Histological Index Research Articles

Density of Biopsy Sampling Required to Ensure Accurate Histological Assessment of Inflammation in Active Ulcerative Colitis.

Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates, and the density of biopsy sampling within mucosal regions of interest required to meet specified benchmarks for accuracy. A total of 994 sequential 1-mm digital microscopic images (virtual biopsies) from consecutive colectomies from patients with clinically severe UC were scored by 2 pathologists. Agreement statistics for Geboes subscores and Nancy (NHI) and Robarts Histological Indices (RHI) between random samples from 1 to 10 biopsies and a reference mean score across a 2-cm region of mucosa were calculated using bootstrapping with 2500 iterations. The agreement statistics improved across all indices as the biopsy density increased, with the largest proportional gains occurring with addition of the second and third biopsies. One biopsy achieved moderate to good agreement with 95% confidence for NHI and RHI corresponding to scale-specific errors of 0.40 (0.25-0.66) and 3.02 (2.08-5.36), respectively; and 3 biopsies achieved good agreement with 95% confidence corresponding to scale-specific errors of 0.22 (0.14-0.39) and 1.87 (1.19-3.25), respectively. Of the individual histological features, erosions and ulcers had the greatest impact on the agreement statistics. In the setting of active colitis, up to 3 biopsy samples per region of interest may be required to overcome microscopic heterogeneity and ensure accurate histological grading.

Lupus pathogenesis and autoimmunity are exacerbated by high fat diet-induced obesity in MRL/lpr mice

ObjectiveSLE is an autoimmune disease characterised by persistent inflammation and autoantibody production. Genetic predisposition and environmental factors such as a high-fat diet (HFD) may contribute to lupus development. However, the...

Risk of colorectal neoplasia according to histologic disease activity in patients with inflammatory bowel disease and colonic post-inflammatory polyps.

While post-inflammatory polyps (PIPs) have historically been a risk factor for colorectal neoplasia (CRN), histologic activity may explain this association. We aimed to assess the impact of histologic activity on CRN occurrence in IBD patients with colonic PIPs. Patients with PIPs on surveillance colonoscopy at Saint-Antoine hospital between 1 January 1996 and 31 December 2020 were included and subsequent colonoscopies were assessed. Histologic IBD activity was assessed by the Nancy histologic index. Survival and Cox regression analysis were performed to assess the strength of the association of PIPs and other patient variables with progression to CRN. A total of 173 patients with at least two surveillance colonoscopies with PIPs at index colonoscopy were compared to a similar group of 252 patients without PIPs. In survival analysis, the presence or PIPs at index colonoscopy did not impact the risk of CRN in patients with histological inflammation (p = 0.83) and in patients without histological inflammation (p = 0.98). The risk of CRN was associated with increasing Nancy index score of 3 or 4 (HR: 4.16; 95% CI 1.50-11.52 and HR: 3.44; 95% CI 1.63-7.24), age (HR per 10-year increase: 1.37; 95% CI 1.13-1.66) and first-degree family history of colorectal cancer (HR: 5.87; v 1.31-26.26), but not PIPs (HR: 1.17; 95% CI 0.63-2.17). After controlling for histologic activity, PIPs do not increase the risk of CRN in IBD patients. Histologic activity rather than PIPs should be considered in the risk assessment of CRN.

Cinnamon (Cinnamomum cassia) hot water extract improves inflammation and tight junctions in the intestine in vitro and in vivo

The natural byproduct Cinnamomum cassia was widely used in ancient Asia to cure disease because of its various pharmacological effects. Despite its ethnomedicinal benefits, few studies on the intestinal anti-inflammatory effect of C. cassia have been reported. Therefore, this study aimed to evaluate the potential beneficial effects of C. cassia on the intestine in vitro and in vivo. Herein, the effects of cinnamon hot water extract (CWE) on tight junction (TJ) barrier function, transepithelial electrical resistance, and mRNA expression were confirmed in Caco-2 cells. The CWE treatment groups showed significantly enhanced cell permeability, proinflammatory cytokine mRNA expression, and TJ expression. CWE-treated mice showed an improved histological index and decreased cytokine concentrations compared with those of colitis model mice. These results suggest that CWE alleviated inflammatory damage and improved the TJ barrier, indicating that CWE may be used as a functional food to improve intestinal health.

The effects of MDR-1 gene polymorphisms on the clinical course of chronic hepatitis B infection

Aims: Chronic HBV infection is associated with high morbidity and mortality rate due to increased risk of hepatic cirrhosis and hepatocellular cancer. Treatment modilities and resistance is currently investigated. Several mechanisms were underlying in drug resistance. P-glycoprotein (P-gp), the product of multidrug resistance gene (MDR-1), is well-known mechanism of MDR phenotype. MDR gene C1236T polymorphism is associated with decreased p-gp function. The mutation of MDR gene can affect the clinical course of disease and response rate to treatment. It was aimed to investigate the relationship between MDR gene polymorphism and clinical course and treatment responses in chronic HBV infection in our study. Methods: A total of 90 (male/female:69/21) patients with chronic HBV infection under Lamivudine treatment was enrolled in this study. Mean ages were 49.8±12.6 (range:22-75) years. The patients were categorized as: Treatment responded (group 1: HBV-DNA is negative at 24th week) and treatment refractory (group 2: HBV-DNA is still positive after 24th week). Group 1 was consisted of 51 (M/F: 38/13) and group 2 was consisted of 39 (M/F: 31/9) patients. There was no significant difference between ages and genders of two groups. Histologic activity indexes (HAI), total bilirubin, AST and ALT levels, HBV-DNA titers were significantly higher in the patients in group 2 than group 1 (p<0.05). Results: Genotype distributions; homozygous CC genotype was in 8 (15.7%),heterozygous CT genotype was in 37 (%72.5), homozygous TT genotype wasin 6 (11.8%) in patients at group 1. Homozygous CC genotype was in 13 (33.3%), heterozygous CT genotype was in 21 (53.8%), homozygous TT genotype was in 5 (12.8%) in patients at group 2. CC genotype was more common in group 2 than group 1 (p=0.044). C and T alleles’ frequencies in the group 1 and 2 were 51.96% and 60.26%, 48.04% and 39.74%, respectively (p>0.05). The patients with YMDD mutation positive at group 2 (n:11), 5 (45%) had have CC genotype, 5 (45%) had have CT, 1 (9%) had have TT genotype.The patients with YMDD mutation negative at group 2 (n:8), 3 (37%) patients had have CC and 5 (63%) patients had have CT genotype. CC genotype was more common in the patients with YMDD mutation positive than group 1 (p=0.043). Moreover, CC genotype was more common in the patients with HBV-DNA positive at 12nd month of Lamivudine treatment than group 1 (p=0.042). Conclusion: Consequently; MDR-1 and p-gp polymorphisms are important factors in the clinical course of chronic HBV infection and may influence the treatment responses. In the current study, it was found that the CC genotype of MDR-1 gene C1236T was more common in the patients with lamivudine resistant HBV infection.

Biopsies from ulcer edge yield higher histological activity scores than biopsies from non-ulcerated mucosa in active ulcerative colitis.

The appropriate location for biopsy collection in ulcerative colitis is unknown. We aimed to determine the location for biopsy collection in the presence of ulcers which yields the highest histopathological score. This prospective cross-sectional study enrolled patients with ulcerative colitis and ulcers in the colon. Biopsy specimens were obtained at the edge of the ulcer; at a distance of one open forceps (7-8 mm) from the ulcer edge; at a distance of three open forceps (21-24 mm) from the ulcer edge; further referred to as locations 1, 2 and 3 respectively. Histological activity was assessed using Robarts Histopathology Index and the Nancy Histological Index. Statistical analysis was performed using mixed effects models. A total of 19 patients were included. Decreasing trends with distance from the ulcer edge (P < 0.0001) were observed. Biopsies procured from the edge of the ulcer (location 1) yielded a higher histopathological score compared to biopsies procured at locations 2 and 3 (P ≤ 0.001). Biopsies from the ulcer edge yield higher histopathological scores than biopsies next to the ulcer. In clinical trials with histological endpoints, biopsies should be obtained from the ulcer edge (if ulcers are present) to reliably assess histological disease activity.

Composite Assessment Using Intestinal Ultrasound and Calprotectin Is Accurate in Predicting Histological Activity in Ulcerative Colitis: A Cohort Study.

Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices. Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index. Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score. Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%. Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC.

Effect of dietary vitamin E supplementation on growth, fatty acid composition, intestinal histology, and haemato-immune indices of milkfish, Chanos chanos, larvae

ABSTRACT Vitamin E is one of the most important vitamins in aquatic animal breeding, larval growth, and development. It is also considered to be a functional feed addtitive for its antioxidant and immunity-improvement role resulting in better survival and growth during early life stages. However, the role of vitamin E in the diet of milkfish larvae has not been studied in detail. Moreover, the optimal requirement of vitamin E for improved survival and growth in the larval stages of milkfish is yet to be ascertained. A 45-day feeding experiment was conducted to elucidate the effect of dietary vitamin E (alpha tocopherol) supplementation on the growth, survival, and fatty acid composition of milkfish, Chanos chanos, larvae. During the trial, five iso-nitrogenous and iso-energetic (~580 g kg−1 crude protein, 120 g kg−1 crude lipid) experimental larval diets with varying levels of vitamin E 0 (control E0), 100 (E100), 200 (E200), 300 (E300) and 400 (E400) mg kg−1 were tested in 18 days posthatch larvae (mean weight: 48.25 ± 0.08 mg). Milkfish larvae (1,500) were randomly distributed into 15 fiber-reinforced plastic (FRP) rectangular tanks of 100 L capacity (n = 100) in a flow-through rearing system. The results revealed that larvae fed with a diet containing vitamin E supplementation at 200 mg (E200) enhanced (p < .05) the growth performance, final body weight (371.7 ± 12.80 mg), weight gain percentage (628.76 ± 63.12%), and specific growth rate (4.31 ± 0.80%) compared with the E0 fed diet. Also, fish feed with E200 diet had a significantly higher protein efficiency ratio (0.53 ± 0.08) than the control (E0) (0.40 ± 0.01). Vitamin E and lipid content of postfed whole larvae were linearly correlated (R 2 = 0.956) with dietary vitamin E inclusions up to 300 mg kg−1. Histological examinations revealed that the length of intestinal villi and the concentration of lymphoid cells in the lamina propria of the treatments E200, E300, and E400 were higher, compared to E0 and E100 treatments. Red blood cell (p < 0.05) and white blood cell (p < 0.01) counts were significantly higher in E200 treatment than in the rest of the treatments. Larvae fed with an E200 and E300 diet showed significantly (p < 0.05) increased total lymphocyte count, while myelocyte count was significantly decreased (p < 0.01). Based on a curvilinear (polynomial) regression analyses, the optimum specific growth rate, final body weight, weight gain, protein efficiency ratio, and feed efficiency ratio were obtained at dietary vitamin E levels of 210, 205, 207, 243, and 242 mg kg−1 diet, respectively. Accordingly, the optimum dietary vitamin E required for milkfish in a range of 205 to 243 mg kg−1 is beneficial for better health, survival, and growth. The findings of this study can be used as the baseline scientific information on the vitamin E requirement for the formulation of a cost‐effective diet for milkfish larvae.

Artificial Intelligence Enabled Histological Prediction of Remission or Activity and Clinical Outcomes in Ulcerative Colitis

Microscopic inflammation has significant prognostic value in ulcerative colitis (UC); however, its assessment is complex with high interobserver variability. We aimed to develop and validate an artificial intelligence (AI) computer-aided diagnosis system to evaluate UC biopsies and predict prognosis. A total of 535 digitalized biopsies (273 patients) were graded according to the PICaSSO Histologic Remission Index (PHRI), Robarts, and Nancy Histological Index. A convolutional neural network classifier was trained to distinguish remission from activity on a subset of 118 biopsies, calibrated on 42 and tested on 375. The model was additionally tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months. The system output was compared with human assessment. Diagnostic performance was reported as sensitivity, specificity, prognostic prediction through Kaplan-Meier, and hazard ratios of flares between active and remission groups. We externally validated the model in 154 biopsies (58 patients) with similar characteristics but more histologically active patients. The system distinguished histological activity/remission with sensitivity and specificity of 89% and 85% (PHRI), 94% and 76% (Robarts Histological Index), and 89% and 79% (Nancy Histological Index). The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UC endoscopic index of severity and Paddington International virtual ChromoendoScopy ScOre, respectively. The hazard ratio for disease flare-up between histological activity/remission groups according to pathologist-assessed PHRI was 3.56, and 4.64 for AI-assessed PHRI. Both histology and outcome prediction were confirmed in the external validation cohort. We developed and validated an AI model that distinguishes histologic remission/activity in biopsies of UC and predicts flare-ups. This can expedite, standardize, and enhance histologic assessment in practice and trials.

Bone adaptation and osteoporosis prevention in hibernating mammals

Hibernating bears and rodents have evolved mechanisms to prevent disuse osteoporosis during the prolonged physical inactivity that occurs during hibernation. Serum markers and histological indices of bone remodeling in bears indicate reduced bone turnover during hibernation, which is consistent with organismal energy conservation. Calcium homeostasis is maintained by balanced bone resorption and formation since hibernating bears do not eat, drink, urinate, or defecate. Reduced and balanced bone remodeling protect bear bone structure and strength during hibernation, unlike the disuse osteoporosis that occurs in humans and other animals during prolonged physical inactivity. Conversely, some hibernating rodents show varying degrees of bone loss such as osteocytic osteolysis, trabecular loss, and cortical thinning. However, no negative effects of hibernation on bone strength in rodents have been found. More than 5000 genes in bear bone tissue are differentially expressed during hibernation, highlighting the complexity of hibernation induced changes in bone. A complete picture of the mechanisms that regulate bone metabolism in hibernators still alludes us, but existing data suggest a role for endocrine and paracrine factors such as cocaine- and amphetamine-regulated transcript (CART) and endocannabinoid ligands like 2-arachidonoyl glycerol (2-AG) in decreasing bone remodeling during hibernation. Hibernating bears and rodents evolved the capacity to preserve bone strength during long periods of physical inactivity, which contributes to their survival and propagation by allowing physically activity (foraging, escaping predators, and mating) without risk of bone fracture following hibernation. Understanding the biological mechanisms regulating bone metabolism in hibernators may inform novel treatment strategies for osteoporosis in humans.

Potential therapeutic effect of medium chain triglyceride oil in ameliorating diabetic liver injury in a streptozotocin-induced diabetic murine model.

Diabetes mellitus is one of the most commonly arising endocrine conditions. The disorder gives rise to enduring damage to a number of body tissues and viscera as a result of related macrovascular and microvascular complications. In patients who are unable to maintain their nutritional status independently, medium-chain triglyceride (MCT) oil is frequently added as a supplement to parenteral nutrition. The aim of the present research is to establish whether MCT oil has a therapeutic influence on the hepatic damage occurring in male albino rats as a result of streptozotocin (STZ)-induced diabetes. 24 male albino rats were randomized into four cohorts, i.e., controls, STZ-diabetic, metformin-treated and MCT oil-treated. The rodents were fed a high-fat diet for 14 days; a low dose of intraperitoneal STZ was then administered in order to induce diabetes. The rats were subsequently treated for 4 weeks with metformin or MCT oil. Analysis included an appraisal of liver histology and biochemical indices, i.e., fasting blood glucose (FBG), hepatic enzymes and glutathione (GSH), the latter obtained from hepatic tissue homogenate. A rise in FBG and hepatic enzymes was observed, but in the STZ-diabetic cohort, hepatic GSH levels were diminished. Treatment with either metformin or MCT oil led to a decline in FBG and hepatic enzyme titers whereas GSH concentrations increased. Liver histology findings were notable amongst rodents within control, STZ-diabetic and metformin-treated groups. The majority of histological changes were resolved following therapy with MCT oil. The anti-diabetic and antioxidant characteristics of MCT oil have been substantiated by this work. MCT oil led to a reversal of the hepatic histological changes seen in STZ-induced diabetes in rats.

Ectoparasitic diversity, gill alterations in Hoplerythrinus unitaeniatus (Characiformes: Erythrinidae) and Cichlasoma bimaculatum (Perciformes: Cichlidae) and quality of fishing water in the Quilombola zone in Maranhão State, Brazil

The current study aimed to investigate the ectoparasitic diversity and gill alterations in Hoplerythrinus unitaeniatus (Characiformes: Erythrinidae) and Cichlasoma bimaculatum (Perciformes: Cichlidae) and evaluate the microbiological and physicochemical quality of water samples deriving from a Quilombola zone in Maranhão State, Brazil. Water samples and 42 fish specimens, 21 H. unitaeniatus and 21 C. bimaculatum, were collected from a floodable environment. Water samples were subjected to physicochemical and microbiological analyses in the laboratory environment. Fish specimens were euthanized to collect and identify ectoparasites in animals' mucus, body surface, and gills, as well as to enable the histological analysis of the second right gill arch. The herein-identified ectoparasites have shown 30.95% prevalence and comprised three phyla: Platyhelminthes, Trematoda and Arthropoda. The herein-identified main histological changes comprised incomplete and complete fusion of several lamellae, lifting of respiratory epithelium, lamellar disorganization, lamellar epithelial hyperplasia, and blood sinus dilation. The herein calculated histological alteration index has shown that 23.80% of specimens presented mild-to-moderate tissue damage, 4.77% presented moderate-to-severe tissue changes, and 9.52% presented irreparable tissue damage. It was possible concluding that histological gill lesions identified in fish specimens analyzed may be adaptive responses to the affected environment and the incidence of ectoparasites.

The Diagenetic Alterations of Historic Skeletons from the Crown Mines Cemetery, South Africa

Human skeletons associated with early gold mining in Johannesburg, South Africa are investigated. An unmarked cemetery was buried beneath a mine dump which resulted in macroscopically stained and poorly preserved bones. Histological assessments were conducted to understand the postmortem treatment of the remains, determine the extent of bone degradation, and understand how this environment affected the bone's microstructure. Various diagenetic alterations and the general histological index were assessed using normal and polarized light microscopy of thin anterior midshaft femur sections (n = 50). Degradation was identified in the periosteal and endosteal regions, while the intra-cortical region remained well-preserved. Bacterial bioerosion, microcracks, infiltrations, inclusions, and staining were found throughout the sample. Numerous non-Wedl micro-foci of destruction were observed, filled with exogenous material. The degradation suggested that the remains were buried in neutral soil that was subsequently covered by acidic mine dumps which resulted in a corrosive environment. Although the skeletons were poorly preserved, their histological integrity was more promising, especially the intra-cortical area. This is important for future investigations of archaeological bone, as this area can lead to more accurate descriptions of skeletal assemblages. Targeted sampling of this region could produce promising estimates of age, descriptions of pathology, and biomolecular results, which require further study.

Postmortem treatment of preterm infants at the Gangshang site during the Late Neolithic period, Shandong Province, China

AbstractJar burial is a particular burial practice generally used in the Neolithic period of China. However, the rarity of finding prenatal individuals limits the ability to study their treatment in jar burial contexts. In this paper, to study the postmortem treatment of this specific age further, we focus on three jar burials of infant individuals excavated in 2021 at the Gangshang site in China, where the skeletal remains were relatively well preserved. The skeletal remains of three well‐preserved individuals are presented into inverted ceramic tripods near the residential area and with a crouched posture. In terms of this condition, we apply the osteometric method to estimate the range and mean of age at death for each individual investigated. Meanwhile, we use micro‐computed tomography (CT) scans to help judge the degree of microbial bioerosion. Besides, histological analysis on skeletal remains combined with the Oxford Histological Index (OHI) assessment allows us to estimate the developmental stage at the time of death by analyzing the results of micro‐CT scans. By using osteometric methods, the results show that the gestational age of the three individuals is 22–26, 24–28, and 22–26 weeks, respectively. The results of the micro‐CT scans indicate that all three fetuses died shortly after birth, or had died in their mother's uterus before birth, with the OHI score of 5. Moreover, we indeed observe infant skeleton remains with no bacterial bioerosion, indicating that it is effective using this method to judge the developmental stage at the time of death with a specific taphonomic environment in the Gangshang site of the Dawenkou culture period. Combined with the placement of the jars in which the three infants were buried, it is believed that this unique placement method was intentional and specific to the infant deaths. These results are instructive for exploring the postmortem treatment of dead infants by ancient residents of the Dawenkou culture period (4200 bc–2600 bc) in Shandong Province, China, and the significance and possible causes of the unique burial type.

Correlation Between the Nancy Histopathology Index and Markers of Disease Activity in Pediatric Ulcerative Colitis.

The Nancy Histological Index (NHI) was developed to assess histological disease activity in adult ulcerative colitis (UC) patients. However, data in pediatrics is limited. Our aim was to determine whether the NHI correlates with different indices of disease activity in pediatric UC patients. We retrospectively reviewed the NHI in rectal biopsies from 61 pediatric UC patients (median age 14.3 years), of whom 34 (55.7%) were newly diagnosed. The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score among participants was 30 (interquartile range 5-55). Most patients exhibited an NHI of 3 (41/61, 67.2%) or 4 (8/61, 13.1%), reflecting moderate-severe histologic inflammation. A moderate positive correlation was identified between the NHI and PUCAI, fecal calprotectin, and Mayo endoscopic scores ( r = 0.60, 0.54, and 0.56 respectively, P ≤ 0.001), but not with CRP or albumin. These results indicate that the NHI has a modest correlation with clinical, laboratory and endoscopic indices of disease activity in pediatric UC patients.

A new practical method of estimating tumoral microenvironment parameters of possible prognostic significance in patients with invasive breast carcinoma: Combined microenvironment score

Background and objectiveIn recent years, the tumor microenvironment has become increasingly recognized as an influential factor in breast cancer development and growth. The parameters that form the microenvironment are the tumor stroma ratio and tumor infiltrating lymphocytes. In addition, tumor budding, which shows the ability of the tumor to metastasize, gives information about the progression of the tumor. In this study, the combined microenvironment score (CMS) was determined with these parameters, and the relationship between CMS and prognostic parameters and survival was evaluated. Materials and methodsIn our study, tumor stroma ratio, tumor infiltrating lymphocytes, and tumor budding were evaluated in hematoxylin-eosin sections of 419 patients with invasive ductal carcinoma. Patients were scored separately for each of these parameters, and these scores were summed to determine the CMS. The patients were divided into 3 groups according to CMS and the relationship between CMS and prognostic parameters and the survival of the patients was studied. ResultsThe patients with CMS 3 had higher histological grade and Ki67 proliferation index compared to CMS 1 and 2. Additionally, lymphovascular invasion, axillary lymph node and distant metastasis were more common. Disease-free, and overall survival were significantly shortened in the CMS 3 group. CMS was found as an independent risk factor for DFS (HR: 2.144 (95 % CI: 1.219–3.77) p: 0.008), but not an independent risk factor for OS. ConclusionCMS is a prognostic parameter that can be easily evaluated and does not require extra time and cost. Evaluating the morphological parameters of the microenvironment with a single scoring system will contribute to routine pathology practice and predict patient prognosis.

Artificial Intelligence Enables Quantitative Assessment of Ulcerative Colitis Histology

Ulcerative colitis is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Assessment of disease activity critically informs treatment decisions. In addition to endoscopic remission, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, manual pathologist evaluation is semiquantitative and limited in granularity. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, enabling precise quantitation of clinically relevant features. Here, we report the development and validation of convolutional neural network models that quantify histologic features pertinent to ulcerative colitis disease activity, directly from hematoxylin and eosin–stained whole slide images. Tissue and cell model predictions were used to generate quantitative human-interpretable features to fully characterize the histology samples. Tissue and cell predictions showed comparable agreement to pathologist annotations, and the extracted slide-level human-interpretable features demonstrated strong correlations with disease severity and pathologist-assigned Nancy histological index scores. Moreover, using a random forest classifier based on 13 human-interpretable features derived from the tissue and cell models, we were able to accurately predict Nancy histological index scores, with a weighted kappa (κ = 0.91) and Spearman correlation (⍴ = 0.89, P < .001) when compared with pathologist consensus Nancy histological index scores. We were also able to predict histologic remission, based on the absence of neutrophil extravasation, with a high accuracy of 0.97. This work demonstrates the potential of computer vision to enable a standardized and robust assessment of ulcerative colitis histopathology for translational research and improved evaluation of disease activity and prognosis.

Assessing the extent of bone bioerosion in short timescales – A novel approach for quantifying microstructural loss

The evaluation of bone diagenetic phenomena in archaeological timescales is well established, but little is known about the extent of bone diagenesis in short forensic timescales. In particular, the use of the Oxford Histological Index (OHI) has become synonymous with assessing bioerosion in archaeological bone samples, but it may not be ideal for use on samples with shorter, forensic post-depositional timescales. Here, we present a novel method of quantifying the extent of bioerosion occurring on samples with short post-depositional periods by counting the number of normal and diagenetic osteocyte lacunae observed within the microstructure of the bone, which enables calculation of the percentage of destroyed bone within the sample. Due to the potential for condition of the remains, or depositional environment to affect bone diagenesis, this study investigated multiple conditions; whole rat carcasses, defleshed rat long bones, and excised fleshed rat limbs that were either placed in soil in plastic boxes or exposed on a clean plastic surface, and left to decompose from four to 28 weeks, to allow bone bioerosion to occur. Statistically significant differences in the number of average diagenetic lacunae observed were found between the three conditions, while a statistically significant difference was observed between OHI scores of samples in the two deposition environments. The number of diagenetic osteocyte lacunae increased in all conditions, showing statistically significant increase in the percentage of destroyed bone over time. Diagenetic changes were seen as early as 4-weeks post-deposition. Comparisons between the OHI scores and the lacunae counts showed that, while the use of OHI could not distinguish between samples with discrete microstructural deterioration, counting the normal and diagenetic lacunae could distinguish such diagenetic changes.

P479 Reliability and responsiveness of histologic disease activity indices in Crohn’s Disease

Abstract Background The operating properties of histologic indices are poorly characterized in Crohn’s disease (CD) and no validated index exists. We assessed the reliability and responsiveness of histologic indices/items, developed an exploratory index, and compared different methods of scoring. Methods Using baseline and week 12 histologic image sets from the EXTEND placebo-controlled trial, blinded central readers scored 4 histologic indices (the Global Histologic Activity Score [GHAS], Geboes Score [GS], Robarts Histopathology Index [RHI], and Nancy Index [NHI]) and 3 additional novel items identified by an expert panel (mucin depletion, basal plasmacytosis, and pyloric gland metaplasia in the ileum). Reliability and responsiveness were evaluated for a global score (4 colonic segments + ileum), colonic score (4 colonic segments) and ileal score (ileum only) using the intraclass correlation coefficient (ICC) and area under the receiver operating curve (AUC), respectively. Change was defined using treatment assignment and improvement in histologic disease activity as measured on a 100-mm visual analogue scale (VAS) in responsiveness testing. Exploratory indices were developed using backward stepwise linear regression analysis. Candidate independent variables were items with an ICC ≥0.4 and AUC ≥0.56. The VAS served as the dependent variable. Results Paired histologic images were analysed from 55 subjects. Inter-rater reliability was substantial to almost perfect (ICC=0.73-0.85) and responsiveness was small to large (treatment assignment AUC=0.50-0.65; VAS AUC=0.71-0.94). The GHAS, GS, RHI, and NHI reached the minimum threshold for reliability (ICC ≥0.4) and responsiveness (AUC ≥0.56) regardless of whether the global and colonic scores were calculated using the worst affected segment, average of the included segments, or sum of the included segments (Table 1-3). Five items were tested as candidate predictors. Three exploratory indices were developed, each consisting of 3 items: a global index (neutrophils in the lamina propria, neutrophils in the epithelium, and erosion/ulceration), colonic index (chronic inflammatory infiltrate, neutrophils in the lamina propria, and erosion/ulceration) and ileal index (chronic inflammatory infiltrate, neutrophils in the epithelium, and erosion/ulceration). The novel indices highly correlated with the GHAS, GS, RHI, and NHI, with correlation coefficients ≥0.80 (Table 4). Conclusion The 4 existing indices were similarly reliable and responsive in measuring CD histologic activity, regardless of the method for calculating global and colonic scores and could be used in clinical trials. Attempts at novel index development did not offer benefit over current histologic indices.

P802 Relationships between validated clinical, endoscopic and histological indices in ulcerative colitis

Abstract Background The simple clinical colitis activity index (SCCAI) is increasingly used in practice for monitoring symptoms, because it documents urgency and nocturnal stool frequency, which are excluded from other indices. The question is how the SCCAI relates to validated endoscopic and histological indices, so that SCCAI thresholds for remission and active disease can be defined. Methods The SCCAI (range 0-19) was collected in real time from patients with ulcerative colitis (UC) using web-based TrueColours-IBD monitoring and collated with endoscopic activity (UCEIS, 0-8) and Nancy histological index (NHI, 0-4) for patients who had recorded SCCAI data up to 14d before endoscopy. Results 482 SCCAI/endoscopy/biopsy trios were analysed from 323 unique patients (162 male) aged 18 to 86 years (male: mean = 43.8, SD = 15.9; female: mean = 44, SD = 14.9). Disease extent for male: Normal=48, E1=23, E2=116, E3=43, female: Normal=45, E1=42, E2=110, E3=27. Spearman's rank correlation coefficient between UCEIS and NHI scores was r=0.77 (95% confidence interval [CI] 0.72 - 0.82, p &amp;lt;0.001). When the UCEIS was ≤ 1, or NHI ≤ 1, which is consistent with remission, the median (IQR) SCCAI was 2 (1 to 4) (Fig 1A, 1B). When the SCCAI was ≥5, the median (IQR) UCEIS was 4 (3 to 5) and the median (IQR) NHI was 3 (2 to 4). For patients with both histologic and endoscopic mucosal remission (HEMR), defined as NHI ≤ 1 and UCEIS ≤ 1, the median (IQR) SCCAI was 2 (0.25 to 4) (Fig 1C). Patients with SCCAI scores outside the IQR (n=8 for UCEIS, n=5 for NHI) had symptoms primarily driven by bowel urgency or poor general wellbeing. Four groups of patients could be identified using linear regression analysis modelling of relationships between bowel urgency and UCEIS score: ‘no urgency without active disease’; ‘urgency without active disease’; ‘urgency with active disease’; and ‘no urgency with active disease’ (Fig 2). Conclusion There is a ‘grey zone’ at low scores of symptom-based indices that cannot discriminate endoscopic or histologic remission from mildly active disease. The SCCAI threshold for active UC is &amp;gt;5, but with wide confidence intervals. Mechanisms behind symptoms in the absence of active inflammation need investigating.