Effect of Everolimus versus Bone Marrow-Derived Stem Cells on Glomerular Injury in a Rat Model of Glomerulonephritis: A Preventive, Predictive and Personalized Implication.

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

Analysis of Medium-Term Weight Regain 5 Years After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: Some patients fail to maintain weight loss after bariatric surgery. Weight regain (WR) disturbs the patients due to possible reappearance of obesity-related comorbidities. This study aimed to assess WR 5 years after laparoscopic sleeve gastrectomy (LSG). PATIENTS AND METHODS: This retrospective study included 100 adults who underwent LGS. The percentage of excess weight loss (%EWL) was recorded. WR was defined as an increase of at least 10% of the lowest postoperative weight. Patients with WR were subjected to CT gastric volumety. Eating behavior was assessed by the Three-Factor Eating Questionnaire-Revised 18-Items (TFEQ-R18). RESULTS: Preoperative comorbidities improved in 89.5% of the patients. Twenty-five females (32.5%) got pregnant within 3 years after surgery. Age, maximum weight loss, and uncontrolled and emotional eating scales of the TFEQ-R18 were independently affecting %EWL. Also, pregnancy negatively affected %EWL. Fourteen patients regain weight: 11 females and three males. CT volumetry of the 14 patients showed a median stomach volume of 515 mL (range 172-1066 mL). CT estimated gastric volume was negatively correlated with % EWL (r = - 0.674, p = 0.008). Patients who developed WR were significantly older (p = 0.006), with lower maximum weight loss, and having higher scores of uncontrolled and emotional eating scales of TFEQ-R18. CONCLUSION: Medium-term postsurgical weight regain and unsuccessful weight loss in patients who had undergone LSG is associated with older age, maladaptive eating behavior, larger residual stomach, and pregnancy.

Low turnover bone disease in Egyptian children with acute leukemia.

The aim of this work was to study bone turnover markers, calcium homeostasis and bone mineral density (BMD) in children with acute leukemia at diagnosis, after induction chemotherapy, and during maintenance therapy to delineate abnormalities present. After evaluation of L2-L4 BMD using dual-energy X-ray absorptiometry in patients with acute myeloid and lymphoid leukemia at presentation and after treatment, the results were compared to 352 healthy age- and sex-matched Egyptian controls. Calcium homeostasis parameters and bone turnover biochemical markers (serum osteocalcin and urinary deoxypyridinoline) were also assayed and the results were compared to 12 healthy age- and sex-matched controls. Osteopenia was observed at diagnosis and during treatment in patients with acute leukemia. At diagnosis osteopenia was observed in 27 patients (62.8%): 10 (23.3%) had non severe osteopenia and 17 (39.5%) had severe osteopenia. This low BMD persisted in those who were followed up. Parathyroid hormone (PTH) (pg/ml) levels demonstrated non significant differences between children with acute leukemia at different stages of therapy and controls, while, 25 (OH) D3 (ng/ml) was significantly lower in acute leukemia patients at different stages of therapy compared to controls (p<0.001). Osteocalcin (ng/ml) is significantly lower in patients at different stages of the disease compared to controls (p<0.001) but there was no significant difference between patients at different stages of therapy. Deoxy-pyridoline cross links showed non-significant difference between the different types of acute leukemia and with controls. Osteopenia is a significant problem in children with acute leukemia at presentation and after chemotherapy. Osteopenia in acute leukemia appears to be of the low turnover type (decreased osteoblastic activity and decreased bone mineralization).