Grade Inflammation Research Articles

Insights into the role of nucleotide methylation in metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by fatty infiltration of the liver. In recent years, the MAFLD incidence rate has risen and emerged as a serious public health concern. MAFLD typically progresses from the initial hepatocyte steatosis to steatohepatitis and then gradually advances to liver fibrosis, which may ultimately lead to cirrhosis and carcinogenesis. However, the potential evolutionary mechanisms still need to be clarified. Recent studies have shown that nucleotide methylation, which was directly associated with MAFLD's inflammatory grading, lipid synthesis, and oxidative stress, plays a crucial role in the occurrence and progression of MAFLD. In this review, we highlight the regulatory function and associated mechanisms of nucleotide methylation modification in the progress of MAFLD, with a particular emphasis on its regulatory role in the inflammation of MAFLD, including the regulation of inflammation-related immune and metabolic microenvironment. Additionally, we summarize the potential value of nucleotide methylation in the diagnosis and treatment of MAFLD, intending to provide references for the future investigation of MAFLD.

Histological Assessment of the Oral Soft Tissue Regenerative Capacity of Hyaluronic Acid and Ozonated Oil in Vivo.

Aims: The objective of this study is to compare the wound healing potential between two different biomaterials after induced surgical intraoral incisions. Materials and methods: The study was conducted on (12) male New Zealand rabbits, randomly divided into two groups (6 animals per group) according to the healing periods (3rd,7th, and 14th) days. Two incisions were made on the buccal mucosa of each rabbit bilaterally. For the first group, the defects were filled with (PerioKIN Hyaluronic 1%) gel, O3OHEAL-M gel for the second group, applied three times daily, two rabbits were randomly selected each group at the (3rd, 7th, and 14th) days, and biopsies were taken. The biopsy specimens were subjected to histological evaluation to assess the physiological parameters of the wound-healing process. Results: median results of Inflammatory Cells Infiltration grading in which day 3 group II was the highest and day 14 was lowest and Granulation tissue formation in which day 7 was highest and re-epithelization scoring showed highest at day 14, according to the time period and their were no significant differences of Group versus group (within the same day). So, there is very close activity of the two materials in relation to their use in wounds with tissue loss. Conclusions: use of PerioKIN Hyaluronic 1% gel and O3OHEAL-M gel application three times daily for bare wounds give a satisfactory result for better healing and isolation to get rid of the infection in the appropriate time.

Desaturation of sebaceous-type saturated fatty acids through the SCD1 and the FADS2 pathways impacts lipid neosynthesis and inflammatory response in sebocytes in culture.

Sebum is a lipid-rich mixture secreted by the sebaceous gland (SG) onto the skin surface. By penetrating through the epidermis, sebum may be involved in the regulation of epidermal and dermal cells in both healthy and diseased skin conditions. Saturated and monounsaturated fatty acids (FAs), found as free FAs (FFAs) and in bound form in neutral lipids, are essential constituents of sebum and key players of the inflammatory processes occurring in the pilosebaceous unit in acne-prone skin. Little is known on the interplay among uptake of saturated FFAs, their biotransformation, and induction of proinflammatory cytokines in sebocytes. In the human SG, palmitate (C16:0) is the precursor of sapienate (C16:1n-10) formed by insertion of a double bond (DB) at the Δ6 position catalysed by the fatty acid desaturase 2 (FADS2) enzyme. Conversely, palmitoleate (C16:1n-7) is formed by insertion of a DB at the Δ9 position catalysed by the stearoyl coenzyme A desaturase 1 (SCD1) enzyme. Other FFAs processed in the SG, also undergo these main desaturation pathways. We investigated lipogenesis and release of IL-6 and IL-8 pro-inflammatory cytokines in SZ95 sebocytes in vitro after treatment with saturated FFAs, that is, C16:0, margarate (C17:0), and stearate (C18:0) with or without specific inhibitors of SCD1 and FADS2 desaturase enzymes, and a drug with mixed inhibitory effects on FADS1 and FADS2 activities. C16:0 underwent extended desaturation through both SCD1 and FADS2 catalysed pathways and displayed the strongest lipoinflammatory effects. Inhibition of desaturation pathways proved to enhance lipoinflammation induced by SFAs in SZ95 sebocytes. Palmitate (C16:0), margarate (C17:0), and stearate (C18:0) are saturated fatty acids that induce different arrays of neutral lipids (triglycerides) and dissimilar grades of inflammation in sebocytes.

Chemerin and Chemokine-like Receptor 1 Expression Are Associated with Hepatocellular Carcinoma Progression in European Patients.

The chemoattractant protein chemerin is protective in experimental hepatocellular carcinoma (HCC), and high expression in HCC tissues of Asian patients was related to a favorable prognosis. Studies from Asia found reduced expression of chemerin in HCC compared to para-tumor tissues while our previous analysis observed the opposite. Aim of this study was to correlate chemerin expression in HCC tissues with disease severity of European patients Hepatocyte chemerin protein expression was assessed by immunohistochemistry in HCC tissue of 383 patients, and was low in 24%, moderate in 49% and high in 27%. High chemerin protein in the HCC tissues was related to the T stage, vessel invasion, histologic grade, Union for International Cancer Control (UICC) stage and tumor size. Chemokine-like receptor 1 (CMKLR1) is a functional chemerin receptor. CMKLR1 protein in hepatocytes was low expressed in HCC tissues of 36%, moderate in tissues of 32% and high in 32% of the HCCs. Tumor CMKLR1 was associated with the T stage, vessel invasion, histologic grade and UICC stage. Notably, sex-specific analysis revealed that associations of chemerin and CMKLR1 expression with HCC progression were significant in males but not in females. The tumor chemerin and CMKLR1 protein expression were not related to steatosis, inflammation and fibrosis grades. In summary, chemerin as well as CMKLR1 protein were related to disease severity of European HCC patients, and this was significant in males. This observation is in contrast to Asian patients where higher chemerin in the tumors was protective. Current analysis provides evidence for ethnicity and sex-related differences of tumor expressed chemerin and HCC severity.

Is it Possible to Avoid Liver Biopsy in Living Donors for Liver Transplantation by Using Two-Dimensional Shear Wave Elastography?

The present study aims to evaluate the correlation of two-dimensional shear wave elastography results with histopathological findings performed simultaneously with liver biopsy (LB) in healthy liver transplant donors. A total of 53 living donors, 35 male and 18 female, were included in this prospective, observational, single-center study. Patients with abnormal liver function tests were not included in our study. Hepatosteatosis, fibrosis, and inflammation were evaluated with the Fatty Liver Inhibition of Progression and Steatosis, Activity, and Fibrosis algorithm of donor LB. The mean age of the donors was 33.04 ± 9.07 years and the mean body mass index was 23.41 ± 6.23 kg/m2. The mean elastography kilo pascal (kPA) value of all donors was determined as 6.03 ± 2.32 kPa. The mean LB activity scores of the donors were found to be 1.64 ± 1.18 and ranged from 0 to 5. There was no significant correlation between elastography kPa value and pathologic activity score, steatosis score, balloon degeneration, and inflammation grade fibrosis scores (P > .05). Shear wave elastography measurements showed that the predictive power of pathologic findings in donor LB was not sufficient.

Brolucizumab for Wet Age-Related Macular Degeneration: One-Year Real-World Experience from a Tertiary Center

Introduction: The aim of this study was to explore the early efficacy and safety of treatment with intravitreal injections (IVIs) of brolucizumab in patients presenting with neovascular age-related macular degeneration (nAMD) in a real-world setting. Methods: This retrospective study included 194 eyes of 180 patients with nAMD treated with standard 6-mg IVIs of brolucizumab in our clinic between March 11, 2021, and June 15, 2022. Both treatment-naive (33 eyes) and switch therapy patients (161 eyes) were included in the study. Best corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid distribution (classified as intraretinal, subretinal, under the pigmented epithelium), treatment intervals, and adverse event rates were collected for analysis. Results: Average follow-up time was 37.2 ± 16.6 weeks. Mean baseline BCVAs were 38.1 ± 4.5 and 41.9 ± 6.7 letters in the treatment-naive and switch therapy groups, with a final gain of 16.0 ± 4.9 (p < 0.0001) and 10.7 ± 5.9 (p < 0.0001) letters in the two groups, respectively. Throughout the study period, CST significantly decreased in both treatment naïve (from 352.0 ± 129.4 to 284.2 ± 93.8 µm; p = 0.0015) and switch therapy (from 369.9 ± 140.5 to 307.4 ± 123.5 µm; p < 0.0001). Significant fluid control rates were achieved at the end of the study period (45% and 27% eyes were completely free of fluid in naïve and switch groups, respectively). Five eyes (2.6%) developed adverse events with different grades of intraocular inflammation and visual outcomes. Conclusion: Brolucizumab IVI showed very good anatomical and functional outcomes in both naive and switch patients in this real-world experience. Nevertheless, even showing a favorable risk/benefit profile, clinicians and patients should be aware of the possibility of a small rate of severe complications.

Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence.

Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1β. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1β improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1β was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1β, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint.

Analysis of clinical and pathological features of chronic hepatitis B combined with metabolic-associated fatty liver disease

Objective: To analyze the clinical and histopathological features of patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD). Methods: Clinical data of 529 cases who had liver biopsies at the First Affiliated Hospital of Zhengzhou University between January 2015 and October 2021 were collected. Among them were 290 cases with CHB, 155 cases with CHB combined with MAFLD, and 84 cases with MAFLD. Three groups of patients clinical data, including general information, biochemical indicators, FibroScan indicators, viral load, and histopathology, were analyzed. A binary logistic regression analysis was used to explore the factors influencing MAFLD in patients with CHB. Results: (1) Age, male status, proportion of hypertension and diabetes, body mass index, fasting blood glucose, γ-glutamyl transpeptidase, low-density lipoprotein, cholesterol, triglycerides, uric acid, creatinine, and the controlled attenuation parameter for hepatic steatosis were higher in CHB combined with MAFLD than in CHB patient groups. In contrast, the high-density lipoprotein, HBeAg positivity rate, viral load level, and liver fibrosis grade (S stage) were lower in CHB patients, and the differences were statistically significant (P < 0.05). (2) Alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, triglycerides, uric acid, creatinine, and the controlled attenuation parameter for hepatic steatosis in CHB combined with the MAFLD were lower than those in MAFLD patient groups, while high-density lipoprotein was higher than that of MAFLD patients, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in the grade of liver inflammation and fibrosis (GS stage) between the two groups (P > 0.05). Binary multivariate logistic regression analysis showed that overweight/obesity, triglycerides, low-density lipoprotein, the controlled attenuation parameter for hepatic steatosis, and HBeAg positivity were independent influencing factors for MAFLD in CHB patients. Conclusion: Patients with CHB combined with metabolic disorders are prone to developing MAFLD, and there is a certain correlation between HBV viral factors, the degree of liver fibrosis, and the fatty degeneration of hepatocytes.

The association between KRAS mutational status, clinicopathological factors including the preoperative systemic inflammatory response and outcomes in TNM stage I-III colon cancer.

193 Background: TNM Stage is the most significant prognostic indicator in colon cancer however other tumour and host factors (eg the systemic inflammatory response (SIR)) are associated with long-term outcomes. The relationship between the tumour and the host SIR remains poorly understood. KRAS mutations are associated with adverse outcomes in metastatic disease and have been reported to have an inflammatory phenotype however this has not been widely studied in non-metastatic disease. The present study investigates the association between KRAS mutations, clinicopathological factors including the SIR and outcomes in TNM I-III colon cancer. Methods: Two cohorts of patients (single centre–2000-2008 and regional-2011-2014) undergoing curative surgery for TNM I-III colon cancer in the West of Scotland were shown to be well-matched and combined. Mutational status was analysed retrospectively. The SIR was stratified using Systemic Inflammatory Grade (SIG). 3-year overall and cancer specific survival (OS and CSS) were measured from date of surgery until date of death. Results: 267 patients were identified, 45% with KRAS mutations. KRAS mutations were associated with: right sided (p=0.013), well differentiated (p=0.011), BRAF-wt (p&lt;0.001), PIK3CA-wt (p=0.027) and P53-wt (p=0.002) tumours. A trend was seen between KRAS mutations and female sex (p=0.074) and increased SIG (p=0.072). No association was seen with age, deprivation, smoking, ASA Grade, TNM Stage or EMVI. KRAS mutant status was associated with adverse 3-year CSS (74% versus 82%, p=0.006) and OS (69% versus 78%, p=0.070). For CSS, TNM Stage (HR 2.92, p&lt;0.001), KRAS mutant status (HR 1.64, p=0.050) and Systemic Inflammatory Grade (HR 1.34, p=0.004) were independently prognostic. For OS: age (HR 1.39, p=0.022), TNM Stage (HR 1.50, p=0.016) and SIG (HR 1.25, p=0.005) were independently prognostic. A trend was seen between KRAS mutant status and adverse OS (HR 1.47, p=0.079). Conclusions: The present results show an association between KRAS mutational status and SIG. Furthermore, both of these factors were associated with adverse oncological outcomes. Further investigation into the association between KRAS-mutant status and the local/systemic inflammatory response in TNM I-III colon cancer is warranted. While comprehensive genomic profiling is likely to become increasingly common place, staging the host (SIR) should also be routinely undertaken.

P308 A new endoscopic scoring system corresponding to histological healing using linked color imaging in ulcerative colitis: SOUL study

Abstract Background An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, recently, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients (median age, 46 years; male/female ratio, 48/34) with a Mayo endoscopic subscore (MES) ≤1 who underwent colonoscopy for UC in clinical remission between November 2016 and January 2019 were included. LCI index was defined as degree of redness (R) (grade 0–2), area of inflammation (A) (grade 0–3), and visibility of lymphoid follicles (L) (grade 0–3). Endoscopic scores were determined by three central endoscopic judgment committee members who are experts in colonoscopy for UC. Discussions were held among the three members, and when two or more of them had the same judgment this was adopted as the final evaluation. Each biopsy was performed from an identical site of colonoscopic image. Histological healing was defined as Geboes score &amp;lt;2B.1. Histopathological scores were also determined by central judgment. Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. Percentage of judgments that were consistent in two or more central endoscopic judgment committee members were 167/169 (98.8%) cases in MES, 164/169 (97.0%) cases in LCI index-R, 152/169 (89.9%) cases in LCI-index-A, and 150/169 (88.8%) cases in LCI-index-L. Regarding the κ-score in diagnosing by the two pathologists, “Chronic inflammatory infiltrate”, “Crypt destruction”, and “Crypt destruction” had a moderate agreement, and others had a stationary agreement. The overall histological healing rate was 84.0% (142/169). There were 22/117/30 cases of grade 0/1/2 in LCI index-R, 113/34/17/5 cases of grade 0/1/2/3 in LCI index-A, and 124/27/14/4 cases of grade 0/1/2/3 in LCI index-L. Histological healing was achieved in 84.1% (142/169) of the cases, and there were significant associations with histological healing/non-healing in LCI index-R (P=0.013) and A (P=0.0014). Conclusion A new LCI index is useful for predicting histological healing in UC patients with MES ≤1 and clinical remission.

Single Breath-Hold 3-Dimensional Magnetic Resonance Elastography Depicts Liver Fibrosis and Inflammation in Obese Patients.

Three-dimensional (3D) magnetic resonance elastography (MRE) measures liver fibrosis and inflammation but requires several breath-holds that hamper clinical acceptance. The aim of this study was to evaluate the technical and clinical feasibility of a single breath-hold 3D MRE sequence as a means of measuring liver fibrosis and inflammation in obese patients. From November 2020 to December 2021, subjects were prospectively enrolled and divided into 2 groups. Group 1 included healthy volunteers (n = 10) who served as controls to compare the single breath-hold 3D MRE sequence with a multiple-breath-hold 3D MRE sequence. Group 2 included liver patients (n = 10) who served as participants to evaluate the clinical feasibility of the single breath-hold 3D MRE sequence in measuring liver fibrosis and inflammation. Controls and participants were scanned at 60 Hz mechanical excitation with the single breath-hold 3D MRE sequence to retrieve the magnitude of the complex-valued shear modulus (|G*| [kPa]), the shear wave speed (Cs [m/s]), and the loss modulus (G" [kPa]). The controls were also scanned with a multiple-breath-hold 3D MRE sequence for comparison, and the participants had histopathology (Ishak scores) for correlation with Cs and G". For the 10 controls, 5 were female, and the mean age and body mass index were 33.1 ± 9.5 years and 23.0 ± 2.1 kg/m 2 , respectively. For the 10 participants, 8 were female, and the mean age and body mass index were 45.1 ± 16.5 years and 33.1 ± 4.0 kg/m 2 (obese range), respectively. All participants were suspected of having nonalcoholic fatty liver disease. Bland-Altman analysis of the comparison in controls shows there are nonsignificant differences in |G*|, Cs, and G" below 6.5%, suggesting good consensus between the 2 sequences. For the participants, Cs and G" correlated significantly with Ishak fibrosis and inflammation grades, respectively ( ρ = 0.95, P < 0.001, and ρ = 0.84, P = 0.002). The single breath-hold 3D MRE sequence may be effective in measuring liver fibrosis and inflammation in obese patients.

Role of inflammatory factors in prediction of Gleason score and its upgrading in localized prostate cancer patients after radical prostatectomy.

To investigate the role of inflammatory factors including systemic immune-inflammation index (SII) and neutrophil to lymphocyte ratio (NLR) in predicting Gleason Score (GS) and Gleason Score upgrading (GSU) in localized prostate cancer (PCa) after radical prostatectomy (RP). The data of 297 patients who underwent prostate biopsy and RP in our center from January 2014 to March 2020 were retrospectively analyzed. Preoperative clinical characteristics including age, values of tPSA, total prostate volume (TPV), f/t PSA ratio, body mass index (BMI), biopsy GS and inflammatory factors including SII, NLR, lymphocyte to monocyte (LMR), neutrophil ratio (NR), platelet to lymphocyte ratio (PLR), lymphocyte ratio (LR), mean platelet volume (MPV) and red cell distribution (RDW) as well as pathological T (pT) stage were collected and compared according to the grades of RP GS (GS ≤ 6 and GS≥7), respectively. ROC curve analysis was used to confirm the discriminative ability of inflammatory factors including SII, NLR and their combination with tPSA for predicting GS and GSU. By using univariate and multivariate logistic regression analysis, the association between significant inflammatory markers and grades of GS were evaluated. Patients enrolled were divided into low (GS ≤ 6) and high (GS≥7) groups by the grades of GS. The median values of clinical factors were 66.08 ± 6.04 years for age, 36.62 ± 23.15 mL for TPV, 26.16 ± 33.59 ng/mL for tPSA and 0.15 ± 0.25 for f/t PSA ratio, 22.34 ± 3.14 kg/m2 for BMI, 15 (5.1%) were pT1, 116 (39.1%) were pT2 and 166 (55.9%) were pT3. According to the student's t test, patients in high GS group had a greater proportion of patients with pT3 (P<0.001), and higher NLR (P=0.04), SII (P=0.037) and tPSA (P=0.015) compared with low GS group, the distribution of age, TPV, f/t PSA ratio, BMI, LMR, NR, PLR, LR, MPV and RDW did not show any significantly statistical differences. The AUC for SII, NLR and tPSA was 0.732 (P=0.007), 0.649 (P=0.045) and 0.711 (P=0.015), with threshold values of 51l.08, 2.3 and 10.31ng/mL, respectively. According to the multivariable logistic regression models, NLR ≥ 2.3 (OR, 2.463; 95% CI, 0.679-10.469, P=0.042), SII ≥ 511.08 (OR, 3.519; 95% CI 0.891-12.488; P=0.003) and tPSA ≥ 10.31 ng/mL (OR, 4.146; 95% CI, 1.12-15.35; P=0.033) were all independent risk factors associated with higher GS. The AUC for combination of SII, NLR with tPSA was 0.758 (P=0.003) and 0.756 (P=0.003), respectively. GSU was observed in a total of 48 patients with GS ≤ 6 (55.17%). Then patients were divided into 2 groups (high and low) according to the threshold value of SII, NLR, tPSA, SII+tPSA and NLR+tPSA, respectively, when the GSU rates were compared with regard to these factors, GSU rate in high level group was significantly higher than that in low level group, P=0.001, 0.044, 0.017, <0.001 and <0.001, respectively. High SII, NLR and tPSA were associated with higher GS and higher GSU rate. SII was likely to be a more favorable biomarker for it had the largest AUC area compared with tPSA and NLR; the combination of SII or NLR with tPSA had greater values for predicting GS and GSU compared with NLR, SII or tPSA alone, since the AUC area of combination was much higher. SII, NLR were all useful inflammatory biomarkers for predicting GS and detecting GSU among localized PCa patients with biopsy GS ≤ 6.

Interferon-gamma release assay and chest X-ray to classify intraocular tuberculosis among clinically undifferentiated uveitis

BACKGROUND Tuberculosis (TB) is a common cause of intraocular inflammation in Indonesia. As no accurate biomarker can confirm the diagnosis, ophthalmologists often rely on systemic findings, such as tuberculin skin test, interferon-gamma release assay (IGRA), and chest X-ray (CXR) for TB suspicion. This study aimed to evaluate IGRA and CXR in classifying intraocular TB among patients with a clinically undifferentiated cause of uveitis.&#x0D; METHODS This cross-sectional study included 116 patients (a total of 163 affected eyes) with a clinically undifferentiated cause of uveitis. IGRA and CXR were performed as part of the workup. Data on visual acuity, anterior chamber inflammation grade, and anatomical classification of uveitis were recorded. As there were no confirmed ocular tuberculosis (OTB) in our cases, eyes were classified into probable OTB, possible OTB, and unclassified.&#x0D; RESULTS Overall, 93 patients (80.2%) with a clinically undifferentiated cause of uveitis had positive IGRA, whereas 10 (8.6%) had CXR results suggestive of TB. More than one-third of the patients were blind (visual acuity &lt;3/60), and panuveitis was the commonest anatomical classification. A trend was identified in patients with panuveitis, who often showed ≥2+ cell anterior chamber inflammation (p for trend = 0.023), according to OTB criteria (probable OTB = 3/4, 75.0%; possible OTB = 44/67, 65.7%; unclassified = 2/9, 22.2%). Furthermore, the clinically undifferentiated uveitis cases were eligible to be stratified into probable (8.6%) and possible (75.0%) OTB categories after IGRA and CXR examinations.&#x0D; CONCLUSIONS The combination of IGRA and CXR is valuable for classifying and diagnosing TB-related uveitis. A multidisciplinary approach is essential when the cause of uveitis is unknown.

Histologic changes in immune-tolerant patients with chronic hepatitis B: a systematic review and meta-analysis

The serological diagnostic criteria for the immune-tolerant (IT) phase have not been strictly defined and it is hard to determine an accurate rate for significant histologic changes among IT patients. The aim of this study was to establish a baseline rate of significant histologic changes and to determine the main characteristics of IT patients. We systematically searched PubMed, Embase, and Web of Science. Studies reporting liver biopsy results (inflammation grade or fibrosis stage) for adults with chronic hepatitis B virus (HBV) infection in the IT phase diagnosed by serological criterion were included to pool the rate of significant histologic changes. Studies that enrolled subjects with confirmed chronic HBV infection in the IT phase diagnosed by serological and liver biopsy criteria (dual criteria) were included to pool the mean values of main characteristics among IT patients. Of 319 studies screened, 15 were eventually included in the meta-analysis. The pooled rates of significant liver fibrosis and inflammatory activity for 10 studies were 10% (95% confidence interval [CI] 0.06–0.18) and 16% (95% CI 0.07–0.31), respectively. The pooled mean values of age, alanine aminotransferase level, HBV DNA level, and HBsAg level for another 5 studies with IT patients diagnosed by dual criteria were 30.7 years (95% CI 27.31–34.09), 26.64 IU/mL (95% CI 24.45–28.83), 8.41 log10 cp/mL (95% CI 7.59–9.23), and 4.24 log10 IU/mL (95% CI 3.67–4.82), respectively. Significant histologic changes were not rare events among IT patients. Strictly defined serological diagnostic criteria for the IT phase are warranted.

Efficacy and Safety of Adalimumab in Patients with Behçet Uveitis: A Systematic Review and Meta-Analysis

ABSTRACT Purpose To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU). Methods A systematic review and meta-analysis of observational studies was performed. Pooled results are presented as mean difference or standardized mean difference (std diff) and 95% confidence intervals (CI). Visual acuity (VA), intraocular inflammation grade, central macular thickness, corticosteroid (CS) sparing effect and adverse events were evaluated. Results Ten studies were included finally for quantitative and qualitative synthesis. ADA therapy resulted in 0.124 (95%CI: 0.084, 0.165) logMAR improvement in VA. In addition, ADA therapy resulted in decreased grade of intraocular inflammation [std diff, −1.187 (95%CI: -1.508, -0.866)] and macular thickness [std diff, −0.564 (95%CI: -0.843, -0.286)] and caused a decrease in CS dosage [std diff, −1.809 (95%CI: -2.420, -1.198)]. The pooled rate of overall adverse events for ADA in 301 patients was 8.5% (95%CI: 0.039, 0.177). Conclusion ADA is an efficient therapy that improves VA and controls intraocular inflammation, macular edema and retinal vasculitis. As the disease exposure time increased, improvement in VA was less. The safety and CS-sparing effect of ADA were demonstrated with few adverse effects. The results provided evidence that ADA can be used safely and efficiently as the first-line drug in patients with BU.

The relationship between the modified frailty index score (mFI-5), malnutrition, body composition, systemic inflammation and short-term clinical outcomes in patients undergoing surgery for colorectal cancer

BackgroundWhile the current literature suggests an association with frailty and clinical outcomes in patients undergoing surgery for colorectal cancer (CRC), the basis of this relationship is unclear.AimExamine the relationship between frailty, malnutrition, body composition, systemic inflammation and short-term clinical outcomes in patients undergoing surgery for colorectal cancer.MethodsConsecutive patients who underwent potentially curative resection for colorectal cancer, between April 2008 and April 2018, were identified from a prospectively maintained database. Frailty was defined using the modified five-item frailty index (mFI-5). Body composition measures included CT-derived skeletal muscle index (SMI) and density (SMD). Systemic inflammatory status was determined using Systemic Inflammatory Grade (SIG). Outcomes of interest were the incidence of post-operative complications and thirty-day mortality. Associations between categorical variables were examined using χ2 test and binary logistics regression analysis.Results1002 patients met the inclusion criteria. 28% (n = 221) scored 2 or more on the mFI-5. 39% (n = 388) of patients had a post-operative complication (Clavien-Dindo I-IV) and 1% (n = 11) died within thirty days of surgery. On univariate analysis, mFI-5 frailty score, was significantly associated with advanced age (p < 0.001), colonic tumours (p < 0.001), reduced use of neo-adjuvant chemotherapy (p < 0.05), higher BMI (p < 0.05), low SMD (p < 0.001), elevated NLR (p < 0.05), elevated mGPS (p < 0.05), elevated SIG (p < 0.05), incidence of post-operative complications (p < 0.001) and thirty-day mortality (p < 0.05). On multivariate analysis, male sex (p < 0.05), elevated SIG (p < 0.05) and mFI-5 score (p < 0.01) remained significantly associated with the incidence of post-operative complications. mFI-5 frailty was found to remain significantly associated with the incidence post-operative complications in patients who were SIG 0 (p < 0.05).ConclusionmFI-5 frailty score was found to be significantly associated with age, systemic inflammation and post-operative outcomes in patients undergoing potentially curative resections for CRC. Incorporation of an assessment of systemic inflammatory status in future frailty screening tools may improve their prognostic value.

Long-term prognosis and the need for histologic assessment of chronic hepatitis B in the serological immune-tolerant phase.

The histologic status of the immune-tolerant (IT) phase of chronic hepatitis B relative to long-term outcomes is unclear. This study aimed to discover how the serological criteria currently in use correspond to histologic criteria in determining the IT phase and indication for liver biopsy. Patients in the serological IT phase determined by positive hepatitis B e antigen, hepatitis B virus (HBV) DNA ≥106 IU/mL, and normal or minimally elevated alanine aminotransferase (ALT) ≤60 IU/L, who underwent liver biopsy at three different hospitals were included. The distribution of the histologic IT phase, defined as fibrosis of stage 1 or less and inflammation of grade 1 or less, was compared with that of the serological IT phase. The risk factors for the incidence of liver-related events, such as hepatocellular carcinoma, liver cirrhosis, liver transplantation, and death, were also analyzed. Eighty-two (31.7%) out of 259 clinically suspected IT phase patients belonged to the histologic IT phase. Age over 35, high AST, and low albumin were useful for ruling out the histologic IT phase. Risk factors predicting liver-related events were age and significant fibrosis stage. There was no significant difference in the proportion of histologic IT phase and clinical prognosis between normal ALT and mildly elevated ALT groups. However, even in patients with normal ALT, age was an important factor in predicting the presence of the histologic IT phase. A significant number of patients who belonged to the serological IT phase were not in the histologic IT phase. Patients over 35 years and those with high AST, low albumin, and low HBV DNA levels were more likely to experience poor long-term clinical outcomes. Therefore, additional histologic assessment should be considered.

Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative.

Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. 85 HBV DNA-negative and HBeAg-negative patients were 37.90 ± 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 ± 10.70 vs 34.80 ± 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) μmol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 ± 2156.00 vs 8988.00 ± 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 ± 61.40 vs 194.00 ± 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology.

RELATIONSHIP OF HELICOBACTER PYLORI CAGA AND VACA STATUS TO MORPHOLOGICAL CHANGES OF GASTRIC MUCOSA AND PRIMARY CLARITHROMYCIN RESISTANCE RATE IN PATIENTS WITH CHRONIC GASTRITIS: A CROSS-SECTIONAL STUDY.

The aim: To investigate the relation of H. pylori CagA and VacA status to morphological changes of gastric mucosa and primary clarithromycin resistance rate in patients with chronic gastritis. Materials and methods: A cross-sectional study was conducted between May 2021 and January 2023, involving 64 patients with H. pylori-associated chronić gastritis. The patients were assigned to two groups according to the H. pylori virulence factors (CagA and VacA) status. The grades of inflammation, activity, atrophy, and metaplasia were determined according to the Houston-updated Sydney system. The identification of H. pylori genetic markers of antibiotic resistance and pathogenicity was performed by the polymerase chain reaction using paraffin stomach biopsies. Results: Patients with CagA- and VacA-positive H. pylori strains had significantly higher grades of inflammation both in the antrum and in the corpus of the stomach, activity of gastritis in the antrum, higher incidence and grade of atrophy in the antrum. Primary resistance to clarithromycin was significantly more prevalent in patients with CagA- and VacA-negative H. pylori strains (58.3% vs. 11.5%, p=0.002). Conclusions: Positive CagA and VacA status is related to more severe histopathological changes of gastric mucosa. In contrast, the rate of primary clarithromycin resistance is higher in patients CagA- and VacA-negative H. pylori strains.

Tympanometry and endoscopic diagnosis of eustachian tube dysfunction in patients with chronic rhinosinusitis.

This study assessed the eustachian tube (ET) function in adult patients with chronic rhinosinusitis (CRS) using tympanometry and nasal endoscope. This was a hospital-based cross-sectional study conducted for 9 months. All participants underwent endoscopic evaluation of the pharyngeal end of their ETs, and the middle ear function was assessed using tympanometry. Endoscopic findings were graded based on a validated mucosal inflammatory endoscopic grading scale. Statistical analysis was carried out using SPSS version 24. A total of 102 CRS patients and age- and sex-matched controls were recruited. Tympanograms suggestive of eustachian tube dysfunction (ETD) types B and C were found among 7.8% and 12.8% of the right and left ears of the CRS groups, respectively. Mucosal inflammatory endoscopic grade that is diagnostic of ETD Grades 3 and 4 was found among 24.5% and 38.2% of the right and left ET of CRS cases, respectively. CRS predisposes patients to anatomical and functional impairment of ET. The relationship between tympanometry and mucosal inflammatory endoscopic grading scale in detecting ETD among CRS patients showed a strong relationship. However, a combination of the two will improve the diagnosis of ETD by evaluating the ET function directly and indirectly.