Prevention of Right Heart Failure After Left Ventricular Assist Device Implantation by Phosphodiesterase 5 Inhibitor

Right ventricular (RV) function immediately after left ventricular assist device (LVAD) implantation is a crucial prognostic factor. RV failure is linked to increased mortality and worse outcome. A phosphodiesterase 5 inhibitor, sildenafil, was shown to decrease pulmonary vascular resistance and pulmonary artery pressure post‐LVAD. We report on a series of heart failure patients, and the effect of sildenafil on the incidence of RV failure after LVAD implantation. We retrospectively analyzed the data of end‐stage heart failure patients who underwent LVAD implantation with pulmonary hypertension and RV dysfunction prior to surgery. Patients were divided into two groups; group 1: patients who received sildenafil perioperatively, and group 2: patients who did not receive sildenafil. Hemodynamic and echographic data were collected before and after surgery. Fourteen patients were included, 8 patients in group 1 and 6 in group 2. Sildenafil was administered with a mean dose of 56.2 ± 9.4 mg in group 1 and was able to significantly reduce right heart failure incidence, and to demonstrate a significant reduction in pulmonary vascular resistance, pulmonary artery pressure, transpulmonary gradient, and a significant increase in cardiac output. In conclusion, sildenafil seems to have a promising role perioperatively in preventing acute RV failure postsurgery in patients with RV dysfunction and pulmonary hypertension, requiring LVAD therapy.     

Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin,variability, and outcome

Purpose

Maintaining target hemoglobin (Hb) with minimal variability is a challenge in hemodialysis (HD) patients. The aim of this study is to compare the long- and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets.

Methods

Randomized, prospective, open-labeled study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target was set at (105–125 g/l). Primary end points were percentage of patients achieving target Hb, hemoglobin variability, and number of dose changes in each group.

Results

This study consisted of 139 HD patients: 72 in the Aranesp and 67 in the Eprex—mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex (p < 0.001). There was no difference in hospitalization and death number between the 2 groups.

Conclusions

Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb, with less dose changes and minor vascular access complications.     

Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ETB receptor cascade

Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET_B receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β₁, TGF-β₁). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET_B receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET_B receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ET_B receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET_B receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats.     

Diagnostic potential of magnetic resonance imaging (MRI) of the first carpometacarpal joint in hand osteoarthritis

Aim of this workTo assess the magnetic resonance imaging (MRI) findings compared to plain X-ray in patients with primary nodal osteoarthritis (OA) of first the carpometacarpal (CMC) joint of the thumb.Patients and methodsThis study included 35 Egyptian patients with primary nodal hand OA (HOA) and 15 healthy subjects of matched age. Each subject had plain X-rays graded by Kellgren and Lawrence (K–L) score for HOA. MRI testing of both hands done by using T1/T2 weighted axial and coronal images.ResultsThe mean age was 57.2 ± 8.3 years (45–72 years) and they were 24 females and 11 males. Disease duration of patients ranged (8 months to 10 years, 2.04 ± 1.06 years). In all HOA patients there were signs of knee OA involvement; synovial thickening in 51.4% of patients, knee effusion in 8.6%, limited knee ROM in 28.6% and night pain in 60%. There was a superiority of the MRI in detecting synovitis (71.4%), flexor tenosynovitis (71.4%), collateral ligament (60%), bone marrow lesion (85.7%) and cysts (57.1%) compared to the X-ray which could not detect them. MRI significantly detected osteophytes (88.6%), joint space narrowing (91.4%), erosions (85.7%) and malalignment (57.1%) compared to X-ray (51.4%, 62.9%, 34.3% and 14.3% respectively) (p < 0.001, p = 0.004, p < 0.001 and p < 0.001).ConclusionMRI is superior in detecting HOA changes compared to conventional radiography. As OA is recognized to involve the whole joint, modern imaging techniques such as MRI could be a valuable tool for better evaluation of HOA.     

Serum growth differentiation factor-15 (GDF-15) level in behcet's disease patients: Relation to clinical characteristics,musculoskeletal ultrasound findings and disease activity

Aim of the workThis study was conducted to assess serum level of growth differentiation factor-15(GDF-15) in Behcet’s disease (BD) patients and its relationship with clinical characteristics, ultrasound findings and disease activity.Patients and methodsStudy included 30 BD patients and 20 matched healthy controls. Visual analog scale (VAS)-pain of affected joints and Behcet’s disease current activity form (BDCAF) were assessed. The most affected joints and surrounding soft tissues were assessed by musculoskeletal ultrasound (MSUS).Serum GDF-15 level was measured.ResultsPatients were 23 males and 7 females (M:F 3.3:1) with a mean age of 34.6 ± 8.6 years and mean disease duration of 6.6 ± 4.5 years. 18(60%) had arthritis and arthralgia. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were 26.2 ± 21.2 mm/1^sthr and 50.4 ± 37 mg/dl respectively. There was significant increase of GDF-15 levels in patients with articular affection (3492.3 ± 4618.8 ng/ml) compared to those without (338.9 ± 90.3 ng/ml) and controls (322 ± 78.8 ng/ml) (p < 0.001).As regard MSUS, knee (n = 8) and ankle joints (n = 8) were the most commonly affected joints. Synovitis was present in 13 patients, enthesopathy was present in 10. GDF-15 significantly correlated with ESR and CRP (r = 0.48;p = 0.008 and r = 0.73, p = 0.005) and both remained significant on regression analysis that ESR (p = 0.019 and p = 0.007 respectively). At a serum GDF-15 cut-off point of 570 ng/ml for patients with peripheral arthritis/arthralgia the sensitivity and specificity were 88.9% and 91.7% respectively.ConclusionSerum GDF-15 can be used as a marker for articular affection in BD patients and is associated with the MSUS imaging visualizing subclinical inflammatory changes.