Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study.

Pulmonary arterial hypertension (PAH) is a rare condition with the potential to progress to right heart failure. Point-of-Care Ultrasonography (POCUS), used and interpreted in real time at the bedside to further the cardiopulmonary assessment, has the potential to improve the longitudinal care of PAH patients in the ambulatory setting. Patients from PAH clinics at two academic medical centers were randomized to either a POCUS assessment cohort or non-POCUS standard care (ClinicalTrials.gov identifier NCT05332847). The POCUS group received blinded heart, lung, and vascular ultrasound assessments. Thirty-six patients were randomized to the study and followed over time. Mean age was 65 in both groups and majority female (76.5% and 88.9% females in POCUS and control, respectively). Median time for POCUS assessment was 11 min (range 8-16). There were significantly more changes in management in the POCUS group than control (73% vs. 27%, p-value < 0.001). Multivariate analysis revealed that management changes were more likely to occur with a POCUS assessment, with an odds ratio (OR) of 12 when POCUS was added to physical exam vs. OR of 4.6 compared to physical examination alone (p < 0.001). POCUS in the PAH clinic is feasible and, when combined with physical examination, increases the number of findings and results in changes in management without significantly prolonging visit encounters. POCUS may help support clinical evaluation and decision making in ambulatory PAH clinics.

Intravascular Ultrasound Pulmonary Artery Denervation to Treat Pulmonary Arterial Hypertension (TROPHY1): Multicenter, Early Feasibility Study.

OBJECTIVES: The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) on a minimum of dual oral therapy. BACKGROUND: Early studies have suggested that PDN can reduce PVR in patients with PAH. METHODS: TROPHY1 (Treatment of Pulmonary Hypertension 1) was a multicenter, international, open-label trial undertaken at 8 specialist centers. Patients 18 to 75 years of age with PAH were eligible if taking dual oral or triple nonparenteral therapy and not responsive to acute vasodilator testing. Eligible patients underwent PDN (TIVUS System). The primary safety endpoint was procedure-related adverse events at 30 days. Secondary endpoints included procedure-related adverse events, disease worsening and death to 12 months, and efficacy endpoints that included change in pulmonary hemodynamic status, 6-min walk distance, and quality of life from baseline to 4 or 6 months. Patients were to remain on disease-specific medication for the duration of the study. RESULTS: Twenty-three patients underwent PDN, with no procedure-related serious adverse events reported. The reduction in PVR at 4- or 6-month follow-up was 94 ± 151 dyn·s·cm-5 (p = 0.001) or 17.8%, which was associated with a 42 ± 63 m (p = 0.02) increase in 6-min walk distance and a 671 ± 1,555 step (p = 0.04) increase in daily activity. CONCLUSIONS: In this multicenter early feasibility study, PDN with an intravascular ultrasound catheter was performed without procedure-related adverse events and was associated with a reduction in PVR and increases in 6-min walk distance and daily activity in patients with PAH on background dual or triple therapy.

Feasibility and safety of the antecubital venous access for right heart catheterization in patients with pulmonary hypertension.

BACKGROUND: The diagnosis of pulmonary arterial hypertension requires right heart catheterization (RHC) which is typically performed via proximal venous access (PVA). Antecubital venous access (AVA) is an alternative approach for RHC that can minimize complications, decrease procedural duration and allow for immediate patient recovery. A direct comparison between the two procedures in patients with pulmonary hypertension (PH) is lacking. OBJECTIVES: To determine the feasibility, safety, and adoption rates of AVA-RHC as compared with ultrasound-guided PVA in a subpopulation of patients with PH. METHODS: All patients who underwent RHC for evaluation of PH between December 2014 and March 2017 at a single large academic medical center were included in this study. Demographic, procedural and outcomes data were retrieved from the medical records. RESULTS: In total, 159 RHC were included (124 AVA, 35 PVA). The duration of RHC was significantly shorter in the AVA compared with PVA group (53 (IQR 38-70) vs. 80 (IQR 56-95) min, respectively, p < 0.001). 19% of AVA (24/124) procedures were switched to PVA. Failed attempts at AVA were more common in scleroderma (50% failure rate). Success rate of AVA increased from 81.2% to 93.3% from the first to last quartile. Fluoroscopy time was similar in both groups, the difference between the groups in the radiation dose are not statistically significant (54.5 (IQR 25-110) vs. 84.5 (IQR 30-134)). CONCLUSION: AVA-RHC is a feasible and safe alternative to PVA in patients with PH who are evaluated for pulmonary arterial hypertension diagnosis. Our experience and rapid adoption rate support the use of AVA as the preferred access site for RHC in uncomplicated PH patients.

NLRP3 inflammasome activity is upregulated in an in-vitro model of COPD exacerbation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function. Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes. NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD. The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model. METHODS: A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1µg/ml) for 24 hours. Cell viability was assessed by using XTT test. Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1ß) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry. RESULTS: Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner. Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone. NLRP3 inflammasome activity and IL-1ß levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone. CONCLUSIONS: NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation. Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research.

Sampling pleural nodules with an EBUS scope: A novel application.

Convex endobronchial ultrasound transbronchial needle aspiration (C-EBUS-TBNA) has become an essential modality for diagnosis and staging of hilar, mediastinal, and central pulmonary lesions. A Trans-thoracic pleural biopsy is the accepted practice for diagnosing pleural nodules. However, the diagnostic yield of a pleural biopsy is limited and surgical procedures pose a greater risk. We report a unique case of using a C- EBUS scope for the diagnosis of pleural nodules and mediastinal lymph node metastasis in a man with metastatic renal cell carcinoma.

EBUS-TBNA is Sufficient for Successful Diagnosis of Silicosis with Mediastinal Lymphadenopathy.

BACKGROUND: Silicosis is an occupational lung disease resulting from inhalation of respirable crystalline silica. Recently, an international silicosis epidemic has been noted among artificial stone workers. OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is currently used for patients with unexplained lymphadenopathy. Since silicosis may present with prominent lymphadenopathy, the diagnostic yield of EBUS-TBNA in diagnosing silicosis was evaluated. METHODS: Twenty-eight patients with suspected silicosis referred for outpatient evaluation in three large tertiary hospitals were evaluated. Patients with mediastinal lymphadenopathy underwent EBUS-TBNA, while others underwent TBB and/or video-assisted thoracoscopic surgery (VATS). RESULTS: Eleven patients with mediastinal lymphadenopathy (39%) were evaluated using EBUS-TBNA. The diagnosis was accurate in all cases, demonstrating silica particles under polarized light, with no complications. Among the remaining patients, TBB was only 76% diagnostic, therefore requiring VATS. CONCLUSIONS: EBUS-TBNA is a useful and sufficient tool to diagnose silicosis in patients with mediastinal lymphadenopathy along compatible exposure histories.

Pulmonary artery hypertension following coronary artery bypass grafting: a case report.

Post-operative pulmonary complications in coronary artery bypass grafting (CABG) surgery are mostly reversible. We report a patient who developed pulmonary arterial hypertension (PAH) post-CABG and did not have pulmonary hypertension prior to surgery. PAH Group 1 was diagnosed after right and left heart catheterization. To the best of our knowledge, this is the only reported case of a patient developing PAH post-CABG surgery. This could be explained by immunological and/or haemostatic changes triggered by cardiopulmonary bypass. We hope that as more knowledge is gained regarding the pathophysiology of PAH, cases like these could be better understood.

Prognostic utility of admission cell-free DNA levels in patients with chronic obstructive pulmonary disease exacerbations.

BACKGROUND: Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality. Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD. The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival. METHODS: This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE. Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls. Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival. RESULTS: A total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included. The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016-2,319) compared to 781 ng/mL (IQR 523-855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209-636) for healthy controls (P<0.0001, for both comparisons). cfDNA was correlated with partial arterial pressure of carbon dioxide (PaCO2, r=0.35) and pH (r=-0.35), P=0.01 for both comparisons. In a multivariable analysis, PaCO2 was the only independent predictor of cfDNA. Using a cfDNA level of 1,924 ng/mL (threshold for abnormal PaCO2), those with high levels had a trend for increased 5-year mortality risk adjusted for age, sex and FEV1% (hazard ratio 1.92, 95% confidence interval 0.93-3.95, P=0.08). CONCLUSION: Plasma cfDNA might offer a novel technique to identify COPD patients at increased risk of poor outcomes, but the prognostic utility of this measurement requires further study.

Prediction of Antiphospholipid syndrome using Annexin A5 competition assay in patients with SLE.

A significantly high correlation between reduced activity of Annexin A5 by the flow cytometric assay (FCA) and the diagnosis of antiphospholipid syndrome (APS) has been reported. The aim of this study was to assess the clinical and laboratory significance of the Annexin A5 competition assay among patients with systemic lupus erythematosus (SLE). The FCA competition assay was performed on blood samples from 57 consecutive SLE patients. The FCA was performed according to a previously validated method. Forty-seven patients (82.5 %) had SLE without APS and ten (17.5 %) had SLE with APS. Twenty-four (42 %) of the patients had mean levels of AnxA5 fluorescence below the mean and standard deviation of the controls and were considered positive. SLE patients with a positive FCA were found to have an increased risk for a hypercoagulable or vascular state (86 % of the patients had cerebrovascular disease, 89 % had Raynaud's phenomenon, and 80 % had deep vein thrombosis). The risk for any hypercoagulable or vascular state was significantly increased (P = 0.012, RR-2.3, 95 % CI 1.4-3.8). A positive FCA assay was found in 90 % of the patients with APS (P < 0.001), with a sensitivity of 90 % and a specificity of 68 % for this diagnosis. The positive and negative predictive values were 0.4 and 0.97, respectively. Correlations were found between positive FCA and positive Anti-Cardiolipin antibody (P < 0.001), and Anti-ß2 glycoprotein I levels (P = 0.013). Our findings suggest that the FCA is a practical assay for the detection of clinically relevant APS among patients with SLE.

Measurement of circulating cell-free DNA levels by a simple fluorescent test in patients with breast cancer.

OBJECTIVES: To evaluate circulating cell-free DNA (CFD) measured by a simple fluorescent assay as a biomarker of breast cancer. METHODS: We enrolled 38 patients with breast cancer before surgery, two patients with noncancerous breast lesions, nine patients after surgery, 16 healthy participants, and 29 control women admitted to the hospital emergency ward and released without hospitalization. CFD levels were measured by a direct fluorescence assay. RESULTS: Presurgery patients with cancer had elevated CFD levels (1,010 ± 642 ng/mL), which were higher than those measured in the healthy control group (395 ± 248 ng/mL, P < .001), the noncancer breast lesion group (386 ± 40 ng/mL), the nonhospitalized control group (492 ± 193 ng/mL, P < .001), and the postsurgery cancer group (398 ± 162 ng/mL, P < .01). The area under the receiver operating characteristic curve of the presurgery vs healthy patient group was 0.83. CFD levels correlated with tumor size (P = .03, ρ = 0.36), nodal involvement (P = .0003, ρ = 0.56), and TNM stage (P = .0002, ρ = 0.56). All patients with axillary node involvement had a CFD value greater than 600 ng/mL. CONCLUSIONS: CFD measured using a simple fluorometric assay has shown good correlation to stage and enhanced sensitivity to locally advanced disease. A large prospective study is warranted to evaluate if inclusion of this method as a decisive marker before mammography is advantageous.

Admission cell free DNA levels predict 28-day mortality in patients with severe sepsis in intensive care.

AIM: The aim of the current study is to assess the mortality prediction accuracy of circulating cell-free DNA (CFD) level at admission measured by a new simplified method. MATERIALS AND METHODS: CFD levels were measured by a direct fluorescence assay in severe sepsis patients on intensive care unit (ICU) admission. In-hospital and/or twenty eight day all-cause mortality was the primary outcome. RESULTS: Out of 108 patients with median APACHE II of 20, 32.4% have died in hospital/or at 28-day. CFD levels were higher in decedents: median 3469.0 vs. 1659 ng/ml, p<0.001. In multivariable model APACHE II score and CFD (quartiles) were significantly associated with the mortality: odds ratio of 1.05, p = 0.049 and 2.57, p<0.001 per quartile respectively. C-statistics for the models was 0.79 for CFD and 0.68 for APACHE II. Integrated discrimination improvement (IDI) analyses showed that CFD and CFD+APACHE II score models had better discriminatory ability than APACHE II score alone. CONCLUSIONS: CFD level assessed by a new, simple fluorometric-assay is an accurate predictor of acute mortality among ICU patients with severe sepsis. Comparison of CFD to APACHE II score and Procalcitonin (PCT), suggests that CFD has the potential to improve clinical decision making.

Major respiratory adverse events after laparascopic gastric banding surgery for morbid obesity.

BACKGROUND: Laparoscopic adjustable gastric banding surgery has become one of the most common restrictive surgical procedures for treatment of morbid obesity worldwide. Although short-term respiratory complications are well known, long-term data is scarce. We investigated the manifestations of major pulmonary complications showed at least six months after the procedure. METHODS: A retrospective cohort study was conducted at a tertiary university medical center in the five years period of 2006-2010. We included every patient who had had major respiratory complication who needed hospitalization, at least 6 months after laparoscopic adjustable gastric banding procedure. Demographic, pre-operative and post-operative clinical data were collected. We documented respiratory symptoms, results of physical examination, pulmonary function tests, and imaging as well as therapies given and outcome. RESULTS: Out of 2100 patients who underwent LAGB, thirty subjects, mean age of 45.7 (range 29-64) with an equal number of males and females were included. Mean interval between operation and onset of respiratory symptoms was 51.5 months (range 10-150 months). All had dyspeptic complaints which included: regurgitation, fullness after meals, dysphagia and food aspiration with esophageal dilatation. Major respiratory complications included aspiration pneumonia (19) including pulmonary abscess (4) and empyema (2), exacerbation of asthma (3) and hemoptysis (1). Additionally we documented the emergence of chronic diseases such as interstitial lung disease (5) and bronchiectasis (3). One patient developed acute respiratory distress syndrome due to aspiration pneumonia and eventually died in the intensive care unit. The main mode of therapy was deflation of the gastric band. Those who refused to deflate or remove the gastric banding continued to suffer from dyspeptic and respiratory symptoms including recurrent pulmonary abscess. CONCLUSION: Although laparoscopic adjustable gastric banding surgery has few short-term risks and is highly effective at achieving weight reduction, we found an increased risk for major respiratory complications in the long-term period. The obesity epidemic and the increased use of surgical techniques to treat obesity will most likely lead to an increase in the incidence of long-term post-operative respiratory complications. This entity is probably under-reported and needs further research into how to reduce its incidence and morbidity.

[Incidence of hospitalizations among chronic obstructive pulmonary disease (COPD) patients with anemia].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive exertional and resting dyspnea and is associated with major co-morbidities. Hemoglobin level disorders (anemia and polycythemia) prevalence among patients and the relationship between them and the clinical expression are still not characterized unequivocally. The main purpose of this work is to test the association between anemia and hospitalizations. The presence of such a link may promote the diagnosis and treatment aimed at the patient's hemoglobin levels. HYPOTHESIS: Anemia in patients with COPD is associated with an increased number of hospitalizations. METHODS: A retrospective cohort study analysis, conducted on a group of COPD patients (n = 333) followed in the Pulmonology Institute of the Soroka University Medical Center in the years 2003-2009. Demographic physiological and clinical characteristics were compared between anemic, polycythemic and normal hemoglobin patients. Using statistical models, we examined the relationship between the presence of anemia and clinical outcome. RESULTS: Anemia was found in 79 patients (24%) and polycythemia among seven patients (2%). No difference was found between the groups in terms of number of hospitalizations, number of hospitalization days and ventilator events. There was a higher rate of co-morbidities (such as heart failure, chronic kidney disease) among anemic patients. There were also lower values of BMI and lung function and a higher proportion of men among anemic patients. CONCLUSIONS: Anemia in patients with COPD was not associated with an increase in the number of severe exacerbations. More studies are needed to clarify the threshold of a hemoglobin level below which there is an increase in the rate of hospitalizations.

Quality of life at the Dead Sea region: the lower the better? An observational study.

BACKGROUND: The Dead Sea region, the lowest in the world at 410 meters below sea level, is considered a potent climatotherapy center for the treatment of different chronic diseases. OBJECTIVE: To assess the prevalence of chronic diseases and the quality of life of residents of the Dead Sea region compared with residents of the Ramat Negev region, which has a similar climate, but is situated 600 meters above sea level. METHODS: An observational study based on a self-administered questionnaire. Data were collected from kibbutz (communal settlement) members in both regions. Residents of the Dead Sea were the study group and of Ramat Negev were the control group. We compared demographic characteristics, the prevalence of different chronic diseases and health-related quality of life (HRQOL) using the SF-36 questionnaire. RESULTS: There was a higher prevalence of skin nevi and non-inflammatory rheumatic diseases (NIRD) among Dead Sea residents, but they had significantly higher HRQOL mean scores in general health (68.7 ± 21 vs. 64.4 ± 22, p = 0.023) and vitality (64.7 ± 17.9 vs. 59.6 ± 17.3, p = 0.001), as well as significantly higher summary scores: physical component score (80.7 ± 18.2 vs. 78 ± 18.6, p = 0.042), and mental component score (79 ± 16.4 vs. 77.2 ± 15, p = 0.02). These results did not change after adjusting for social-demographic characteristics, health-related habits, and chronic diseases. CONCLUSIONS: No significant difference between the groups was found in the prevalence of most chronic diseases, except for higher rates of skin nevi and NIRD among Dead Sea residents. HRQOL was significantly higher among Dead Sea residents, both healthy or with chronic disease.

Measurement of circulating cell-free DNA levels by a new simple fluorescent test in patients with primary colorectal cancer.

Elevated circulating cell-free DNA (CFD) levels were found in patients with cancer. The standard CFD assays are work-intensive and expensive. The aim was to evaluate in patients with cancer a new simple CFD assay. In mice inoculated with cancer cells, CFD levels correlated with tumor size. Compared with healthy subjects, 38 patients with colorectal cancer (CRC) had higher preoperative CFD levels (798 ± 409 vs 308 ± 256 ng/mL; P < .0001). Compared with patients free of disease at 1 year, CFD levels were elevated in patients who remained with disease or died (DD). CFD correlated with DD (P = .033), and a combined index of carcinoembryonic antigen × CFD exhibited a better correlation to DD than did pathologic staging (P = .0027 vs P = .0065). For patients with CRC, CFD levels were prognostic of death and disease. A large prospective study will need to be performed to truly evaluate the efficacy of this method for early detection, follow-up, and evaluation of patient response to treatment.

Intermittent balneotherapy at the Dead Sea area for patients with knee osteoarthritis.

BACKGROUND: Balneotherapy, traditionally administered during a continuous stay at the Dead Sea area, has been shown to be effective for patients suffering from knee osteoarthritis. OBJECTIVES: To evaluate the effectiveness of an intermittent regimen of balneotherapy at the Dead Sea for patients with knee osteoarthritis. METHODS: Forty-four patients with knee osteoarthritis were included in a prospective randomized single-blind controlled study. The patients were divided into two groups: a treatment group (n=24), which were treated twice weekly for 6 consecutive weeks in a sulfur pool heated to 35-36 degrees C, and a control group (n=20) treated in a Jacuzzi filled with tap water heated to 35-36 degrees C. Participants were assessed by the Lequesne index of osteoarthritis severity, the WOMAC index, the SF-36 quality of health questionnaire, VAS scales for pain (completed by patients and physicians), and physical examination. RESULTS: A statistically significant improvement, lasting up to 6 months, was observed in the treatment group for most of the clinical parameters. In the control group the only improvements were in the SF-36 bodily pain scale at 6 months, the Lequesne index at 1 month and the WOMAC pain score at the end of the treatment period. Although the patients in the control group had milder disease, the difference between the two groups was not statistically significant. CONCLUSIONS: Intermittent balneotherapy appears to be effective for patients with knee osteoarthritis.