Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.

Bilateral Retinal Nerve Fiber Layer Loss and Recovery with Teprotumumab in Thyroid Eye Disease

Background: Thyroid Eye Disease (TED) is known to alter tissues of the orbital cavity, including the optic nerve. However, its effect on measured global Retinal Nerve Fiber Layer (gRNFL) is not well elucidated. This case evaluates the effect of teprotumumab on gRNFL in a patient with moderate TED. Observations: A 60-year-old female with controlled ocular hypertension and moderate TED received 8 standard IV teprotumumab infusions. Comprehensive ocular evaluations were performed pre-, during-, and post-treatment. Bilateral gRNFL thickness decreased (10 m OD;12 m OS) at 4 months post-treatment start, persisting at 8 months, but recovered at 20 months. Conclusions and Importance: Teprotumumab treatment in patients with TED led to a transient bilateral decrease in gRNFL thickness, which was restored to baseline levels with no adverse events reported. Monitoring gRNFL changes in teprotumumab-treated patients is crucial as gRNFL thinning indicates retinal ganglion cell damage. Teprotumumabs ability to dampen the IGF-IR inflammatory cascade may have reduced retinal inflammation, leading to recovery.

Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic(type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.

FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation

AIM: To examine the effect of farnesoid X receptor (FXR) activation by GW4064 on endotoxin-induced hepatic inflammation in nonalcoholic fatty liver disease (NAFLD) and the underlying mechanism.

LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver

Background: Nonalcoholic fatty liver disease(NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver(NAFL) and nonalcoholic steatohepatitis(NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. Methods: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson’s trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score(NAS) was analyzed. Results: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine(PC)(P-22:0/18:1), sphingomyelin(SM)(d14:0/18:0), SM(d14:0/24:0), SM(d14:0/22:0), phosphatidylethanolamine(PE)(18:0/22:5), PC(O-22:2/12:0), and PC(26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC(14:0/18:2), PE(18:0/22:5) and PC(26:1/11:0)] or plasmalogens [PC(O-22:0/0:0), PC(O-18:0/0:0), PC(O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC(14:0/18:2), phosphatidic acid(18:2/24:4) were positively correlated with NAS;whereas PC(18:0/0:0) was correlated positively with fibrosis score. Conclusions: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

Efficacy of Sitagliptin on Nonalcoholic Fatty Liver Disease in High-fat-diet-fed Diabetic Mice

Objective Nonalcoholic fatty liver disease(NAFLD)is a common cause of clinical liver dysfunction and an important prepathological change of liver cirrhosis.Central obesity,type 2 diabetes mellitus,dyslipidemia,and metabolic syndrome are the major risk factors for NAFLD.Sitagliptin(Sig)is a novel hypoglycemic agent that improves blood glucose levels by increasing the level of active incretin.Sig has been shown to prevent the development of fatty livers in mice on a fructose-rich diet.The purpose of this study was to observe the efficacy of Sig on NAFLD in type 2 diabetic mice.Methods The diet-induced obesity mouse model was established,and the diabetic mice were screened by an intraperitoneal glucose tolerance trial.The mice were randomly divided into four groups for 8 weeks of intervention:high-fat diet(HFD)group,Sig group,metformin(Met)group,and Sig+Met group.After the intervention,the liver function indexes as well as the blood glucose and blood lipid levels of the mice were measured.In addition,the wet weight of the liver was measured;the pathological sections of the liver tissues were stained to observe the hepatocyte fatty degeneration,inflammation,necrosis,and fibrosis;and the hepatic histological injury was recorded as the NAFLD activity score(NAS).Results Compared with the normal control group,the body weight,liver weight,blood glucose level,insulin resistance(IR),blood lipid level,and transaminase level of the mice in the HFD group were significantly increased,showing typical metabolic syndrome.After treatment with Sig and/or Met,the mice gained less weight,had lower levels of blood glucose,triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and transaminase,and had improved IR compared with the HFD group.The liver pathological NASs in the Sig group(P=0.01),Met group(P=0.028),and Sig+Met group(P<0.001)were lower than those in the HFD group(P<0.05),suggesting that the use of the two drugs alone or in combination can improve the state of liver inflammation.In terms of fibrosis,there was no fibrosis in the control group but there was significant fibrosis in the HFD group(P<0.001).There was no significant difference between the drug intervention groups and the HFD group,indicating that the drug therapy(Sig and/or Met)did not significantly improve the pre-existing fibrosis.Conclusion Our experiment proved that Sig can improve NAFLD,including improvement of the serum transaminase level,hepatic pathological inflammation level,and hepatocyte adiposis,suggesting that Sig may play a role by improving glucose and lipid metabolism,reducing the body weight and liver weight,improving insulin sensitivity,and inhibiting fatty liver inflammation.Sig may be a new direction for the treatment of patients with a nonalcoholic fatty liver and diabetes,delaying the progression of NAFLD.

Evaluation of a new Tunisian version of behcet’s disease current activity form

Background: Beh&#231;et’s Syndrome (BS) is characterized by a heterogeneous vessel involvement, a fluctuating natural history and by the absence of biological markers correlated to disease activity that’s why objective clinical scores are needed for the assessment of its activity. The Beh&#231;et’s Disease Clinical Activity Form (BDCAF) is the most recent and widely used clinical activity score. Objectives: To perform a cross-cultural adaptation of the Beh&#231;et’s Disease Current Activity Form (BDCAF) to the Tunisian Dialect (Arabic Language) and to evaluate the metrological characteristics of the Tunisian version (Tu-BDCAF) especially its reliability in BD activity evaluation. Methods: Cross-cultural adaptation was done according to the established guidelines. Reliability of Tu-BDCAF was tested among 40 BD patients (mean age: 38 years, sex ratio: 1.37). Patients were questioned by two BD specialists at 20 minutes interval to evaluate inter-observer reproducibility and twice by the same physician at 48 hours interval to assess the intra-observer reproducibility. k Coefficient was used to test the concordance between qualitative variables and correlation between quantitative variables was evaluated used Pearson coefficient and Bland and Altman graphical method. Results: There was a good correlation between global scores calculated by the two physicians on the same day (r = 0.94, p < 0.0001) and also between the scores calculated by the same clinician at different times (r = 0.98, p k Coefficient analyses demonstrated a good intra and inter observer reliability for all the Tu-BDCAF items excepted for diarrhea and Clinician’s impression. As the original version, Tu-BDCAF is an objective, easy-calculated and reliable index for assessing disease activity in BD. The main limit of the BDCAF score remains the absence of a cut-off point defining BD activity. Conclusion: Tu-BDACF is a Tunisian version of the BDCAF score which can be used in routine to assess BD activity but also in international studies and clinical trials.

The relationship between serum zinc levels and rheumatoid arthritis activity

OBJECTIVES： Rheumatoid arthritis （RA） is one of the most prevalent chronic autoimmune diseases; it typically involves the hands, wrists, ankles, and eventually all joints. Some studies have reported that zinc serum levels are lower in patients with RA than in healthy individuals. MATERIALS and METHODS： Seventy-nine patients with RAwere selected. The patients were all less than 75 years old and were diagnosed by a rheumatologist. Serum zinc levels were measured using the flame photometry method with a blood sample of 5 mL. The relationship between the average serum zinc level and disease activity was analyzed based on the DAS28 scoring scale for different RA groups. The significance threshold was set atp 〈 0.05. Data analyses were implemented in SPSS 22.0. RESULTS： There was a significant inverse relationship between the serum zinc levels and disease activity. Chi-square tests were used to compare zinc serum levels with respect to disease activity. There were significant differences in zinc levels among three groups of patients with different levels of disease severity, such that disease activity increased as the serum zinc level decreased （p 〈 0.001）. CONCLUSION： There was a significant inverse relationship between the serum zinc level and RA activity based on the DAS28 score. Therefore, it is recommended that mineral deficiencies should be addressed by optimizing the zinc supply along with other standard medications in order to reduce RA activity.