Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease.

BACKGROUND: No therapies are currently approved for the treatment of pulmonary hypertension in patients with interstitial lung disease. The safety and efficacy of inhaled treprostinil for patients with this condition are unclear. METHODS: We enrolled patients with interstitial lung disease and pulmonary hypertension (documented by right heart catheterization) in a multicenter, randomized, double-blind, placebo-controlled, 16-week trial. Patients were assigned in a 1:1 ratio to receive inhaled treprostinil, administered by means of an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths (total, 72 µg) four times daily, or placebo. The primary efficacy end point was the difference between the two groups in the change in peak 6-minute walk distance from baseline to week 16. Secondary end points included the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level at week 16 and the time to clinical worsening. RESULTS: A total of 326 patients underwent randomization, with 163 assigned to inhaled treprostinil and 163 to placebo. Baseline characteristics were similar in the two groups. At week 16, the least-squares mean difference between the treprostinil group and the placebo group in the change from baseline in the 6-minute walk distance was 31.12 m (95% confidence interval [CI], 16.85 to 45.39; P<0.001). There was a reduction of 15% in NT-proBNP levels from baseline with inhaled treprostinil as compared with an increase of 46% with placebo (treatment ratio, 0.58; 95% CI, 0.47 to 0.72; P<0.001). Clinical worsening occurred in 37 patients (22.7%) in the treprostinil group as compared with 54 patients (33.1%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40 to 0.92; P = 0.04 by the log-rank test). The most frequently reported adverse events were cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. CONCLUSIONS: In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline, assessed with the use of a 6-minute walk test, as compared with placebo. (Funded by United Therapeutics; INCREASE ClinicalTrials.gov number, NCT02630316.).

Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study.

INTRODUCTION: The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD. METHODS: Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil. Assessments included 6MWD, pulmonary function testing, N-terminal pro-brain natriuretic peptide (NT-proBNP), quality of life and adverse events. Hospitalisations, exacerbations of underlying lung disease and death were recorded. RESULTS: At INCREASE OLE baseline, patients had a median age of 70 years and a mean 6MWD of 274.2 m; 52.1% were male. For the overall population, the mean 6MWD at week 52 was 279.1 m and the mean change from INCREASE RCT baseline was 3.5 m (22.1 m for the prior inhaled treprostinil arm and -19.5 m for the prior placebo arm); the median NT-proBNP decreased from 389 pg·mL-1 at RCT baseline to 359 pg·mL-1 at week 64; and the absolute (% predicted) mean forced vital capacity change from RCT baseline to week 64 was 51 mL (2.8%). Patients who received inhaled treprostinil versus placebo in the RCT had a 31% lower relative risk of exacerbation of underlying lung disease in the OLE (hazard ratio 0.69 (95% CI 0.49-0.97); p=0.03). Adverse events leading to drug discontinuation occurred in 54 (22.3%) patients. CONCLUSIONS: These results support the long-term safety and efficacy of inhaled treprostinil in patients with PH-ILD, and are consistent with the results observed in the INCREASE RCT.

Association between aspirin use and deep venous thrombosis in mechanically ventilated ICU patients.

Deep venous thrombosis (DVT) is common in intensive care unit (ICU) patients. It is often silent and may be complicated by pulmonary embolism and death. Thromboprophylaxis with heparin does not always prevent venous thromboembolism (VTE). Aspirin (ASA) reduces the risk of VTE in surgical and high-risk medical patients but it is unknown if ASA may prevent DVT in mechanically ventilated ICU patients. We performed a retrospective chart review of critically ill patients who received mechanical ventilation for >72 h and underwent venous ultrasonography for suspected DVT between Jan 2012 and Dec 2013. We excluded patients who were on therapeutic doses of anticoagulation or had coagulopathy. We used multivariable logistic regression to evaluate association between aspirin use and DVT during hospitalization. There were 193 patients. The mean ± SD age was 58 ± 15.7 years. Half were male. DVT was found in 49 (25.4%). DVT was found in the first 15 days of hospitalization in 67.3% of the patients. The majority (82.8%) received thromboprophylaxis with unfractionated or low molecular weight heparin. Fifty-six (29%) were on ASA. On multivariable regression analysis, ASA use was associated with a significant reduction in the odds of finding DVT (OR 0.39, 95% CI 0.16-0.94; p = 0.036). DVT is common in mechanically ventilated ICU patients despite the use of thromboprophylaxis. Aspirin may prevent DVT in such patients.

The relationship of intravenous fluid chloride content to kidney function in patients with severe sepsis or septic shock.

BACKGROUND: Previous studies suggest a relationship between chloride-rich intravenous fluids and acute kidney injury in critically ill patients. OBJECTIVES: The aim of this study was to evaluate the relationship of intravenous fluid chloride content to kidney function in patients with severe sepsis or septic shock. METHODS: A retrospective chart review was performed to determine (1) quantity and type of bolus intravenous fluids, (2) serum creatinine (Cr) at presentation and upon discharge, and (3) need for emergent hemodialysis (HD) or renal replacement therapy (RRT). Linear regression was used for continuous outcomes, and logistic regression was used for binary outcomes and results were controlled for initial Cr. The primary outcome was change in Cr from admission to discharge. Secondary outcomes were need for HD/RRT, length of stay (LOS), mortality, and organ dysfunction. RESULTS: There were 95 patients included in the final analysis; 48% (46) of patients presented with acute kidney injury, 8% (8) required first-time HD or RRT, 61% (58) were culture positive, 55% (52) were in shock, and overall mortality was 20% (19). There was no significant relationship between quantity of chloride administered in the first 24 hours with change in Cr (ß = -0.0001, t = -0.86, R(2) = 0.92, P = .39), need for HD or RRT (odds ratio [OR] = 0.999; 95% confidence interval [CI], 0.999-1.000; P = .77), LOS >14 days (OR = 1.000; 95% CI, 0.999-1.000; P = .68), mortality (OR = 0.999; 95% CI, 0.999-1.000; P = .88), or any type of organ dysfunction. CONCLUSION: Chloride administered in the first 24 hours did not influence kidney function in this cohort with severe sepsis or septic shock.

Use of pulmonary arterial hypertension-specific therapy in non-WHO group I pulmonary hypertension.

OBJECTIVES: The development of pulmonary hypertension (PH) in non-World Health Organization group I PH adversely affects exercise capacity. It is unclear whether pulmonary artery hypertension (PAH)-specific drugs improve pulmonary hemodynamics and exercise capacity in such patients. METHODS: We performed a retrospective chart review of consecutive patients with non-World Health Organization group I PH treated with PAH-specific therapy. RESULTS: We identified 24 patients. The mean (standard deviation) age was 48 (14.8) years. Seventeen (71%) patients were women. The 6-minute walk distance improved significantly for the whole group in an initial follow-up period of 4.6 (2.3) months; however, the improvement was seen only in patients with obstructive sleep apnea (OSA) or severe PH and it was not sustained during a longer follow-up period of 11.5 (4.1) months, except in patients with OSA. PH was treated with a variety of PAH-specific drugs, including combination therapy in five patients. CONCLUSIONS: The use of PAH-specific therapy in selected patients with PH secondary to lung diseases, OSA, or sarcoidosis may result in significant improvement in 6-minute walk distance, particularly in patients with OSA or severe PH.

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). MATERIAL AND METHODS: Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. RESULTS: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. CONCLUSION: In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

Evidence-based review of the management of hepatic hydrothorax.

Hepatic hydrothorax (HH) is an example of a porous diaphragm syndrome. Portal hypertension results in the formation of ascitic fluid which moves across defects in the diaphragm and accumulates in the pleural space. Consequently, the treatment approach to HH consists of measures to reduce the formation of ascitic fluid, prevent the movement of ascitic fluid across the diaphragm, and drain or obliterate the pleural space. Approximately 21-26% of cases of HH are refractory to salt and fluid restriction and diuretics and warrant consideration of additional treatment measures. Ideally, liver transplantation is the best treatment option; however, most of the patients are not candidates and most of those who are eligible die while waiting for a transplant. Treatment measures other than liver transplantation may not only provide relief from dyspnea but also improve patient survival and serve as a bridge to liver transplantation.

Pleural Schwannoma Presenting As Musculoskeletal Type Pain: A Case Report.

Schwannomas are benign peripheral nerve sheath tumors typically found in the neck, flexor surfaces of the extremities, mediastinum, posterior spinal roots, cerebellopontine angle, and retroperitoneum. Pleural schwannomas are a type of neoplasm that arises from autonomic nerve fiber sheaths in the pleura and rarely originate in the thoracic cavity. These schwannomas tend to be asymptomatic, benign, and slow-growing neoplasms. Although pleural schwannomas commonly occur in males, our report highlights a unique presentation of a pleural schwannoma presenting as musculoskeletal-type chest pain in an adult female. Our patient's diagnosis of pleural schwannoma was supported after X-Ray, Computed Tomography (CT) Scan, and Positron Emission Tomography (PET) Scan imaging was complete. All imagining and immunohistochemical staining yielded pleural schwannoma as the final diagnosis. We aim to bring awareness to the necessity of imaging and histopathological staining in atypical clinical cases of pleural schwannoma. Our novel case highlights pleural schwannoma as a differential diagnosis for patients with intermittent, musculoskeletal-type chest pain.

BREEZE: Open-label clinical study to evaluate the safety and tolerability of treprostinil inhalation powder as Tyvaso DPI™ in patients with pulmonary arterial hypertension.

Inhaled treprostinil is an approved therapy for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease in the United States. Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer preparation, maintenance, and treatment. A small, portable treprostinil dry powder inhaler has been developed for the treatment of PAH. The primary objective of this study was to evaluate the safety and tolerability of treprostinil inhalation powder (TreT) in patients currently treated with treprostinil inhalation solution. Fifty-one patients on a stable dose of treprostinil inhalation solution enrolled and transitioned to TreT at a corresponding dose. Six-minute walk distance (6MWD), device preference and satisfaction (Preference Questionnaire for Inhaled Treprostinil Devices [PQ-ITD]), PAH Symptoms and Impact (PAH-SYMPACT®) questionnaire, and systemic exposure and pharmacokinetics for up to 5 h were assessed at baseline for treprostinil inhalation solution and at Week 3 for TreT. Adverse events (AEs) were consistent with studies of inhaled treprostinil in patients with PAH, and there were no study drug-related serious AEs. Statistically significant improvements occurred in 6MWD, PQ-ITD, and PAH-SYMPACT. Forty-nine patients completed the 3-week treatment phase and all elected to participate in an optional extension phase. These results demonstrate that, in patients with PAH, transition from treprostinil inhalation solution to TreT is safe, well-tolerated, and accompanied by statistically significant improvements in key clinical assessments and patient-reported outcomes with comparable systemic exposure between the two formulations at evaluated doses (trial registration: clinicaltrials.gov identifier: NCT03950739).

Automated prone positioning and axial rotation in critically ill, nontrauma patients with acute respiratory distress syndrome (ARDS).

The objective of this study was to evaluate the use of kinetic therapy beds for automated prone positioning and axial rotation in critically ill nontrauma patients with acute respiratory distress syndrome (ARDS). There were 17 patients with ARDS who underwent automated prone positioning using a kinetic therapy bed. The mean age was 51 + 14 years; 12 were females and 12 were Caucasian. The most common admission diagnosis was sepsis (n = 5). The mean Acute Physiology and Chronic Health Evaluation (APACHE) 2 score was 30 + 9 with mean predicted mortality of 65% + 25%. At the time of prone positioning, all patients met the criteria for ARDS. The mean ratio of PaO2 to FIO2 (P/F ratio) before initiation of prone positioning was 89 + 33 and rose to 224 + 92 after at least 30 minutes of prone positioning (P < .0001). There was no significant change in PaCO2 or mean airway pressure. There were no instances of accidental endotracheal tube and central or peripheral venous or arterial catheter dislodgement. Eleven (65%) patients developed new pressure ulcers, 10 (59%) patients developed new skin tears, and all had conjunctival edema during the course of prone positioning. The median duration of automated prone positioning was 6 (interquartile range [IQR] 3.5-8.5) days. Eleven (65%) patients died during hospitalization and 7 required percutaneous tracheostomy for long-term ventilator support. Automated prone positioning using a kinetic therapy bed is a safe and effective means of improving oxygenation in critically ill patients with ARDS. Larger randomized studies are needed to compare it to conventional ventilation strategies, conventional prone positioning, and to assess the impact on mortality.

Diagnostic accuracy of echocardiography combined with chest CT in pulmonary hypertension.

BACKGROUND: Transthoracic echocardiography (TTE) and computerized axial tomography (CT) are complementary imaging techniques. It is possible that a combination of the two may offer a better way of identifying pulmonary hypertension (PH) than either one alone. OBJECTIVES: To determine the diagnostic accuracy of TTE combined with chest CT in pulmonary hypertension. METHODS: We performed a retrospective review of consecutive patients who had undergone TTE, CT and right heart catheterization (RHC) between 7/1/2008 and 6/30/2012. PH was defined as systolic pulmonary artery pressure >40 mm Hg or tricuspid regurgitant (TR) jet velocity >2.8m/s on TTE, ratio of diameter of pulmonary artery to ascending aorta (rPA) >1 or diameter of PA (dPA) >30 mm on CT, and mean PAP (mPAP) >25 mm Hg on RHC. RESULTS: There was a total of 87 patients. The mean ± SD age was 54.3 ± 15.9 years and 69 (79%) were female. The prevalence of PH was 75%. The mean ± SD mPAP was 35.8 ± 14.2 mm Hg. The majority of the patients belonged to World Health Organization group I PH. Fifty per cent of the CT scans were done with intravenous contrast dye. The combination of TR jet velocity and rPA provided the best combination of sensitivity (98%) and specificity (70%) with an ROC area under the curve of 0.84. CONCLUSION: The combination of TTE and chest CT is better than either imaging technique alone in identifying patients with PH in a heterogeneous population and may exclude PH.

The safety and tolerability of inhaled treprostinil in patients with pulmonary hypertension and chronic obstructive pulmonary disease.

The primary aim was to explore the safety and tolerability of inhaled treprostinil when used in patients with pulmonary hypertension (PH) with concomitant chronic obstructive pulmonary disease (COPD). Patients with a diagnosis of pre-capillary PH (defined as pulmonary artery mean pressure of ≥ 25 mmHg and pulmonary artery wedge pressure or left ventricular end diastolic pressure of ≤ 15 mmHg) who were being initiated on inhaled treprostinil and had concomitant COPD (defined as FEV1/FVC ratio ≤ 70% with FEV1 ≥ 40% predicted) were considered for inclusion in this pilot study. Assessments included adverse events, physical exam, World Health Organization (WHO) functional class, 6-minute walk test (6MWT), modified Borg dyspnea score, and concomitant medication. At baseline and week 16 St. George's Respiratory Questionnaire (SGRQ), arterial blood gas (ABG), and pulmonary function test (PFT) were assessed. The median age was 65 years (age range, 56-80 years) and five patients (56%) were men. Among the nine patients, a majority had an increase in 6MWT from baseline to week 16 (median change, 19 m). Only three of the nine patients (33%) had an increase in A-a gradient at week 16 (median change, -7). There was no difference in any of the following: arterial blood gases, WHO functional class, 6MWT results, or SGRQ scores from baseline to week 16. There was a statistically significant decline in several of the PFT measures, including FEV1 (median change, -0.18 L; P = 0.004; median change, -7% of predicted; P = 0.016), FVC (median change, -0.23 L; P = 0.027), and diffusion capacity for carbon monoxide (DLCO) (median change, -5% of predicted; P = 0.023). The small number of patients limits firm conclusions; however, inhaled treprostinil did not seem to adversely impact oxygenation in the majority of the study patients with pre-capillary PH and COPD. While there may have an adverse impact on some pulmonary function parameters, the clinical significance is unclear.

Operator dependent factors implicated in failure of non-invasive positive pressure ventilation (NIPPV) for respiratory failure.

BACKGROUND: Non-invasive Positive Pressure Ventilation (NIPPV) is employed for the management of acute respiratory failure and studies have shown that it can prevent the need for endotracheal intubation, mechanical ventilation and associated complications. Given limited studies evaluating the factors, other than those related patient or underlying disease severity, that may lead to NIPPV failure, we performed this study to gain insight into current practices in terms of utilization of NIPPV and operator dependent factors that may possibly contribute to failure of NIPPV. METHOD: After institutional board review approval a retrospective chart review was performed of consecutive patients who were initiated on and failed NIPPV between January 2009 and December 2009. Data was recorded regarding baseline demographics, admission diagnosis, indications for NIPPV, presence of contraindications, type of NIPPV and initial settings, ABG analysis before and after initiation, whether a titration of the settings was performed or not, operator related factors that may have contributed to failure of NIPPV and clinical outcomes. RESULTS: Among 1095 patients screened, 111 failed NIPPV. The mean age was 60 years with 59% males. The most frequent indication for initiating NIPPV was COPD exacerbation (N = 27) followed by pneumonia (N = 26). CPAP was used in 5(6%) patients. Median inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) setting were 10 and 5 cm of H2 O respectively. Three most common reasons for failure were an inappropriate indication (33%), Progression of underlying disease (30%) and lack of titration (23%). Overall mortality was 22%. Mortality was higher when NIPPV failure was seen among patients with an inappropriate indication or an overlooked contraindication compared to those with an appropriate indication (27% vs 17%). CONCLUSIONS: Excluding progression of underlying disease, operator dependent factors linked to NIPPV failure are; inappropriate indication, lack of adequate titration and an overlooked contraindication. Inappropriate utilization of NIPPV in respiratory failure is associated with higher mortality.

A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study.

PURPOSE: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. RESULTS: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. CONCLUSIONS: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.

A case of disseminated intravascular coagulation secondary to Acinetobacter lwoffii and Acinetobacter baumannii bacteremia.

Bacteremia is currently one of the infections with the highest mortality in hospitals [1]. Acinetobacter lwoffii and Acinetobacter baumannii are gram-negative bacteria and both represent opportunistic pathogens. In certain cases, the management can be challenging since these organisms can be highly resistant to antimicrobial agents. Clinical illnesses associated with Acinetobacter include pneumonia, meningitis, peritonitis, endocarditis and infections of the urinary tract and skin [1]. Acinetobacter bacteremia represents a serious and ever increasing problem because of the high associated morbidity and mortality.

Severe Pulmonary Arterial Hypertension: Comprehensive Evaluation by Magnetic Resonance Imaging.

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery (PA) pressure, which negatively affects the right ventricular (RV) function. This report shows a patient with severe PAH, on whom a comprehensive MRI exam was performed to evaluate both PA and RV. New imaging sequences were implemented for obtaining additional parameters about the patient's condition. The results show the capabilities of the developed exam of providing complete picture of the cardiovascular system in PAH, which helps the physician optimize treatment.

Assessment of Pulmonary Arterial Hypertension by Magnetic Resonance Imaging.

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressure (PAP), altered pulmonary artery (PA) hemodynamics, and vessel wall characteristics that affect the right ventricular (RV) function. Magnetic resonance imaging (MRI) has recently been considered in PAH and has shown promising results for estimating PAP, measuring PA hemodynamic parameters, assessing PA vessel wall stiffness, and evaluating RV global and regional functions. In this article, we review various MRI techniques and image analysis methods for evaluating PAH, with an emphasis on the resulting images and how they are interpreted for both qualitatively and quantitatively assessing the PA and RV conditions.

Use of endobronchial ultrasound to evaluate nonthrombotic endovascular lesions in pulmonary arteries: a systematic review.

BACKGROUND: The finding of a filling defect in a pulmonary artery (PA) sometimes raises the possibility of cancer. Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) may confirm the underlying nature of the endovascular lesion. However, little is known about the use of this procedure for this purpose. METHODS: We searched PubMed and abstracts of major international conferences. RESULTS: There was a total of 12 cases: 8 female, 3 male, and 1 unknown. The median (range) age was 60 (51 to 79) years. EBUS was performed to evaluate mass-like lesion involving the PA (n=5), persistent or progressive filling defects in the PA despite anticoagulation (n=3), filling defect in the PA with multiple areas of consolidation, air-fluid levels in the lung (n=1), and hilar density (n=1). Moreover, an endovascular lesion was incidentally noted in the PA during EBUS for evaluating lymph nodes (n=2). EBUS-TBNA was diagnostic in 9 of the 10 cases in which it was performed. The final diagnoses were: sarcoma (n=6), lung cancer (n=2), thyroid cancer (n=1), renal cell cancer (n=1), melanoma (n=1), and pulmonary embolism (n=1). The cancer was a recurrence in 6 of the 7 cases with a known history of cancer. CONCLUSIONS: EBUS should be considered as a possible method for evaluating endovascular lesions when PA sarcoma or tumor macroembolism is suspected.

Predicting the Need for Upfront Combination Therapy in Pulmonary Arterial Hypertension.

BACKGROUND: Combination therapy is commonly used for pulmonary arterial hypertension (PAH) treatment. We aimed to identify factors that may predict the need for future combination therapy. METHODS: We conducted a retrospective chart review of consecutive patients with PAH in an aim to describe baseline clinical, echocardiogram, and hemodynamic characteristics of patients who eventually required combination therapy during the course of their disease and compared them to the ones who were maintained on monotherapy. RESULTS: The monotherapy group was followed for an average of 31.8 ± 18.8 months and the combination therapy group was followed for an average of 28.7 ± 13.6 months. Among the 71 patients analyzed, a significantly higher number of patients who eventually required combination therapy belonged to World Health Organization functional class 3 (45% vs 37%) and 4 (23% vs 0) at baseline, compared with those on monotherapy (P < .05). Combination group also had a higher Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) PAH risk score at presentation. End of 6-minute walk test (6MWT), oxygen saturation (Spo 2) was also lower in the combination therapy group, 86% ± 8% versus 91% ± 7% (P < .05). Patients who eventually required combination therapy were more frequently noticed to have right ventricular enlargement, right atrial enlargement, and had a higher resting estimated right ventricular systolic pressure (RVSP). Right heart catheterization-derived hemodynamics data at baseline showed that the combination therapy group had a higher mean pulmonary artery (PA) pressure, lower pulmonary capillary wedge pressure, lower cardiac output, and higher pulmonary vascular resistance (PVR). On univariate analysis, only PVR ≥300 dyne·s/cm(5), mean PA pressure of ≥40 mm Hg, estimated RVSP ≥ 60 mm Hg, PAH risk score ≥ 10, and end of 6MWT saturation of ≤ 90% were of significance. CONCLUSION: Patients with PAH who require combination therapy in the course of their disease have worse hemodynamics, PAH risk score, functional class, and end of 6MWT oxygen saturation at the time of presentation compared to patients maintained on monotherapy.

Is There Any Association between PEEP and Upper Extremity DVT?

Background. We hypothesized that positive end-exploratory pressure (PEEP) may promote venous stasis in the upper extremities and predispose to upper extremity deep vein thrombosis (UEDVT). Methods. We performed a retrospective case control study of medical intensive care unit patients who required mechanical ventilation (MV) for >72 hours and underwent duplex ultrasound of their upper veins for suspected DVT between January 2011 and December 2013. Results. UEDVT was found in 32 (28.5%) of 112 patients. Nineteen (67.8%) had a central venous catheter on the same side. The mean ± SD duration of MV was 13.2 ± 9.5 days. Average PEEP was 7.13 ± 2.97 cm H2O. Average PEEP was ≥10 cm H2O in 23 (20.5%) patients. Congestive heart failure (CHF) significantly increased the odds of UEDVT (OR 4.53, 95% CI 1.13-18.11; P = 0.03) whereas longer duration of MV (≥13 vs. <13 days) significantly reduced it (OR 0.29, 95% CI 0.11-0.8; P = 0.02). Morbid obesity showed a trend towards significance (OR 3.82, 95% CI 0.95-15.4; P = 0.06). Neither PEEP nor any of the other analyzed predictors was associated with UEDVT. Conclusions. There is no association between PEEP and UEDVT. CHF may predispose to UEDVT whereas the risk of UEDVT declines with longer duration of MV.