Avital Avriel

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.

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.

Quality of life at the dead sea region: the lower the better? an observational study

BackgroundThe 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.ObjectiveTo 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.MethodsAn 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.ResultsThere 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.ConclusionsNo 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.

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.

Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome in Patients With Pulmonary Arterial Hypertension

Diastolic dysfunction may influence perioperative outcome, early graft function, and long‐term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5–32.6] vs 22.4 [IQR 19.9–25.3] kg/m2) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator‐free days (2.5 [IQR 6.5–32.5] vs 17 [IQR 3–23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One‐year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3–22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3–22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx.

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

BackgroundSilicosis is an occupational lung disease resulting from inhalation of respirable crystalline silica. Recently, an international silicosis epidemic has been noted among artificial stone workers.ObjectiveEndobronchial 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.MethodsTwenty-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).ResultsEleven 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.ConclusionsEBUS-TBNA is a useful and sufficient tool to diagnose silicosis in patients with mediastinal lymphadenopathy along compatible exposure histories.

Cerebral air emboli complicating trans-bronchial needle aspiration using endo-bronchial ultrasound

A 71-year-old patient underwent trans-bronchial needle aspiration (TBNA) from mediastinal lymph nodes using endo-bronchial ultrasound (EBUS). The procedure was performed under conscious intravenous sedation through a peripheral vein, using a 21-gauge needle and was associated with only minimal bleeding. After the procedure, he remained comatose. CT angiography revealed diffuse cerebral air emboli (Fig. 1) and ruled out pneumothorax and pneumomediastinum. Echocardiography using color Doppler and bubbles ruled out PFO. Air emboli following bronchoscopy are exceedingly rare. Few cases have been described, mostly after Argon plasma coagulation or Nd-YAG laser. Lung biopsy may cause traumatic break of the blood–air interface potentially leading to gas embolism. Spontaneous breathing and coughing may further augment the pressure gradient forcing air into the vasculature. Systemic embolization may occur through a cardiac right to left shunt or arterio-venous anastomoses in the lungs, resulting in arterial gas emboli (AGE). AGE may have serious CNS and cardiovascular manifestations. Air in the unsealed needle and the high lymph node vascularity may serve as risk factors for AGE caused by transient broncho-vascular fistula while performing EBUS-guided TBNA. The patient was treated in a hyperbaric chamber within 8 h of the procedure. He eventually regained normal neurologic function.

Pulmonary artery hypertension following coronary artery bypass grafting: a case report: PAH post CABG

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.