-melanoma skin cancers, myeloid disorders) has been underestimated. Methotrexate is well-tolerated, but its potential for disease modification is unknown. Achieving mucosal healing in patients with early Crohn's disease might be the best way to change disease course and patients' life. In 2014, anti-TNF treatment should be the first-line therapy in patients with Crohn's disease who suffer from severe and/or complicated disease and in those with poor prognostic factors. In the remaining patients, a rapid step-up approach based on a tight monitoring is recommended.