Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer's disease.

Discoidin Domain Receptor (DDR)-1 is activated by collagen. Nilotinib is a tyrosine kinase inhibitor that is FDA-approved for leukemia and potently inhibits DDR-1. Individuals diagnosed with mild-moderate Alzheimer's disease (AD) treated with nilotinib (versus placebo) for 12 months showed reduction of amyloid plaque and cerebrospinal fluid (CSF) amyloid, and attenuation of hippocampal volume loss.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy.

DOOMED: Direct Online Optimization of Modeling Errors in Dynamics.

It has long been hoped that model-based control will improve tracking performance while maintaining or increasing compliance. This hope hinges on having or being able to estimate an accurate inverse dynamics model. As a result, substantial effort has gone into modeling and estimating dynamics (error) models.

Use of percutaneous transluminal septal myocardial ablation for relief of outflow tract obstruction in cardiac amyloidosis: a novel therapeutic target.

Cardiac amyloidosis typically presents with diastolic heart failure, but asymmetrical septal hypertrophy with outflow tract obstruction has been described. We illustrate the case of a 71-year-old woman with biopsy-proven cardiac amyloidosis and severe medical comorbidities with refractory severe heart failure who had asymmetric septal hypertrophy, systolic anterior motion (SAM) of the mitral valve, and a resting left ventricular outflow tract gradient of 86 mm Hg, increasing to 102 mm Hg on Valsalva maneuver. She underwent percutaneous transluminal septal myocardial ablation (PTSMA) with a dramatic resolution of her SAM and outflow tract obstruction, confirmed by intracavitary pressure wire measurements.

Plexiform pigmented schwannoma of the uvea.

Schwannoma is a slow growing solitary tumor that preferentially involves spinal nerve roots, and sympathetic, cervical, and vagus nerves. There are several clinico-pathologic variants of schwannoma, including schwannoma with a degenerative change (ancient schwannoma), cellular schwannoma, plexiform schwannoma, epithelioid schwannoma, and melanotic schwannoma. About 10% of cases of schwannomas are associated with multi-system disorders such as neurofibromatosis, schwannomatosis, multiple meningiomas, and Carney complex.

The impact of CytoGam on cardiac transplant recipients with moderate hypogammaglobulinemia: a randomized single-center study.

Background: We have previously shown that the preemptive use of cytomegalovirus (CMV) immunoglobulin (Ig) replacement (CytoGam) decreases the incidence of opportunistic infections in cardiac transplant recipients with severe hypogammaglobulinemia. However, the impact of Ig replacement in moderately hypogammaglobulinemic patients is unknown.

Methods: Periodic monitoring of the IgG levels was done in 300 heart transplant recipients.

The impact of donor gender on cardiac peri-transplantation ischemia injury.

Background: Cardiac allografts from female donors have been shown to be associated with increased risk of transplant vasculopathy. However, the influence of donor gender on peri-transplantation ischemic injury has not been evaluated.

Methods: A total of 361 patients (mean age, 52 +/- 10 years) underwent cardiac transplantation between January 1998 and December 2002.

Small intestinal submucosa intracardiac patch: an experimental study.

In this experimental study, small intestinal submucosa was implanted as an atrial prosthesis in calves. Echocardiography and histology showed this to be an impermeable prosthesis that develops a neointimal nonthrombogenic surface making it safe for repair of defects in a low-pressure system. Further study with small intestinal submucosa in an intracardiac position is warranted.

Peritransplant ischemic injury is associated with up-regulation of stromal cell-derived factor-1.

Objectives: We evaluated chimerism and stromal cell-derived factor-1 (SDF-1) expression in response to peritransplant ischemic injury following human heart transplantation.

Background: Myocardial ischemia has been shown to trigger mobilization of stem cells to the heart in animal experiments.

Methods: Between January 1998 and April 2002, a total of 114 male recipients received hearts from female donors.

Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.

Background: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation.

The influence of donor gender on allograft vasculopathy: evidence from intravascular ultrasound.

Background: Allograft vasculopathy is a major risk factor for mortality following cardiac transplantation. Several immune and nonimmune factors have been evaluated as risk factors for the development of coronary vasculopathy.

Objective: We evaluated the influence of donor gender on the progression of coronary vasculopathy in heart transplant recipients.

Donor intracranial bleeding is associated with advanced transplant coronary vasculopathy: evidence from intravascular ultrasound.

Objectives: We evaluated the impact of spontaneous intracranial bleeding (ICB) in the donor on transplant coronary vasculopathy using serial intravascular ultrasound examinations.

Materials And Methods: Between January 1995 and December 2000, 72 recipients underwent cardiac transplantation from donors who had experienced spontaneous ICB (ICB group). Their findings using serial intravascular ultrasound analysis at baseline (within 1 month) and 1 year after transplantation were compared with 90 recipients who had undergone transplantation from trauma donors (trauma group).

Lack of usefulness of electron beam computed tomography for detecting coronary allograft vasculopathy.

Fifty-five patients with cardiac allografts were studied by electron beam computed tomography for coronary calcification (EBCT CC) and coronary arteriography, and from the latter, a coronary index was calculated using the size, degree of obstruction, and linear extent of disease of each vessel. There was a significant correlation between EBCT CC score and coronary index, but receiver-operating characteristic (ROC) analysis demonstrated unsatisfactory performance of EBCT CC, and 6 patients had no coronary calcification despite having very abnormal coronary indexes. There are pathologic differences between coronary allograft vasculopathy and atherosclerosis, and correspondingly, EBCT CC has limited usefulness in the cardiac transplant population.

Biomechanical and echocardiographic characterization of flail mitral leaflet due to myxomatous disease: further evidence for early surgical intervention.

Background: Flail mitral leaflet (FML) is a common complication of mitral valve prolapse, often leading to severe mitral regurgitation (MR) and left ventricular dysfunction. In the absence of timely surgical correction, survival is significantly impaired. Early recognition of FML and identification of risk factors is important because early intervention increases the chances of survival.

Systemic up-regulation of angiotensin II type 1 receptor in cardiac donors with spontaneous intracerebral hemorrhage.

Donor spontaneous intracerebral hemorrhage (ICH) is a potential risk factor for morbidity and mortality after cardiac transplantation. We hypothesized that donor ICH is associated with systemic up-regulation of angiotensin II receptor type 1 (AT1R). We evaluated mRNA expression of AT1R and AT2R in donor spleen lymphocytes and in heart biopsies from 20 recipients of hearts from donors with spontaneous ICH which were compared with 20 recipients from trauma donors.

Angiotensin II receptors from peritransplantation through first-year post-transplantation and the risk of transplant coronary artery disease.

Objectives: We evaluated whether the angiotensin II (Ang II) receptors from perioperation through one-year post-transplantation predict the transplant coronary artery disease (TCAD) progression.

Background: The role of Ang II receptors (type 1: AT(1)R; type 2: AT(2)R) in TCAD is uncertain.

Methods: We investigated 28 heart donors and the corresponding recipients.

Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation.

Aims: We tested the hypothesis that cardiac angiotensin II (Ang II) receptor gene transcription may predict the development of transplant coronary artery disease (TCAD) following heart transplantation.

Methods And Results: We examined the gene transcripts of Ang II type 1 (AT1R) and type 2 receptors (AT2R) in endomyocardial biopsy specimens from 50 heart transplant recipients. The progression of TCAD was measured as change in maximal intimal thickness (CMIT) and change in plaque volume (CPV) by intravascular ultrasound (IVUS) examinations from baseline to one year after transplantation.

Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation.

Background: It is possible, but unproven, that hepatitis C (HCV) infection accelerates atherosclerosis. We evaluated the hypothesis that donor HCV seropositivity predicts mortality and the development of coronary vasculopathy in cardiac transplant recipients.

Methods: Thirty-four cardiac transplant recipients who were seronegative for HCV at the time of transplantation received hearts from HCV-seropositive donors.

Does acute cellular rejection correlate with cardiac allograft vasculopathy?

Background: Previous studies of the association between acute cellular rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute cellular rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association.

Methods: We investigated 140 patients (mean age, 51 +/- 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT).

Impact of donor spontaneous intracranial hemorrhage on outcome after heart transplantation.

Donor cause of death has been suggested to have a significant impact on cardiac transplant morbidity and mortality. Our objective was to evaluate the impact of donor spontaneous intracranial bleeding on clinical outcome after heart transplantation. A group of 160 recipients underwent cardiac transplantation from donors with spontaneous intracranial bleeding (ICB group).

Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice.

Cardiac hypertrophy and heart failure remain leading causes of death in the United States. Many studies have suggested that, under stress, myocardium releases factors triggering protein synthesis and stimulating myocyte growth. We identified and cloned myotrophin, a 12-kDa protein from hypertrophied human and rat hearts.