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Pericardial effusion (PEF) in PAH may be a marker of worsening disease or associated with autoimmune conditions. Sotatercept was not initially reported as associated with the development or progression of PEF. We describe PAH patients taking sotatercept who were found to have new or worsening PEF and examine associated comorbidities.

Pulmonary hypertension is a condition with high morbidity and mortality. Resting transthoracic echocardiography is a pivotal diagnostic and screening test for pulmonary hypertension. The role of exercise stress echocardiography in the diagnosis of pulmonary hypertension is not well-established. We studied right ventricular size changes during exercise using exercise stress echocardiography to assess differences between normal and pulmonary hypertension patients and evaluate test safety, feasibility, and reproducibility. Healthy control and pulmonary hypertension patients performed recumbent exercise using a bicycle ergometer. Experienced echocardiography sonographers recorded the following resting and peak exercise right ventricular parameters using the apical four chamber view: end-diastolic area; end-systolic area; mid-diameter; basal diameter; and longitudinal diameter. Two cardiologists masked to clinical information subsequently analyzed the recordings. Parameters with acceptable inter-rater reliability were analyzed for statistical differences between the normal and pulmonary hypertension patient groups and their association with pulmonary hypertension. We enrolled 38 healthy controls and 40 pulmonary hypertension patients. Exercise stress echocardiography testing was found to be safe and feasible. Right ventricular size parameters were all readily obtainable and all had acceptable inter-observer reliability except for right ventricular longitudinal diameter. During exercise, healthy controls demonstrated a decrease in right ventricular end-systolic area, end-diastolic area, mid-diameter, and basal diameter (P < 0.05). Conversely, pulmonary hypertension patients demonstrated an increase in right ventricular end-systolic area, end-diastolic area, and mid-diameter (P < 0.05). These changes were unaffected by multivariate corrections. The sensitivity for pulmonary hypertension of an increase in right ventricular size was 97.2% with a negative predictive value of 95.2%. The ROC C-statistic for increase in right ventricular size was 0.93. This transient exertional dilation (TED) of the right ventricle is observed in pulmonary hypertension patients but not in healthy controls. Recumbent right ventricular exercise stress echocardiography is a feasible and safe diagnostic test for pulmonary hypertension which warrants additional study.

Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications. Studies reporting on three or more adult patients published in the English language reporting on transitions between FDA-approved PAH medications were extracted and tabulated. Forty-one studies met the selection criteria, nine of which included less than eight patients (and thus were reported separately in the supplement), for a total of 32 studies. Transitioning from parenteral epoprostenol to parenteral treprostinil appears to be safe and efficacious in patients who have less severe disease and more favorable hemodynamics. Transitioning from a prostacyclin analogue to an oral medication may be successful in patients who have favorable hemodynamics and stable disease. There is conflicting evidence supporting the transition from a parenteral to an inhaled prostacyclin analogue, even in patients who are on background oral therapy. Currently, the only evidence in support of transitioning between oral PDE5 inhibitors is from sildenafil to tadalafil. Patients on higher doses of sildenafil are more likely to fail. In patients with liver abnormalities due to bosentan or sitaxentan, the transition to ambrisentan appears to be safe and can result in clinical improvement. Studies regarding PAH medication transitions are limited. Patients who have less severe disease, better functional status, and are on lower medications doses may be more successful at transitioning.

Purpose of Review Prostacyclin pathway medications have been shown to be highly efficacious in the treatment of pulmonary arterial hypertension (PAH) through multiple prospective clinical trials and more than two decades of clinical experience. The strongest support for prostacyclin use in PAH management is with parenteral administration. Numerous risks and limitations of parenteral delivery systems as well as significant patient burdens restrict widespread parenteral use. Highly effective and tolerable oral prostacyclin preparations to manage PAH have long been sought. We review the development of the oral prostacyclin agents beraprost, treprostinil, and selexipag and including current indications and limitations. Research into new approaches to the management of PAH, expanding indications for existing agents, and development of novel agents are also discussed. Recent Findings Two oral prostacyclin pathway medications, oral treprostinil and selexipag, were FDA approved in December 2013 and 2015, respectively. Current guidelines recommend use of selexipag in WHO-FC II and III (class 1, level B recommendation) and oral treprostinil in WHO-FC III (class 2b, level B recommendation). The use of these medications is challenging due to complexity in dosing and their side effect profiles which limit patient tolerability and acceptance. Summary There is a promising role for oral prostacyclin pathway medications in patients with PAH. Future investigations are underway of alternative dose regimens and transitioning from parenteral therapies in order to improve efficacy and tolerability.

To study the clinical characteristics and prognosis of patients with diffuse pulmonary arteriovenous malformations (AVMs). Retrospective chart review of all patients (n = 16) with diffuse pulmonary AVMs seen at Yale New Haven Hospital, Johns Hopkins Hospital, and St. Michael's Hospital. Up-to-date follow-up information was obtained in all living patients. All patients were severely hypoxic. Neurologic complications (stroke or brain abscess) had occurred in 70% of patients by the time of diagnosis. During the follow-up period (mean, 6 years), three patients died and two others developed new neurologic complications. One of the deaths occurred perioperatively during lung transplantation. All patients underwent transcatheter embolotherapy of any large pulmonary AVMs. A selected group underwent pulmonary flow redistribution, a novel technique. Oxygenation did not improve significantly with embolotherapy of the larger AVMs, but there was a small significant improvement in those patients who underwent pulmonary flow redistribution. The majority (85%) of the living patients are currently working or studying full-time. Patients with diffuse pulmonary AVMs are at increased risk of neurologic complications. Transcatheter embolotherapy does not significantly improve the profound hypoxia, but it may reduce the risk of neurologic complications. Antibiotic prophylaxis is recommended for bacteremic procedures to prevent brain abscess. These patients can live for many years and lead productive lives. We do not recommend lung transplantation because survival with disease is difficult to predict and we have observed a perioperative transplant death.

Myosin diversity in the human epithelial cell line Caco-2BBe, the porcine epithelial cell line LLC-PK1(CL-4), human peripheral blood leukocytes, and human liver was analyzed. PCR amplification yielded 8-11 putative myosins (depending on the cDNA source) representing six distinct myosin classes. Analysis of clones obtained by hybridization screening demonstrated that the original PCR products correspond to bona fide myosins, based on the presence of sequences highly conserved in other myosins. RNase protection analysis confirmed mRNA expression of 11 myosins in Caco-2BBecells. Immunoblot analysis showed that at least 6 myosin immunogens are expressed in Caco-2BBecells. The results reveal the existence of at least 11 unconventional human myosin genes, most of which are expressed in an overlapping fashion in different cell types. The abundance of myosins suggests that the myosin I vs. myosin II paradigm is inadequate to explain actin-based cellular motility.

Objectives The clinical features, airway histology, and detection of hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a patient with HDI asthma are described. Methods lsocyanate asthma was diagnosed by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was performed 24 h after challenge and immunohistochemical staining was performed. Results Airway biopsies obtained at bronchoscopy demonstrated inflammatory changes typical for asthma, including increased airway eosinophils and T cells. Immunohistochemical staining with specific anti-HDI antibodies demonstrated the presence and localization of HDI adducts in human bronchial biopsies. Conclusions These studies confirm epithelial exposure to HDI following workplace challenge and demonstrate the feasibility of detecting and localizing isocyanate adducts in human lung tissue. Identifying and characterizing the airway macromolecules to which isocyanates bind in vivo are probably crucial to the understanding of how isocyanates cause sensitization and asthma. The ability to detect isocyanate adducts may also help characterize isocyanate exposure patterns and exposure-disease relationships.

To study the clinical characteristics andprognosis of patients with diffuse pulmonary arteriovenousmalformations (AVMs). Retrospective chartreview of all patients (n = 16) with diffuse pulmonary AVMs seen at Yale New Haven Hospital, Johns Hopkins Hospital, and St. Michael's Hospital. Up-to-date follow-up information was obtained in all livingpatients. All patients wereseverely hypoxic. Neurologic complications (stroke or brain abscess)had occurred in 70% of patients by the time of diagnosis. During thefollow-up period (mean, 6 years), three patients died and two othersdeveloped new neurologic complications. One of the deaths occurredperioperatively during lung transplantation. All patients underwenttranscatheter embolotherapy of any large pulmonary AVMs. A selectedgroup underwent pulmonary flow redistribution, a novel technique.Oxygenation did not improve significantly with embolotherapy of thelarger AVMs, but there was a small significant improvement in thosepatients who underwent pulmonary flow redistribution. The majority(85%) of the living patients are currently working or studyingfull-time. Patients with diffusepulmonary AVMs are at increased risk of neurologic complications.Transcatheter embolotherapy does not significantly improve the profoundhypoxia, but it may reduce the risk of neurologic complications.Antibiotic prophylaxis is recommended for bacteremic procedures toprevent brain abscess. These patients can live for many years and leadproductive lives. We do not recommend lung transplantation becausesurvival with disease is difficult to predict and we have observed aperioperative transplant death.

We describe a case of pulmonary hypertension, initially thought to be idiopathic, which resolved after treatment of Graves' hyperthyroidism. Results of pulmonary artery catheterization before and after treatment are reported, and the effects of thyrotoxicosis on hemodynamics and pulmonary function are briefly reviewed. Possible mechanisms for development of pulmonary hypertension caused by hyperthyroidism include pulmonary vascular endothelial dysfunction or damage because of autoimmunity or the high cardiac output state, or increased metabolism of intrinsic pulmonary vasodilators.