Histological Activity Research Articles

Intestinal histopathology in pediatric PSC-IBD: Characterization of phenotype and assessment of the Nancy Index.

We aimed to characterize the histologic gut phenotype of pediatric primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) against non-PSC colitis, and to assess Nancy Index (NI) performance in pediatric PSC-IBD. Single-center retrospective cohort study including children diagnosed with PSC-IBD or non-PSC colitis (ulcerative colitis [UC] or IBD-unclassified) from 2000 to 2018, with diagnostic intestinal biopsies. Biopsies were re-reviewed by two independent pathologists who assessed microscopic disease distribution, NI scores, and specific histological features in the right and left colons, overall and stratified by endoscopic severity (moderate-severe vs. no more than mild). We examined NI inter-rater reliability with Fleiss' weighted (quadratic) kappa and NI construct validity against global endoscopic severity (Spearman correlation) and clinical outcomes (logistic regression). Fifty children with PSC-IBD and 81 colitis controls were included. Histologically, pancolitis (84% vs. 55%), right colon-predominant colitis (48% vs. 3%), and backwash ileitis (53% vs. 12%) (all p < 0.01) were significantly more common in PSC-IBD; histologic rectal sparing occurred at similar rates (6% vs. 10%, p = 0.54). Lamina propria-predominant neutrophils, prominent eosinophilic infiltration (left colon), and surface villiform change (right colon) were more common in PSC-IBD than colitis controls (p < 0.01). NI showed excellent inter-rater reliability (kappa > 0.9) and correlated moderately with global endoscopic severity but poorly with clinical activity in PSC-IBD. Pediatric PSC-IBD has a distinct histologic phenotype that largely mirrors the endoscopic phenotype in distribution and includes a greater frequency of features not included in conventional UC histologic activity indices. Future work should investigate whether a PSC-IBD-specific index incorporating these features is warranted.

Evaluation of serum human epididymis protein 4 in children with chronic liver diseases

The aim of this study was to evaluate the role of serum human epididymis protein 4 (HE4) as a non-invasive biomarker for the diagnosis of liver fibrosis in children with chronic liver diseases (CLD). This case-control study was conducted at Benha University Hospital, Egypt, involving 60 children with CLD and 60 healthy children as a control group. HE4 levels were measured by ELISA and compared with liver biopsy results. The CLD group had significant higher HE4 (median: 110.7, IQR: 96.7–120.4 pmol/L) compared to control group (median 42.07, IQR: 41.67–43.05 pmol/L), p < .001. HE4 levels increased significantly with the degree of fibrosis and histological activity index. At a cutoff point >48.3 pmol/L, HE4 diagnosed cases with mild fibrosis with a sensitivity of 95% and specificity of 91.3%. At a cutoff point >144.3 pmol/L, HE4 diagnosed cases with severe fibrosis with a sensitivity of 98% and specificity of 93.1%. Serum HE4 is a potential non-invasive marker for detecting liver fibrosis and its severity in children with CLD.

Histological, But Neither Clinical Nor Endoscopic Activity Predicts the Risk of Colectomy in Patients With Ulcerative Colitis Treated With Biologics.

Biological treatment failure is common in patients with ulcerative colitis (UC), but the predictive value of baseline histological activity is unknown. We aimed to investigate the associations between baseline histological activity and outcomes after biological treatment in patients with UC. Adult biological-naïve patients with UC (n = 150) were followed prospectively during biological treatment. Histological activity was assessed using the Nancy Index and Geboes score. Endoscopic activity was assessed using the Mayo Endoscopic Subscore (MES). Associations with outcomes were assessed in multivariable models. Associations between histological, endoscopic, and biochemical activity were assessed using Spearman's correlation. In biological-treated patients with UC, severe histological activity at baseline was independently associated with colectomy risk during the induction period (Nancy 2 vs 4: odds ratio [OR] 0.18, 95% CI 0.01-0.61, P = 0.024; Nancy 3 vs 4: OR 0.12, 95% CI 0.02-0.63, P = .019; Geboes 3 vs 5: OR 0.06, 95% CI 0.00-0.57, P = .033; Geboes 4 vs 5: OR 0.13, 95% CI 0.01-0.69, P = 0.032) and total follow-up (Nancy 2 vs 4: HR 0.23, 95% CI 0.06-0.98, P = 0.046; Nancy 3 vs 4: HR 0.13, 95% CI 0.04-0.47, P = 0.002; Geboes 4 vs 5: HR 0.28, 95% CI 0.08-0.93, P = 0.038). Meanwhile, baseline MES was not independently associated with colectomy risk. Histological activity was correlated with MES and the levels of C-reactive protein, hemoglobin, and albumin, but not calprotectin. Severe histological activity at baseline as characterized by a higher Nancy Index or Geboes score independently predicted colectomy risk in biological-treated UC patients, whereas MES did not. Thus, histological assessment should be encouraged before initiating biological treatment.

Knowledge and perspectives towards the use of histology in inflammatory bowel disease by gastroenterologists across the Asia-Pacific region.

Recently, histological mucosal assessment has gained momentum as a potential new treatment target for patients with inflammatory bowel disease (IBD) in the Asia-Pacific region. This study aimed to evaluate and compare the knowledge and acceptability of histological assessment among gastroenterologists across the region. A cross-sectional survey among gastroenterologists in the Asia-Pacific region was conducted and compared against a previous Australian survey. The questionnaire assessed knowledge and attitude towards the role and application of histology in IBD practice. Statistical analyses were employed to compare scores and identify predictors. A total of 221 gastroenterologists from 12 countries, including 77 (34.8%) from Australia, responded to questionnaire, with 185 (83.7%) completing the survey. The mean knowledge score was 9.8 ± 3.3 (51.6%). There was no significant difference in the average score among countries (P= 0.53). IBD specialist (P< 0.01), doctoral degree (P= 0.02), and regular participation in IBD multidisciplinary meetings (P= 0.01) were associated with higher scores. Most respondents (90.7%) agreed on the importance of histology in IBD. While 54.6% of Australians perceived the role of histology as established, only 37.0% of Asians respondents considered this similarly (P= 0.02). Histological activity alone minimally influences treatment escalation in patients with endoscopic remission, but achieving combined histo-endoscopic remission often leads to therapy de-escalation. Although gastroenterologists in the Asia-Pacific region are aware of the role of histology in IBD, their knowledge remains limited, and its clinical utility is not widely adopted. There is a need to promote the routine use of standardized histological assessment in IBD practice.

Protective Role of Selenium-Binding Protein 1 (SELENBP1) in Patients with Ulcerative Colitis

Background: The expression of selenium-binding protein 1 (SELENBP1), a molecule responsible for the absorption of selenium in the colon, is crucial for its immunoregulatory effect, but this phenomenon has not been studied in patients with UC. The present study aimed to determine the clinical outcome of SELENBP1 expression in colonic tissue from patients with UC. Methods: The relative mRNA expression of SELENBP1 was analyzed in 34 patients with UC and 20 controls. Statistical analyses were performed with SPSS 19. Results: SELENBP1 gene expression was significantly lower in patients with active UC than those with UC in remission (p = 0.003) and within the controls (p = 0.04). Overexpression of the SELENBP1 gene was associated with a more benign clinical course characterized by initial activity and more than two years of prolonged remission (OR 23.7, p = 0.003) and an intermittent clinical course (OR 47.5, p = 0.001), mild histological activity (OR 0.11; 95% CI: 1.00–1.41, p = 0.05) and severe histological activity (OR 0.08, 95% CI: 0.008–0.866, p = 0.02). SELENBP1-positive cells were found mainly in the submucosa’s inflammatory infiltrate and muscular and adventitia’s internal layers from patients with active UC compared to those in the control group (p ≤ 0.001). Conclusions: The upregulation of SELENBP1 was associated with a benign clinical course of UC. This is the first report suggesting the immunoregulatory role of SELENBP1 in patients with UC.

Oxidative Status and Lipid Metabolism Analytes in Dogs with Mast Cell Tumors: A Preliminary Study

Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1–3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm2 (&gt;23 or ≤23), and KIT pattern (I, II–III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs.

Development of an automated tool for the estimation of histological remission in ulcerative colitis using single wavelength endoscopy technology.

Ulcerative colitis (UC) management employs a strategy targeting histological and endoscopic remission. Correlation of white-light endoscopy (WLE) scores with histological activity is limited. Single-wavelength endoscopy (SWE) addressing microvascular changes reflecting histological disease activity, may better assess histological remission. Our goal was to assess the accuracy of a computer-aided diagnosis (CAD) system for histological activity estimation in UC, based on either WLE or SWE. We collected 6926 sets of corresponding WLE and SWE frames in 112 patients with UC, using a prototype endoscopic system enabling both imaging methods (FUJIFILM, Tokyo, Japan). Histological remission (Geboes score ≤2B.0) assessed at the location of imaging was annotated for all frames and separate WLE-CAD and SWE-CAD models were trained using deep learning for automated detection of histological remission with either imaging modality. Initial training of both models on the same subset of 42 patients, resulted in SWE-CAD outperforming WLE-CAD with a mean sensitivity of 88.0% vs 73.9% (p < 0.001), a mean specificity of 71.7% vs 65.6% (p=0.45), and a diagnostic accuracy of 83.3% vs 67.5% (p<0.005), respectively. Further training of the SWE-CAD model on the entire dataset of 112 patients resulted in SWE-CAD achieving a 95.2% accuracy, 96.4% sensitivity, and 92.9% specificity on a section level. By utilizing automated CAD based on non-magnifying SWE for enhanced capillary visibility versus WLE, histological remission was detected with 95.2% diagnostic accuracy in patients with UC, offering stable objectivity and helping to exclude inter-reader variability.

Effects of kelp meal (Laminaria japonica) on the growth, nutrition, and intestinal health of the largemouth bass (Micropterus salmoides)

Macroalgae are both highly productive and rich in bioactive molecules that have been shown to enhance growth and health of fish. Feed with high starch levels affects the health of fish. This study was conducted to investigate the effects of replacing partial starch with kelp (Laminaria japonica) meal (KM) on the growth performance, nutrient composition, and intestinal microbiota of largemouth bass (Micropterus salmoides, LMB). LMB (initial weight 13.00 ± 0.02 g) were fed three diets containing 0 % (K0), 5 % (K5), and 9 % (K9) kelp meal for 8 weeks. The results showed that with the addition of KM, growth performance and feed intake increased significantly, while hepatosomatic index decreased significantly. The whole body and muscle crude protein contents were significantly increased with the addition of KM. Liver catalase activity was significantly increased in K9, while serum malondialdehyde levels declined accordingly. Serum triglyceride, aspartate aminotransferase and alanine aminotransferase levels were significantly lower in K5 than in K0, suggesting that the addition of KM contributed to healthy liver function. The addition of KM to the diet significantly improved intestinal histology and amylase activity. In addition, the Chao index of the intestinal microbiome in the K5 group was significantly higher than in the K0 group. The relevant abundance of beneficial bacteria (Cetobacterium) tended to increase and that of pathogenic bacteria (Plesiomonas) tended to decrease with the addition of KM. In conclusion, partial replacement of starch with kelp meal increased growth performance, feed intake, muscle protein content, the antioxidant capacity and improved intestinal structure, as well as healthy intestinal microbiome. Kelp meal may be a beneficial substitute for starch for healthy aquaculture of M. salmoides.

The Nancy Histopathological Index has limited value in predicting clinical outcomes in newly diagnosed pediatric patients with ulcerative colitis.

The Nancy Histological Index (NHI) is used to score histologic disease activity in patients with ulcerative colitis (UC). Our goal was to assess the utility of NHI at diagnosis in predicting clinical outcomes in pediatric patients with UC, in comparison to clinical and endoscopic scores. We retrospectively reviewed data at diagnosis of 106 children with UC (59 [55.7%] females; median age 14.4 [11.2-15.9] years, median Pediatric Ulcerative Colitis Activity Index [PUCAI] 35 [25-55]). During a follow-up of 116 (55-171) weeks, 33 patients (31.1%) required azathioprine therapy, and 32 (30.2%) were escalated to anti-tumor necrosis factor alpha (anti-TNFa). The PUCAI and Mayo endoscopic scores at diagnosis were significantly associated with escalation to anti-TNFa (p = 0.036 and p = 0.02, respectively), but not with initiation of azathioprine or subsequent acute severe colitis (ASC) events. However, the NHI was not associated with subsequent immunomodulators or anti-TNFa therapy (p = 0.42 and p = 0.78, respectively), nor with future ASC events (p = 0.70). In conclusion, the NHI failed to predict clinical outcomes in newly diagnosed pediatric patients with UC.

Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis.

Accurate assessment of disease activity is crucial for effective management and treatment of ulcerative colitis (UC). This study evaluated the correlation between clinical, endoscopic, and histologic measures of disease activity in UC. Clinical, biochemical, endoscopic, and histologic disease activity was studied in 347 patients with UC. Agreements among various histologic classification systems, namely the Geboes Score (GS), Continuous GS, Nancy Index (NI), and Robarts Histopathology Index (RHI), were analyzed. The predictive accuracy of fecal calprotectin (FC) for endoscopic and histologic remission was assessed. We demonstrate a fair to moderate correlation between clinical, endoscopic, and histologic measures of disease activity in UC. There was a robust concordance among GS, Continuous GS, NI, and RHI in distinguishing between patients in histologic remission or activity. The NI detected 75% of patients who met the remission criteria according to the RHI, whereas the RHI identified all patients in remission as defined by the NI. FC levels below 150 μg/g had >70% accuracy in predicting endoscopic remission. FC levels below 150 μg/g showed ≥80% accuracy, and FC levels below 100 μg/g demonstrated ≥ 85% accuracy in predicting histologic remission, regardless of the scoring index applied. Elevated FC levels were associated with both acute and chronic inflammatory infiltrates in biopsy samples. FC is a reliable predictor of histologic remission, with higher accuracy at lower thresholds. The GS, Continuous GS, NI, and RHI demonstrate comparable performance. FC could help stratify patients' need for colonoscopy for the assessment of endoscopic and histologic remission.

Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction-Associated Steatotic Liver Disease After Liver Transplantation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading indication for liver transplantation (LT), but also occurs after LT. The prevalence of de novo MASLD (dnMASLD) after LT, based on both surveillance (svLbx) and indication biopsies (indLbx), is unknown. Furthermore, the impact of the distinct cardiometabolic risk factors on histological disease activity has not been assessed. We aimed to evaluate the prevalence of dnMASLD and the association between the cardiometabolic risk factors and histological disease activity. We performed a retrospective single-center study in a LT cohort with indLbx and svLbx. Patients with NAFLD before LT were excluded. We analyzed 249 patients who underwent either svLbx or indLbx. Forty-eight (19.2%) had either dnMASLD (n = 26/249, 10.4%) or metabolic dysfunction associated steatohepatitis (dnMASH) (n = 22/249, 8.8%). Although dnMASLD/dnMASH was more frequent in indLbx (35.1%, p < 0.01), still 16.5% of patients with svLbx had dnMASLD/dnMASH. While overweight (p < 0.01) and diabetes (p = 0.01) were more frequent in patients with dnMASH, only overweight was associated with histological disease activity in the multivariate analysis. No impact of dnMASLD on the overall survival was observed. While dnMASLD is more frequent in patients with indLBX, it also occurs in 16.5% of patients without signs of graft dysfunction. Overweight has the strongest impact on histological disease activity and should be monitored carefully after LT.

Acceptable daily intake of aspartame aggravates enteritis pathology and systemic inflammation in colitis mouse model.

In this study, a dextran sodium sulfate-induced ulcerative colitis model in C57BL/6 mice was used to explore the effect of acceptable daily intake (ADI) of aspartame on inflammation in colonic tissues. The effects of aspartame on the inflammatory state of the colon in mice were comprehensively evaluated by comparing the body weight, colon length/colon length index, splenic index, disease activity index (DAI) score, histological activity index (HAI) score, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, claudin-3, and occludin, the infiltration characteristics of macrophage and neutrophil and the composition of the gut microbiota in the control group, aspartame group, ulcerative colitis model group, and aspartame + ulcerative colitis group. We demonstrated that, in a mouse model of dextran sulfate-induced ulcerative colitis, ADI of aspartame caused a significant decrease in body weight, colon length/colon length index, DAI scores, and expression levels of the proteins claudin-3 and occludin. Moreover, ADI of aspartame caused an increase in the splenic index, HAI scores, the levels of proinflammatory factors TNF-α, IL-1β, and IL-6 both in intestinal tissue and serum and infiltration of macrophages and neutrophils in colon tissues. These results showed that ADI of aspartame promoted intestinal pathology and systemic inflammation in a mouse model of colitis.

Thyme and Oregano Oil Potential Therapeutics against Malathion Toxicity through Biochemical, Histological, and Cytochrome P450 1A2 Activities in Male Wistar Rats.

The widespread use of malathion may offer several hazards to humans and animals; additionally, many medicinal plants provide what is known as a broad antitoxicity treatment. This study was carried out to investigate hazardous biochemical and histological reactions to MOP and evaluate the effectiveness of TEO and OEO essential oils in restoring normal physiological conditions after MOP exposure by measuring enzyme-specific activity for Cytochrome P450 1A2 (CYP1A2). One hundred and twenty rats were divided into six groups of twenty animals each: (i) C - MOP served as the control group, (ii) C + MOP treated with 5 mg/kg/BW of Malathion-D10, (iii) TEO treated with 100 mg/kg/BW of oregano essential oil, (iv) TEO treated with 100 mg/kg/BW of thyme essential oil, (v) MOP + OEO treated with 5 mg/kg/BW of Malathion-D10 and 100 mg/kg/BW of oregano essential oil, and (vi) MOP + TEO treated with 5 mg/kg/BW of Malathion-D10 and 100 mg/kg/BW of thyme essential oil. The results indicated the protective effects of OEO and TEO against MOP-induced weight loss. Additionally, there was a significant improvement in ALT, AST, and ALK-Ph after being treated with OEO and TEO, either alone or after MOP exposure. Also, treatment with OEO and TEO ameliorated these oxidative stress parameters, indicating their antioxidative properties. A histopathological examination of liver tissues showed reduced hepatocellular damage and improved liver architecture in the OEO and TEO, both alone and in combination with MOP, and protective effects were more pronounced in the TEO-treated groups. However, the results indicated that TEO was more effective than OEO in increasing CYP1A2 expression and alleviating MOP-induced toxicity. Specifically, TEO showed higher protein expression and therapeutic action in reducing liver damage. In conclusion, these findings suggest that OEO and TEO may be potent therapeutic agents against MOP toxicity, offering protective effects by enhancing CYP1A2 activity and mitigating organ damage. Such knowledge would be an important step toward developing potentially unique treatment options for natural antitoxins.

Epithelial neutrophil localization and tight junction Claudin-2 expression are innovative outcome predictors in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is a need to identify outcome predictors. Recently, the role of neutrophils in predicting outcomes in ulcerative colitis (UC) has been highlighted. Furthermore, the impairment of intestinal barrier plays a key role in forecasting disease outcomes in IBD. This observational study aimed to assess the predictive role of neutrophils according to tissue localization and intestinal barrier protein expression in IBD. IBD patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were enrolled. Patients with Mayo Endoscopic Score ≤1 (UC) and Simple Endoscopic Score ≤6 (Crohn's disease) were included. Histological activity was assessed using validated scores. Experienced pathologists evaluated neutrophil localization in the epithelium and lamina propria and immunohistochemical expression of Claudin-2 and junctional adhesion molecule A (JAM-A). Of 60 UC and 76 CD patients, 59.7% had histological activity. 25.8% of patients developed an adverse outcome within 12months. Neutrophils in the epithelium predicted adverse outcomes for UC (hazard ratio [HR] 5.198, p=0.01) and CD (HR 4.377, p=0.03) patients in endoscopic remission. Claudin-2 expression correlated with endoscopic and histological activity and predicted outcomes in UC. Similar results were found for JAM-A in CD despite this protein showing less specificity as a barrier predictor of outcome. This study highlights the potential role of epithelial neutrophil localization and Claudin-2 'leaky gut' expression as tools for predicting IBD outcomes and guiding further patient-tailored therapy.

Anti-factor H autoantibodies in patients with lupus nephritis

IntroductionLupus nephritis (LN) is a disease marked by autoantibodies against complement components. Autoantibodies against negative complement regulator factor H (anti-FH) are prevalent in aHUS, are associated with deletion of factor H-related protein 1 (FHR1) gene, and have overt functional consequences. They are also observed in C3 glomerulopathies. The frequency and relevance of anti-FH in LN are poorly studied. AimThe aim of our investigation was to screen for the presence of anti-FH and FHR1 gene deletion in a cohort of LN patients and to evaluate their association with LN activity. MethodELISA test and Western blot for detection of anti-FH and FHR1 deletion were used, respectively. Patients’ clinical and laboratory parameters regarding anti-FH role were processed by statistical analysis. ResultsAnti-FH were found at low level in a small number of LN patients – 11.7% (7/60) and were not associated with deletion of FHR1. Anti-FH did not correlate with ANA titers, anti-dsDNA, C3/C4 hypocomplementemia, eGFR, proteinuria, or active urinary sediment in LN patients. A weak correlation was found between anti-FH and anti-C3 levels. Anti-FH were linked with endocapillary proliferation and histological activity index. Four anti-FH positive patients had severe to moderate LN as per the BILAG renal score. ConclusionsAnti-FH autoantibodies are an accessory finding in LN and are more likely to manifest during the active phase of the disease. Due to their low frequency and plasma levels, they do not seem suitable for routine laboratory investigation in patients with LN.

Noninvasive Assessment of the Presence or Absence of Histologic Activity in Kidney Biopsies from Patients with Lupus Nephritis

Noninvasive Assessment of the Presence or Absence of Histologic Activity in Kidney Biopsies from Patients with Lupus Nephritis

Health State Utility is Substantially Reduced With an Increasing Burden of Patient-Reported Symptoms in Eosinophilic Esophagitis.

We aimed to estimate health state utility in eosinophilic esophagitis (EoE) by histologic activity and assess association with disease parameters. In this cross-sectional study, we measured health state utility by time trade-off and assessed symptoms with the EoE Symptom Activity Index. In 51 adults with EoE, the mean utility was 0.91 (95% CI 0.86, 0.95). Utility was numerically worse in patients with dilation or a smaller stricture diameter. With each ten-point improvement in EoE Symptom Activity Index, utility increased by 0.03 (95% CI 0.01, 0.05). EoE is associated with reduced health state utility, with symptoms most strongly predicting valuation.

Associated Factors for Liver Fibrosis and Histological Activity Index in Treatment-Naïve HBeAg-Positive Chronic Hepatitis B Infection: Insights from a Retrospective Analysis.

The study aimed to identify predictors of advanced fibrosis score and histological activity index (HAI) in HBeAg-positive patients to facilitate early disease detection and reduce the need for invasive biopsies. The single-center retrospective study included treatment-naïve HBeAg-positive chronic hepatitis B (CHB) patients. Patients with HAI ≥6 and/or fibrosis ≥2 were considered to have significant liver damage. Independent determinants were identified by univariate and multivariate logistic regression analysis. Cut-off values for variables were determined by receiver operating characteristics (ROCs) curve analysis. The study enrolled a cohort of 66 patients, with 51.5% male and a median age of 26 (22.7-34.2) years. In assessing necroinflammation, no significant differences were observed in age and gender between patients with HAI <6 and HAI ≥6. However, patients with HAI ≥6 exhibited higher aspartate aminotransferase (AST) levels compared to those with HAI <6. Furthermore, lower albumin levels and platelet (PLT) counts, along with higher fibrosis-4 (FIB-4) scores, were associated with HAI ≥6. In the evaluation of fibrosis, while gender distribution did not differ significantly, patients with fibrosis grade ≥2 were older and had higher HAI scores, HAI ≥6 ratios, and FIB-4 scores compared to those with fibrosis grade <2. Multivariate analysis identified albumin as a significant predictor for both HAI ≥6 and fibrosis grade ≥2. The area under ROC (AUROC) values of albumin for predicting HAI ≥6 and fibrosis ≥2 were 0.696 and 0.698, respectively, indicating moderate predictive ability. Albumin was found to be an independent predictor of liver damage in HBeAg-positive CHB patients. The fact that the optimal threshold values detected for both HAI ≥6 and fibrosis ≥2 in this patient group were close to normal values suggests that clinicians should be more cautious in monitoring albumin levels and other pre-defined parameters to avoid delays in diagnosis.

Assessing Biomarkers of Porcine Kidneys under Normothermic Machine Perfusion-Can We Gain Insight into a Marginal Organ?

To identify potentially transplantable organs in a pool of marginal kidneys, 33 porcine slaughterhouse kidneys were perfused for 4 h with whole blood. During the normothermic perfusion, plasma, urine, and tissue samples were taken. Several biomarkers for tubule injury, endothelial activation, and inflammatory response were evaluated for a potential correlation with macroscopic appearance, histology, and filtration activity. Generally, biomarker levels increased during perfusion. TLR-4, EDN-1, and NGAL were not associated with any classification. In contrast, a steeper increase in NAG and IL-6 in plasma correlated with a poor macroscopic appearance at 4 h, indicating a higher inflammatory response in the kidneys with worse macroscopy early on, potentially due to more damage at the tubules. Although long-term effects on the graft could not be assessed in this setting, early observation under machine perfusion with whole blood was feasible. It allowed the assessment of kidneys under conditions comparable to reperfusion. This setting could give surgeons further insight into the quality of marginal kidneys and an opportunity to pre-treat them.

A nationwide cohort study of inflammatory bowel disease, histological activity and fracture risk.

Individuals with inflammatory bowel disease (IBD) are at increased risk of fracture. It is unclear if this risk varies by recent histological activity. To determine the fracture risk in IBD during periods with and without histological inflammation. We studied a nationwide cohort of 54,591 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies. Fractures were identified by inpatient and hospital-based outpatient diagnoses. We derived Cox regression estimated hazard ratios (HRs) for fracture during 12 months following a histological inflammation (vs. histological remission) record after adjusting for socio-demographics, comorbidities, IBD duration, IBD-related surgery and hospitalization. We adjusted sensitivity analyses for medical IBD treatment including corticosteroids. Mean age of patients was 44.0 (SD = 18.3) and 45.5 (SD = 17.1) years at biopsy with histological inflammation and remission, respectively. For histological inflammation, there were 1.37 (95% CI 1.29-1.46) fractures per 100 years' follow-up versus 1.31 (95% CI 1.19-1.44) for remission (adjusted [a]HR 1.12; 95% CI 1.00-1.26; p = 0.04). HRs were similar with histological inflammation of Crohn's disease (1.11; 95% CI 0.91-1.36) and ulcerative colitis (1.18; 95% CI 1.02-1.36). Estimates were consistent across age groups. An overall small excess risk of any fracture remained after accounting for corticosteroids. A more prominently raised fracture risk was observed in corticosteroid-naïve IBD patients with histological inflammation versus histological remission (aHR 1.41; 95% CI 1.07-1.85). The aHR of hip fracture following histological inflammation was 1.29 (95% CI 0.87-1.92). Histological inflammation in IBD predicted a small increase in short-term fracture risk. Measures to reduce disease activity may reduce fracture risk in IBD.