Histological Index Research Articles

Variability in the Distribution of Histological Disease Activity in the Colon of Patients with Ulcerative Colitis.

Histological activity scores have been developed and validated. However, data on the distribution of histological inflammation within one segment in patients with ulcerative colitis [UC] are lacking. This impacts on the reliability of histological activity scores. The aim of this study was to assess the variability in histological activity within one endoscopic segment in patients with UC. Biopsies were taken in sequential patients with UC in three adjacent contiguous regions within a macroscopically homogeneous colonic segment. Biopsies were scored for Geboes score [GS], Robarts histological index [RHI] and Nancy histological index [NHI]. Variability was assessed by Kappa statistics for categorical outcomes and intraclass correlation coefficient [ICC] for continuous outcomes. A total of 161 biopsy sets from 55 endoscopic segments of 21 patients were analysed. Endoscopically active disease was present in 45% of segments. The continuous histological scores showed excellent agreement between the different regions. The ICC for RHI in all segments was 0.974 (95% confidence interval [CI] 0.958-0.984; p < 0.0001) and 0.98 [95% CI: 0.968-0.988; p < 0.0001] for the numerically converted GS. The categorical NHI showed higher variability: κ = 0.574 [95% CI: 0.571-0.577; p < 0.0001]. In all segments the highest variability was seen in samples with NHI = 2. When dichotomizing based on histological remission, substantial agreement was seen for all scores, with κ > 0.734 for all cut-offs. The homogeneity in the distribution of histological disease activity was comparable between colonic segments. The distribution of histological disease activity in UC follows a homogeneous pattern in different locations of one segment.

The Toxicity Evaluation of Salvia rhytidea and Glycine Max Extracts versus the Biochemical and Histological Indices of Liver and Kidney Functions in Mice

Background: The safety of the use of medicinal plants is a general challenge among consumers. To improve the use, it is necessary to provide complete profiles of the natural medications for quality control and the therapeutic and toxicity effects. This study was conducted to evaluate the structural and functional toxicity of the methanolic extracts of Salvia rhytidea and Glycine max plants in mice. Methods: After determining the LD50, NMRI mice with mean weight of 25-30 g were treated intraperitoneally with 100, 200 and 400 mg/kg, and orally with 800 mg/kg of the extracts for 7 consecutive days. After the last treatment, the serum samples were prepared and used for the biochemical assays. The liver and left kidney were removed from the animals and fixed in 10% formalin for histopathological examinations. Results: The results indicated that the biochemical parameters of liver and kidneys were not significantly different among the experimental and control groups (P&gt;0.05). Mild degenerative changes in the liver and kidneys were observed at the IP dose of 400 mg/kg and oral dose of 800 mg/kg of both extracts. Conclusion: The use of these plants’ extracts did not induce severe toxicity in the short-term; however, caution should be exercised with the long-term use.

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Inhibition of Bruton tyrosine kinase by acalabrutinib dampens lipopolysaccharide/galactosamine-induced hepatic damage

Bruton tyrosine kinase (BTK) sits at the crossroads of adaptive and innate immunities. Nevertheless, the detailed role of BTK activation in hepatic inflammatory disorders is still elusive to date. Accordingly, we investigated the impact of blocking BTK activation by acalabrutinib (ACB) on lipopolysaccharide/galactosamine (LPS/D-GaIN)-induced deleterious manifestations in the liver. This was achieved by pretreating mice with ACB (6, 12 or 24 mg/kg, oral) 2 h before challenge with LPS/D-GaIN (70 μg/kg and 700 mg/kg, respectively, i.p.) for 6 h. The results showed that ACB (6 and 12 mg/kg) (i) curbed LPS/D-GaIN-induced rise in biochemical (serum ALT, AST and LDH) and histological (necrosis, degeneration and congestion scores) indices of hepatocellular injury; (ii) attenuated LPS/D-GaIN-induced elevation in parameters of hepatocellular apoptosis (cleaved caspase 3) and proliferation (PCNA); and (iii) importantly, mitigated LPS/D-GaIN-induced recruitment and infiltration of the inflammatory cells to the liver evidenced by lowering elevated serum MCP-1 concentration and hepatic F4/80 immunostaining. These effects were linked to ACB dose-dependent inhibition of NF-κB nuclear translocation that subsequently reduced LPS/D-GaIN-mediated release of TNF-α, IL-1β and IL-22 in the blood circulation. However, a dose of 12 mg/kg of ACB elevated the hepatic TNF-α, IL-1β and IL-22 concentrations that arose from a compensatory activation of ERK and JNK. Inhibition of BTK also attenuated LPS/D-GaIN-induced overexpression of CD98, which is another contributor alongside cytokines for monocyte recruitment. Therapeutically, targeting BTK by ACB is an efficient approach for hitting multiple points with one agent that can dampen hepatocellular injury, death, immune cell recruitment and inflammation cascade.

Intra‐annual changes in reproductive indices of male and female Himalayan snow trout,Schizothorax richardsonii(Gray, 1832)

Periodic changes in reproductive hormone levels, gonadal histology and gonadosomatic index (GSI) of snow trout, Schizothorax richardsonii, were examined to ascertain annual cycle of gonadal development and reproductive status in their natural habitat. In females, there were coherent changes in plasma 17β-oestradiol and vitellogenin along with GSI, oocyte maturation and vitellogenic progression, collectively indicating two distinct maturation peaks during the months of September and February. Coinciding with this, in males, plasma 11-keto testosterone was also noticeably higher during September and February, with highest GSI values in September. However, plasma 17α, 20β-dihydroxyprogesterone levels in males were found to be persistently high from September to February. This observation suggests the potential presence of matured oozing males over a longer period, unlike in females. Overall, the close association between reproductive hormone levels, GSI and gonadal maturation stages in males and females (particularly, the presence of postovulatory follicle complexes) with apparent natural synchronization clearly indicates that S. richardsonii breeds twice in a year, possibly during late September to early November and late February to early April in the coldwater riverine habitats of the Indian Himalayan region.

Prognostic significance of histologic grade and Ki-67 proliferation index in follicular lymphoma.

The prognostic value of histologic grading and the Ki-67 proliferation index in follicular lymphoma (FL) is controversial. This study investigated the clinical usefulness of these two factors in Asian FL patients. Four hundred and thirty-three patients diagnosed with FL were retrospectively reviewed with a median follow-up time of 47.0 months (range, 24.0-168.0). The 10-year overall survival (OS) rate and progression-free survival (PFS) rate were 91.0% and 47.1%, respectively. Grade 3B and grade 3B with diffuse large B cell lymphoma (DLBCL) showed a better PFS than grade 1-3A (P < 0.001), and similar findings were noted in patients who received rituximab-containing regimens (P = 0.002). In contrast, no significant differences in terms of OS or PFS were observed between grades 1-2 and 3A. In addition, patients with Ki-67 ≥ 30% had a significantly better PFS than patients with Ki-67 < 30% (P = 0.014), although the difference was eliminated in the multivariate analysis. Both grade and Ki-67 index had no impact on prognosis in patients who did not receive rituximab treatment. In conclusion, grade 3A is closely related to grade 1-2, as reflected by a similar indolent clinical course and a lower PFS rate than grade 3B/3B + DLBCL. In addition, a higher Ki-67 index seems to have a positive effect on PFS in FL patients.

Bridelia ferruginea Benth leaves attenuates diabetes nephropathy in STZ-induced rats via targeting NGAL/KIM-1/cystatin c gene

BackgroundRenal failure is among the main complications of diabetes disorders and free radical from hyperglycemia is the major cause of this nephrotic complication. This study investigated the therapeutic effects of Bridelia ferruginea Benth on nephrotic damage in streptozotocin (STZ) induced diabetic rats. Diabetes mellitus was induced by injection of 50 mg/kg b. w. of STZ (intraperitoneal) in rats fasted overnight. Effect on nephropathy was assessed using biochemical, histological indices and gene expression of kidney tissue.ResultsThe total flavonoids and phenolic content of petroleum ether fraction of B. ferruginea (PEFBF) was observed to be higher compared to diethyl ether fraction of B. ferruginea (DEFBF). The 1,1-diphenyl-2-picryl-hydrazyl scavenging activity of the fractions were significantly (P < 0.05) reduced across the concentrations compared to the standard (gallic acid). The STZ-induced diabetic animals treated with 100 and 200 mg/kg b.w. of PEFBF and DEFBF showed significant (P < 0.05) reduction in blood glucose level on days 7, 11 and 14 compared to untreated diabetic rats. STZ-induced diabetic rats significantly (P < 0.05) exhibited increase plasma urea, creatinine, protein and albumin level while treatment with both fractions of B. ferruginea reduced the level of these parameters in treated diabetic rats. B. ferruginea also caused down-regulation of neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and cystatin c genes.ConclusionThese results revealed that, the plant has hypoglycemic activity therefore provides a pharmacological basis for its folkloric use in the management of hyperglycemia and its associated renal dysfunction.

Preventive effect of Stachys lavandulifolia against gentamicin-induced oxidative stress and nephrotoxicity in rats

Gentamicin (GM) is an effective antibiotic against gram-negative bacterial infection. However, GM can produce nephrotoxicity. Stachys lavandulifolia Vahl. (SL) is extensively used in folk medicine as herbal tea and has strong antioxidative effects. The aim of this study was to investigate the protective effect of SL on GM-induced nephrotoxicity in rats. In this study, forty-two male Wistar rats were randomly divided into six equal groups (N = 7 each): control (group I), GM-treated (group II), SL200 mg/kg + GM-treated (group III), SL400 mg/kg + GM-treated (group IV), SL200 mg/kg-treated (group V), and SL400 mg/kg-treated (group VI) groups. The treatment procedures continued for 10 days. At the end of the experiment, serum and the kidneys of all groups were harvested for histological and biochemical examination. No statistical significant improvement in histological and biochemical indices was shown at 200 mg/kg of SL treatment in group III compared with group II; however, at 400 mg/kg of SL, normalized serum levels of uric acid (P < 0.001), urea (P < 0.001), creatinine (P < 0.01), and total proteins (P < 0.05) were shown in group IV. Treatment with SL400 mg/kg also corrected the increased relative kidney weight in GM-treated animals (P < 0.05). GM nephrotoxicity was shown by elevated levels of malondialdehyde (P < 0.001) and decreased amounts of catalase (P < 0.001), superoxide dismutase (P < 0.01), and glutathione (P < 0.01) in renal tissue. The oxidative injury induced by GM was prevented by SL400 mg/kg treatment. Such treatment also normalized abnormal renal histology induced by GM. These data suggest that treatment with SL extract may be helpful to reduce gentamicin-induced nephrotoxicity.

Biological Behavior of Canine Acanthomatous Ameloblastoma Assessed With Computed Tomography and Histopathology: A Comparative Study.

Canine acanthomatous ameloblastoma (CAA) appears to have variable biological behavior with some tumors presenting with slow growth and minimal bone loss while others grow rapidly and cause severe cancellous and cortical bone destruction. The primary aim of the study is to elucidate if variations (grades) of CAA can be identified based on both histological and diagnostic imaging indices, and to compare markers of more aggressive behavior between these 2 commonly used diagnostic tools. This study evaluated 45 cases of CAA and confirmed that there is high degree of variability in tumor invasiveness as measured with computed tomography, with predominantly intraosseous tumors being significantly associated with more invasive behavior. However, the analysis also identified that there was very little correlation between computed tomographic and histological appearance of the tumor. CAA tends to have a highly uniform and predictable histological pattern, with tumors that aggressively invade bone (as seen on CT) not showing features of atypia that might be helpful in predicting the biological behavior of the neoplastic cells. Thus, reliance on diagnostic imaging as a measure of biological behavior is recommended for treatment planning as well as possible creation of a variant/grading scheme. Prospective studies are required to evaluate if differing variants of CAA as based on diagnostic imaging should be treated differently, and how this would affect long term clinical outcome.

What is the reliability, validity, responsiveness and feasibility of histological scoring indices for ulcerative colitis disease activity?

What is the reliability, validity, responsiveness and feasibility of histological scoring indices for ulcerative colitis disease activity?

Diagnostic Performance of Simultaneous [18F]-FDG PET/MR for Assessing Endoscopically Active Inflammation in Patients with Ulcerative Colitis: A Prospective Study.

Background: To investigate the diagnostic performance of simultaneous 18F-fluoro-deoxyglucose ([18F]-FDG) PET/MR enterography in assessing and grading endoscopically active inflammation in patients with ulcerative colitis. Methods: 50 patients underwent PET/MR 24 h before ileocolonoscopy. Inflammatory activities of bowel segments were evaluated with both Mayo endoscopic subscore and Nancy histologic index. MR, DWI (Diffusion-weighted imaging) and PET were utilized as qualitative parameters for detecting endoscopically active inflammation. SUVmaxQuot in each segment (maximum of standard uptake value relative to liver) was calculated to quantify inflammation. Results: In the study arm without bowel purgation, combined reading of PET and MR resulted in significantly increased specificity against each submodality alone (0.944 vs. 0.82 for MR and 0.843 for PET, p < 0.05) and highest overall accuracy. In the study arm with bowel purgation, the significantly lower specificity of PET (0.595) could be markedly improved by a combined reading of PET and MR. Metabolic conditions in bowel segments with both endoscopic and histological remission were significantly lower than in segments with endoscopic remission but persistent microscopic inflammation (SUVmaxQuot 0.719 vs. 0.947, p < 0.001). SUVmaxQuot correlated highly with Mayo endoscopic subscore (ρ = 0.718 and 0.606) and enabled grading of inflammatory activity. Conclusions: Simultaneous [18F]-FDG PET/MR may be considered as an alternative to endoscopy in clinical trials.

Selection of Histological Parameters for the Development of an Analytical Method for Discriminating Fresh and Frozen/Thawed Common Octopus (Octopus vulgaris) and Preventing Frauds along the Seafood Chain

This study aimed at selecting effective histological indicators of the freezing process, for the discrimination of fresh and frozen common octopus Octopus vulgaris. Histological indices of freezing process were selected in mantle and arm muscle and axial nerve tissues. Seven histological parameters were chosen: overall muscle tissue structural organization (a); gaping among muscle bundles (b); presence of optically empty spaces between and within muscle bundles (c); white spaces percentage between and within muscle bundles (d); overall nerve structural organization (e); presence of linear fissures and/or empty spaces within neuropil and axonal tract (f); presence of empty spaces within connective tissue matrix surrounding the nerve (g); empty space percentage within arm axial nerve region (h). The parameters were assessed on 150 mantle muscle sections (a, b, c, d), 150 arm muscle (b, c) and nervous (e, f, g, h) tissue sections belonging to 20 fresh exemplars further subdued to conventional freezing procedure at − 20 °C, 25 fresh curled exemplars, 25 exemplars industrially frozen at − 80 °C, and 20 thawed, curled, and individually quick frozen exemplars. Overall structural organization (a, e), gaping (b), and presence of optically empty spaces (c, f) confirmed significant morphological freezing indices in mantle and arm sections. In mantle, two d values (d < 25% and 25% < d < 33%) were proposed as complementary thresholds to be applied in association with b and c indices for freezing discrimination. These parameters appear eligible to set a method for discriminating fresh/thawed octopus products to be applied both in official control and self-check activities.

Breast cancer during pregnancy: matched study of diagnostic approach, tumor characteristics, and prognostic factors.

Breast cancer is one of the most frequently occurring cancers during pregnancy and its incidence is increasing. Many studies have shown poor outcomes, the causes of which remain unclear. To analyze radiologic characteristics, histology, and prognosis factors of breast cancer during pregnancy. A total of 42 patients with breast cancer diagnosed during pregnancy (BCP) were matched with 84 patients with breast cancer of similar age who were not pregnant. Sensitivity of radiology, tumor characteristics, prognosis factors, disease-free survival, and overall survival were analyzed. The sensitivity of breast ultrasound was higher than that of mammography for both groups. Ultrasound sensitivity for cancer was 95.7% in patients with BCP versus 98% in the not pregnant group, with non-statistically significant differences. Mammography sensitivity for cancer was 56.5% in patients with BCP versus 61% in the not pregnant group, with non-statistically significant differences. The stage at diagnosis according to the TNM staging system was significantly higher in patients with BCP with stage IV cancer: 16.7% in patients with BCP versus 3.7% in the not pregnant group (p = 0.03). No statistically significant differences were observed in histologic grade, Ki-67 index, or molecular subtype. Disease-free survival and overall survival were significantly lower in patients with BCP (p = 0.002 and p = 0.04). Multivariate analysis showed no difference when adjusting for stage and surrogate molecular subtype. Breast ultrasound shows a high sensitivity to detect breast cancer during pregnancy. BCP is diagnosed at a higher stage than in nonpregnant women. In our series, patients with BCP had poorer outcomes than the not pregnant group. These results were not observed when adjusting for stage.

Rubrics for mortality: a real-world observational long-term lupus nephritis cohort.

In this study, we aimed to evaluate long-term patient survival according to demographic data, clinical manifestations of systemic lupus erythematosus (SLE) and previous and current treatments, collected retrospectively. Patient selection required a minimum of four American College of Rheumatology revised criteria for SLE, biopsy-proven lupus nephritis (LN) available for reclassification according to the modified National Institutes of Health proposal for activity and chronicity indices and a minimum follow-up of at least three years since the last renal biopsy. Selection criteria were fulfilled in 25 patients followed for a median of 21 years. Based on the last renal biopsy, an equal number of patients were thus classified as class I/II and IV (n=8) and class III and V (n = 4). The mortality rate for LN was 14%. Having ever been diagnosed with glomerulonephritis (GN) type III or type IV but not class IV alone (p = 0.046), a higher histological chronicity index at the last renal biopsy (p = 0.022), not attaining renal remission one year after induction therapy (p = 0.004), end-stage renal disease on dialysis (p = 0.033) and the extra-renal Systemic Lupus International Collaborating Clinics Damage Index score (p = 0.017) were all significantly associated with mortality. Our results may provide important clues for strict observation protocols in particular categories of LN patients with long-standing disease.

Hematological, biochemical, and histopathological responses in sorubim Pseudoplatystoma spp. experimentally infected with Lactococcus garvieae

This study evaluated the hematological, biochemical, and histopathological responses of sorubim Pseudoplatystoma spp., experimentally infected with Lactococcus garvieae. Sorubim juveniles (n = 66; 21.3 ± 5.5 g; 17.1 ± 1.3 cm) were infected with L. garvieae by coelmatic inoculation (1.5 × 108 CFU mL−1) and sampling to 1, 3, 7, 14, and 21 days post-inoculation (dpi) for evaluation of hematological, biochemical parameters. Histopathological data of the spleen and kidney were estimated according to the histological alteration index (HAIn). Additionally, a decrease of hematocrit (1, 3, and 14 dpi), hemoglobin, and count of erythrocytes (3, 14, and 21 dpi), blood glucose (3 dpi), and proteinemy (14 dpi) were observed. Monocytes decreased at 7, 14, and 21 dpi; neutrophils at 3, 7, and 21 dpi; and lymphocytes at 21 dpi. Edema, hyperemia, hemorrhage, inflammatory infiltrate, and necrosis were the major histological changes observed in the spleen and kidney. HAIn was higher at 7 to 14 dpi in the spleen. Edema, hyperemia, and hyperplasia with hypertrophy of melanomacrophage centers (MMCs) associated with mild focal necrosis areas, particularly in white pulp, were observed. In the head kidney, it was observed that MMCs and melanomacrophages surrounded the capillaries and dispersed inside the sinusoidal capillaries network. Internalized bacteria by macrophages were commonly observed at 3 to 7 dpi. Tubular neogenesis characterized by nephrogenic bodies and rare MMCs at 21 dpi was observed. The experimental infection with L. garvieae caused significant hematological and biochemical responses. Pathological manifestations are closely related to the spleen and head kidneys mainly represented by hyperplasia and hypertrophy of melanomacrophage centers and mild necrosis areas.

Administration of Vitamin D3 Improves Hemoglobin Level by Regulating TNF-a and IL-6 in DSS-induced Colitis Mice

BACKGROUND: Anemia is frequently found in ulcerative colitis (UC) patients and assumed to be related to inflammatory process. Vitamin D3 (VD) is known to have anti-inflammatory and immunomodulatory effects. It also has the potential to be an alternative treatment of the inflammatory process that occurs at UC, however its mechanism has not been clearly established. This study aimed to assess the effect of VD on histopathology and hemoglobin levels in UC through its regulation in tumor necrosis factor (TNF)-α and interleukin (IL)-6.METHODS: Total samples of 24 mice were divided equally into Sham group, UC group, UC+VD group (given 3% dextran sodium sulfate (DSS) followed by VD), and VD+UC group (given VD followed by 3% DSS). Mouse Colitis Histology Index (MCHI) was used to measure histopathological changes. Immunohistochemical staining was used to observe expression of TNF-α and IL-6 in colon. Evaluation of anemia was determined by hemoglobin levels.RESULTS: Based on MCHI scores, significant epithelial damage was found in colon sample of UC group (8.25±3.05) compared to Sham (0.33±0.26), UC+VD (2.33±1.07), and VD+UC group (2.83±0.75) (p&lt;0.05). Significant lower numbers of TNF-α were found in Sham (27.33±3.42), UC+VD (36.33±1.86), and VD+UC group (36.68±1.86) compared with UC group (44.66±4.87) (p&lt;0.05). Significant less IL-6 expression was found in Sham (18.05±2.96), UC+VD (24.78±0.79), and VD+UC group (25.09±2.79) compared to UC group (38.85±3.51) (p&lt;0.05). Differences in hemoglobin levels were significantly lower in UC group (11.85±0.97) compared to Sham (14.25±0.47), UC+VD (13.68±0.68), VD+UC group (13.52±1.07) (p&lt;0.05).CONCLUSION: VD significantly reduced proinflammatory cytokines, increased mucosal repair, and improved hemoglobin levels.KEYWORDS: colitis, ulcerative, interleukin-6, tumor necrosis factor-alpha

Assessing Histological Inflammatory Activity in Patients With Ulcerative Colitis: A Diagnostic Accuracy Study Testing Fecal Biomarkers Lactoferrin and Calprotectin.

Histological remission has arisen as the optimal treatment outcome in ulcerative colitis (UC). The aim of this retrospective study was to explore the diagnostic performance of the noninvasive fecal biomarkers calprotectin (FC) and lactoferrin (FL) compared to the histological indices Nancy Index (NI) and Riley Index (RI). This study is a retrospective diagnostic accuracy study based on secondary analysis of patient data from 2002 to 2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. Patients with UC underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by 2 experienced pathologists according to NI and RI and provided a stool sample within 7 days pre- or post-colonoscopy. Diagnostic accuracy of recommended cutoffs for FC (>50 μg/g) and FL (≥7.25 μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy (effectiveness). The number of patients with UC recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r = 0.980, P < 0.001). Fecal biomarkers correlated moderately with NI (FC: r = 0.383, P < 0.001; FL: r = 0.420, P < 0.001) and RI (FC: r = 0.395, P < 0.001; FL: r = 0.424, P < 0.001). Fecal biomarker concentrations were increased in patients with active histological disease (NI ≥2), median [IQR], FC 69.72 [20.07-254.38], FL 18.59 [6.06-44.42], compared to those with inactive disease (NI ≤1), FC 12.35 [3.89 - 32.16], FL 3.14 [0.75-11.05], z = -6.60, P < 0.001. Fecal biomarker concentrations differed significantly across NI grades 0-4 (FC: H4 = 45.2; FL: H4 = 47.5, both P < 0.001). Patients with grade 0 had significantly lower concentrations of fecal biomarkers than those with grade 3 (median; FC 10.94 vs 72.22; FL 2.30 vs 29.10; both P < 0.001) or grade 4 (FC 10.94 vs 67.00; FL 2.30 vs 27.64; both P < 0.001), as well as grade 2 for FC only (10.94 vs 56.22, P = 0.001). Concentrations were also lower in patients with grade 1 compared to those with grade 3 (FC 17.49 vs 72.22; FL 4.24 vs. 29.10; both P ≤ 0.001) or grade 4 (FC 17.49 vs 67.00; FL 4.24 vs 27.64; both P < 0.001).Receiver operating characteristics area under the curve showed moderate diagnostic accuracy for both FC 0.76 (95% confidence interval [CI] 0.70-0.83) and FL 0.73 (95% CI 0.66-0.80). Optimized cutoffs for both FC (≥34.29) and FL (≥5.85 μg/g) had slightly improved accuracy, compared with the manufacturer's cutoffs (FC: 69.9% vs 65.9%; FL: 71.7% vs 69.0%). Fecal biomarkers calprotectin and lactoferrin correlate with histological disease activity and differentiate between patients in histological remission from those with evidence of moderate to severe disease activity. Their noninvasiveness, in addition to being inexpensive, supports their use in the clinical monitoring of patients with UC.

Fecal Calprotectin Thresholds to Predict Endoscopic Remission Using Advanced Optical Enhancement Techniques and Histological Remission in IBD Patients.

Fecal calprotectin (FC) is a common surrogate marker of mucosal healing (MH) in patients with ulcerative colitis (UC) and Crohn's disease (CD). We investigated the optimum FC thresholds for defining endoscopic remission (ER) and histological remission (HR) using advanced endoscopic techniques. In this cross-sectional study, we collected clinical, endoscopic, histological data, and FC from 76 UC and 41 CD patients. Receiver operating characteristic curves were created to evaluate the optimum cut-off of FC to predict ER evaluated by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and modified PICaSSO (Paddington International Virtual Chromoendoscopy Score) for UC patients and Simple Endoscopic Score (SES-CD) in CD patients; and HR was scored by the Robarts Histology Index (RHI) and Nancy Index for UC and modified Riley for CD. In UC patients, the best thresholds of FC to identify ER calculated with MES, UCEIS, and modified PICaSSO were 112, 148, and 161 mcg/g with accuracy of 86.9% 86.8%, and 81.6%, respectively. The best value of FC to predict HR was 112 mcg/g and 172 mcg/g with accuracy of 84.2% and 81.6% for RHI and Nancy Index, respectively.In CD patients, the best cut-off of FC to predict ER was 96 mcg/g with accuracy of 82.9%. The HR was best predicted by an FC value of 225 mcg/g with accuracy of 75.6%. The FC value threshold between 112 and 172 mcg/g could identify ER and HR in UC patients, whereas a value under 225 mcg/g should be considered for CD patients.

Systematic Review: Histological Scoring of Strictures in Crohn's Disease.

In Crohn's disease, many patients develop a stricture, which can due to inflammation, fibrosis and muscular changes or all at the same time. Determining the predominant component has therapeutic consequences but remains challenging. To develop imaging techniques that assess the nature of a stricture, a gold standard is needed and histopathology is considered as such. This paper provides an overview of published histological scoring systems for strictures in Crohn's disease. A systematic literature review according to PRISMA guidelines was performed of histological scoring indices that assessed whether a stricture was inflammation-predominant or fibrosis-predominant. Multiple libraries were searched from inception to December 2018. Two reviewers independently assessed abstracts and full-texts. Sixteen articles were identified as suitable for this systematic review. A large number of parameters were reported. Extent of neutrophil infiltration and extent of fibrosis in the bowel wall were most frequently described to reflect severity of inflammation and fibrosis, respectively. Among the 16 studies, only two described a numerical scoring system for the inflammatory and fibrotic component separately. Smooth muscle changes were scored in a minority of studies. Multiple scoring systems have been developed. There was large heterogeneity in scoring per parameter and construction of numerical scoring systems. Therefore, we feel that none of the systems is suitable to be used as gold standard. We offer an overview of histological parameters that could be incorporated in a future histological scoring index for strictures.

Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial

Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RIC (induced in the arm through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) or sham (incomplete inflation of the blood-pressure cuff) once daily for 10 days. Outcome variables were measured at baseline and on day 11. When compared with sham, RIC did not affect inflammation in the UC patients measured by fecal calprotectin, plasma C-reactive protein, Mayo Score, Mayo Endoscopic Subscore, Nancy Histological Index or inflammatory cytokines involved in UC and RIC. The mRNA and miRNA expression profiles in the UC patients were measured by RNA sequencing and multiplexed hybridization, respectively, but were not significantly affected by RIC. We used the Langendorff heart model to assess activation of the organ protective mechanism induced by RIC, but could not confirm activation of the organ protective mechanism in the UC patients.