Levels of Salivary IFN-gamma, TNF-Alfa, and TNF Receptor-2 As Prognostic Markers in (Erosive) Oral Lichen Planus

To explore the feasibility of detecting salivary levels of IFN-γ, TNF-α, and sTNFR-2 from erosive oral lichen planus (ELP) patients for clinical application, 20 ELP patients were enrolled in the study as were 20 age-sex-matched controls. From all subjects, saliva level of the tested biomarkers was determined by ELISA. Salivary profiles were assessed in ELP patients by ELISA after being treated with prednisone. A significantly higher level of IFN-γ (P ≤ .01), TNF-α (P ≤ .0001), and sTNFR-2 (P ≤ .01) was detected in ELP patients before treatment than in controls. Following treatment, the salivary levels of IFN-γ (P ≤ .01), TNF-α (P ≤ .05), and sTNFR-2 (P ≤ .01) decreased significantly when compared to their pretreatment levels. This study demonstrated that salivary IFN-γ, TNF-α, and sTNFR-2 can be detectable in ELP patients and decreased significantly after treatment with prednisone, which may reveal the possibility of using these disease-related biomarkers in diagnosis and monitoring

IL-17 and IL-11 GCF Levels in Aggressive and Chronic Periodontitis Patients: Relation to PCR Bacterial Detection

Objectives. This study evaluated IL-17 and IL-11 in gingival crevicular fluid (GCF) of generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP) patients in relation to periodontopathic bacteria. Subjects and Methods. GCF samples were collected from 65 subjects including 25 CP, 25 GAgP, and 15 controls (C) and analyzed for IL-17 and IL-11 by an enzyme-linked immunosorbent assay. Molecular detection of bacteria in the dental plaque was determined by polymerase chain reaction. Results. The total amount of IL-17 was significantly higher in GAgP group than in GCP and C groups (P<0.001). The IL-11 concentration was significantly higher in C and GCP groups than GAgP group (P<0.001). The IL-11/IL-17 ratio was significantly higher in the C group than in GCP and GAgP groups (P<0.05). Moreover, GAgP group showed lower ratios of IL-11/IL-17 when compared to GCP group. The high positivity of P. gingivalis in the dental plaque was associated with significantly increased GCF levels of IL-17 in GCP and GAgP patients. Conclusions. The increased IL-17 level in GCF of GAgP suggests a potential role in the aetiopathogenesis. Meanwhile, the decreased ratio of IL-11/IL-17 might reflect an imbalance between the proinflammatory and anti-inflammatory cytokines in different periodontal diseases

Effect of Periodontal Surgery on Osteoprotegerin Levels in Gingival Crevicular Fluid, Saliva, and Gingival Tissues of Chronic Periodontitis Patients

Objectives. This study was undertaken to investigate the OPG profiles in gingival crevicular fluid (GCF), saliva, and gingival tissues of chronic periodontitis (CP) patients in response to open flap debridement (OFD). Subjects and Methods. The study included 30 subjects divided into 2 groups: 20 CP patients and 10 periodontally healthy subjects. Plaque index, gingival index, pocket depth, and clinical attachment level measurements were recorded for all subjects. GCF, salivary, and gingival samples were collected from all 30 subjects at baseline and 3 and 6 month after OFD from the 20 CP patients. GCF and salivary OPG levels were assessed by ELISA assay, while OPG expression in gingival tissues was examined by immunohistochemistry. Results. GCF, salivary and gingival OPG profiles were significantly higher in control subjects compared to CP patients at baseline (P<0.001). Within CP group, OPG levels in GCF, saliva, and gingival samples showed a significant increase at 3 and 6 months after OFD (P<0.001) compared to baseline. Although OPG values increased significantly in gingival samples and insignificantly in saliva after 3 months compared to 6 months, yet GCF levels were significantly decreased. Conclusions. OPG might be considered as a diagnostic and prognostic biomarker of periodontal bone destruction. This trial is registered with NCT02160613

Inhibition of the Renal Apical Sodium Dependent Bile Acid Transporter Prevents Cholemic Nephropathy in Mice with Obstructive Cholestasis.

BACKGROUND & AIMS Cholemic nephropathy (CN) is a severe complication of cholestasis-associated liver diseases, with no specific treatment. We revisited the pathophysiology to identify therapeutic strategies. METHODS Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI-MSI and LC-MS/MS. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed by ASBT immunostaining in kidney biopsies of CN patients, analysis of mice with humanized BA spectrum, and by analysis of serum bile acids (BA) and kidney injury molecule (KIM-1) in liver disease and hyperbilirubinemia patients. RESULTS Proximal tubular epithelial cells (TEC) reabsorbed and enriched BA, leading to oxidative stress and death of proximal TEC, casts in distal tubules and collecting ducts, peritubular capillaries leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TEC and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In advanced liver disease patients, serum BA were the main determinant of KIM-1 levels. ASBT expression in TEC was preserved in biopsies from CN patients, further highlighting the translational potential of targeting ASBT for treatment of CN. CONCLUSIONS BA enrichment in proximal TEC followed by oxidative stress and cell death is an early key event in CN. Inhibiting renal ASBT and consequently BA enrichment in TEC prevents CN and systemically decreases BA concentrations. IMPACT AND IMPLICATIONS Cholemic nephropathy (CN) is a severe complication of cholestasis with an unmet clinical need for therapy. We demonstrate that CN is triggered by the renal accumulation of bile acids (BA)- that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells (TEC) of the kidney take up BA via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in TEC, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for CN patients

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)