Grade Inflammation Research Articles

Finerenone: Questions and Answers-The Four Fundamental Arguments on the New-Born Promising Non-Steroidal Mineralocorticoid Receptor Antagonist.

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high, and diabetes remains the leading cause of end-stage kidney disease in affected patients. To date, current medications for CKD and type 2 diabetes mellitus have not reset residual risk in patients due to a high grade of inflammation and fibrosis contributing to kidney and heart disease. This question-and-answer-based review will discuss the pharmacological and clinical differences between finerenone and other mineralocorticoid receptor antagonists and then move on to the main evidence in the cardiovascular and renal fields, closing, finally, on the potential role of therapeutic combination with sodium-glucose cotransporter 2 inhibitors (SGLT2is).

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B.

Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

New Generation of Systemic Inflammatory Markers for Respiratory Syncytial Virus Infection in Children.

This study evaluated the relationship between the systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) with clinical findings of respiratory syncytial virus (RSV) infection among children with a diagnosis of lower respiratory tract infection (LRTI). The study was conducted between 1 January 2020 and 1 January 2022 in a pediatric clinic. This retrospective study included 286 consecutive patients between 0 and 12 years of age, 138 of whom were RSV (+) (48.25%) and 148 of whom were RSV (-) (51.75%). The detection of the RSV antigen was carried out using the chromatographic immunoassay method on nasopharyngeal swabbing samples. CRP content was significantly higher in patients with RSV (+) than in children with RSV (-), while NLR, PLR, and SII, as inflammatory parameters, were significantly lower. Fever, coughs, and wheezing were the most common symptoms in the RSV (+) groups (100%). RSV infections were the highest in November, October, and December, in that order. The AUC was statistically significant for parameters in all groups. AUC values were 0.841 (95%: 0.765-0.917) for leukocytes, 0.703 (95%: 0.618-0.788) for lymphocytes, 0.869 (95%: 0.800-0.937) for CRP, 0.706 (95%: 0.636-0.776) for NLR, 0.779 (95%: 0.722-0.836) for PLR, and 0.705 (95%: 0.633-0.776) for SII. CRP was found to have both high sensitivity (80.4%) and high specificity (82.4%) among all parameters. While the ROC analysis results showed similar results for children under two years old, only CRP and NLR were statistically significant in this group. CRP performed better than other blood parameters as a marker. The NLR, PLR, and SII index were significantly lower in LRTI patients with RSV (+) than in those with RSV (-), which implies a higher grade of inflammation. If the cause of the disease can be determined by this method, disease management will be easier, and unnecessary antibiotics could be avoided.

Lean nonalcoholic fatty liver disease: Age-dependent differences in pathology, prognosis, and liver-related events.

This study aimed to evaluate the age-specific characteristics, prognosis, and complications of patients with lean nonalcoholic fatty liver disease (NAFLD). Background factors (age, sex, diabetes, dyslipidemia, hypertension, and PNPLA3 gene polymorphism), blood test results, liver histology findings, muscle mass, and grip strength were investigated in 782 patients with NAFLD who underwent liver biopsy. Prognosis and complications were compared among 549 patients with nonlean or lean NAFLD who were followed up for 6.5years. Additionally, background factors, blood test results, liver histology findings, prognosis, and complications were compared according to age (≥60years vs. <60years) in patients with lean NAFLD. Lean NAFLD patients showed lower aspartate aminotransferase, alanine aminotransferase, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein, ferritin, and leptin but higher adiponectin and hemoglobin A1c (HbA1c) levels than patients with nonlean NAFLD. Furthermore, lean NAFLD patients showed less liver fibrosis, inflammation, steatosis, and ballooning. Among lean NAFLD patients, those aged 60years and older were more frequently female, showed higher rates of hypertension, diabetes, and dyslipidemia, had higher HbA1c and type IV collagen 7S levels, lower platelet count, higher liver fibrosis and inflammation grades, and lower muscle mass and grip strength. Lean NAFLD was associated with a worse prognosis in patients aged 60years and over than in those younger than 60years of age and with a higher incidence of liver-related disease, cerebrocardiovascular events, and nonliver cancer. Age is an important consideration in patients with lean NAFLD. Compared with nonlean NAFLD, lean NAFLD was associated with a worse prognosis and higher risk of complications in patients aged 60years and older.

The relationship between heart rate variability and TNM stage, co-morbidity, systemic inflammation and survival in patients with primary operable colorectal cancer

High vagal nerve activity, reliability measured by HRV, is considered protective in cancer, reducing oxidative stress, inflammation and opposing sympathetic nerve activity. The present monocentric study examines the relationship between HRV, TNM stage, co-morbidity, systemic inflammation and survival in patients who underwent potentially curative resections for colorectal cancer (CRC). Time-domain HRV measures, Standard Deviation of NN-intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), were examined as categorical (median) and continuous variables. Systemic inflammation was determined using systemic inflammatory grade (SIG) and co-morbidity using ASA. The primary end point was overall survival (OS) and was analysed using Cox regression. There were 439 patients included in the study and the median follow-up was 78 months. Forty-nine percent (n = 217) and 48% (n = 213) of patients were categorised as having low SDNN (< 24 ms) and RMSSD (< 29.8 ms), respectively. On univariate analysis, SDNN was not significantly associated with TNM stage (p = 0.830), ASA (p = 0.598) or SIG (p = 0.898). RMSSD was not significantly associated with TNM stage (p = 0.267), ASA (p = 0.294) or SIG (p = 0.951). Neither SDNN or RMSSD, categorical or continuous, were significantly associated with OS. In conclusion, neither SDNN or RMSSD were associated with TNM stage, ASA, SIG or survival in patients undergoing potentially curative surgery for CRC.

Automated evaluation with deep learning of total interstitial inflammation and peritubular capillaritis on kidney biopsies.

Interstitial inflammation and peritubular capillaritis are observed in many diseases on native and transplant kidney biopsies. A precise and automated evaluation of these histological criteria could help stratify patients' kidney prognoses and facilitate therapeutic management. We used a convolutional neural network to evaluate those criteria on kidney biopsies. A total of 423 kidney samples from various diseases were included; 83 kidney samples were used for the neural network training, 106 for comparing manual annotations on limited areas to automated predictions, and 234 to compare automated and visual gradings. The precision, recall and F-score for leukocyte detection were, respectively, 81%, 71% and 76%. Regarding peritubular capillaries detection the precision, recall and F-score were, respectively, 82%, 83% and 82%. There was a strong correlation between the predicted and observed grading of total inflammation, as for the grading of capillaritis (r=0.89 and r=0.82, respectively, all P<.0001). The areas under the receiver operating characteristics curves for the prediction of pathologists' Banff total inflammation (ti) and peritubular capillaritis (ptc) scores were respectively all above 0.94 and 0.86. The kappa coefficients between the visual and the neural networks' scores were respectively 0.74, 0.78 and 0.68 for ti ≥1, ti ≥2 and ti ≥3, and 0.62, 0.64 and 0.79 for ptc ≥1, ptc ≥2 and ptc ≥3. In a subgroup of patients with immunoglobulin A nephropathy, the inflammation severity was highly correlated to kidney function at biopsy on univariate and multivariate analyses. We developed a tool using deep learning that scores the total inflammation and capillaritis, demonstrating the potential of artificial intelligence in kidney pathology.

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

Background and study aims 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, 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. Patients and methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤ 1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (Grade 0-2), area of inflammation (A) (Grade 0-3), and lymphoid follicles (L) (Grade 0-3). Histological healing was defined as Geboes score < 2B.1. Endoscopic and histopathological scores were 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. There were 22, 117, and 30 cases of Grades 0, 1, and 2, respectively in LCI index-R; 113, 34, 17, and five cases of Grades 0, 1, 2, and 3, respectively, in LCI index-A; and 124, 27, 14, and four cases of Grades 0, 1, 2, and 3, respectively, in LCI index-L. Histological healing was achieved in 84.0 % of the cases (142 of 169), and there were significant associations with histological healing or non-healing in LCI index-R ( P = 0.013) and A ( P = 0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤ 1 and clinical remission.

The prognostic value of preoperative systemic inflammation-based scoring in patients undergoing endovascular repair of abdominal aortic aneurysm

ObjectiveAbdominal aortic aneurysm (AAA) is a common condition that is predominantly managed in the United Kingdom by endovascular aneurysm repair (EVAR). Activation of the systemic inflammatory response (SIR) appears to offer prognostic value in patients with vascular disease. The present study examines the relationship between the SIR and survival in patients undergoing standard and complex endovascular aneurysm repair (EVAR and fenestrated/branched [F/B]-EVAR). MethodsConsecutive patients undergoing elective EVAR and F/B-EVAR were retrospectively identified from three tertiary vascular centers over a 5-year period. Neutrophil:lymphocyte ratio and modified Glasgow Prognostic Score were calculated from preoperative blood results and combined into the systemic inflammatory grade (SIG). The primary outcome was all-cause mortality during the follow-up period, which was compared between subgroups of SIGs. ResultsThere were 506 patients included in the final study, with a median follow-up of 68.0 months (interquartile range, 27.3 months), and there were 163 deaths during the follow-up period. Mean survival in the SIG 0 vs SIG 1 vs SIG 2 vs SIG 3 vs SIG 4 subgroups was 80.7 months (95% confidence interval [CI], 76.5-85.0 months) vs 78.7 months (95% CI, 72.7-84.7 months) vs 61.0 months (95% CI, 51.1-70.8 months) vs 65.1 months (95% CI, 45.0-85.2 months) vs 54.9 months (95% CI, 34.4-75.3 months) (P < .05). In the entire cohort, age (P < .001), body mass index (P < .05), high creatinine (P < .05), and SIG (P < .05) were associated with survival on univariate analysis, with retained independent association for age (hazard ratio, 1.72; 95% CI, 1.29-2.31; P < .001) and SIG (hazard ratio, 1.20; 95% CI, 1.02-1.40; P < .05) on multivariate analysis. Increasing SIG (area under the curve, 0.68; 95% CI, 0.58-0.78; P < .01) predicted 1-year mortality. ConclusionsMarkers of the SIR such the SIG may be used to identify patients at higher risk of adverse outcome in patients undergoing EVAR and F/B-EVAR for abdominal aortic aneurysms. These findings warrant further investigation in large prospective cohort studies.

Clinical and Histopathological Effects of Intracameral Ranibizumab in Experimental Trabeculectomy.

Post-surgical scarring is a known cause of trabeculectomy failure. The aim of this study was to investigate the effectiveness of ranibizumab as an adjuvant anti-scarring agent in experimental trabeculectomy. Forty New Zealand white rabbits were randomised into four eye treatment groups: groups A (control), B (ranibizumab 0.5 mg/mL), C (mitomycin C [MMC] 0.4 mg/mL), and D (ranibizumab 0.5 mg/mL and MMC 0.4 mg/mL). Modified trabeculectomy was performed. Clinical parameters were assessed on post-operative days 1, 2, 3, 7, 14, and 21. Twenty rabbits were euthanised on day 7, and the other twenty were euthanised on day 21. Eye tissue samples were obtained from the rabbits and stained with haematoxylin and eosin (H&E). All treatment groups showed a significant difference in IOP reduction compared with group A (p < 0.05). Groups C and D showed a significant difference in bleb status on days 7 (p = 0.001) and 21 (p = 0.002) relative to group A. H&E staining showed significantly low fibrotic activity (p < 0.001) in group C on both days and inflammatory cell grade in group B on day 7 (p < 0.001). The grade for new vessel formation was significantly low in groups B and D on day 7 (p < 0.001) and in group D on day 21 (p = 0.007). Ranibizumab plays a role in reducing scarring, and a single application of the ranibizumab-MMC combination showed a moderate wound-modulating effect in the early post-operative phase.

Adverse Tumour and Host Biology May Explain the Poorer Outcomes Seen in Emergency Presentations of Colon Cancer.

To examine the association between tumor/host factors (including the systemic inflammatory response), mode of presentation, and short/long-term outcomes in patients undergoing curative resectional surgery for TNM I to III colon cancer. Emergency presentations of colon cancer are associated with worse long-term outcomes than elective presentations despite adjustment for TNM stage. A number of differences in tumor and host factors have been identified between elective and emergency presentations and it may be these factors that are associated with adverse outcomes. Patients undergoing curative surgery for TNM I to III colon cancer in the West of Scotland from 2011 to 2014 were identified. Tumor/host factors independently associated with the emergency presentation were identified and entered into a subsequent survival model to determine those that were independently associated with overall survival/cancer-specific survival (OS/CSS). A total of 2705 patients were identified. The emergency presentation was associated with a worse 3-year OS and CSS compared with elective presentations (70% vs 86% and 91% vs 75%). T stage, age, systemic inflammatory grade, anemia (all P < 0.001), N stage ( P = 0.077), extramural venous invasion ( P = 0.003), body mass index ( P = 0.001), and American Society of Anesthesiologists Classification classification ( P = 0.021) were independently associated with emergency presentation. Of these, body mass index [hazard ratio (HR), 0.82], American Society of Anesthesiologists Classification (HR, 1.45), anemia (HR, 1.29), systemic inflammatory grade (HR. 1.11), T stage (HR, 1.57), N stage (HR, 1.80), and adjuvant chemotherapy (HR, 0.47) were independently associated with OS. Similar results were observed for CSS. Within patients undergoing curative surgery for colon cancer, the emergency presentation was not independently associated with worse OS/CSS. Rather, a combination of tumor and host factors account for the worse outcomes observed.

CeAF Ameliorates Diabetic Wound Healing by Alleviating Inflammation and Oxidative Stress via TLR4/NF-κB and Nrf2 Pathways.

With the rise in diabetes incidence, diabetic foot ulcers have become the most common clinically chronic refractory wounds. Persistent chronic inflammation is a typical feature of diabetic cutaneous wounds, and diabetic wound healing can be improved by alleviating inflammation and oxidative stress. Chick early amniotic fluids (ceAF) consist of native conglutinant substances with balanced amounts of growth factors, cytokines, and chemokines. However, whether ceAF modulates inflammation and oxidative stress and thus promotes diabetic wound healing remains unknown. RAW264.7 cells were categorized into four groups: negative control, LPS, LPS + ceAF, and ceAF. 10% of ceAF was selected to treat different groups of mice with a full-thickness skin defect wound. Then, RT-qPCR, western blot, immunofluorescence, and other assays were carried out to explore the effect of ceAF on wound healing and its molecular mechanism. Topical administration of ceAF improved M2 macrophage polarization and inflammatory response in the wound tissues, thereby ameliorating delayed wound healing. Histological improvement could be observed in the grade of inflammation, collagen deposition, and neovascularization in wound edge tissues. ceAF also increased M2 macrophage-specific markers expression and exogenous ceAF suppressed LPS-induced cellular inflammatory response in vitro high glucose environment. Additionally, ceAF could activate TLR4/NF-κB and Nrf2 signal transductions to promote M2 macrophage polarization in vitro. In summary, ceAF downregulates inflammatory response, regulates M2 macrophage transition via TLR4/NF-κB and Nrf2 signaling pathways, and thus improves diabetic wound healing.

IL-22-producing CD3 + CD8- T cells increase in immune clearance stage of chronic HBV infection and correlate with the response of Peg-interferon treatment

Interleukin (IL)-22 regulates host defense. This study investigated the predominant IL-22-producing cell subsets under HBV associated immune stages. We found circulating IL-22-producing CD3 + CD8- T cells were significantly increased in immune active (IA) stage than those in immunotolerant stage, inactive carrier and healthy controls (HCs). The plasma IL-22 level was higher in IA and HBeAg-negative CHB compared to HCs. Importantly, CD3 + CD8- T cells were identified as the predominant source of plasma IL-22 production. Up-regulated IL-22-producing CD3 + CD8- T cells obviously correlated with the grade of intrahepatic inflammation. The proportions of IL-22-producing CD3 + CD8- T cells were significantly down-regulated after 48 weeks of Peg-interferon treatment, and the differences were of great significance in patients with normalize ALT levels at 48 weeks, rather than those with elevated ALT levels. In conclusion, IL-22 might play a proinflammatory function in.chronic HBV infected patients with active inflammation and Peg-interferon treatment could attenuate the degree of liver inflammation through down-regulating IL-22-producing CD3 + CD8- T cells.

Comparative early histologic healing quality of magnetic versus stapled small bowel anastomosis.

Successful anastomotic healing is critical to preventing complications after intestinal surgery. We aimed to compare the early healing of end-to-end small bowel anastomosis by self-forming magnets with surgical stapling in a porcine model. Six Yorkshire pigs underwent 2 simultaneous small bowel anastomoses using a circular stapler and self-forming magnet technique. The primary outcome was healing quality, measured by 4 histologic features: inflammatory cell infiltration, collagen formation, grade of inflammation, and bacterial infiltration at the anastomosis. The samples were evaluated at days 1, 3, and 7. Gross evaluation of anastomotic integrity was a secondary outcome. The self-forming magnet group displayed significant differences at each time point. On day 1, the stapled group displayed dense inflammatory cell infiltration and extensively ulcerated intestinal layers with significant edema. The self-forming magnet group showed less inflammatory infiltrate, and all intestinal layers remained compressed in direct apposition. By day 3, the self-forming magnet group already exhibited neovascularization with scant bacterial colonies. By contrast, stapled anastomoses had large areas of inflammation separating collagen fibers with prevalent bacterial infiltrations. On day 7, self-forming magnet anastomoses were characterized by robust neovascularization, maturing granulation tissue, and mucosal re-epithelization without significant inflammation. Meanwhile, stapled samples had persisting dense inflammation, tissue cavities with hemorrhage, and immature fibrous tissue. Grossly, the self-forming magnet created a patent lumen without defect, whereas stapled anastomoses demonstrated focal areas of serosal separation. Bowel anastomosis by self-forming magnets is associated with superior early histologic healing metrics, including early seal generation through mechanical compression, decreased inflammation, early neovascularization, lower bacterial infiltration, and faster re-epithelization.

Is fatigue related to the severity of liver inflammation in patients with chronic liver disease? A cross-sectional study

ObjectivesFatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing...

Clinical Implications of Low-grade Duodenal Eosinophilia in Functional Dyspepsia: A Prospective Real-life Study.

Functional dyspepsia (FD) is a multifactorial disorder with no targeted therapy. Duodenal eosinophilia and low-grade inflammation are potential pathogenic mechanisms. However, the impact of duodenal eosinophils (D-EO) histologic evaluation in real-life clinical practice was not explored. To evaluate the clinical utility of D-EO and low-grade inflammation in FD in real-life practice. A multicenter prospective study was conducted. A total of 636 patients who meet Rome-III criteria were selected before upper endoscopy and 516 patients were included after normal endoscopy were assessed. Clinical parameters, Helicobacter pylori (H. pylori), and duodenal histology were evaluated. FD subtypes were 231 (45%) patients who had epigastric pain syndrome (EPS), 168 (33%) postprandial distress syndrome (PDS), and 117 (22%) EPS/PDS overlap. Two hundred fifty-nine (50.3%) patients were H. pylori+. Histologic duodenal grading of chronic inflammation and intraepithelial lymphocytes showed no difference between FD subtypes. Increased in D-EO densities (>10 per high power field) was significant in PDS compared with EPS and EPS/PDS overlap subtypes. The odds ratio of PDS in subjects with duodenal eosinophilia densities was 2.28 (95% CI, 1.66-3.14; P<0.0001), adjusting for age, gender, H. pylori and nonsteroidal anti-inflammatory drug the odds ratio was 3.6 (95% CI, 2.45-5.28; P<0.0001). receiver operating characteristic curve analysis further demonstrated that low-grade duodenal eosinophilia, in particular H. pylori-, was highly accurate for PDS with the area under the curve 0.731 compared with H. pylori+ area under the curve 0.598. Furthermore, low-grade duodenal eosinophilia was significantly correlated with treatment response under 4 to 6 weeks of proton pump inhibitor therapy. Our findings suggest that low-grade duodenal eosinophilia is associated with PDS subtype non-H. pylori FD patients and could be a useful marker of treatment response.

PD05-05 THE REAL-LIFE PRACTICE OF INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME - SATISFACTION RATE AND PREDICTIVE FACTORS

You have accessJournal of UrologyCME1 Apr 2023PD05-05 THE REAL-LIFE PRACTICE OF INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME - SATISFACTION RATE AND PREDICTIVE FACTORS Wei-Hsin Chen, Wan-Ru Yu, Jia-Fong Jhang, Yuan-Hong Jiang, and Hann-Chorng Kuo Wei-Hsin ChenWei-Hsin Chen More articles by this author , Wan-Ru YuWan-Ru Yu More articles by this author , Jia-Fong JhangJia-Fong Jhang More articles by this author , Yuan-Hong JiangYuan-Hong Jiang More articles by this author , and Hann-Chorng KuoHann-Chorng Kuo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003229.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Botulinum toxin A (BoNT-A) has been demonstrated to have anti-inflammatory and antinociceptive effects on bladder sensory disorders and has been shown effective in reducing bladder oversensitivity and increasing functional bladder capacity, however, the real-world treatment outcome on interstitial cystitis/bladder pain syndrome (IC/BPS) is still lacking. This study investigated the real-life practice of intravesical BoNT-A injection for patients with IC/BPS. METHODS: This retrospective study included IC/BPS patients treated with 100U BoNT-A intravesical injection in the past twenty years. The treatment outcomes were assessed by the global response assessment (GRA) at 6 months post treatment. The treatment outcome was assessed by classification according to the GRA, clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urine biomarkers, and the predictive factors for a satisfactory outcome were investigated. RESULTS: Of a total of 220 patients (180 females, 40 males) enrolled in this study who received the BoNT-A injection, only 87 (40%) of patients had significantly satisfactory treatment outcomes; the satisfactory group has a significantly larger voided-volume, a lower urinary inflammatory protein MCP-1, and oxidative stress biomarker 8-isoprostane than the unsatisfactory group (Table 1). The IC severity and detrusor pressure are predictive factors to affect treatment outcomes under BoNT-A injection (Figure 1). CONCLUSIONS: IC/BPS patients with less inflammation in the bladder have a satisfactory outcome to intravesical BoNT-A injection. Patients with higher grade of bladder inflammation might need more intravesical BoNT-A injections to achieve a satisfactory outcome. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e150 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei-Hsin Chen More articles by this author Wan-Ru Yu More articles by this author Jia-Fong Jhang More articles by this author Yuan-Hong Jiang More articles by this author Hann-Chorng Kuo More articles by this author Expand All Advertisement PDF downloadLoading ...

Serum HBsAg and HBcrAg is associated with inflammation in HBeAg-positive chronic hepatitis B patients.

Liver inflammation is the main risk factor for developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma in chronic hepatitis B (CHB) patients. To replace biopsy, additional non-invasive biomarkers to diagnose and grade liver necroinflammation are urgently required in clinical practice. Ninety-four CHB patients, including 74 HBeAg-positive and 20 HBeAg-negative patients, were enrolled and started entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), ALT and AST levels, as well as intrahepatic HBV DNA and cccDNA were measured at baseline and during treatment. Liver inflammation was assessed at baseline and month 60 by liver biopsy. Inflammation regression was defined as a ≥1-grade decrease according to the Scheuer scoring system. In HBeAg-positive CHB patients, at baseline, serum HBsAg and HBcrAg levels negatively correlated with inflammation grade, while ALT and AST levels positively correlated with inflammation grade. AST plus HBsAg exhibited excellent diagnostic ability for significant inflammation with an AUROC of 0.896. After 60 months of antiviral treatment, almost all the patients' liver inflammation ameliorated to G1, and no patients had inflammation progression. Besides ALT and AST, serum HBsAg and HBcrAg correlated with inflammation grade in HBeAg-positive CHB patients before NAs treatment. Moreover, the combination of HBsAg and AST exhibited excellent diagnostic ability for significant inflammation.

Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study.

Liquid biopsy based on the analysis of circulating cell-free DNA (cfDNA), as well as on detection of point mutations by digital droplet PCR (ddPCR), has revolutionized the research in oncology. In recent years, this technique has been pioneering in veterinary medicine since it is a minimally invasive approach with very promising results for characterization of tumors. The aim of this study was, firstly, to analyze the concentration and the fragmentation pattern of cfDNA of dogs with mammary tumors (n = 36) and healthy dogs (n = 5) and its correlation with clinicopathological data. Secondly, analysis of TP53 gene expression and the point mutation in the codon 245 were performed in cfDNA and in tumor tissues to assess their potential as plasma biomarkers. Our results highlighted that those dogs with worse clinicopathological characteristics (simple or undifferentiated carcinomas, higher histological grade and presence of peritumoral inflammation) shown higher cfDNA concentration and higher concentrations of short-fragments (<190 bp) than healthy dogs. In addition, although no detection of the point mutation in codon 245 of TP53 gene could be detected neither in plasma nor tumor tissue, an increased TP53 expression was detected in animals with tumors bearing malignant characteristics. Finally, a high concordance with TP53 gene expression in plasma and tumor tissue and cfDNA concentration was also found. The results derived from this work confirm the valuable potential of cfDNA and its fragments, as well as the analysis of TP53 expression in plasma as useful liquid biomarkers for clinical application in veterinary oncology.

Clinical determinants and impact of hemorrhagic lesions on intestinal pathology in preterm infants with surgical necrotizing enterocolitis.

We sought to determine the clinical and histopathological factors associated with intestinal hemorrhage and its correlation with clinical outcomes in neonates with surgical necrotizing enterocolitis (NEC). A retrospective study compared clinical and histopathology information in neonates following surgical NEC with severe hemorrhage and those with mild/moderate hemorrhagic lesions seen on resected intestine pathology. The infants with severe hemorrhage (Grade 3-4, 81/148, 54.7%) had significantly lower exposure to antenatal steroids (52.5 % vs 76.9 %; p = 0.004), had higher gestational age (28.5 weeks [7.14] vs. 26.58 [2.90]; p = 0.034), lost more bowel length (p = 0.045), had higher CRP levels at 2 weeks (p = 0.035), and had less intestinal failure ([30.3 % vs 52.5 %]; p = 0.014) than mild/moderate (Grade 0-2, 67/148, 45.2%) hemorrhage group. Those with severe hemorrhage had significantly higher mean inflammation score (2.67 [0.94] vs. 1.63 [0.92]; p = <0.001), higher necrosis scores (1.95 [1.28] vs. 1.49 [1.35]; p = 0.037), higher neovascularization (p = 0.01), higher fibroblasts (p = 0.023) and higher lymphocyte percentages up to 48 hours (p < 0.05) following NEC than mild/ moderate hemorrhage group.On multivariable regression, less exposure to antenatal steroids (OR 0.18 [95% CI 0.05-0.58]; p = 0.005), higher inflammation (OR 3.7 [95% CI 2.09-7.32]; p = 0.001), and lymphocyte count on the day of onset/24 hours following NEC (OR 1.06 [95% CI 1.02-1.11]; p = 0.005) were independently associated with a higher odd of severe intestinal hemorrhage. The surgical NEC infants with intestinal hemorrhage were less likely to have antenatal steroid exposure but had higher inflammation grade and lymphocyte counts following NEC onset on multivariable regression modeling.

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.