Chronic Thromboembolic Pulmonary Hypertension Medical Management

Chronic thromboembolic pulmonary hypertension (CTEPH) is a common long-term complication of pulmonary embolism characterized by thromboembolic obstruction of the pulmonary arteries, vascular arteriopathy, vascular remodeling, and ultimately pulmonary hypertension (PH). Although pulmonary endarterectomy (PEA) surgery is the standard of care, approximately 40% of patients in the international CTEPH registry were deemed inoperable. In addition to lifelong anticoagulation, the cornerstone of PH-specific medical management is riociguat, a soluble guanylate cyclase stimulator. Medical management should be started early in CTEPH patients and may be used as a bridge to PEA surgery or balloon pulmonary angiography. Medical management is indicated for inoperable CTEPH patients and patients who have recurrence of PH after PEA surgery.     

Portopulmonary hypertension: an update

Portopulmonary hypertension (POPH) is a serious complication of cirrhosis that is associated with mortality beyond that predicted by the Model for End-Stage Liver Disease (MELD) score. Increased pulmonary vascular resistance (PVR) may be initiated by pulmonary vasoconstriction, altered levels of circulating mediators, or shear stress, and can eventually lead to the classic vascular remodeling (plexiform lesion) that characterizes POPH. Portal hypertension is a prerequisite for the diagnosis of POPH, although the severity of pulmonary hypertension is unrelated to the severity of portal hypertension or the nature or severity of liver disease. POPH precludes liver transplantation (LT) unless the mean pulmonary artery pressure (MPAP) can be reduced to a safe level. The concept of an acceptable pressure has changed: we now consider both MPAP and PVR in the diagnosis, and we include the transpulmonary pressure gradient so that we can factor in fluid overload and left ventricular failure. Pulmonary vasodilator therapy includes oral, inhaled, and parenteral agents, and one or more of these agents may significantly lower pulmonary artery pressures to the point that LT becomes possible. The United Network for Organ Sharing recommends MELD exception points for patients with medically controlled POPH, but this varies by region. Patients who undergo LT need specialized intraoperative and postoperative management, which includes the availability of intraoperative transesophageal echocardiography for assessing right ventricular function, and rapidly acting vasodilators (eg, inhaled nitric oxide and/or epoprostenol). Published case series suggest excellent outcomes after LT for patients who respond to medical therapy.     

Gender Differences in Acute and Chronic Pain in the Emergency Department: Results of the 2014 Academic Emergency Medicine Consensus Conference Pain Section

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician–patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings.     

Organization,Execution and Evaluation of the 2014 Academic Emergency Medicine Consensus Conference on Gender‐Specific Research in Emergency Care – An Executive Summary

With the goal of reducing inequalities in patient care, the 2014 Academic Emergency Medicine (AEM) consensus conference, “Gender‐Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes,” convened a diverse group of researchers, clinicians, health care providers, patients, and representatives of federal agencies and policy‐makers in Dallas, Texas, in May 2014. The executive and steering committees identified seven clinical domains as key to gender‐specific emergency care: cardiovascular, neurological, trauma/injury, substance abuse, pain, mental health, and diagnostic imaging. The main aims of the conference were to: 1) summarize and consolidate current data related to sex‐ and gender‐specific research for acute care and identify critical gender‐related gaps in knowledge to inform an EM research agenda; 2) create a consensus‐driven research agenda that advances sex‐ and gender‐specific research in the prevention, diagnosis, and management of acute diseases and identify strategies to investigate them; and 3) build a multinational interdisciplinary consortium to disseminate and study the sex and gender medicine of acute conditions. Over a 2‐year period, this collaborative network of stakeholders identified key areas where sex‐ and gender‐specific research is most likely to improve clinical care and ultimately patient outcomes. The iterative consensus process culminated in a daylong conference on May 13, 2014, with a total of 133 registrants, with the majority being between ages 31 and 50 years (57%), females (71%), and whites (79%). Content experts led the consensus‐building workshops at the conference and used the nominal group technique to consolidate consensus recommendations for priority research. In addition, panel sessions addressed funding mechanisms for gender‐specific research as well as gender‐specific regulatory challenges to product development and approval. This special issue of AEM reports the results of the 2014 consensus conference as well as related original research with the goal of bringing high‐quality equitable care to male and female emergency patients.     

Gender‐specific Regulatory Challenges to Product Approval: A Panel Discussion

On May 13, 2014, a 1‐hour panel discussion session titled “Gender‐specific Regulatory Challenges to Product Approval” was held during the Academic Emergency Medicine consensus conference, “Gender‐specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes.” The session sought to bring together leaders in emergency medicine (EM) research, authors, and reviewers in EM research publications, as well as faculty, fellows, residents, and students engaged in research and clinical practice. A panel was convened involving a representative from the Office of Women's Health of the U.S. Food and Drug Administration, two pharmaceutical executives, and a clinical EM researcher. The moderated discussion also involved audience members who contributed significantly to the dialogue. Historical background leading up to the session along with the main themes of the discussion are reproduced in this article. These revolve around sex‐ and gender‐specific research, statistical analysis of sex and gender, clinical practice, financial costs associated with pharmaceutical development, adaptive design, and specific recommendations on the regulatory process as it affects the specialty of EM.     

Successful Immunosuppressive Treatment of Erythroid Aplasia Appearing after Thymectomy

S ummary . A unique case of red cell aplasia appearing 2 yr after removal of a thymoma and a transient episode of myasthenic crisis is presented. When the marrow cells of this patient were incubated in vitro a marked increase in haem synthesis occurred, suggesting that the marrow had been freed from an inhibitor of erythroid function. An antibody to erythroblast nuclei was also present. The patient failed to respond to an initial course of immunosuppressive therapy, but after splenectomy he had a second course of immunosuppressive treatment which was followed by a complete haematologic remission. Guidelines for the future therapeutic use of immunosuppressive agents in pure erythroid aplasia are presented.