Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.     

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data

Purpose

The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury.

Methods

We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume.

Results

Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P?=?0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P?=?0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P?=?0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T.

Conclusions

Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

     

Pathophysiology,Diagnosis, and New Therapeutic Approaches for Ischemic Mitral Regurgitation

Ischemic mitral regurgitation (MR) is a valvular complication frequently seen in patients with coronary artery disease and is associated with increased mortality and morbidity. Ischemic mitral regurgitation has a complex, heterogeneous, and still incompletely understood pathophysiology involving both the mitral valve and the left ventricle. The occurrence of valve regurgitation in patients with ischemic cardiomyopathy in return accelerates left ventricular remodelling and dysfunction, ultimately leading to irreversible heart failure. Diagnostic evaluation of ischemic MR is unique and different from the other causes of MR. The severity thresholds associated with outcomes are different from primary MR, and specific imaging characteristics are potentially useful to guide therapy. The use of imaging modalities such as 3-dimensional echocardiography and cardiac magnetic resonance imaging can refine the diagnostic evaluation and help in choosing the correct management. Although multiple treatments are available to improve ischemic MR, each therapeutic option is associated with limitations and incomplete success. Therapy has therefore to be individualised for each patient. Current options include optimal medical therapy, cardiac resynchronisation therapy, percutaneous or surgical revascularisation, surgical mitral repair or replacement, and new percutaneous interventions. This review aims to discuss the latest insights regarding the pathophysiology, diagnosis, and treatment of ischemic MR.     

Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism

The adhesion of haematopoietic progenitor cells (HPC) to the bone marrow microenvironment is a process regulated by cytokines. In this study, we have shown that flt3-ligand (FL), a growth factor that controls early haematopoiesis, regulated the function and expression of the beta-1 integrins, very late antigen (VLA)-4 and VLA-5 on HPC. The modulation of the adhesiveness of HPC by FL was studied by adhesion assays on umbilical vein endothelial cells (HUVEC). Stimulation by FL induced two peaks of increased adhesiveness of HPC. The first peak was at around 30 min and was mechanistically related to an activation of the beta-1 integrins, mainly VLA-4 and VLA-5. The second peak was at around 12 h and was related to increased expression of VLA-4 and VLA-5. The control of HPC adhesiveness by FL is a previously unreported property of FL that may be important for the homing and the retention of flt3-expressing HPC within the bone marrow microenvironment.     

Lymphocytic hypophysitis with lachrymal, salivary and thyroid gland involvement

We report on hypophysitis associated with a prominent lymphoid infiltration of salivary and lachrymal glands in a 35-year-old woman with a dramatic response to steroids. Four years later, overt Graves' disease developed. To our knowledge, pseudotumoral lymphocytic infiltration of both lachrymal and salivary glands has never been described in association with hypophysitis. Benign lymphocytic hypophysitis may belong to a spectrum that extends from low-grade lymphoid proliferation to autoimmune disease. Such a process may follow a regional tissue distribution including pituitary, thyroid, lachrymal and salivary glands.     

The Immediate Effects of Foam Rolling and Stretching on Iliotibial Band Stiffness: A Randomized Controlled Trial

BackgroundIliotibial Band Syndrome (ITBS) is a common clinical condition likely caused by abnormal compressive forces to the iliotibial band (ITB). Stretching interventions are common in ITBS treatment and may predominantly affect tensor fascia latae (TFL). Another ITBS treatment is foam rolling, which may more directly affect the ITB. Shear wave ultrasound elastography (SWUE) measures real-time soft tissue stiffness, allowing tissue changes to be measured and compared.PurposeTo examine effects of foam rolling and iliotibial complex stretching on ITB stiffness at 0˚ and 10˚ of hip adduction and hip adduction passive range of motion (PROM).Study DesignRandomized controlled trial.MethodsData from 11 males (age = 30.5 ± 9.0 years, Body Mass Index (BMI) = 27.8 ± 4.0) and 19 females (age = 23.5 ± 4.9, BMI = 23.2 ± 2.1) were analyzed for this study. Subjects were randomly assigned to one of three groups: control, stretching, and foam rolling. Shear wave ultrasound elastography measurements included ITB Young’s modulus at the mid-thigh, the distal femur and the TFL muscle belly. ITB-to-femur depth was measured at mid-thigh level. Hip adduction PROM was measured from digital images taken during the movement.ResultsNo significant interactions or main effects were found for group or time differences in ITB Young’s modulus at the three measured locations. The ITB stiffness at the mid-thigh and distal femur increased with 10° adduction, but TFL stiffness did not increase. A main effect for adduction PROM was observed, where PROM increased 0.8˚ post-treatment (p = 0.02).ConclusionA single episode of stretching and foam rolling does not affect short-term ITB stiffness. The lack of ITB stiffness changes may be from an inadequate intervention stimulus or indicate that the interventions have no impact on ITB stiffness.Levels of Evidence1b