Diagnostic significance of miR‐21, miR‐141, miR‐18a and miR‐221 as novel biomarkers in prostate cancer among Egyptian patients

Prostate cancer (PC) is considered as the fifth cause of cancer deaths worldwide. The exact etiopathogenesis is unclear; however, genetic predisposition, hormonal influencers, lifestyle and environmental factors act as major contributors. It has been found that several miRNAs may play a crucial role in cancer initiation and progression. Here, in this study, we evaluated the peripheral blood levels of miR‐21, miR‐141, miR‐221 and miR‐18a expression among 80 prostate cancer patients (50 localised and 30 metastatic) and 30 benign prostatic hyperplasia patients compared to 50 normal control subjects, using RT‐PCR. Our results of analysis of miR‐21, miR‐141, miR‐18a and miR‐221 in the plasma of PC patients showed that miR‐18a is a powerful discriminator of PC patients from healthy controls as it had the highest AUC (0.966; 95% CI, 0.937–1.000), while miR‐221 provided better differentiation of metastatic from localised PC (sensitivity was 92.9% at 100% specificity), and when we combine miR‐18a and miR‐221 for differentiating patients with MPC, it will increase the sensitivity to 96.4% at a specificity of 100% (AUC, 0.997; 95% CI, 0.988–1.0) (p < .000). This current study recommends that analysis of these miRNAs might have clinical value in enhancing PSA testing.     

Iatrogenic iliac artery rupture and type a dissection after endovascular repair of type B aortic dissection

We report a case of two iatrogenic complications after endovascular repair of a type B aortic dissection treated for abdominal aortic branch ischemia. A rupture of the common iliac artery occurred first during the procedure. A type A dissection occurred 12 days later. The proximal part of the aortic endovascular graft had created a tear in the aortic wall resulting in a retrograde type A dissection. Although aortic endovascular grafting is apparently associated with less morbidity and mortality, potentially lethal complications, both acute and delayed, may arise.     

Contrast enhanced spiral computerized tomography in patients with chronic obstructive uropathy and normal serum creatinine: a single session for anatomical and functional assessment

PURPOSE: We evaluated contrast enhanced spiral computerized tomography (CT) as a single session for the anatomical and functional assessment of patients with chronic obstructive uropathy and normal serum creatinine. MATERIALS AND METHODS: The study included 65 patients with unilateral or bilateral chronic renal obstruction and normal serum creatinine. Five patients had bilateral obstruction and the remaining 60 had unilateral obstruction and a normal contralateral kidney. Therefore, the total number of renal units was 130, that is 70 obstructed and 60 normal. All patients underwent contrast enhanced spiral CT together with excretory urography (IVP) and Tc-mercaptoacetyltriglycine renal scan. CT was used to identify the cause of obstruction and selectively determine the glomerular filtration rate (GFR) of the 2 kidneys. The diagnostic accuracy of CT for identifying the cause of hydronephrosis was compared with that of IVP. Moreover, a correlation was made between CT GFR and isotope GFR. RESULTS: Obstruction was caused by ureteropelvic junction narrowing in 25 cases, ureteral stones in 21, ureteral stricture in 20 and extrinsic ureteral obstruction in 4. Contrast enhanced spiral CT identified the cause of hydronephrosis in all obstructed kidneys (100% sensitivity), while IVP identified the cause in 52 (74% sensitivity), which was a significant difference (p <0.05). CT and IVP excluded obstruction in all normal kidneys (100% specificity). A comparison between the isotope GFR of obstructed kidneys with the corresponding CT GFR showed a perfect correlation (r = 0.78, p <0.0001). Moreover, a similar comparison between isotope GFR and CT GFR of normal kidneys showed an excellent correlation (r = 0.73, p <0.0001). In obstructed and normal kidneys mean isotope clearance was not significantly different from that of mean CT clearance. CONCLUSIONS: Contrast enhanced spiral CT is more sensitive than IVP for identifying the cause of chronic obstructive uropathy. Moreover, it is as accurate as radioisotope renal scan for calculating the total and separate kidney function. We recommend spiral CT with contrast medium as a single radiological diagnostic modality for the assessment of patients with chronic renal obstruction and normal serum creatinine.     

Subcoronary implantation of a stentless valve in patients with aortic aneurysms

Experience with a new operation for patients with aortic valve disease and aneurysm or dissection of the ascending aorta is described. Twenty-four patients aged 66-87 years were operated on using a subcoronary implantation technique with a stentless aortic valve bioprosthesis and an extension using a vascular tube prosthesis. No major adverse cardiac events were observed in the postoperative period. This operation offers a safe alternative to the technically more demanding procedures of composite bioprosthetic ascending aortic replacement or full root replacement.     

Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells

Although mature dendritic cells (DCs) are potent initiators of adaptive immune response, immature steady-state DCs contribute to immune tolerance. In this study, we show that ex vivo splenic DCs are capable of inducing conversion of naïve CD4⁺ T cells to adaptive Foxp3⁺CD4⁺ regulatory T cells (aTreg) in the presence of TGF-β. In particular, when compared with splenic CD8α⁻ DCs, the CD8α⁺ DC subset were superior in inducing higher frequencies of conversion. This was not attributable to the difference in basal level of costimulation, because deficiency of CD40 or CD80/86 signaling did not diminish the differential induction of Foxp3. Conversion was regulated by DC maturation status. Further insights into the molecular mechanisms of conversion were gained by analyzing the contribution of several costimulatory and coinhibitory receptors. Costimulatory signals through GITR suppressed conversion, whereas coinhibitory signaling via programmed death 1 ligand (PD-L1) but not PD-L2 was required for conversion. Ex vivo PD-L1^−/− DCs failed to support Foxp3 induction in the presence of TGF-β. In vivo blocking PD-L1 signaling abolished conversion in a tumor-induced aTreg conversion model. Collectively, this study highlights the cellular and molecular parameters that might be exploited to control the de novo generation of aTregs and peripheral tolerance.     

Inferior vena cava anomalies-a common cause of DVT and PE commonly not diagnosed

A 62-year-old white male presented with recurrent pulmonary embolism (PE) despite having an inferior vena cava (IVC) filter. Investigations ruled out upper limb deep vein thrombosis (DVT) and IVC thrombus, the common causes for a PE in the presence of IVC filter. The culprit was double IVC with a persisting left supracardinal vein that allowed an alternate route for the leg DVT to cause PE. IVC anomalies have a propensity to cause lower limb DVT. Although rarely suspected recent studies have revealed that IVC anomalies are not rare if anticipated and evaluated. Chest CT scans in cases of suspected idiopathic PE should extend up to the renal veins as this will identify common IVC anomalies. Therapy to prevent recurrent DVT can be instituted. A good quality venacavagram should always precede any IVC filter placement as this will identify almost all IVC anomalies and appropriate steps can prevent a recurrent PE.     

Insulin like growth factor-1 increases fatty liver preservation in IGL-1 solution

AIM: To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1) solution to protect fatty liver against cold ischemia reperfusion injury. METHODS: Steatotic livers were preserved for 24 h in IGL-1  solution supplemented with or without IGF-1 and then perfused "ex vivo " for 2 h at 37℃. We examined the effects of IGF-1 on hepatic damage and function (transaminases, percentage of sulfobromophthalein clearance in bile and vascular resistance). We also studied other factors associated with the poor tolerance of fatty livers to cold ischemia reperfusion injury such as mitochondrial damage, oxidative stress, nitric oxide, tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinases.RESULTS: Steatotic livers preserved in IGL-1 solutionsupplemented with IGF-1 showed lower transaminase levels, increased bile clearance and a reduction in vascular resistance when compared to those preserved in IGL-1solution alone. These benefits are mediated by activation of AKT and constitutive endothelial nitric oxide synthase (eNOS), as well as the inhibition of inflammatory cytokines such as TNF-α. Mitochondrial damage and oxidative stress were also prevented.CONCLUSION: IGL-1  enrichment with IGF-1 increasedfatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.