An Update on the Diagnosis and Management of Acute Right Heart Failure.

Right ventricular (RV) dysfunction and resultant acute right heart failure (ARHF) is a rapidly growing field of interest, driven by increasing appreciation of its contribution to heart failure morbidity and mortality. Understanding of ARHF pathophysiology has advanced dramatically over recent years and can be broadly described as RV dysfunction related to acute changes in RV afterload, contractility, preload, or left ventricular dysfunction. There are several diagnostic clinical signs and symptoms as well as imaging and hemodynamic assessments that can provide insight into the degree of RV dysfunction. Medical management is tailored to the different causative pathologies, and in cases of severe or end-stage dysfunction, mechanical circulatory support can be utilized. In this review, we describe the pathophysiology of ARHF, how its diagnosis is established by clinical signs and symptoms and imaging findings, and provide an overview of treatment options, both medical and mechanical.

A 44-year-old stone worker with progressive dyspnea: lessons from a new twist on an old foe.

Silicosis is typically an indolent lung disease caused by long-standing occupational exposure to respirable crystalline silica, classically in professions such as sandblasting and mining.  An increasingly popular industry that has earned particular interest because of its association with silicosis is customization and installation of artificial stone countertops for domestic applications. In addition to causing a spike in cases of chronic and accelerated silicosis, both quite familiar to respiratory clinicians, outbreaks of artificial stone silicosis have brought to the fore a historically rare entity known as acute silicosis, or silicoproteinosis, a more rapid presentation of the disease. Failure to suspect this uncommon condition can lead to diagnostic confusion and therefore ineffective treatment as was true initially of the patient we describe herein.  The case description is followed by a clinical, radiological, and pathological overview of acute artificial stone silicosis (or silicoproteinosis), which is an emerging pneumoconiosis with sparse coverage in the literature to date.  This case also adds to the few existing reports on the use of therapeutic whole lung lavage for silicoproteinosis.

Detectable Digoxin Concentrations in 3 Patients with Ramps Misadventure.

Allium tricoccum (commonly known as "ramps") is an edible plant known for its strong garlic-like odor and onion flavor. Unfortunately, A tricoccum mimics such as Lily of the Valley (Convallaria majalis) and False Hellebore (Veratrum viride) can lead to foraging errors and subsequent patient harm/toxicity. We describe 3 adults who foraged and ate what they believed were A tricoccum and then subsequently became symptomatic with detectable digoxin concentrations. A 41-y-old woman, 41-y-old man, and a 31-y-old man presented to the emergency department after ingesting an unknown plant that was believed to be A tricoccum. On arrival to the emergency department, the patients were hypotensive and bradycardic. They had detectable digoxin concentrations ranging from 0.08 ng·mL-1 to 0.13 ng·mL-1. One patient received 20 vials of digoxin antibody fragments. All 3 patients recovered without complication. Laboratory analysis of plant specimen was positive for cyclopamine, a teratogenic alkaloid found in Veratrum californicum. A tricoccum foraging errors can be a source of morbidity given their similarity in appearance to plants like C majalis and V viride. C majalis causes a detectable digoxin concentration via its cardiac steroid compound (convallatoxin) that is similar to digoxin. V viride contains alkaloid compounds (such as veratridine) that can cross react with digoxin assays and lead to a falsely elevated digoxin concentration. Clinicians should be prompted to think about ingestion of C majalis or Veratrum spp. when patients present with bradycardia, gastrointestinal symptoms, and detectable digoxin concentrations after plant ingestion and/or foraging for A tricoccum.

A new strategy to increase RNA editing at the Q/R site of GluA2 AMPA receptor subunits by targeting alternative splicing patterns of ADAR2.

BACKGROUND: The GluA2 subunit of AMPA receptors (AMPARs) undergoes RNA editing at a specific base mediated by the enzyme ADAR2, changing the coded amino acid from a glutamine to arginine at the so-called Q/R site, which is critical for regulating calcium permeability. ADAR2 exists as multiple alternatively-spliced variants within mammalian cells with differing editing efficiency. NEW METHOD: In this study, phosphorodiamidate morpholino oligomers (PMOs) were used to increase Q/R site editing, by affecting the alternative splicing of ADAR2. RESULTS: PMOs targeting the ADAR2 pre-mRNA transcript successfully induced alternative splicing around the AluJ cassette leading to expression of a more active isoform with increased editing of the GluA2 subunit compared to control. COMPARISON WITH EXISTING METHOD(S): Previously PMOs have been used to disrupt RNA editing via steric hindrance of the GluA2 RNA duplex. In contrast we report PMOs that can increase the expression of more catalytically active variants of ADAR2, leading to enhanced GluA2 Q/R RNA editing. CONCLUSIONS: Using PMOs to increase Q/R site editing is presented here as a validated method that would allow investigation of downstream cellular processes implicated in altered ADAR2 activity.

Impact of Sacubitril/Valsartan on Patient Outcomes in Heart Failure: Evidence to Date.

With an estimated 6.2 million adults affected in the USA, heart failure remains a leading cause of morbidity, mortality, and health-care costs, despite the use of guideline-based medical therapies. The search for a more efficient therapy was rekindled when findings from the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial demonstrated evidence for cardiovascular and mortality benefit of sacubitril/valsartan, a dual angiotensin receptor blocker and neprilysin inhibitor (ARNI), over enalapril (an angiotensin-converting enzyme inhibitor) in patients with heart failure and reduced rjection fraction (HFrEF). Following the trial's compelling results, recommendations for the use of sacubitril/valsartan as a replacement for an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker were incorporated into the 2016 American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America recommended (HFSA) guidelines for the management of heart failure. This review aims to gain insight into the benefits as well as limitations associated with the use of sacubitril/valsartan in the treatment of heart failure (HF) through exploration of various subgroup analyses of the PARADIGM-HF trial, subsequent retrospective analyses, and randomized controlled trials that followed this landmark trial.

Role of one, two and three doses of high-dose chemotherapy with autologous transplantation in the treatment of high-risk or relapsed testicular cancer: a systematic review.

Approximately 20-30% of patients with metastatic germ cell cancers (GCCs) can develop relapsed or refractory (RR) disease, about 40-50% of patients who relapse after salvage chemotherapy may reach long-term remission. The goal of this review was to identify patients who appear to benefit from high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). To access this, we performed a systematic medical literature review to evaluate the effectiveness of HDCT in the frontline setting, as well as in patients with RR testicular cancer. We searched databases for interventional clinical studies and identified 5883 studies. We selected 49 studies for inclusion, which included a total of 5985 patients. Seventeen studies reported results of newly diagnosed poor-risk GCC patients and 32 studies reported results of RR patients. For newly diagnosed patients with poor prognostic predictors, a risk adjusted strategy using unfavorable tumor marker decline with initial standard chemotherapy regimen and upfront HDCT demonstrated improved outcomes. Our data suggest a minimum of two HDCT cycles with ASCT should be standard of care for patients with RR GCC. Failure of HDCT results in a poor prognosis with only 10% of patients achieving lasting remission with salvage therapy.