Isadora Rosa

Acute lower gastrointestinal bleeding management in Portugal: a multicentric prospective 1-year survey

Introduction Acute lower gastrointestinal bleeding (ALGIB) is a common event, which consumes considerable human and economic resources. Its incidence is expected to rise in the coming years due to an increasing aging population. Patients and methods Multicentric prospective analysis of patients was carried out with ALGIB in 13 Portuguese hospitals from April 2008 to May 2009, using a protocol designed by the French Association Nationale des Hépato-Gastroentérologues des Hôpitaux Généraux. Statistical analysis was carried out with SPSS 16.0. Results In a total of 371 hemorrhagic events in 364 patients (51.4% men, mean age: 72 years), 28.4% patients showed hemodynamic instability and 54.2% were under single/combined medication with antiaggregants/NSAIDs/heparin/anticoagulants; blood transfusion was administered in 34.8% of patients. Sigmoidoscopy was the first endoscopic procedure performed in 61.3% of patients and rectal enema was the first method of bowel preparation in 67.3% of them. Endoscopic hemostasis was performed in 22.2% of all cases with efficacy ranging from 84.6 to 96.2%. Most frequent diagnoses were ischemic colitis (23.7%), diverticulosis (20.8%), and colorectal malignancies (12.4%). Surgery was needed in 8% of patients, and global mortality rate was 2.2%. Risk factors for poor outcome on multivariate analysis were heparin use before bleeding (hazards ratio: 10.6; 95% confidence interval: 0.94–119.48) and in-hospital bleeding (hazards ratio: 5.6; 95% confidence interval: 1.01–19.70). Conclusion ALGIB seems to occur frequently in Portugal with a low mortality rate. Previous heparin use and in-hospital bleeding are associated with worse prognosis. Our management relies on early endoscopic examinations, which are highly available, safe, and accurate. A successful endoscopic therapeutic approach was possible in one fifth of the patients.

Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point‐of‐care quantitative test with two established ELISA assays

Therapeutic drug monitoring is a powerful strategy known to improve the clinical outcomes and to optimise the healthcare resources in the treatment of autoimmune diseases. Currently, most of the methods commercially available for the quantification of infliximab (IFX) are ELISA‐based, with a turnaround time of approximately 8 h, and delaying the target dosage adjustment to the following infusion.

Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assays:

Background: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays. Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs. Results: The three assays showed 81–96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 µg/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 µg/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 µg/ml. However, in samples with high levels of ADAs (>25 µg/ml) interference was only observed at IFX concentrations higher than 100 µg/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA- and IFX-/ADAs+ were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination. Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs-) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances.

Impact of Early Surgery and Immunosuppression on Crohnʼs Disease Disabling Outcomes

Background and Aims: The definition of early therapeutic strategies to control Crohns disease aggressiveness and prevent recurrence is key to improve clinical practice. This study explores the impact of early surgery and immunosuppression onset in the occurrence of disabling outcomes. Methods: This was a multicentric and retrospective study with 754 patients with Crohns disease, who were stratified according to the need for an early surgery (group S) or not (group I) and further divided according to the time elapsed from the beginning of the follow-up to the start of immunosuppression therapy. Results: The rate of disabling events was similar in both groups (S: 77% versus I: 76%, P = 0.700). The percentage of patients who needed surgery after or during immunosuppression therapy was higher among group S, both for first surgeries after the index event (38% of groups S versus 21% of group I, P < 0.001) and for reoperations (38% of groups S versus 12% of group I, P < 0.001). The time elapsed to reoperation was shorter in group I (HR = 2.340 [1.367–4.005]), stratified for the onset of immunosuppression. Moreover, reoperation was far more common among patients who had a late start of immunosuppression (S36: 50% versus S0–6: 27% and S6–36: 25%, P < 0.001) and (I36: 16% versus I0–6: 5% and I6–36: 7%, P < 0.001). Conclusions: Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition

To test the cross‐immunogenicity of anti‐CT‐P13 IBD patients’ sera to CT‐P13/infliximab originator and the comparative antigenicity evoked by CT‐P13/infliximab originator sera.

Clinical performance of an infliximab rapid quantification assay

Background: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. Methods: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. Results: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman’s rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791–0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g. Conclusions: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.

Adenoma incidence decreases under the effect of polypectomy

AIM To investigate whether, under the influence of polypectomy, the incidence of adenoma decreases with age. METHODS Consecutive patients with colonic adenomas identified at index colonoscopy were retrospectively selected if they had undergone three or more complete colonoscopies, at least 24 mo apart. Patients who had any first-degree relative with colorectal cancer were excluded. Data regarding number of adenomas at each colonoscopy, their location, size and histological classification were recorded. The monthly incidence density of adenomas after the index examination was estimated for the study population, by using the person-years method. Baseline adenomas were excluded from incidence calculations but their characteristics were correlated with recurrence at follow-up, using the χ(2) test. RESULTS One hundred and fifty-six patients were included (109 male, mean age at index colonoscopy 56.8 ± 10.3 years), with follow-up that ranged from 48 to 232 mo. No significant correlations were observed between the number, the presence of villous component, or the size of adenomas at index colonoscopy and the presence of adenomas at subsequent colonoscopies (P = 0.49, 0.12 and 0.78, respectively). The incidence of colonic adenomas was observed to decay from 1.4% person-months at the beginning of the study to values close to 0%, at 12 years after index colonoscopy. CONCLUSION Our results suggest the sporadic formation of adenomas occurs within a discrete period and that, when these adenomas are removed, all neoplasia-prone clones may be extinguished.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels

Objective Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems—Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. Design Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients’ Mayo Endoscopic Score and FC levels. Result GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. Conclusions GS, NI and RHI histopathological scoring systems are comparable in what concerns patients’ stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

Therapeutic drug monitoring of CT-P13: a comparison of four different immunoassays

Background: The commercialization of CT-P13, an infliximab (IFX) biosimilar, has the potential to decrease health-related costs and enhance access to biological therapies. This study aimed to address the accuracy and inter-assay agreement of the CT-P13 quantification using four different assays initially developed to assess IFX. Methods: The four different methods, one in-house method and three commercially available kits, were used to quantify exogenously-spiked samples and the sera from 185 inflammatory bowel disease (IBD) patients on CT-P13 therapy. Results: The quantification of the spiked samples unveiled a consistent and accurate behaviour of three of the tested methods, with average percentage recoveries of 90%, 102% and 109%. Results from the clinical samples demonstrated that these three assays were also highly correlated, both concerning Spearman’s rank coefficients (range 0.890–0.947) and intraclass correlation coefficients (range 0.907–0.935). There were a few systematic deviations among them, but their impact in the clinical stratification of the patients using different cut-offs was minimal, particularly when these cut-offs were in the 3–4 µg/ml range, for which the strength of agreement (as assessed by the Kappa statistics that ranged from 0.732 to 0.902) was substantial to almost perfect. Conclusions: Our results indicate that three of the tested IFX quantification methods can be used to accurately quantify CT-P13 without any adjustments.

Familial Adenomatous Polyposis and Crohn's Disease in One Patient: Dilemmas and Concerns

Familial adenomatous polyposis (FAP) and Crohns disease (CD) are two entities with no known etiologic or physiopathogenic relation. The rarity of the former makes the coincidence of both diagnoses in one patient very unlikely. Nevertheless, management in such cases can be puzzling as surgical options must be considered, and immunosuppression/immunomodulation is set in a territory of accelerated carcinogenesis. We report the case of a 29-year-old male with a diagnosis of FAP since adolescence, already submitted to prophylactic proctocolectomy, presenting with anemia and bloody diarrhea, revealing small bowel CD. This case allows for a rich discussion of the clinical dilemmas presenting when FAP and CD are diagnosed in the same patient and for a deep analysis of the concerns inherent to the available therapeutic options.