The Efficacy and Safety of Endoscopic Balloon Dilatation in the Treatment of Functional Post-Sleeve-Gastrectomy Stenosis.

Background and Objectives: Functional gastric stenosis, a consequence of sleeve gastrectomy, is defined as a rotation of the gastric tube along its longitudinal axis. It is brought on by gastric twisting without the anatomical constriction of the gastric lumen. During endoscopic examination, the staple line is deviated with a clockwise rotation, and the stenosis requires additional endoscopic manipulations for its transposition. Upper gastrointestinal series show the gastric twist with an upstream dilatation of the gastric tube in some patients. Data on its management have remained scarce. The objective was to assess the efficacy and safety of endoscopic balloon dilatation in the management of functional post-sleeve gastrectomy stenosis. Patients and Methods: Twenty-two patients with functional post-primary-sleeve-gastrectomy stenosis who had an endoscopic balloon dilatation between 2017 and 2023 were included in this retrospective study. Patients with alternative treatment plans and those undergoing endoscopic dilatation for other forms of gastric stenosis were excluded. The clinical outcomes were used to evaluate the efficacy and safety of balloon dilatation in the management of functional gastric stenosis. Results: A total of 45 dilatations were performed with a 30 mm balloon in 22 patients (100%), a 35 mm balloon in 18 patients (81.82%), and a 40 mm balloon in 5 patients (22.73%). The patients' clinical responses after the first balloon dilatation were a complete clinical response (4 patients, 18.18%), a partial clinical response (12 patients, 54.55%), and a non-response (6 patients, 27.27%). Nineteen patients (86.36%) had achieved clinical success at six months. Three patients (13.64%) who remained symptomatic even after achieving the maximal balloon dilation of 40 mm were considered failure of endoscopic dilatation, and they were referred for surgical intervention. No significant adverse events were found during or following the balloon dilatation. Conclusions: Endoscopic balloon dilatation is an effective and safe minimally invasive procedure in the management of functional post-sleeve-gastrectomy stenosis.

Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy.

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson's trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor ß1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines' tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.

Does Hepatitis C Virus Treatment by Directly Acting Antivirals Obligate Shifting Patients with Type 2 Diabetes from Oral Hypoglycemic Drugs to Insulin Therapy?

Purpose: The aim of the present work was to investigate whether hepatitis C virus treatment by directly acting antivirals obligate shifting patients with type 2 diabetes from oral hypoglycemic drugs to insulin therapy. Methods: This was a prospective study including 92 treatment-naïve patients with chronic hepatitis C virus infection and type 2 diabetes who were eligible for treatment with directly acting antivirals (sofosbuvir + daclatasvir ± ribavirin). Patients in the study were divided into two groups; group 1 included 22 patients on insulin therapy and group 2 included 70 patients on oral antidiabetic medications. Patients were advised to keep on their anti-diabetic treatment. Results: All our patients achieved sustained virologic response with significantly lower HbA1c 12 weeks after the end of therapy (p. values 0.001 for group 1 and group 2). There was no statistically significant difference in HbA1c level post-treatment between both groups (p. value 0.352). Conclusion: Achievement of sustained virologic response using interferon free, directly acting antivirals-based regimen was associated with significantly lower HbA1c 12 weeks after the end of therapy. The type of treatment used for type 2 diabetes (oral drugs or insulin) did not affect improved glycemic control observed after achieving sustained virologic response.

Diagnostic efficacy of serum and urinary netrin-1 in the early detection of diabetic nephropathy.

This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to compare its efficacy of estimation in serum with that in the urine. This study was carried out on 135 patients with T2DM and 45 healthy subjects. The patients with diabetes were divided according to urinary albumin creatinine ratio (UACR) into: T2DM with normoalbuminuria, incipient DN with microalbuminuria, and overt DN with macroalbuminuria groups. Serum and urinary levels of netrin-1 were measured by ELISA. The mean levels of serum and urinary netrin-1 were significantly higher in the microalbuminuric and macroalbuminuric patients with DN than those in the normoalbuminuric patients with T2DM, with the highest values detected in macroalbuminuric patients with DN. Urinary netrin-1 level was significantly higher in the normoalbuminuric T2DM group than control group, whereas no significant difference existed regarding serum netrin-1 level. In T2DM groups, the urinary and serum netrin-1 correlated with each other and were independently related to fasting blood glucose, UACR, and estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed that the area under the curve of urinary netrin-1 was 0.916 which is significantly higher than that of serum netrin-1 (0.812) for the detection of incipient DN and reached 0.938 on coestimation of both urinary and serum netrin-1. In conclusion, netrin-1 is a potential diagnostic marker for early detection of DN with its estimation in urine has higher accuracy than that of serum.

Effect of treatment with direct antiviral agents (DAAs) on glycemic control in patients with type 2 diabetes mellitus & hepatitis C virus genotype 4.

BACKGROUND AND AIMS: It is widely recognized that chronic hepatitis C is a metabolic disease that is strongly associated with type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The evidence behind the effect of Direct Anti-Viral Agents (DAAs) therapy on T2DM is conflicting. The aim of the present study was to evaluate the effect of treatment with DAAs on glycemic control in patients with type-2 diabetes mellitus and chronic hepatitis C virus genotype 4. METHODS: This study was a prospective study that conducted on 100 patients with chronic hepatitis C and Type-2 diabetes mellitus, selected from Kafr El-Sheikh Liver Research Center treated with Direct Anti-Viral Agents (DAAs) during the period from September 1, 2017 to last of August 2018. All patients in the study were subjected to the following: Full history taking stressing on the age, gender, previous treatment; clinical examination and laboratory investigations. HBA1C was assessed before and after DAAs treatment. RESULTS: In the present study, there was a significant decrease of baseline fasting blood glucose levels after treatment when compared with before treatment. Also, there was a significant decrease of 2 h post prandial blood glucose after treatment when compared with before treatment. There was significant decrease of HBA1c levels after treatment when compared with before treatment. CONCLUSIONS: DAAs treatment significantly improved the fasting blood glucose and help better glycemic control. This study augments the importance and the benefits of new Direct Anti-Viral Agents interferon free regimens in diabetic HCV infected patients.

Expression of LRP1 and CHOP genes associated with peripheral neuropathy in type 2 diabetes mellitus: Correlations with nerve conduction studies.

AIM: Diabetic peripheral neuropathy (DPN) is a frequent and debilitating complication of diabetes mellitus. The low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional cell surface receptor playing critical roles in lipoprotein metabolism and several cell signaling processes. C/EBP homologous protein (CHOP) is a main conduit to endoplasmic reticulum stress-induced apoptosis. We aimed to investigate LRP1 and CHOP gene expression in peripheral blood cells of type 2 diabetes mellitus (T2DM) subjects to clarify its possible relation to DPN pathogenesis. METHOD: The study included 20 non-complicated T2DM subjects, 20 subjects with DPN and 20 healthy controls. Quantitative real time PCR was used to study gene expression. RESULTS: There was a significant reduction in LRP1 mRNA expression and a significant increase in CHOP mRNA expression in subjects with DPN compared to non-complicated group and healthy controls. Both LRP1 and CHOP expression levels were inversely correlated, and both showed significant correlation with HbA1c, hyperlipidemia, hs-CRP, and different electrophysiological parameters. Receiver operating characteristics (ROC) analysis suggested that both LRP1 and CHOP mRNA expression and hs-CRP levels had great potential advantages to predict the progression of DPN. CONCLUSION: LRP1 and CHOP might be involved in DPN pathogenesis and progression, thus providing opportunities for early detection and treatment.

Circulating miR-21, miR-210 and miR-146a as potential biomarkers to differentiate acute tubular necrosis from hepatorenal syndrome in patients with liver cirrhosis: a pilot study.

BACKGROUND: Acute kidney injury (AKI) in cirrhotic patients may be functional (hepatorenal syndrome [HRS]) or structural (acute tubular necrosis [ATN]). The differentiation between these two conditions remains challenging; no definite biomarker with a clear cutoff value had been declared. miRNAs seem to be attractive innovative biomarkers to identify the nature of kidney injury in cirrhotic patients. This study aimed to investigate the possibility of using miR-21, miR-210 and miR-146a as differentiating markers between HRS and ATN. METHODS: This pilot case control study included 50 patients with liver cirrhosis; 25 with HRS and another 25 with ATN beside 30 healthy controls. Real-time qPCR was used to measure the circulating miRNA tested. RESULTS: Higher levels of miR-21 were observed in both ATN and HRS vs. controls with statistically significant difference between ATN and HRS. The means were 9.466±3.21 in ATN, 2.670±1.387 in HRS and 1.090±0.586 in controls. miR-146a and miR-210 were both significantly lower in ATN and HRS compared to controls with statistically significant differences between ATN and HRS. The means of miR-210 were 1.020±0.643, 1.640±0.605 and 3.0±0.532 in ATN, HRS and controls, respectively. The means of miR-146a were 2.543±1.929, 4.98±1.353 and 6.553±0.426 in ATN, HRS and controls, respectively. ROC analyses proved that the three studied mi-RNAs can be used as differentiating biomarkers between ATN and HRS with the best performance observed with mi-21 achieving specificity and sensitivity equal 96%. CONCLUSIONS: miR-21, miR-210 and miR-146a may be candidate differentiating markers between HRS and ATN in cirrhotic patients.