Background: Plexiform lesions comprising proliferative endothelial cells are hallmarks of pulmonary arterial hypertension. Results: Granzyme B cleaves intersectin-1s and generates a fragment with endothelial cell proliferative potential via phosphorylation of p38MAPK and Elk-1 transcription factor. Conclusion: Granzyme B cleavage of intersectin-1s and subsequent p38 MAPK /Elk-1 activation are critical for endothelial cell proliferation. Significance: The novel pathogenic p38 MAPK /Elk-1 signaling may explain the formation of plexiform lesions.

Pulmonary arterial hypertension (PAH) is a progressive condition that can lead to right ventricular failure and death. Treprostinil is a prostacyclin analogue that has proven clinical efficacy in patients with PAH. Difficulties in the administration of inhaled and parenteral prostacyclins led to the development of extended-release treprostinil diolamine for oral use. Limited data exist on the transition to oral treprostinil. The purpose of this case series is to describe the transition from subcutaneous or inhaled treprostinil to oral treprostinil in the outpatient setting. With the current availability of oral prostacyclins and prostacyclins analogues, most transitions to oral therapy are done in the hospital setting resulting in increased cost and risk of hospital-acquired infections. Four patients on background phosphodiesterase type 5 therapy with baseline World Health Organization functional class (WHO FC) II PAH were transitioned at home. Three of the 4 patients were safely transitioned as outpatients and maintained WHO FC II status at 10 and 12 months. The fourth patient had worsening right heart failure and was admitted within 2 months of the transition and started back on parenteral prostacyclin therapy. The 6-minute walk distance (6MWD) increased in patients transitioning from inhaled therapy and decreased in the patient transitioning from subcutaneous therapy. The most common adverse event was nausea.

Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilot study measuring tricuspid annular plane systolic excursion (TAPSE), Tei index, RV-fractional area change (RV-FAC), pulmonary artery systolic pressure (PASP), and septal shift, reevaluated by an independent blinded cardiologist (JK). Thirty-eight patients were included. Patients were divided on the basis of 30-day survival. Thirty-day mortality was 47%. Survivors were younger than nonsurvivors. Survivors had a higher pH, PaO 2 ∶ FiO 2 ratio, and TAPSE. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were lower in survivors. TAPSE has the strongest association with increased 30-day mortality from date of TTE. Accordingly, TAPSE has a strong positive correlation with PaO 2 ∶ FiO 2 ratios, and Tei index has a strong negative correlation with PaO 2 ∶ FiO 2 ratios. Septal shift was associated with lower PaO 2 ∶ FiO 2 ratios. Decrease in TAPSE, increase in Tei index, and septal shift were seen in the severe ARDS group. In multivariate logistic regression models, TAPSE maintained a significant association with mortality independent of age, pH, PaO 2 ∶ FiO 2 ratios, positive end expiratory pressure, PCO 2 , serum bicarbonate, plateau pressures, driving pressures, APACHE II, SAPS II, and SOFA scores. In conclusion, TAPSE and other TTE parameters should be used as novel predictive indicators for RV dysfunction in ARDS. These parameters can be used as surrogate noninvasive RV hemodynamic measurements to be manipulated to improve mortality in patients with ARDS and contributory RV dysfunction.Keywords: pulmonary hypertension, tricuspid annular plane systolic excursion, transthoracic echocardiography. Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory syndrome characterized by hypoxemia, noncardiogenic pulmonary edema, pulmonary inflammation, and decreased pulmonary compliance. Despite our best efforts, mortality rates associated with ARDS still remain between 30% and 40%.1,2 Current management of ARDS is mainly supportive with mechanical ventilation and hemodynamic support. 3 Pulmonary hypertension and right ventricular (RV) dysfunction are independent predictors of mortality associated with poorer outcomes in patients with ARDS. [4][5][6][7][8] The increased lung mass in ARDS due to accumulation of inflammatory exudate in the alveolar space compresses not only the dependent alveoli but also the pulmonary vessels, leading to increased pulmonary vascular resistance. 9 In addition to direct compression, pulmonary endothelial cell dysfunction and microvascular thrombosis from systemic inflammatory response lead to development of pulmonary hypertension in ARDS. 10...

IntroductionCOPD is the third leading cause of death in the world. Utilizing care bundles during acute COPD exacerbations results in fewer complications and lower costs. Our aim was to construct a COPD exacerbation care bundle and evaluate the effects on patient care.MethodsWe conducted a prospective analysis of 44 patients admitted with a COPD exacerbation to a single tertiary care facility. Primary outcomes included length of stay, readmission rates, and hospital costs. Secondary outcomes included patient education, pulmonologist follow-up, and timeliness of medication administration. Two cohorts were analyzed: those treated with an electronic COPD care bundle (cases; N=22) versus those treated without the care bundle (controls; N=22).ResultsMean length of stay (51.2 vs 101.1 hours in controls; P-value =0.001), 30-day readmission rates (9.1% vs 54.4% in controls; P-value =0.001), and 60-day readmission rates (22.7% vs 77% in controls; P-value =0.0003) decreased in the care bundle group. Ninety-day hospital costs had a significant difference in the care bundle group (US$7,652 vs US$19,954 in controls; P-value =0.044). Secondary outcomes included a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001), 59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P-value =0.005), and a mean reduction in time to steroid administration (7.0 hours; P-value =0.015) seen in the care bundle cases.ConclusionOur significant findings coupled with the recent success of standardized algorithms in managing COPD exacerbations stress the importance of enforcing clinical guidelines that can enhance patient care. We demonstrated improved care for COPD exacerbation patients during hospitalizations, thereby decreasing morbidity and the financial burden hospitals face in regard to this increasingly prevalent disease.

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