Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis—A Pilot Study

Takayasu arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Elevated Plasma Matrix Metalloproteinase-8 associates with Sputum Culture Positivity in Pulmonary Tuberculosis

Current methods for tuberculosis (TB) treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during TB treatment as biomarkers. Plasma MMP-1, -8 and -10 significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture positive relative to culture negative participants, prior to (median 4609 pg/ml, IQR 2353-9048 vs 775 pg/ml, IQR 551-4920, p=0.019) and after 6 months (median 3650, IQR 1214-3888 vs 720, IQR 551-1321, p=0.008) of TB treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance TB treatment monitoring and screen for possible culture positivity.

Urinary procollagen III aminoterminal propeptide/creatinine (PIIINP/Cr) ratio and transforming growth factor beta/creatinine (TGF-β/Cr) ratio in children with idiopathic nephrotic syndrome on corticosteroid and cyclosporine A treatment

Idiopathic nephrotic syndrome is a common nephropathy in children basically treated with corticosteroids and, in some cases, with cyclosporin A. There are concerns that proteinuria itself and cyclosporin A could cause renal fibrosis via activation of transforming growth factor beta (TGF-β), which may stimulate deposition of collagen type III, synthesised as procollagen III amino terminal propeptide (PIIINP). The aim of this study was to assess urinary TGF-β and PIIINP to creatinine (Cr) ratio as markers of renal fibrosis in children with idiopathic nephrotic syndrome put on corticosteroid and cyclosporin A treatment. Materials and methods: The study comprised 20 children with idiopathic nephrotic syndrome in remission on prednisone, aged 6.87 years [interquartile range (IQR): 6.37]; 21 children with idiopathic nephrotic syndrome in remission on cyclosporin A, aged 9.66 years (IQR: 5.0); and 21 healthy subjects, aged 7.16 years (IQR: 9.0). First morning urinary PIIINP/Cr and TGF-β/Cr were obtained and compared with Mann–Whitney U test, with the level of significance at p ≤ 0.05. Results: PIIINP/Cr ratio was significantly elevated in the cyclosporin A group [3.44 (2.5) vs. 1.12 (0.96) μg/mmol], p = 0.000, as well as in the prednisone group when compared to controls [1.33 (1.58) vs. 1.12 (0.96) μg/mmol], p = 0.042. The TGF-β/Cr ratio was significantly higher only in the cyclosporin A group when compared to controls [4.03 (3.25) vs. 2.33 (1.62) μg/mmol], p = 0.004. Conclusions: Increased urinary PIIINP/Cr ratio in children with idiopathic nephrotic syndrome either on steroid or on cyclosporin A therapy may suggest that renal fibrosis is a process generally involved in idiopathic nephrotic syndrome. Elevated urinary TGF-β/Cr and PIIINP/Cr ratios in patients with idiopathic nephrotic syndrome on cyclosporin A may reflect nephrotoxicity of this drug.

NaHS-Hydrogel and Encapsulated Adipose-Derived Stem Cell Evaluation on an Ex Vivo Second-Degree Burn Model

Second-degree burns result in the loss of the epidermal barrier and could lead to delayed complications during the healing process. Currently, therapeutic options to treat severe burns are limited. Thus, this work aims to evaluate the effect of NaHS, a hydrogen sulfide (H2S) donor, in poloxamer hydrogel in topical application and the potentiating effect of injected encapsulated adipose-derived stem cells (ASCs) compared to monolayer ASCs using our previous second-degree burn model on human skin explants. Indeed, our model allows testing treatments in conditions similar to a clinical application. The observed benefits of NaHS may include an antioxidant role, which might be beneficial in the case of burns. Concerning ASCs, their interest in wound healing is more than well documented. In order to evaluate the efficiency of our treatments, we analyzed the kinetics of wound closure, keratinocyte proliferation, and dermal remodeling. The effect of NaHS led to a delay in re-epithelialization, with a decrease in the number of proliferating cells and a decrease in the synthesis of procollagen III. On the contrary, intradermal injection of ASCs, encapsulated or not, improves wound healing by accelerating re-epithelialization and collagen I synthesis; however, only encapsulated ASCs accelerate keratinocyte migration and increase the rate of procollagen III and collagen III. In conclusion, NaHS treatment did not improve burn healing. However, the injection of ASCs stimulated wound healing, which is encouraging for their therapeutical use in burn treatment.

Serum N-glycan fingerprint nomogram predicts liver fibrosis: a multicenter study

Objectives Liver cirrhosis (LC) is the end-stage of fibrosis in chronic liver diseases, non-invasive early detection of liver fibrosis (LF) is particularly essential for therapeutic decision. Aberrant glycosylation of glycoproteins has been demonstrated to be closely related to liver abnormalities. Methods This study was designed to enroll a total of 1,565 participants with LC/LF, chronic hepatitis virus (CHB) and healthy controls. Fibrosis was confirmed by liver biopsy. Using capillary electrophoresis N-glycan fingerprint (NGFP) analysis, we developed a nomogram algorithm (FIB-G) to discriminate LC from non-cirrhotic subjects. Results The FIB-G demonstrated good diagnostic performances in identifying LC with the area under the curve (AUC) 0.895 (95%CI: 0.857–0.915). Furthermore, the diagnostic efficiencies of FIB-G were superior to that of log (P2/P8), procollagen III N-terminal (PIIINP), type IV collage (IV-C), laminin (LN), hyaluronic acid (HA), aspartate transaminase to platelets ratio index (APRI), and FIB-4 when detecting significant fibrosis (S0–1 vs. S2–4, AUC: 0.787, 95%CI: 0.701–0.873), severe fibrosis (S0–2 vs. S3–4, AUC: 0.844, 95%CI: 0.763–0.924), and LC (S0–3 vs. S4, AUC: 0.773, 95%CI: 0.667–0.880). Besides, changes of FIB-G were associated well with the regression of fibrosis and liver function Child–Pugh classification. Conclusions FIB-G is an accurate multivariant N-glycomic algorithm for LC prediction and fibrosis progression/regression monitoring. The high throughput feasible NGFP using only 2 μL of serum could help physicians make the more precise non-invasive staging of LF or cirrhosis and reduce the need for invasive liver biopsy.

Collagenofibrotic Glomerulopathy: Report a Rare Case

Collagenofibrotic glomerulopathy is a rare clinical entity with fewer than 40 cases reported worldwide. We describe a case of adult onset nephrotic syndrome with partial villous atrophy of the intestine who was diagnosed with this rare entity. Collagenofibrotic glomerulopathy is characterized by subendothelial and mesangial collagen type III deposition and increased procollagen III peptide levels. Extra renal involvement has been described in the form of hypertension, anemia and microangiopathic hemolytic anemia but villous atrophy has not been associated with this condition so far, possibly reflecting the paucity of literature. We describe this case and review the condition in this report.

Effects of Novel Dual GIP and GLP-1 Receptor Agonist, Tirzepatide, on Biomarkers of Non-Alcoholic Steatohepatitis in Patients with T2DM

<b>Objective</b>: To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in T2DM patients. <p><b>Research Design and Methods</b>: T2DM patients received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), Keratin-18 (K-18), Procollagen III (Pro-C3), and adiponectin, were analyzed in a modified intent-to-treat population.</p> <p><b>Results</b>: Significant (p<0.05) reductions from baseline in ALT (all groups), AST (all groups, except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg) and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg), and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10 and 15 mg).</p> <p><b>Conclusions</b>: In post-hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in T2DM patients. </p>

Effects of Novel Dual GIP and GLP-1 Receptor Agonist, Tirzepatide, on Biomarkers of Non-Alcoholic Steatohepatitis in Patients with T2DM

<b>Objective</b>: To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in T2DM patients. <p><b>Research Design and Methods</b>: T2DM patients received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), Keratin-18 (K-18), Procollagen III (Pro-C3), and adiponectin, were analyzed in a modified intent-to-treat population.</p> <p><b>Results</b>: Significant (p<0.05) reductions from baseline in ALT (all groups), AST (all groups, except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg) and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg), and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10 and 15 mg).</p> <p><b>Conclusions</b>: In post-hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in T2DM patients. </p>