Grade Inflammation Research Articles

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage

BackgroundThe timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years.MethodsA retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system.ResultsThe liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels.ConclusionsA considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

Clinicopathological Significance of Tumor Budding in Breast Carcinoma.

Tumour budding Tuberculosis is a new prognostic marker whose role in breast cancer is still under evaluation. Our aim was to study Tuberculosis in breast carcinoma and correlate it with other prognostic markers. A descriptive cross-sectional study was conducted over 2 years on 75 invasive breast carcinoma specimens and biopsies. Hematoxylin and Eosin sections were examined for tumour grade, stage, molecular subtype, necrosis, lymphovascular invasion inflammation and counting of Tuberculosis. Lymph node metastasis was studied only in mastectomies. TB was defined as a cluster of 1-5 tumour cells and counted in 10 consecutive 400X fields. The cut-off for high grade TB was taken as ?10 per 10 HPFs. Immunohistochemical staining was done for molecular subtyping and differentiating Tuberculosis from mimickers. Statistical analysis was done using chi square test and Fischer's exact test. Tuberculosis was present in 66/75 cases; 53% (n=35) were high grade. Among these, majority were of T2 (74%, n= 26), grade 2 (52%, n= 18), luminal A (34%, n= 12), had 3+ inflammation (46%, n= 16) and peripheral tumour buds (54%). Necrosis and lymphovascular invasion were absent in 77% and 71%, respectively. Lymph node metastasis was seen in 63% (n= 25/28) cases. Statistically significant association (p= 0.016) was observed between degree of inflammation and Tuberculosis grade. However, no significant association was observed between TB and other prognostic markers of breast carcinoma. In our study, association of Tuberculosis with different prognostic markers was appreciated but was not statistically significant. However, it highlights need for standardization of Tuberculosis reporting.

CT-derived body composition: Differential association with disease, age and inflammation in a retrospective cohort study.

Low skeletal muscle mass and density, as assessed by CT-body composition (CT-BC), are recognised to have prognostic value in non-cancer and cancer patients. The aim of the present study was to compare CT-BC parameters between non-cancer (abdominal aortic aneurysm, AAA) and cancer (colorectal cancer, CRC) patients. Two retrospective multicentre cohorts were compared. Thresholds of visceral fat area (VFA, Doyle), skeletal fat index (SFI, Ebadi), skeletal muscle index (SMI, Martin), and skeletal muscle density (SMD, Martin) were applied to these cohorts and compared. The systemic inflammatory response (SIR) was measured by the systemic inflammatory grade (SIG). 1695 patients were included; 759 patients with AAA and 936 patients with CRC. Low SMD (33% vs. 66%, p <0.001) was more prevalent in the CRC cohort. Low SMI prevalence was similar in both cohorts (51% vs. 51%, p = 0.80). Compared with the AAA cohort, the CRC cohort had a higher prevalence of raised SIG (p <0.001). Increasing age (OR 1.54, 95% CI 1.38-1.72, p < 0.001) and elevated SIG (OR 1.23, 95% CI 1.09-1.40, p = 0.001) were independently associated with increased odds of low SMI. Increasing age (OR 1.90, 95% CI 1.66-2.17, p < 0.001) CRC diagnosis (OR 5.89, 95% CI 4.55-7.62, p < 0.001), ASA > 2 (OR 1.37, 95% CI 1.08-1.73, p = 0.01), and elevated SIG (OR 1.19, 95% CI 1.03-1.37, p = 0.02) were independently associated with increased odds of low SMD. Increasing age and systemic inflammation appear to be important determinants of loss of skeletal muscle mass and quality irrespective of disease.

Novel bioactive nanospheres show effective antibacterial effect against multiple endodontic pathogens

AimThe current study evaluated the antibacterial activity of a newly developed quaternary ammonium polymethacrylate (QAPM)-containing bioactive glasses (BGs) via a two-step method by our group, namely BGs-HAEMB, and explored its cytotoxicity and biocompatibility. MethodsThe antibacterial effects of the BGs-HAEMB against planktonic bacteria, bacterial biofilm formation, and experimental root canal biofilms of persistent pathogens (Enterococcus faecalis, Streptococcus sanguis and Porphyromonas endodontalis) associated with endodontic infection were evaluated in vitro by agar diffusion tests, direct contact tests and live/dead staining. The cytotoxicity and biocompatibility of BGs-HAEMB were evaluated by CCK-8 assays in vitro and a skin implantation model in vivo. ResultsCompared to three clinically used endodontic sealers (Endofill, AH Plus, and iRoot SP), BGs-HAEMB exhibited the relatively strongest antibacterial effect against E. faecalis, S. sanguis and P. endodontalis after sitting for 14 and 28 days (P < 0.01). SEM images and CLSM images also showed that for each tested bacteria, BGs-HAEMB killed the most microorganism among all the experimental groups, regardless of treatment for 7 days or 28 days (P < 0.05). Besides, the BGs-HAEMB-treated groups showed a relatively low cytotoxicity (RGRs ranging from 88.6% to 102.9%) after 1, 3, and 7 days of exposure. Meanwhile, after 28 days of implantation, the inflammatory grade in BGs-HAEMB treated group was assessed as Grade I, in which the average numbers of inflammatory cells (6.7 ± 2.1) were less than 25. ConclusionsBGs-HAEMB exerted a long-term and stable antibacterial effect. The remarkable biocompatibility of BGs-HAEMB in vitro and in vivo confirmed its possible clinical application as a potential alternative in the development of the next generation of endodontic sealers.

Quantitative digital pathology enables automated and quantitative assessment of inflammatory activity in patients with autoimmune hepatitis

BackgroundChronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. MethodsWhole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). ResultsID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. ConclusionQuantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.

Hip and pelvis region MRI reference image atlas for scoring inflammation in peripheral joints and entheses according to the OMERACT-MRI WIPE scoring system in patients with spondyloarthritis

ObjectiveTo develop a reference image atlas for scoring the hip/pelvis region according to the OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (MRI-WIPE). MethodsWe collected image examples of each pathology, location and grade, discussed them at web-based, interactive meetings and, finally, selected reference images by consensus. ResultsReference images for each grade and location of osteitis, synovitis and soft tissue inflammation are provided, as are definitions, reader rules and recommended MRI-sequences. ConclusionA reference image atlas was created to guide scoring whole-body MRIs for arthritis and enthesitis in the hip/pelvis region in spondyloarthritis/psoriatic arthritis clinical trials and cohorts.

P440 Myenteric plexitis and active inflammation at surgical margins are high-risk predictors for postoperative clinical recurrence of Crohn’s disease

Abstract Background Preventing postoperative recurrence is an important issue for clinical management of Crohn’s disease (CD). Identification of practical risk factors and an effective prophylactic treatment strategy has been desired for the prevention of postoperative recurrence. Although some of the clinical risk factors have been applied to select candidates for prophylactic treatments, these attempts have not fully prevented postoperative recurrence. In this study, we investigate the histological features at resected margins which predicted postoperative recurrence, and whether the initiation of prophylactic treatments could prevent postoperative recurrence in these cases. Methods We retrospectively reviewed the clinical recurrence rate in CD patients who underwent intestinal resection between January 2019 and December 2021. Clinical recurrence was defined by combination of serological, radiographic, and endoscopic findings or treatment escalation. To assess the histological risk factors for postoperative recurrence, resection margins of the surgical specimens were evaluated for the presence of myenteric plexitis, granulomas, and active inflammation. Each histological feature was evaluated from Grade 0 to 3. We also examined the ability of prophylactic treatments to prevent postoperative recurrence stratified with histological findings related to clinical recurrence rates. Results Of the 141 patients included in this study, 61.9% had plexitis (grade 3:Inflammatory cells at myenteric plexus, 10&amp;gt;HPF) at the proximal margin and 13.5% had active inflammation (grade 3: erosion or ulcer) at the distal margin. Log rank test identified the presence of plexitis (Grade3) (HR:1.84, 95%CI [1.05-3.22], p=0.029) at the proximal margin and active inflammation (Grade3) at the distal margin (HR:1.29, 95%CI [1.05-1.58], p=0.012) as possible risks of clinical recurrence (Figure). Multivariate analysis confirmed that the presence of plexitis (Grade3) at the proximal margin (HR 1.82, 95% CI 1.04-3.21, P=0.038) and active inflammation (Grade 3) at the distal margin (HR 2.31, 95% CI 1.18-4.46, P=0.013) were associated with postoperative clinical recurrence. Prophylactic use of immunomodulators (IM) and biologics did not show a significant reduction of clinical recurrence compared to treatment without IM and/or biologics in patient with histological risk factors (Table). Conclusion Our results indicate that the presence of plexitis in the proximal margin and active inflammation in the distal margin of the resected intestine are risk factors for postoperative recurrence. In these cases, initiation of prophylactic treatments with biologics and/or IM may not prevent the clinical recurrence.

Protozoan-Derived Cytokine-Transgenic Macrophages Reverse Hepatic Fibrosis.

Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage-based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor-transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN-γ-treated macrophages, making macrophage-based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF-κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.

Reporting of Facet Joint Inflammation in Lumbar Spine MRI Studies in Patients With Low Back Pain.

Retrospective. We aimed to assess the frequency of facet joint inflammatory features noted in routine radiology reports of lumbar spine magnetic resonance imaging (MRI) studies among patients with chronic low back pain. Facet joint arthropathy is one of the most common causes of chronic low back pain. It may encompass various inflammatory imaging characteristics, such as facet joint effusion, bone marrow edema, and soft tissue edema. The extent to which radiology reports mention inflammatory features of the lumbar facet joints and the accuracy of these reports have not been investigated. The authors performed a chart review on 49 subjects with previous facet-related interventions ( i.e . medial branch blocks or intra-articular facet joint injection) and MRI available in the medical record. One senior musculoskeletal radiologist and a musculoskeletal radiology fellow graded the inflammatory features using a published facet joint inflammation grading system [Gold Standard (GS)]. The authors identified the inflammatory markers mentioned in the radiology reports and calculated the sensitivity and positive predictive value of the radiology reports compared with GS readings. Compared with the GS, the sensitivity of radiology reports for facet joint effusion, bone marrow, and soft tissue edema ranged from 6% to 22%, and the positive predictive value ranged from 25% to 100%. L4/5 had the highest number of cases with inflammatory features noted on the reports. Inflammatory findings, such as facet joint effusion, bone marrow edema, and soft tissue edema, are not commonly identified in radiology reports. Further investigations are needed to determine the clinical importance of MRI-detected lumbar facet joint inflammatory features as a potential mechanism of nociception and as a predictor of outcomes following injections or other therapies.

Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients.

We examine how well ozone/oxygen gas therapy treats chronic hepatitis C patients with varying degrees of liver fibrosis. Also to study the effect of giving multiple anti-oxidants with the ozone/oxygen gas mixture, to see if this addition would have any additive or synergistic effect. Two hundred and twenty three patients with chronic hepatitis C. Liver biopsies were carried out at after 12weeks of administering an ozone/oxygen gas mixture. The mean stage of fibrosis decreased from 1.98 to 1.41 and the mean grade of inflammation decreased from 10.08 to 7.94, both with a p value less than 0.001. After 12weeks of treatment, mean PCR values increased. No single significant complication was recorded in a total of >9,000 settings of ozone therapy. Ozone oxygen gas mixture is safe and effective in treatment of hepatic fibrosis due to chronic viral hepatitis C.

Mixed Eimeria and Cryptosporidium infection and its effects on pathology and clinical outcomes in juvenile Asian seabass (Lates calcarifer) cultured in Thailand.

Coccidiosis is an important disease in juvenile fish because of severe intestinal injury during infection. We first reported the mixed infection of intestinal coccidia and its association with health status and pathological findings in juvenile Asian seabass (Lates calcarifer) cultured in Thailand. Two groups of Asian seabass, 60-day fish and 90-day fish, were sampled to investigate prevalence and coccidian infection intensity using morphological characterization and PCR. Phylogenetic analysis of 18S rRNA gene amplified from the intestines revealed Eimeria sp. and Cryptosporidium sp. infection. The prevalence of Eimeria sp. and Cryptosporidium sp. in sampled fish was 100%. Clinical outcomes assessed, using health assessment index (HAI) scoring and semi-quantitative grading of intestinal lesions and inflammation, demonstrated that all fish developed variety of pathology and clinical illness; however, infection intensity in 60-day fish was significantly higher (p < .05) than 90-day fish. The HAI score of 60-day fish was poorer than 90-day fish, which correlated to a high infection intensity (r = .397), analysed by Pearson correlation coefficient. Overproduction of intestinal oxidants contributing to mucosal injury was examined by nitrotyrosine expression. The high production of reactive nitrogen species indicated severe inflammatory response, and intestinal injuries occurred mainly in the 60-day fish.

Evaluation of the effect of ozonated water in treatment of denture stomatitis associated with removable prosthetics

BackgroundOzone therapy is highly demarcated in the dental field owing to its efficient antimicrobial action in its gaseous and aqueous forms. One of the most common difficulties accompanied by utilizing dentures is denture stomatitis (DS) which is principally triggered by Candida albicans (C. albicans).ObjectivesAssessing and comparing the impact of ozonated water versus chlorhexidine mouthwash on healing of intra-oral inflammations associated with complete dentures.Subjects and methodsFifty middle-aged male completely edentulous patients wearing complete dentures were screened for the possibility of having any accompanied DS and/or C. albicans. Patients were randomly distributed into two groups. Group I patients were treated with chlorhexidine mouthwash and oral hygiene measures (OHM); while, Group II patients received ozonated water as a mouthwash and OHM. Evaluation of inflammation, pain grade, and oral Candidiasis count took place for all patients in all visits; from the initial day of treatment and after 7, 14, and 30 days.ResultsThe inflammation’s area and severity together with pain grade showed a significant decrease with time when using both chlorhexidine mouthwash and ozonated water. Comparing the use of chlorhexidine mouthwash and ozonated water together showed insignificant differences. Regarding the Candida forming units (CFU) there was a significant decrease in the colonies number over time, but with insignificant difference between the two groups.ConclusionsOzonated water showed favorable results in reducing the area and severity of inflammation and pain grade. Ozonated water has an antifungal effect and can be used as an alternative mouth rinse in treating denture stomatitis.

Allogeneic serum eye drops Sjogren syndrome‐related dry eye disease: Clinical evaluation of the ocular surface and in vivo confocal microscopy of the cornea

Aims/Purpose: To evaluate the symptomatic and clinical efficacy and in vivo confocal microscopy (IVCM) changes of the cornea after allogeneic serum eye drop therapy in patients with Sjögren's syndrome (SS)‐related Dry Eye Disease (DED).Methods: In this prospective clinical study 15 patients (30 eyes) with primary or secondary SS‐related DED were evaluated for Ocular Surface Disease Index (OSDI) questionnaire, ocular inflammation grade, Schirmer's test, tear film break‐up time (TBUT), corneal and conjunctival staining, and in vivo confocal microscopy (IVCM) analysis.Results: The average age of patients was 63.87 ± 9.18 years. The patients received treatment for a mean of 81.13 ± 56.84 days. The difference between before and after treatment with allogeneic serum eye drop therapy was statistically significant for OSDI parameters (p = 0.001), ocular inflammation (p = 0.004), TBUT (p = 0.007), Oxford Staining Scale (p = 0.007), Van Bijsterveld score (p = 0.006), basal epithelium density (p = 0.005), intermediate epithelium density (p = 0.041), Corneal Nerve Branch Density (CNBD) (p = 0.040), Beadings density (p = 0.047) and Fibre Tortuosity (p = 0.002).Conclusions: Allogeneic SEDs treatment in SS related DED patients, showed great results in terms of improvement in dry eye symptoms, clinical signs and IVCM changes. Further studies that aim at propagating and standardizing its production with clear international guidelines are needed.

Electron Microscopic Studying the Impact of Ozone on Chronic Hepatitis C Patients as Antifibrotic

We aimed to evaluate the histopathological and ultrastructural changes detected by light and electron microscopy, induced in patients having chronic hepatitis C receiving ozone/oxygen gas treatment. Twenty six patients with chronic hepatitis C who were at different stages of liver fibrosis, non-responders to interferon plus ribavirin therapy (n = 9), had contraindications (n = 2), or were not compliant (n = 15) were included. At baseline and 12 weeks after administering the ozone/oxygen gas mixture, liver biopsies were carried out utilizing both the major rectal insufflations and auto-hemotherapy along with clinical evaluation, kidney and liver function assessments, liver biopsies and abdominal ultrasonography. Before and 12 weeks after the treatment of ozone, quantitative PCR was performed. Two pathologists evaluated the histological activity index (HAI) using Ishak's score while working in blind settings, taking into account the degree of inflammation and the stage of fibrosis. Electron microscopy was done for all cases before and after treatment. Significant improvements in liver enzymes in hepatic fibrosis and inflammatory activity based on Ishak scoring system were detected. The mean grade of inflammation dropped from 10.3 to 8.4 and the mean stage of fibrosis dropped from 2.3 to 2.0 both with P value &lt; 0.001 and &lt; 0.05 respectively. Mean PCR values showed significant increase after 12 weeks of treatment from 17059 to 218736 with P value &lt;0.05. As regards electron microscopy findings, the ultra-structural manifestations of HCV infection were disclosed in liver specimens exposed or not to ozone treatment. Stellate cells were often encountered in unexposed samples to ozone, meanwhile they disappeared after ozone exposure. Apoptotic hepatocytes which were frequently encountered before treatment are rarely seen in specimens after treatment with ozone. Signs of cellular regeneration in the form of binucleated cells, RER enveloping mitochondria, hepatocyte progenitors insinuating between the cells at the sinusoid pole are seen after treatment. Circulating inflammatory cells in the sinusoids and infilterating the lobule were decreased after treatment. Peroxisomes were increased after exposure to ozone with longitudinal orientation of mitochondrial cristae thus increasing the antioxidative activity of hepatocytes. No single significant complication was recorded in a total of &gt;1000 settings of ozone therapy. In conclusion, ozone oxygen gas mixture is a direct anti-fibrotic and anti-inflammatory agent in treatment of chronic hepatitis C patients without improving viral PCR as evidenced by histopathology, electron microscopy and quantitative PCR.

Microscopic Colitis: A Diagnostic Challenge in Patients with Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS) is one of the most frequently diagnosed gastrointestinal disease with a prevalence of 4.1% in the general population. It is diagnosed using the Rome IV criteria. Microscopic colitis (MC), collagenous/lymphocytic colitis is a cause of chronic, watery, non-bloody diarrhea. It is a real challenge to diagnose MC in patients with IBS. The aims of the study were to determine the prevalence of MC in patients initially diagnosed with IBS, as well as to correlate fecal calprotectin levels with the endoscopic findings and microscopic inflammation in MC. This is a retrospective study conducted in a single tertiary center with over 89 IBS patients for a period of 4 years. The patients included were patients diagnosed with IBS predominant diarrhea (IBS-D) and mixed IBS (IBS-M) using the Rome IV criteria. Total colonoscopy was performed in these patients, multiple biopsies being taken and calprotectin levels were measured. Out of a total of 89 IBS-D patients, 58 patients (65.2%) had no microscopic lesions, 12 patients (13.5%) had diverticular disease, 9 patients (10.1%) had non-specific chronic inflammation of the colon mucosa and 10 patients (11.2%) were diagnosed with MC. The calprotectin levels ranged from 49 μg/g to 213 μg/g. Of a total of 10 patients diagnosed with MC, 6 (60%) of them had calprotectin levels <100 μg/g and 4 (40%) had calprotectin levels >100 μg/g. The fecal calprotectin levels were higher in patients diagnosed with MC compared to those who had no microscopic lesions at the histological exam and it was also correlated with the grade of colonic microscopic inflammation. Microscopic colitis is less familiar to physicians and can be clinically misdiagnosed as IBS-D. An early and correct diagnosis is important for an accurate therapy.

Imaging-based diagnosis and classification of radioactive iodine-induced sialadenitis.

To establish an inflammation grading system for radioactive iodine-induced sialadenitis (RAIS) based on spiral computed tomography (CT), ultrasonography and sialography. In all, 120 RAIS patients (18 males and 102 females) were retrospectively included. Spiral CT, ultrasonography and sialography appearances were analysed and categorized as follows: grade I, approximately normal or mild sialadenitis; grade II, moderate sialadenitis; and grade III, severe sialadenitis. Adenitis severity was analysed relative to sex, age, RAI treatment sessions and cumulative doses. Spiral CT showed heterogeneous (78.9%) and atrophic changes (36.8%) in the parotid glands (PGs) and duct ectasia (24.8%) in the submandibular glands (SMGs). Ultrasonography showed heterogeneous echogenicity (54.3%) and diminished gland size (30.2%) in PGs and duct ectasia in SMGs (34.7%). Sialography showed duct obliteration in 25.3% PGs and 3.2% SMGs. Statistical analysis showed good consistency among the three imaging grading results. The incidence and severity of PG lesions were significantly higher than that of SMGs (p < 0.001). As for PGs, adenitis severity was associated with both treatment sessions and cumulative doses; but in SMGs, disease severity was only related to treatment sessions. A grading system for severity of RAIS was established based on spiral CT, ultrasonography and sialography appearances.

Associations of Wnt5a expression with liver injury in chronic hepatitis B virus infection

BackgroundAberrant Wnt5a expression contributes to immunity, inflammation and tissue damage. However, it remains unknown whether Wnt5a is associated with liver injury in chronic hepatitis B virus (HBV) infection. We aimed to explore the potential role of Wnt5a expression in liver injury caused by chronic HBV infection.MethodsWnt5a mRNA levels in peripheral blood mononuclear cells (PBMCs) were analyzed in 31 acute-on-chronic hepatitis B liver failure (ACHBLF) patients, 82 chronic hepatitis B (CHB) patients, and 20 healthy controls using quantitative real-time polymerase chain reaction. Intrahepatic Wnt5a protein expression from 32 chronic HBV infection patients and 6 normal controls was evaluated by immunohistochemical staining.ResultsWnt5a mRNA expression was increased in CHB patients and ACHBLF patients compared to healthy controls and correlated positively with liver injury markers. Additionally, there was a significant correlation between Wnt5a mRNA expression and HBV DNA load in all patients and CHB patients but not in ACHBLF patients. Furthermore, intrahepatic Wnt5a protein expression was elevated in chronic HBV infection patients compared to that in normal controls. Moreover, chronic HBV infection patients with higher hepatic inflammatory grades had increased intrahepatic Wnt5a protein expression compared with lower hepatic inflammatory grades. In addition, the cut-off value of 12.59 for Wnt5a mRNA level was a strong indicator in predicting ACHBLF in CHB patients.ConclusionsWe found that Wnt5a expression was associated with liver injury in chronic HBV infection patients. Wnt5a might be involved in exacerbation of chronic HBV infection.

Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

Background and objectiveNoninvasive non-alcoholic steatohepatitis (NASH) assessment is a clinical challenge to the management of non-alcoholic fatty liver disease. We aim to develop diagnostic models based on sequential ultrasound molecular imaging (USMI) for the noninvasive identification of NASH in mouse models. MethodsAnimal experiments were approved by the Animal Ethics Committee of South China Agricultural University. Forty-nine C57BL/6 mice were divided into normal control, non-alcoholic fatty liver, NASH, and hepatitis groups. Sequential USMI was implemented using CD36-targeted microbubbles (MBs-CD36) and intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles (MBs-ICAM-1) to visualize hepatic steatosis and inflammation. The targeting signal of USMI was quantified as the normalized intensity difference (NID) with the destruction-replenishment method. Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBs-ICAM-1 and pathological inflammation score. Finally, diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis. ResultsMBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice. NID-MBs-CD36 values increased with the progression of steatosis, while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation. A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade (rs = 0.9078, P < 0.0001) and between NID-MBs-ICAM-1 and pathological inflammation grade (rs = 0.9071, P < 0.0001). Among various sequential USMI-based diagnostic models, the serial testing model showed high diagnostic performance in detecting NASH, with 95% sensitivity, 97% specificity, 95% positive predictive values, 97% negative predictive values, and 96% accuracy. ConclusionsSequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation. Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.

Plasma oxylipin profile of postpartum dairy cows categorized into different systemic inflammatory grades in the first week after parturition

Oxygenated polyunsaturated fatty acids (oxylipins) are important mediators of inflammation ranging from pro- to anti-inflammatory actions. Research investigating differences in the oxylipin profile of dairy cows suffering from different degrees of systemic inflammation in the early postpartum period is lacking and can help advance knowledge on potential mechanisms leading to excessive inflammation. The objective of this preliminary study was to evaluate the plasma oxylipin profile of cows classified in 1 of 4 systemic inflammation categories based on plasma haptoglobin (Hp) concentrations assessed on days in milk (DIM) 1, 2, 3, 4, 5, and 7, in addition to the presence or absence of metritis within 10 DIM, and of cows without any clinical diseases within 21 DIM. Groups were classified as follows: (1) cows with a peak Hp concentration ≤3 DIM (EarlyHp) and diagnosed with metritis; (2) cows with a peak Hp concentration 3 < DIM ≤7 (LateHp) and diagnosed with metritis; (3) cows suffering from persistently elevated Hp concentrations assessed on DIM 4 and 7 while remaining apparently healthy during the first 21 DIM (PersistentHp); and (4) apparently healthy cows not suffering from persistently elevated Hp concentrations (LowHp). Six cows from each category were randomly selected from a plasma bank of a parent cohort study including 380 multiparous cows. Plasma samples on DIM 1 and 2, 3 and 4, and 5 and 7 were proportionally pooled to create 3 samples per cow for lipidomic analysis (i.e., pool 1 = DIM 1 and 2; pool 2 = DIM 3 and 4; pool 3: DIM 5 and 7). Statistical analyses were performed using SAS v9.4 (SAS Institute Inc.) and least squares means adjusted for multiple comparisons using the Tukey-Kramer test. Comparisons for EarlyHp and LateHp were only performed on pooled samples from DIM 1 and 2 (i.e., before metritis diagnosis). EarlyHp cows had decreased concentrations of 9(S)-HOTrE compared with LowHp cows of DIM 1-2 pooled samples. LateHp cows had decreased concentrations of 9(10)-DiHOME compared with LowHp cows. Next, we sought to investigate whether cows classified as PersistentHp had time-dependent differences in oxylipin profile versus LowHp cows. PersistentHp cows had decreased concentrations of 19(R)-HETE compared with LowHp cows in a time-dependent manner (only in pooled samples from DIM 5 and 7). Our results identified oxylipins of interest that warrant further investigation to elucidate their in vitro and in vivo functions in the postpartum inflammatory process of dairy cows.

BIOM-36. PREOPERATIVE IMMUNE AND INFLAMMATORY FACTORS IN PERIPHERAL BLOOD PREDICT PROGNOSIS OF GLIOMA AND CORRELATE WITH GRADES AND SUBTYPES: A PROSPECTIVE MULTI-INSTITUTIONAL STUDY OF 1282 PATIENTS

Abstract BACKGROUND Peripheral blood immune and inflammatory factors can reflect glioma patients' immune status and inform anti-tumor immunotherapy, but research in this field is limited compared to tumor microenvironment studies. We aim to investigate the relationship between these circulating factors and glioma grades, subtypes, and prognosis. METHODS From October 2006 to April 2022, 1282 patients with primary gliomas were enrolled in this study, and their preoperative peripheral blood was collected. Correlations between immune and inflammatory factors and different glioma grades and subtypes were analyzed using ANOVA, t-test, and Ordinal Logistic Regression. ROC curve analysis was used to evaluate the diagnostic efficiency of these factors. In addition, the Cox regression model, K-M survival analysis, and other methods were used to study the relationship between these factors and the prognosis and survival of patients. RESULTS The results showed that with the higher clinical grade, the percentage of NK cells in peripheral blood increases while the percentage of Th and T lymphocytes decreases. C4 levels and percentage of B lymphocytes were higher in grade I gliomas than in other grades. The percentage of NK and Th cells also correlated with glioma subtypes. Immunoglobulin light chains were associated with a favorable prognosis, whereas a higher percentage of peripheral B lymphocytes in grade IV patients was associated with a poor prognosis. CONCLUSIONS The relationship between immune and inflammatory factors and the grades and subtypes of glioma can offer potential opportunities to intervene in these factors that could improve the prognosis of glioma patients. Additionally, it may be helpful to screen glioma and anti-tumor immunotherapy.