Asymmetric Dimethylarginine and NT-proBNP Levels Provide Synergistic Information in Pulmonary Arterial Hypertension.

BACKGROUND: Plasma asymmetric dimethylarginine (ADMA) is elevated in pulmonary arterial hypertension (PAH) and is associated with unfavorable outcomes. OBJECTIVES: The aim of this study was to assess changes in ADMA plasma levels for monitoring disease progression and outcomes during PAH-specific therapy. METHODS: ADMA was measured at baseline and after at least 6 months of follow-up using enzyme-linked immunosorbent assay and high-performance liquid chromatography. Changes in ADMA were analyzed in relation to changes in established PAH markers, including hemodynamic status, N-terminal pro-brain natriuretic peptide (NT-proBNP) and risk assessment scores. Impact on survival was assessed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Between 2008 and 2019, ADMA samples were collected prospectively from 215 patients with PAH. Change in ADMA plasma level was a predictor of disease progression and survival. ΔADMA (median -0.03 µmol/L; 95% CI: -0.145 to 0.0135) was correlated with change in mean pulmonary arterial pressure (P < 0.005; rS = 0.287) but was not significantly correlated with ΔNT-proBNP (P = 0.056; rS = 0.135). Patients with decreased ADMA plasma levels at follow-up had better 3-year and 5-year survival rates (88% and 80%, respectively, vs 72% and 53% in those without decreases in ADMA) (P < 0.005; pulmonary hypertension-related mortality or lung transplantation). Patients with decreases in both ADMA and NT-proBNP had better survival rates compared with patients in whom only 1 parameter improved (P < 0.005). ΔADMA was a significant predictor of survival in Cox regression analysis and also when corrected for ΔNT-proBNP (HRs: 1.27 and 1.35, respectively; P < 0.005). CONCLUSIONS: ADMA and NT-proBNP provide synergistic prognostic information for patients with PAH. ADMA could be used as an objective and distinct biomarker for monitoring treatment response in PAH.

Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia in Patients Treated With Anti-CD20 Monoclonal Antibodies.

We report 8 cases of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in patients previously treated with anti-CD20 monoclonal antibodies. Polymerase chain reaction of nasopharyngeal swabs for SARS-CoV-2 was negative in most cases; viral cell cultures confirmed that viable SARS-Co-2 virus was present. Four patients were treated with anti-SARS-CoV-2 hyperimmune globulins with rapid resolution of disease.

Management of acute COPD exacerbations in the internal medicine departments in Israel-a national survey.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Acute exacerbations of COPD (AECOPD) drastically affect the clinical course of the disease. We aimed to evaluate the treatment of AECOPD in the internal medicine departments in Israel, nationwide. Methods: The COPD Israeli survey (COPDIS) is the first national survey of patients admitted with AECOPD to internal medicine departments between 2017 and 2019. The survey includes prospective (n = 344) and retrospective (n = 1,166) data from 13 medical centers. We analyzed the pre-hospital, in-hospital, and pre-discharge care. Hospital evaluation, outcomes and discharge recommendations were assessed as well. Results: The mean (±SD) age was 74 (±8) years, and 54% were males. 74% had comorbidities, and 88% had a diagnosis of COPD in their history. 70% of the patients received systemic steroids and antibiotics during their hospitalization, yet upon discharge, a lower rate of antibiotics prescription (10%) was found. Treatment with most long-acting bronchodilators dramatically dropped during admission, compared with their pre-hospital use. Overall, a long-acting bronchodilator (LABD) was used by 47% before admission, 28% in-hospital, and was prescribed to 54% at discharge. The discharge plan included a referral to pulmonary rehabilitation in only 11% and a smoking cessation recommendation in 43% of active smokers. The in-hospital mortality was 3% and the 1-year mortality rate was 25%. In multivariate analysis, performing a chest X-ray (adjusted OR 0.64, 95% CI 0.46-0.90) and prescribing LABD at discharge (AOR 0.73, 95% CI 0.57-0.95) were independent predictors for lower 1-year mortality. Conclusion: Our results demonstrate AECOPD characteristics in Israel, and highlight several important gaps in AECOPD healthcare, which must be addressed to improve patient care.

Nontuberculous mycobacteria infections of the pleura: A systematic review.

BACKGROUND: Nontuberculous mycobacterial (NTM) pleuritis is an uncommon manifestation of NTM infection. Case reports and small case series have shown a variable clinical course and high mortality rates. OBJECTIVE: To describe patients' characteristics, clinical presentation and outcomes of NTM pleural infections. METHODS: A systematic review of cases of NTM pleural infections published in PubMed-indexed journals from 1980 to 2021. RESULTS: A total of 206 cases of NTM pleural infections were found and analyzed. Fifty-eight percent of cases were males. The mean age was 57.5 yrs (range 9-87 yrs). Forty-three percent of patients were immunosuppressed, and 43% had a chronic lung disease; thirty-two percent had neither risk factor. In addition to the pleural infection, 67% of cases had a concurrent pulmonary NTM infection, and in 18 cases there was another extrapulmonary site of NTM infection. In 29% of cases the pleural infection was the sole manifestation of NTM disease. The most common isolated mycobacterium was Mycobacterium avium complex (65%). Fifty-three percent and 26% of patients required pleural effusion drainage and a surgical intervention, respectively, to treat the infection, in addition to anti-NTM chemotherapy. Forty percent of patients developed pneumothorax, 16% suffered from empyema, and 16.5% had broncho-pleural fistula. The reported mortality rate was 24%. CONCLUSION: NTM pleural infections may arise in immunocompetent and immunosuppressed patients, with or without chronic lung disease or concurrent NTM pulmonary infection. These infections carry a poor prognosis and a high risk of complications requiring surgical interventions in addition to anti-NTM chemotherapy.

Pleuritis due to Mycobacterium xenopi without pulmonary infection.

Nontuberculous mycobacteria (NTM) may cause pulmonary and extra-pulmonary disease in both immunocompetent and immunocompromised patients. Pleuritis is an uncommon manifestation on NTM disease, and pleuritis caused by Mycobacterium xenopi has only been described once before. Because it is considered to be an environmental contaminant, isolation of M. xenopi from bronchopulmonary secretions or other sites is often dismissed. The disease caused by M. xenopi is usually a pulmonary infection and typically occurs in severely immunocompromised individuals or in immunocompetent patients with an underlying chronic lung disease. We describe an unusual case of pleuritis caused by M. xenopi in a patient without an underlying chronic lung disease and with no evidence of a concurrent M. xenopi pulmonary infection.

GATA2 Deficiency in Adult Life Is Characterized by Phenotypic Diversity and Delayed Diagnosis.

The transcription factor GATA2 plays a key role in the survival and self-renewal of hematopoietic stem and progenitor cells. Autosomal dominant variants in GATA2 cause a broad spectrum of heterogeneous phenotypes. Here, we present our experience with GATA2 deficiency in a retrospective multicenter analysis of computerized medical records of adult patients (age ≥18 years) treated between 2018 and 2022 at Shaare Zedek Medical Center in Jerusalem and Sheba Tel-Hashomer Medical Center in Ramat Gan, Israel. Two male and two female patients with GATA2 deficiency were identified. Three of the patients presented with symptoms in adult life and all patients were diagnosed as adults. Age at presentation was 10.5-36 years and age at diagnosis 24-47 years. Diagnosis was delayed in all patients by 1-24.5 years. The phenotypic diversity was notable. Patients presented with myelodysplastic syndrome (n=2), pulmonary alveolar proteinosis (n=1), and recurrent viral (n=1), bacterial (n=3), and mycobacterial (n=1) infections. Bone marrow biopsy revealed cytogenetic abnormalities in one patient (monosomy 7). Patients were diagnosed by exome sequencing (n=3) and Sanger sequencing of the coding exons in GATA2 (n=1). Novel heterozygous GATA2 variants (c.177C>A, p.Y59* and c.610dup, p.R204Pfs*78) were identified in two patients. Immune workup revealed B cell lymphopenia and monocytopenia in all tested patients. One patient died from overwhelming sepsis despite all patients being treated with antibiotics and anti-mycobacterials. Our cohort highlights the phenotypic diversity, late presentation, and delayed diagnosis of GATA2 deficiency. Increased awareness of this primary immune deficiency presenting in adult life is needed and should involve a high index of suspicion.

The importance of having good quality indicators for care of patients with COPD: a look at hospital readmission rates.

BACKGROUND: Readmission after hospitalization for acute COPD exacerbation (AE-COPD) has been proposed as a healthcare quality indicator (QI) in Israel. We studied patients hospitalized for AE-COPD, towards determining whether AE-COPD readmission is an appropriate national QI in order to improve COPD patient care. METHODS: Data were retrieved for all Clalit Health Service (CHS) members age 40-90 years hospitalized in CHS hospitals during 2016 with a diagnosis of acute COPD exacerbation. Information retrieved included demographics, medical history, Charleson comorbidity score, readmissions within 90 days, chronic medication use and family physician and pulmonologist visits. Patients readmitted within 90 days were compared to those who were not readmitted. Patients were also analyzed according to whether they were hospitalized during the year before the index hospitalization. RESULTS: In 2016 there were 70,601 members with a recorded diagnosis of COPD in CHS. Of these, 1,203 patients (1.7%) were hospitalized in a CHS hospital with a diagnosis of acute COPD exacerbation during 2016. Average age was 70.6 years, 63% were men. 78% were active smokers. 61% of the patients were readmitted to internal medicine wards within 90 days of the index hospitalization. Patients who were readmitted were more likely to have been hospitalized during the year before the index hospitalization (Odds ratio (OR) 2.5, Confidence Interval ((CI)(1.85, 3.38)) and had a higher Charlson comorbidity score (OR 1.07 (CI 1.01, 1.11)). Healthcare utilization by patients who were readmitted, both before and after admission, was generally greater. One yr mortality was 15.1% and 9.2% in those readmitted and not readmitted, respectively (p = 0.003). CONCLUSIONS: Readmitted COPD patients appear to be the sickest group of COPD patients with advanced disease and poor prognosis, and it may not be possible to prevent readmissions. This questions the utility of COPD readmissions as a healthcare quality indicator.

The role of inspiratory capacity and tidal flow in diagnosing exercise ventilatory limitation in Cystic Fibrosis.

BACKGROUND: Exercise ventilatory limitation conventionally defined by reduced breathing reserve (BR) may underestimate the effect of lung disease on exercise capacity in patients with mild to moderate obstructive lung diseases. OBJECTIVE: To investigate whether ventilatory limitation may be present despite a normal BR in Cystic Fibrosis (CF). METHODS: Twenty adult CF patients (age 16-58y) with a wide range of pulmonary obstruction severity completed a symptom-limited incremental exercise test on a cycle ergometer. Operating lung volumes were derived from inspiratory capacity (IC) measurement during exercise and exercise tidal flow volume loop analysis. RESULTS: six patients had a severe airway obstruction (FEV1<45% predicted) and conventional evidence of ventilatory limitation (low BR). Fourteen patients had mild to moderate-severe airway obstructive (FEV1 46-103% predicted), and a normal BR [12-62 L/min, BR% (17-40)]. However, dynamic respiratory mechanics demonstrated that even CF patients with mild to moderate-severe lung disease had clear evidence of ventilatory limitation during exercise. IC was decreased by (median) 580 ml (range 90-1180 ml) during exercise, indicating dynamic hyperinflation. Inspiratory reserve volume at peak exercise was 445 ml (241-1350 ml) indicating mechanical constraint on the respiratory system. The exercise tidal flow met or exceeded the expiratory boundary of the maximal flow volume loop over 72% of the expiratory volume (range 40-90%), indicating expiratory flow limitation. CONCLUSION: Reduced BR as a sole criterion underestimates ventilatory limitation during exercise in mild to moderate-severe CF patients. Assessment of dynamic respiratory mechanics during exercise revealed ventilatory limitation, present even in patients with mild obstruction.

Oxygen uptake kinetics during exercise reveal central and peripheral limitation in patients with iliofemoral venous obstruction.

OBJECTIVE: Pulmonary oxygen uptake (V˙O2) kinetics measured during the initiation of exercise mirror energetic transition during daily activity. The aim of this study was to elucidate the pathophysiological mechanisms of exercise limitation of patients with chronic iliofemoral vein obstruction after deep vein thrombosis by measuring V˙O2 kinetics compared with patients with peripheral arterial disease (PAD) and healthy individuals. METHODS: Eleven patients with iliofemoral vein obstruction (7 men; age, 20-65 years), seven patients with PAD (all men; age 44-60 years) and eight healthy participants (5 men; age 28-58 years) were studied. Participants performed upper and lower limb symptom-limited cardiopulmonary exercise tests on cycle ergometers; and four repeat lower limb tests at a constant work rate corresponding with 90% of the gas exchange threshold for determining V˙O2 kinetics. RESULTS: Phase I V˙O2 amplitude in the constant work rate tests (percent increase over resting V˙O2), representing the initial surge in cardiac output caused by the emptying of leg veins, was 59 ± 19% in the iliofemoral vein obstruction group, 73 ± 22% in PAD, and 85 ± 26% in healthy participants (P = .055 for iliofemoral vein obstruction vs healthy). Phase II V˙O2 kinetics, which largely reflect the kinetics of O2 consumption in the exercising muscles, were slower in iliofemoral vein obstruction (tau = 42 ± 6 seconds), and PAD (tau = 49 ± 19 seconds), compared with healthy participants (23 ± 4 seconds; P < .01). CONCLUSIONS: Slow phase II V˙O2 kinetics reflect a slow onset of muscular aerobic metabolism in both iliofemoral vein obstruction and PAD. The low amplitude phase I of V˙O2 kinetics observed in iliofemoral vein obstruction suggests a damped cardiodynamic phase, consistent with decreased venous return from the obstructed veins. These abnormalities of V˙O2 kinetics may contribute to exercise intolerance in iliofemoral vein obstruction and PAD.

Chronic thromboembolic pulmonary hypertension in patients with antiphospholipid syndrome: Risk factors and management.

BACKGROUND: Antiphospholipid syndrome (APS) may cause chronic thromboembolic pulmonary hypertension (CTEPH). Current knowledge regarding prevalence and risk factors for CTEPH among APS patients is limited. We sought to determine clinical features and biomarkers that could identify APS subjects suffering from CTEPH, and describe the prevalence, course and treatment outcomes of patients with APS-CTEPH. METHODS: 504 APS patients were treated in our center during 2008 to 2019. We studied clinical and laboratory features of 69 APS patients, comparing 19 patients diagnosed with CTEPH (APS-CTEPH) and treated accordingly, with 50 consecutive age and gender matched patients with no evidence of pulmonary hypertension (APS-No-CTEPH). RESULTS: CTEPH prevalence was 3.8% in our APS cohort and was linked with the following parameters: primary APS (p < 0.05); prior pulmonary embolism (p < 0.001); recurrent venous thromboembolism (VTE) (p < 0.001); lower platelet counts (p < 0.001); triple anti-phospholipid antibodies positivity (p < 0.001), higher titers of anti-cardiolipin IgG (p < 0.001), anti-B2GPI IgG (p < 0.001), and high Russell viper venom time ratio (RVVT-ratio) (p < 0.05). Additionally, history of catastrophic APS was more prevalent in APS-CTEPH vs APS-No-CTEPH (p < 0.05). Of APS-CTEPH patients, 15/19 underwent pulmonary endarterectomy (PEA): In 12/15 the procedure was elective and resulted in good perioperative and long-term outcomes, while only 1 of 3 patients that underwent urgent PEA survived. CONCLUSIONS: CTEPH is relatively common in APS. Primary APS, prior PE, recurrent VTE, thrombocytopenia and specific anti-phospholipid antibodies predict CTEPH in APS. Active assessment for CTEPH in APS patients should be considered, as PEA was found to be effective and relatively safe, especially if electively performed.

Echocardiographic Ventricular Septal Motion Abnormalities Are Associated With Pre-Capillary Pulmonary Hypertension in Patients With Preserved Left Ventricular Function.

BACKGROUND: Ventricular septal motion abnormalities (VSMA) are common echocardiographic finding in patients with pulmonary hypertension (PHTN). This study sought to evaluate the relationship between echocardiographic findings and the classification of PHTN. METHODS: This study retrospectively studied 146 consecutive patients referred for right heart catheterisation for clinically suspected PHTN. VSMA were defined as any echocardiographic description of leftward abnormal septal motion or position. RESULTS: VSMA were present in 42 patients (29%). Patients with VSMA were younger and more likely to have prior pulmonary embolism. They also had less obstructive sleep apnoea, hypertension and dyslipidaemia. By echocardiography, patients with VSMA had lower left ventricular mass, left atrial size and lateral wall E/e' ratio. At cardiac catheterisation, PHTN was confirmed in all (100%) patients with VSMA (compared with 75% in patients without VSMA); 98% with VSMA had elevated pulmonary vascular resistance (compared with 55% without VSMA; p<0.005 for all). VSMA were found to have 91% sensitivity and 51% specificity for the diagnosis of pre-capillary PHTN. On multivariate analysis, VSMA were found to be strong independent predictors for the diagnosis of pre-capillary PHTN (HR, 9.15; 95% CI, 3.0-28.2; p<0.001). Left atrial enlargement was also a strong negative predictor for pre-capillary PHTN (HR, 0.14; 95% CI, 0.05-0.36; p<0.001). CONCLUSION: Ventricular septal motion abnormalities were strongly associated with pre-capillary PHTN in patients with suspected PHTN. The findings suggest that patients with VSMA should be further evaluated by right heart catheterisation.

Pulmonary Hypertension Is Associated With Systemic Arterial Hypertension Among Patients With Normal Left Ventricular Diastolic Function.

Background The association of pulmonary and systemic arterial hypertension is believed to be mediated through hypertensive left heart disease. The purpose of the current study was to investigate whether pulmonary hypertension (PHT) is associated with systemic arterial hypertension among patients with apparently normal left ventricular diastolic function. Methods and Results Consecutive patients who had echocardiographic evaluation between 2007 and 2019 were enrolled. Patients with disease states that are known to be associated with PHT, including diastolic dysfunction, were excluded from the analysis. Estimated right ventricular systolic pressure was extracted for all patients from the echocardiographic reports. PHT was defined as estimated right ventricular systolic pressure >40 mm Hg. Multivariate logistic regression models were applied. Final study population included 25 916 patients with a median age of 59 (interquartile range, 44-69) years, of whom 12 501 (48%) were men and 13 265 (51%) had systemic arterial hypertension. Compared with normotensive patients, hypertensive patients were 3.2 times more likely to have PHT (95% CI, 2.91-3.53; P<0.001). A multivariate model adjusted for clinical and echocardiographic parameters that are known to be associated with PHT demonstrated that hypertensive patients are almost 3 times more likely to have PHT (95% CI, 2.45-3.15; P<0.001). The association was significant in multiple subgroups but was more significant among women compared with men (odds ratio, 3.1 versus 2.4; P for interaction <0.001). Conclusions PHT is associated with systemic arterial hypertension irrespective of left heart disease. The association is more pronounced among women.

A Machine Learning Approach to the Interpretation of Cardiopulmonary Exercise Tests: Development and Validation.

OBJECTIVE: At present, there is no consensus on the best strategy for interpreting the cardiopulmonary exercise test's (CPET) results. This study is aimed at assessing the potential of using computer-aided algorithms to evaluate CPET data for identifying chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). METHODS: Data from 234 CPET files from the Pulmonary Institute, at Sheba Medical Center, and the Givat-Washington College, both in Israel, were selected for this study. The selected CPET files included patients with confirmed primary CHF (n = 73), COPD (n = 75), and healthy subjects (n = 86). Of the 234 CPETs, 150 (50 in each group) tests were used for the support vector machine (SVM) learning stage, and the remaining 84 tests were used for the model validation. The performance of the SVM interpretive module was assessed by comparing its interpretation output with the conventional clinical diagnosis using distribution analysis. RESULTS: The disease classification results show that the overall predictive power of the proposed interpretive model ranged from 96% to 100%, indicating very high predictive power. Furthermore, the sensitivity, specificity, and overall precision of the proposed interpretive module were 99%, 99%, and 99%, respectively. CONCLUSIONS: The proposed new computer-aided CPET interpretive module was found to be highly sensitive and specific in classifying patients with CHF or COPD, or healthy. Comparable modules may well be applied to additional and larger populations (pathologies and exercise limitations), thereby making this tool powerful and clinically applicable.

Baseline spirometry parameters as predictors of airway hyperreactivity in adults with suspected asthma.

BACKGROUND: Methacholine challenge tests (MCTs) are used to diagnose airway hyperresponsiveness (AHR) in patients with suspected asthma where previous diagnostic testing has been inconclusive. The test is time consuming and usually requires referral to specialized centers. Simple methods to predict AHR could help determine which patients should be referred to MCTs, thus avoiding unnecessary testing. Here we investigated the potential use of baseline spirometry variables as surrogate markers for AHR in adults with suspected asthma. METHODS: Baseline spirometry and MCTs performed between 2013 and 2019 in a large tertiary center were retrospectively evaluated. Receiver-operating characteristic curves for the maximal expiratory flow-volume curve indices (angle ß, FEV1, FVC, FEV1/FVC, FEF50%, FEF25-75%) were constructed to assess their overall accuracy in predicting AHR and optimal cutoff values were identified. RESULTS: A total of 2983 tests were analyzed in adults aged 18-40 years. In total, 14% of all MCTs were positive (PC20 ≤ 16 mg/ml). All baseline spirometry parameters were significantly lower in the positive group (p < 0.001). FEF50% showed the best overall accuracy (AUC = 0.688) and proved to be useful as a negative predictor when applying FEF50% ≥ 110% as a cutoff level. CONCLUSIONS: This study highlights the role of FEF50% in predicting AHR in patients with suspected asthma. A value of ≥ 110% for baseline FEF50% could be used to exclude AHR and would lead to a substantial decrease in MCT referrals.

Balloon Pulmonary Angioplasty for Inoperable Chronic Thromboembolic Pulmonary Hypertension: First Experience at the Israeli National CTEPH Referral Center.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease caused by chronic obstruction of major pulmonary arteries, which can be cured by pulmonary endarterectomy. However, many CTEPH patients are not surgical candidates. Balloon pulmonary angioplasty (BPA) is an emerging technique used to treat inoperable CTEPH. OBJECTIVES: To describe the first Israeli experience with BPA for inoperable CTEPH. METHODS: In 2017 we established a BPA program at our institution. We reviewed the outcomes to date of BPA in our center. RESULTS: Forty-seven BPA procedures were performed in five patients with inoperable CTEPH (4-17 procedures/patient). Mean pulmonary artery pressure improved in all patients (median decrease 17 mmHg, range 10-26 mmHg). Pulmonary vascular resistance also improved (median decrease 11 Woods Units/m2, range 8-16 Woods Units/m2). Cardiac output increased in 4 of 5 patients and decreased in one. Functional capacity improved from New York Heart Association (NYHA) III to II in four patients; one patient was NYHA II at baseline without change after BPA. Six-minute walking distance improved by a median of 97 meters. (range 21-197 meters). Hemodynamic and functional improvements were sustained at follow-up 5-11 months after the last BPA procedure. BPA enabled 2 of 3 patients treated with parenteral prostanoids to be switched to oral therapy. There were no major complications. CONCLUSIONS: We successfully established BPA as a treatment for inoperable CTEPH in our center. BPA resulted in hemodynamic and clinical improvements that were sustained over time.

Predictors of mortality in inflammatory bowel disease patients treated for pneumonia.

BACKGROUND: Community-acquired pneumonia is among the most common infections affecting ulcerative colitis and Crohn's disease patients. Data regarding epidemiology and outcomes of pneumonia in inflammatory bowel disease patients is lacking. We aimed to identify predictors of adverse outcomes among inflammatory bowel disease patients treated for pneumonia. METHODS: This was a retrospective cohort study that included adult patients admitted to Sheba Medical Center for pneumonia between 2012 and 2018. Data was collected from an electronic repository of all emergency department admissions and included tabular demographic and clinical variables and free-text physician records. Pneumonia cases were extracted using the International Classification of Diseases (ICD-10) coding. RESULTS: Of 16,732 admissions with pneumonia, 97 were inflammatory bowel disease patients (45 Crohn's disease; 52 ulcerative colitis). We found a similar rate of 30-day mortality among inflammatory bowel disease and non-inflammatory bowel disease patients (12.1% versus 11.3%, p = 0.824) and between Crohn's disease and ulcerative colitis patients (11.1% versus 11.5%, p = 0.947). There was an increased hospitalization rate among inflammatory bowel disease patients (92.8% versus 85.6%, p = 0.045), but similar hospitalization duration (4 versus 4 days, p = 0.384). Crohn's disease patients had a shorter hospitalization duration compared with ulcerative colitis patients (3 versus 5.5 days, p = 0.029). Bronchiectasis (adjusted odds ratio 60.95, 95% confidence interval 2.72-1364.39, p = 0.01) and opioids use (adjusted odds ratio 13.21, 95% confidence interval 1.29-135.18, p = 0.03) were associated with an increased 30-day mortality rate in inflammatory bowel disease patients. CONCLUSION: This is the first study to identify predictors of mortality in inflammatory bowel disease patients with pneumonia. The rate of mortality and hospitalization duration of stay were similar among inflammatory bowel disease and non-inflammatory bowel disease patients. Use of opioids and presence of bronchiectasis were associated with a higher risk of mortality in inflammatory bowel disease patients with pneumonia.

Pulmonary Endarterectomy Surgery for Chronic Thromboembolic Pulmonary Hypertension: A Small-Volume National Referral Center Experience.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience. OBJECTIVES: To describe the establishment of a national CTEPH-PEA center in Israel and present results of surgery. METHODS: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH-PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center. RESULTS: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity. CONCLUSIONS: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.

Acute Respiratory Distress Syndrome following Cardiac Surgery: Comparison of the American-European Consensus Conference Definition versus the Berlin Definition.

BACKGROUND: Lung injury with development of the acute respiratory distress syndrome (ARDS) is a serious complication which can occur after major surgery, including cardiac surgery. OBJECTIVE: The aim of our study was to compare the prevalence, risk factors, and mortality of ARDS following cardiac surgery according to the American-European Consensus Conference (AECC) definition and the new Berlin definition of ARDS. METHODS: We performed a retrospective, observational study that included prospectively collected data from consecutive adult patients, aged from 18 to 92 years, who had undergone cardiac surgery (both on and off pump) at a large tertiary university hospital over 5 years (from September 2012 to September 2017). RESULTS: During the study period, 3,972 patients underwent cardiac surgery, and 3,946 patients were included in the study. Fifty-five patients developed ARDS (1.14%) according to the AECC definition and 59 patients (1.15%) according to the Berlin definition, with a mortality of 32.7 and 30.5%, respectively (18 patients). Multivariate regression analysis identified prior cardiac surgery, complex cardiac surgery, emergency procedures, and transfusion of > 3 packed red blood cell units as predictors for ARDS. CONCLUSION: The development of ARDS in patients after cardiac surgery is a rare but serious complication associated with significant mortality. Moreover, our findings showed that prevalence, mortality, and risk factors for developing ARDS were similar according to both the AECC and the new Berlin definition.

Chronic iliofemoral vein obstruction - an under-recognized cause of exercise limitation.

Local symptoms of chronic venous insufficiency after deep vein thrombosis (DVT) are well described, but little is known about the effect of residual venous obstruction on exercise capacity. We tested our hypothesis that chronic residual iliofemoral vein occlusion (IFVO) after DVT may impair exercise capacity. Nine post-DVT patients with residual IFVO and effort intolerance were studied; a comparison cohort consisted of 11 healthy volunteers. Exercise tolerance was assessed by bimodality incremental symptom-limited cardiopulmonary testing, using leg and arm ergometers. In healthy subjects, leg vein obstruction was modelled by application to the thighs of cuff tourniquets inflated to 30-40 mmHg. Leg exercise tolerance as measured by oxygen uptake at peak exercise (peak ⩒'O2) was reduced in patients (median 50% predicted (range 36-83%) vs. 88% predicted (67-129%) in normal subjects, p < 0.001). Arm exercise tolerance was also reduced in patients, but less severely than in the legs - the median arm: leg ratio of peak ⩒'O2 was 0.95 (0.77-1.43) in patients vs. a normal ratio of 0.73 (0.6-1.0) in healthy subjects (p < 0.003). In healthy subjects, bilateral leg vein obstruction by tourniquets reduced peak ⩒'O2 in leg exercise to 76% predicted (range 55-108%; p < 0.001 vs. standard test). In conclusion, the comparison of arm vs. leg exercise capacity in post-DVT patients with residual IFVO and the effect of experimental venous obstruction (thigh tourniquets) in healthy subjects suggest that reduced exercise capacity in patients was at least partially caused by reduced venous return. Chronic venous obstruction should be recognized as a cause of exercise limitation.

Determination of asthma control using administrative data regarding short-acting beta-agonist inhaler purchase.

BACKGROUND: Symptom control is a primary goal in asthma. We hypothesized that administrative data regarding rescue inhaler purchases may correlate with asthma symptom control. METHODS: We identified all patients who purchased short-acting beta-agonist (SABA) inhalers during the course of one year in the database of a Health Maintenance Organization (HMO). Primary physicians identified asthma patients and classified their asthma symptom control into three groups according to the Global Initiative for Asthma (GINA) guidelines. Asthma patients were asked to answer symptom questionnaires and grade their asthma control. SABA inhaler purchases were compared between asthma control groups as classified by the guidelines, the physicians and the patients. We also compared the agreement on asthma control between the three methods of classification. RESULTS: Of 241 asthma patients, 83 completed the questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. SABA inhaler purchases were not significantly lower in the controlled group. Using patients' overall impression of their asthma control, the mean numbers of SABA inhalers purchased were 1.5, 4.4 and 6.4 per year in the controlled, partially controlled and uncontrolled groups, respectively (p = 0.03). Patients' classification of asthma control had better agreement (kappa = 0.34) with GINA guidelines than physician's' agreement (kappa = 0.05). CONCLUSION: When using administrative data for asthma patients, 2 or more SABA inhaler purchases in one year should alert the physician for the need for asthma control evaluation. Purchase of at least 4 SABA inhalers a year may be regarded as a marker for asthma that is not controlled.