CC-CLEAR (Colon Capsule Cleansing Assessment and Report): the novel scale to evaluate the clinical impact of bowel preparation in capsule colonoscopy - a multicentric validation study.

BACKGROUND: Colon Capsule Cleansing Assessment and Report (CC-CLEAR) is a novel quantitative bowel preparation scale for colon capsule. AIM: The aim of this study is to validate the association between CC-CLEAR's classification and major CC outcomes: lesion detection rate, surveillance recommendations and post-CC endoscopic treatment. METHODS: Multicentric cohort of consecutive CCs. An expert's panel decided post-CC recommendations. Data included CC-CLEAR and Leighton-REX scales. Major CC outcomes were associated with the different cleansing grades. RESULTS: From 168 CC's included, findings were reported in 123 (73.2%), 67 (54.4%) of those being colorectal polyps. CC-CLEAR influenced CC's lesion detection (OR 1.25 95% IC [1.07-1.46], p-value .004) and polyp detection rate (OR 1.22 95% IC [1.04-1.43], p-value.014). Thirty-two (19%) post-CC colonoscopies were recommended, including 22 (68.75%) with at least one polypectomy. CC-CLEAR was associated with post-CC colonoscopy treatment (OR 1.40 95% IC [1.07-1.84], p-value .015). Regarding surveillance, CC-CLEAR influenced the decision for immediate CC repetition (OR 0.21 95% IC [0.12-0.36], p-value < .001) and the recommendation for CC in 3-5 years' time (OR 1.47 95% IC [1.50-1.86], p-value < .002). The Leighton-Rex scale was not correlated with major CC outcomes. CONCLUSION: CC-CLEAR impacts major CC outcomes: lesion detection, surveillance recommendations and post-CC endoscopic treatment.

Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy.

BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Comparing the Continuous Geboes Score With the Robarts Histopathology Index: Definitions of Histological Remission and Response and their Relation to Faecal Calprotectin Levels.

BACKGROUND AND AIMS: The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. METHODS: This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. RESULTS: The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. CONCLUSION: The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.

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.

Accuracy of Faecal Calprotectin and Neutrophil Gelatinase B-associated Lipocalin in Evaluating Subclinical Inflammation in UlceRaTIVE Colitis-the ACERTIVE study.

BACKGROUND AND AIMS: Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. METHODS: This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. RESULTS: Macroscopic lesions [i.e. endoscopic Mayo score ≥1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 µg/g for faecal calprotectin and 12 µg/g for neutrophil gelatinase B-associated lipocalin were proposed. CONCLUSIONS: Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.

Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).

BACKGROUND: About 70 loci are associated with susceptibility to Crohn's disease (CD), particularly in pathways of innate immunity, autophagy, and pathogen recognition. Phenotype-genotype associations are inconsistent. METHODS: CD susceptibility polymorphisms ATG16L1 rs2241880, ICAM1 rs5498, IL4 rs2070874, IL17F rs763780, IRGM rs13361189, ITLN1 rs2274910, LRRK2 rs11175593, and TLR4 rs4986790 were genotyped in a Portuguese population (511 CD patients, 626 controls) and assessed for association with CD clinical characteristics. RESULTS: There is a significant association of CD with the single nucleotide polymorphisms (SNPs) in ATG16L1 (odds ratio [OR] 1.36 [1.15-1.60], P = 2.7 × 10(-6) for allele G), IRGM (OR 1.56 [1.21-1.93], P = 3.9 × 10(-4) for allele C), and ITLN1 (OR 1.55 [1.28-1.88], P = 4.9 × 10(-4) for allele C). These SNPs are associated with ileal location (OR, respectively, 1.49, 1.52, and 1.70), ileocolonic location (OR, respectively, 1.31, 1.57, and 1.68), and involvement of the upper digestive tract (OR, respectively for ATG16L1 and IRGM, 1.96 and 1.95). The risk genotype GG in ATG16L1 is associated with patients who respond to steroids (OR 1.89), respond to immunosuppressants (OR 1.77), and to biologic therapy (OR 1.89). The SNPs in ITLN1 and IRGM are both associated with a positive response to biologic therapy. The risk for ileal, ileocolonic, and upper digestive tract locations increases with the number of risk alleles (OR for three alleles, respectively, 7.10, 3.54, and 12.07); the OR for positive response to biologic therapy is 3.66. CONCLUSIONS: A multilocus approach using autophagy-related genes provides insight into CD phenotype-genotype associations and genetic markers for predicting therapeutic responses.

Preservation of viability and antibacterial activity of Lactobacillus spp. in calcium alginate beads.

The objective of the study was to produce calcium alginate beads able to deliver Lactobacillus spp. (Lactobacillus plantarum, Lactobacillus rhamnosus GG, Lactobacillus bulgaricus and Lactobacillus lactis) with preserved viability and antibacterial activity. Four types of beads, containing entrapped (E), surface and entrapped (ES), surface (S) and concentrated surface and entrapped lactobacilli (C(ES)) were prepared and physically characterized. The antibacterial activity of lactobacilli cultures before and after immobilization, freeze-drying and throughout storage was studied in relationship to the viable number of lactobacilli. Multi-resistant clinical isolates (methicillin-resistant Staphylococcus aureus, vancomycine-resistant Enterococcus faecalis, VIM-2-metalo-ß-lactamase producing Pseudomonas aeruginosa and CTX-M-15-ß-lactamase producing strains: Escherichia coli and Klebsiella pneumoniae) were used as indicator strains. Alginate beads in which lactobacilli proliferated to the beads surface (ES and C(ES)) differed significantly from the other types of beads in their physicochemical properties, showing smoother surface morphology, more spherical shape, bigger weight, lower calcium content, density and crushing force. Lactobacilli cultures, at high cell concentrations (10(8)cfu/ml) were active against both Gram-positive and negative multi-resistant bacteria. Beads containing both entrapped and surface lactobacilli (ES) resulted in viability and antibacterial activity most similar to non-processed lactobacilli cultures. The viability and antibacterial activity of the immobilized lactobacilli remained stable after 6 months storage.

Ulcerative colitis in a Southern European country: a national perspective.

BACKGROUND: The incidence, prevalence, and even the clinical behavior of ulcerative colitis (UC) are highly variable in different world regions. In previous studies, Portugal was reported as having a milder clinical behavior. The aim of this study was to apply the Montreal Classification in a large group of UC Portuguese patients in order to describe their clinical characteristics and evaluate variables potentially useful for outcome prediction. METHODS: A cross-sectional study based on data collected from a nationwide online registry was undertaken. RESULTS: In all, 2863 patients with UC were included. Twenty-one percent had ulcerative proctitis, 52% left-sided colitis, and 28% extensive colitis. Sixty percent of patients had taken steroids, 14% immunosuppressors, 1% biologicals, and 4.5% were submitted to surgery. Patients with extensive colitis had more severe activity, needing more steroids, immunosuppressors, and surgery. At the time of diagnosis 61% were less than 40 years old and 5% less than 16. Younger patients also had a more aggressive initial course. Thirty-eight percent of patients had only taken salicylates during the disease course and were characterized by a lower incidence of systemic symptoms at presentation (3.8% versus 8.8%, P < 0.001), fewer extraintestinal manifestations (7.7% versus 24.0%, P < 0.001), and a higher prevalence of proctitis (32.1% versus 10.0%). CONCLUSIONS: A more aggressive phenotype was found in extensive colitis and in the initial course of younger patients, with an increased need for steroids and immunosuppressors. In addition, a significant percentage of patients, particularly with proctitis, showed a milder clinical evolution and were maintained in remission only with salicylates.

Comportamiento de las enfermedades del SOMA tratadas con terapia acupuntural y sus modalidades en Bahía Honda / Behavior of the OMAS' diseases treated with acupuntural therapy and its modalities in Bahia Honda

El alivio del dolor como síntoma importante y prácticamente obligado en el enfermo, que solicita ayuda a los profesionales de la medicina, ha sido siempre motivo de estudio e investigación en todas partes del mundo. Se realizó un estudio transversal descriptivo y retrospectivo sobre una muestra constituida por todos los pacientes con diagnóstico de enfermedades del SOMA y que recibieron tratamiento con métodos tradicionales. La muestra estuvo constituida por los pacientes que fueron tratados en el Centro Municipal de Referencia de (MNT) de Bahía Honda, en el período comprendido entre enero a diciembre del 1999. Para determinar el efecto del tratamiento y la realización del estudio, los datos necesarios se obtuvieron a través de las hojas de cargo y las historias clínicas individuales de cada paciente. Las principales variables comprendidas en el estudio fueron: edad, sexo, ocupación laboral, diagnóstico, modalidad de tratamiento aplicado, número de sesiones utilizadas, y la evolución clínica del enfermo. Para la valoración estadística, se utilizó el porcentaje y el test de chi cuadrado por el sistema computadorizado microstat. El sexo femenino y el grupo de edad entre 30 y 59 años fueron los más afectados, la sacrolumbalgia y las enfermedades de la columna cervical fueron los diagnósticos más frecuentes, más de la mitad del total de los pacientes tratados mejoraron con un total de 5-9 sesiones de tratamiento(AU)

The relief of pain as an important symptom and practically compulsory in the sick patient seeking for health professional assistance has always been a reason of study and investigation everywhere in the world. A cross-sectional, descriptive and retrospective study was conducted in a sample composed of all the patients with diagnosis of OMAS' diseases and that received treatment with traditional methods. These patients were treated at the Municipal Referral Center of Bahia Honda from January to December, 1999. The necessary data for conducting the study were collected from the individual medical histories to determine the effect of the treatment, The main variables under study were age, sex, occupation, diagnosis, treatment modality applied, number of sessions used and the clinical evolution of the patient. The percentage and the Chi square test by microstat computerized system were used for the statistical evaluation. Females and the age group 30-59 were the most affected. Low back pain and the cervical region diseases were the most frequent diagnoses. More than half of the total of the patients treated improved with with a total of 5-9 sessions of treatment(AU)

Comportamiento de las enfermedades del SOMA tratadas con terapia acupuntural y sus modalidades en Bahía Honda / Behavior of the OMAS' diseases treated with acupuntural therapy and its modalities in Bahia Honda

El alivio del dolor como síntoma importante y prácticamente obligado en el enfermo, que solicita ayuda a los profesionales de la medicina, ha sido siempre motivo de estudio e investigación en todas partes del mundo. Se realizó un estudio transversal descriptivo y retrospectivo sobre una muestra constituida por todos los pacientes con diagnóstico de enfermedades del SOMA y que recibieron tratamiento con métodos tradicionales. La muestra estuvo constituida por los pacientes que fueron tratados en el Centro Municipal de Referencia de (MNT) de Bahía Honda, en el período comprendido entre enero a diciembre del 1999. Para determinar el efecto del tratamiento y la realización del estudio, los datos necesarios se obtuvieron a través de las hojas de cargo y las historias clínicas individuales de cada paciente. Las principales variables comprendidas en el estudio fueron: edad, sexo, ocupación laboral, diagnóstico, modalidad de tratamiento aplicado, número de sesiones utilizadas, y la evolución clínica del enfermo. Para la valoración estadística, se utilizó el porcentaje y el test de chi cuadrado por el sistema computadorizado microstat. El sexo femenino y el grupo de edad entre 30 y 59 años fueron los más afectados, la sacrolumbalgia y las enfermedades de la columna cervical fueron los diagnósticos más frecuentes, más de la mitad del total de los pacientes tratados mejoraron con un total de 5-9 sesiones de tratamiento(AU)