Evaluation of urinary FOXP3 mRNA as a biomarker of lupus nephritis in Egyptian patients with systemic lupus erythematosus.

AIM: Lupus nephritis (LN) is one of the most serious complications of SLE. Tregs (Regulatory T lymphocytes) are thought to play a part in the pathogenesis of SLE. According to recent research, Foxp3, a Treg identification marker, plays a significant role in the pathogenesis of SLE. This study aimed to compare the urinary Foxp3 mRNA levels of patients with active and inactive forms of LN and healthy control subjects to see whether it played a role in disease activity. METHODS: We measured FOXP3 messenger RNA (mRNA) expression in the urine of 50 people with active LN, 50 people with inactive lupus, and 50 healthy people. RESULTS: We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (22.93 ± 4.13 vs 5.66 ± 0.47 vs 0.57 ± 0.15copy; P < 0.001).Urinary FOXP3 mRNA level significantly correlated with SLEDAI (0.000057) In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (< 0.00001). CONCLUSION: We concluded that urinary FOXP3 mRNA is elevated in patients with active LN and that it is linked to the SLEDAI and the severity of the disease. FOXP3 mRNA in urine sediment may be used as a non-invasive biomarker for evaluating the severity of LN and risk stratification.

Impact of laparoscopic sleeve gastrectomy on fibrosis stage in patients with child-A NASH-related cirrhosis.

PURPOSE: Bariatric surgery can improve non-alcoholic fatty liver disease (NAFLD). Yet data on the effect on fibrosis are insufficient and controversial. This work endeavored to evaluate the safety of laparoscopic sleeve gastrectomy (LSG) in cases that have compensated non-alcoholic steatohepatitis (NASH)-related cirrhosis and its impact on fibrosis stage. METHODS: The current prospective work involved 132 cases with Child-A NASH-related cirrhosis suffering from morbid obesity scheduled for LSG. They were subjected to preoperative assessment, wedge biopsy, and ultrasound-guided true-cut liver biopsy after 30 months. Patients were included if proved to have F4 fibrosis initially. The liver condition was assessed based on the NALFD Activity Score (NAS). The primary outcome measure was the impact of LSG on fibrosis stage and its relation to weight loss. RESULTS: The analysis included only 71 patients who completed the 30-month follow-up period. By the end of the follow-up interval, there was a substantial weight loss with a reasonable resolution of comorbidities. The median NAS decreased significantly from 6 (1-8) to 3 (0-6) after surgery. Fibrosis score regressed to F2 in 19 patients (26.8%) and F3 in 29 (40.8%). Patients with improved scores had a significantly higher amount of weight loss (p < 0.001). Improvement was more frequent in males (p = 0.007). By 30 months after treatment, 53.8% of cases with borderline NASH and 36.8% of those with probable NASH showed complete resolution, and 44.7% of patients with NASH showed improvement. Steatosis improved in 74.6% of patients (p < 0.001). CONCLUSION: In patients with NASH-related liver cirrhosis of Child class A, LSG may be a secure approach for the management of morbid obesity. It has a long-term benefit for both obesity and liver condition with significant improvement of steatosis, steatohepatitis, and fibrosis.

Effect of weight loss induced by laparoscopic sleeve gastrectomy on liver histology and serum adipokine levels.

BACKGROUND & AIM: Bariatric surgery is a valid treatment option for persons with non-alcoholic fatty liver disease. This study prospectively examined the impact of laparoscopic sleeve gastrectomy (LSG) on liver histopathology, and blood levels of adiponectin, leptin, resistin, and pre-B cell enhancing factor/Nampt/visfatin. PATIENTS & METHODS: In 81 patients with non-alcoholic fatty liver disease who underwent LSG, paired liver biopsies and blood specimens were obtained before and 18 months after LSG. Differences between preoperative and 18 months postoperative data were tested by paired Student's t-test or Wilcoxon rank test as appropriate. RESULTS: At follow up, there was a significant improvement in biochemical markers for glucose homeostasis, including fasting glucose, HbA1c, insulin levels, and homeostatic model assessment index. Postoperative liver function tests, namely serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase level, showed a significant improvement compared to before weight loss. The number of patients who had definite, borderline, or no non-alcoholic steatohepatitis was 43 (53%), 27 (33%), and 11 (14%), respectively, at baseline, and 9 (11%), 32 (40%), and 40 (49%) at 18-month post-surgery follow up. A significant reduction in steatosis, liver fibrosis, lobular inflammation, and hepatocyte ballooning was observed in the postoperative biopsies (P < 0.001 each). In addition, at the follow-up assessment, there was a significant increase in serum adiponectin levels and significant decline in serum levels of leptin, resisitin, and pre-B cell enhancing factor/Nampt/visfatin. CONCLUSION: Weight loss after sleeve gastrectomy was associated with a significant improvement in several metabolic parameters, liver enzyme levels, liver histopathology, and changes in serum adipokine levels towards antidiabetic and anti-inflammatory profiles.

Acceleration of Gastric Emptying and Improvement of GERD Outcome After Laparoscopic Sleeve Gastrectomy in Non-diabetic Obese Patients.

PURPOSE: Obesity has become a pandemic nowadays. Bariatric surgery is increasingly performed to manage obesity. Currently, laparoscopic sleeve gastrectomy (LSG) is a widely accepted procedure given its feasibility and efficacy. Previous studies revealed conflicting results regarding the change of gastric emptying following sleeve gastrectomy. The primary aim of the present study is to assess gastric motor function by gastric emptying scintigraphy in a cohort of non-diabetic patients undergoing laparoscopic sleeve gastrectomy (LSG) for treatment of severe obesity. METHODS: This prospective observational study included 100 obese, non-diabetic patients attending the surgery clinic at Cairo University Hospitals and Al Azhar University Hospitals. LSG was performed following a standardized protocol, with no complications observed. All patients had gastric emptying scintigraphy done through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99, pre-operatively and 3 months after LSG. RESULTS: The mean age was 38.71 years (9.2) and males comprised 57% of the cohort. The body mass index, low-density lipoproteins, and glycated hemoglobin declined significantly at 3-month postsurgery. The scintigraphy study revealed a significantly reduced percent retention at equivalent time points 3 months after LSG. In addition, the percent of patients suffering from GERD decreased significantly after LSG. CONCLUSION: Gastric emptying becomes faster after LSG in morbidly obese non-diabetic patients. GERD symptoms improve after surgery.

Urinary podocalyxin: Is it a real index of disease activity in egyptian patients lupus nephritis?

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by production of a number of antinuclear antibodies. Podocyte injury is an important feature and can be detected by several markers including podocalyxin. We aimed to evaluate the impact of SLE on urinary levels of podocalyxin and to determine its relationship to renal biopsy, proteinuria, and disease activity in lupus nephritis (LN) patients. Sixty individuals were recruited; 30 SLE patients with LN as well as 30 healthy volunteers and they were subjected to full history, clinical examination, kidney function, protein/creatinine ratio, urinary podocalyxin, and kidney biopsy. Patients with LN had higher level of urinary podocalyxin (3.96 ± 2.24) than the other group (0 ± 0), (P <0.001). Class IV LN was the most common class found among LN patients [18 cases (60%)]. There was a statistically significant positive correlation between SLE disease activity index score, protein/creatinine ratio, and urinary podocalyxin (P <0.001, r = 0.98) (P <0.001, r = 0.765). There was a statistically significant negative correlation between serum albumin, serum calcium, and urinary podocalyxin (P = 0.001, r = -0.589) (P = 0.025, r = -0.407). Urinary podocalyxin level significantly predicts the pathological impact of SLE on the kidney and could be used as a noninvasive marker for such effect and its progression.

Study of changes of obesity-related inflammatory cytokines after laparoscopic sleeve gastrectomy.

BACKGROUND: Chronic inflammation in adipose tissue may play a substantial role in the pathogenesis of obesity-related metabolic disorders. The present study aims to evaluate the changes in adipocytokines, bile acids, fibroblast growth factor 19 (FGF-19) and pro-inflammatory cytokines 6 months after laparoscopic sleeve gastrectomy (LSG). METHODS: This prospective study included 75 obese patients with body mass index >35 kg/m2 who underwent LSG. All patients were recruited preoperatively and followed up post-operatively at 6 months, with laboratory assessment of their cytokines including adiponectin, leptin, resistin, bile acid, interleukin (IL)-6, IL-8, tumour necrosis factor-α, monocyte chemotactic protein-1, high-sensitivity C-reactive protein, plasminogen activator inhibitor-1, serum amyloid-A and FGF-19. RESULTS: There were statistically highly significant changes regarding anthropometric parameters (weight, body mass index and waist-to-hip ratio), blood glucose and lipid profile as well as liver enzymes at 6 months post-sleeve gastrectomy. The present study showed that the levels of serum adiponectin and FGF-19 significantly increased at 6 months of follow-up after surgery (P < 0.001), while the levels of serum leptin, resistin, high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 and serum amyloid-A significantly decreased at 6 months of follow-up after surgery (P < 0.001). There were no significant differences regarding serum bile acid, IL-6, IL-8, tumour necrosis factor-α and monocyte chemotactic protein-1. CONCLUSION: Weight loss after LSG is associated with significant improvement of the adipokine levels towards anti-diabetic and anti-inflammatory profiles. Future studies should use a larger sample size and longer follow-up periods.