Israel Medical Association Journal

Background: Trabectedin is a marine-derived chemotherapy, which has received U.S. Food and Drug Administration approval for use in anthracycline-resistant advanced soft tissue sarcoma (STS), especially liposarcoma and leiomyosarcoma (L-sarcomas).

Objectives: To describe our 10 year real-life experience with trabectedin regarding safety and efficacy in a cohort of 86 patients.

Methods: In our study cohort, 46.51% were diagnosed with liposarcoma and 43.02% with leiomyosarcoma. A total of 703 cycles of trabectedin were given, with a median of five cycles per patient (range 1–59). Median overall survival was 13.5 months for the whole cohort, 11 months for liposarcoma patients (range 1–63), and 15 months for leiomyosarcoma patients (range 1–35).

Results: There was no statistically significant difference in progression free survival when stratified according to previous treatment lines given. Trabectedin exhibited a favorable safety profile, with only 22% requiring dose reductions. Grade 3 and higher toxicity was noted in 25% of the patients, mostly due to myelosuppression. There were no treatment-related deaths.

Conclusions: Trabectedin is a safe and effective drug for treating advanced STS. Our results reflect real-life data with patients receiving the drug as a third and even fourth line of treatment, or with a suboptimal performance status, yet achieving impressive clinical benefit rates and survival.

Background: Pacemaker pocket early post-implantation inflammation (EPII) is defined as clinical signs of local erythema without any systemic signs of infection occurring early after implantation. Data on the best treatment regimen for apparent superficial EPII is scarce. 

Objectives: To investigate the prognostic value of medical treatment, rather than extraction surgery, in patients with EPII. 

Methods: Data from 6013 consecutive patients who underwent cardiac implantable electronic device (CIED) implantation or replacement from 2007–2015 were retrospectively analyzed; 40 (0.7%) presented with EPII. Our goal was the absence of major complications and to avoidance of extraction. 

Results: Patients with EPII were initially treated medically. Nineteen (47%) (group A) recovered with antibiotic treatment only. In the other 21 patients (53%) (group B), CIED extraction was performed. Group B had more major complications compared to group A (15 [71%] vs. 0 [0%], P < 0.001). The only significant difference in baseline characteristics was history of non-initial procedure. While 86% of group B patients had a previous non-initial procedure, only 53% of group A patients underwent previous replacement (P < 0.05). In multivariate analysis, previous non-initial procedure was the only predictor for need of extraction at 1 year, hazard ratio 3.5, 95% confidence interval 1.001–11.73, P < 0.05.

Conclusions: Conservative treatment in patients with EPII after non-initial procedure can lead to serious adverse events resulting in the need for extraction. Close follow-up and aggressive treatment should be considered early in the therapeutic course.

Background: Adjuvant radiotherapy for breast cancer reduces local recurrence and improves survival. In patients with left sided breast cancer, anterior heart position or medial tumor location may cause inadequate breast coverage due to heart shielding. Respiration gating using the Real-time Position Management (RPM) system enables pushing the heart away from the tangential fields during inspiration, thus optimizing the treatment plan.

Objectives: To compare breathing inspiration gating (IG) techniques with free breathing (FB), focusing on breast coverage.

Methods: The study comprised 49 consecutive patients with left sided breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due to insufficient breast coverage caused by an anterior heart position or medial lumpectomy cavity. FB and IG computed tomography simulations were generated for each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as the target areas. Optimized treatment plans were created for each scan. A dosimetric comparison was made for breast coverage and heart and lungs doses.

Results: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36% vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95% and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung Dmean was higher. No statistical difference was found for left lung V20.

Conclusions: In patients with suboptimal treatment plans due to anterior heart position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed coverage and reduced cardiac doses.

Background: Heart transplantation (HT) is the treatment of choice for patients with end-stage heart failure. The HT unit at the Sheba Medical Center is the largest of its kind in Israel.

Objectives: To evaluate the experience of HT at a single center, assess trends over 3 decades, and correlate with worldwide data.

Methods: Between 1990 and 2017, we reviewed all 285  adult HT patients. Patients were grouped by year of HT: 1990–1999 (decade 1), 2000–2009 (decade 2), and 2010–2017 (decade 3).

Results: The percentage of women undergoing HT has increased and etiology has shifted from ischemic to non-ischemic cardiomyopathy (10% vs. 25%, P = 0.033; 70% vs. 40% ischemic, for decades 1 vs. 3, respectively). Implantation of left ventricular assist device as a bridge to HT has increased. Metabolic profile has improved over the years with lower low-density lipoprotein, diabetes, and hypertension after HT (101 mg/dl, 27%, and 41% at decade 3, respectively). There has been a prominent change in immunosuppressive treatments, currently more than 90% are treated with tacrolimus, compared with 2.7% and 30.9% in decades 1 and 2, respectively (P < 0.001). Cardiac allograft vasculopathy (CAV) rates have declined significantly (47% vs. 17.5% for decades 1 and 2, P < 0.001) as have the combined endpoint of CAV/death. Similarly, the current incidence of acute rejections is significantly lower.

Conclusions: Our analysis of over 25 years of a single-center experience with HT shows encouraging improved results, which are in line with worldwide standards and experience.

Background: A patient`s individual chance of being diagnosed with cardiovascular disease can be determined by risk scores.

Objectives: To determine the risk score profiles of patients presenting with a first acute coronary event according to pre-admission risk factors and to evaluate its association with long-term mortality.

Methods: The research was based on a retrospective study of a cohort from the 2010 and 2013 Acute Coronary Syndrome Israeli Surveys (ACSIS). Inclusion criteria included first event and no history of coronary heart disease or cardiovascular disease risk equivalent. The Framingham Risk Score, the European Systematic COronary Risk Evaluation (SCORE), and the American College of Cardiology/American Heart Association/ (ACC/AHA) risk calculator were computed for each patient. The risk profile of each patients was determined by the three scores. The prognostic value of each score for 5 year survival was evaluated.

Results: The study population comprised 1338 patients enrolled in the prospective ACSIS survey. The ACC/AHA score was the most accurate in identifying patients as high risk based on pre-admission risk factors (73% of the subjects). The Framingham algorithm identified 53%, whereas SCORE recognized only 4%. After multivariate adjustment for clinical factors at presentation, we found that no scores were independently associated with 5 year mortality following the first acute coronary event.

Conclusions: Patients with first acute coronary event had a higher pre-admission risk scores according to the ACC/AHA risk algorithm. No risk scores were independently associated with 5 year survival after an event.

Background: Skin colonization of microorganisms in blood cultures (BCs) are generally considered clinically non-significant and can be the source of a true infection, particularly in immunosuppressed patients.

Objectives: To study the epidemiology and risk factors for bacteremia caused by contaminants.

Methods: This retrospective, descriptive study is based on adult BCs collected (2004–2013) and categorized as positive (True bacteremia [TrueB] or contamination) or negative. Clinical, demographic, and laboratory characteristics of BCs positive for the six most common potential contaminant pathogens (PCPs) that can cause TrueB and contamination (Coagulase-negative Staphylococcus [CoNS], Streptococcus viridans, Propionibacterium acnes, Corynebacterium spp., Bacillus spp., Clostridium spp.) were assessed. Ninety-two TrueB were identified vs. 196 contaminations (1:2 ratio).

Results: From 74,014 BCs, PCPs were found in 3735 samples, of which 3643 (97.5%) were contaminations and 92 (2.5%) were TrueB. The overall rate of BC contamination decreased during the study period from 6.7% to 3.8%. CoNS was the most common PCP. Bacillus spp. were only contaminants. Clostridium spp. and Streptococcus viridans were more often TrueB. In a multivariate model, predictors of TrueB included high creatinine levels, Streptococcus viridans in BC, and multiple positive BCs. A single culture of CoNS was strongly predictive of contamination.

Conclusions: Ten years of data on BCs, focusing on six PCPs, demonstrates a significant, yet insufficient reduction in the rate of contamination. High creatinine level, isolation of Streptococcus viridans, and multiple positive BCs were predictors of TrueB, while growth of CoNS was strongly predictive of contamination. This model could assist in diagnostic and therapeutic decision making.

Background: About half of all patients with heart failure are diagnosed with heart failure preserved ejection fraction (HFpEF). Until now, studies have failed to show that medical treatment improves the prognosis of patients with HFpEF.

Objectives: To evaluate changes in exercise capacity of patients with HFpEF compared to those with heart failure with reduced ejection fraction (HFrEF) following an exercise training program.

Methods: Patient data was retrieved from a multi-center registry of patients with heart failure who participated in a cardiac rehabilitation program. Patients underwent exercise testing and an echocardiogram prior to entering the program and were retested6  months later.

Results: Of 216 heart failure patients enrolled in the program, 170 were diagnosed with HFrEF and 46 (21%) with HFpEF. Patients with HFpEF had lower baseline exercise capacity compared to those with HFrEF. Participating in a 6 month exercise program resulted in significant and similar improvement in exercise performance of both HFpEF and HFrEF patients: an absolute metabolic equivalent (MET) change (1.45 METs in HFrEF patients vs. 1.1 in the HFpEF group, P = 0.3).

Conclusions: An exercise training program resulted in similar improvement of exercise capacity in both HFpEF and HFrEF patients. An individualized, yet similarly structured, cardiac rehabilitation program may serve both heart failure groups, providing safety and efficacy.

Background: The identification of the etiology of a pleural effusion can be difficult. Measurement of serum B-type natriuretic peptide (BNP) levels is helpful in the diagnosis of congestive heart failure (CHF) as a cause of respiratory failure, but pleural fluid BNP measurement is still not part of the workup for pleural effusion.

Objectives: To identify the correlation between pleural fluid BNP levels and clinical diagnosis.

Methods: In this cross-sectional study, data from 107 patients admitted to the department of internal medicine between November 2009 and January 2015 were obtained from medical records. Patients underwent a diagnostic thoracocentesis as part of their evaluation. They were grouped according to final diagnosis at discharge and clinical judgment of the attending physician.

Results: Serum BNP levels were significantly higher in the CHF patients compared to patients with non-cardiac causes of pleural effusion (1519.2 and 314.1 respectively, P < 0.0001). Mean pleural fluid BNP was also significantly higher in the CHF patients (1063.2 vs. 208.3, P < 0.0001). Optional cutoff points to distinguish between cardiac and non-cardiac etiology of pleural effusion were 273.4 pg/ml (sensitivity 83.3%, specificity 72.3%, accuracy 76.7%) or 400 pg/ml (sensitivity 78.6%, specificity 86.2%, accuracy 83.0%). A strong correlation was found between serum BNP and pleural fluid BNP levels.

Conclusions: High levels of serum BNP in patients presenting with pleural effusion suggest CHF. In cases with doubt regarding the etiology of pleural effusion, high levels of pleural fluid BNP can support the diagnosis, but are not superior to serum BNP levels.

Background: When a patient arrives at the emergency department (ED) presenting with symptoms of acute decompensated heart failure (ADHF), it is possible to reach a definitive diagnosis through many different venues, including medical history, physical examination, echocardiography, chest X-ray, and B-type natriuretic peptide (BNP) levels. Point-of-care ultrasound (POCUS) has become a mainstream tool for diagnosis and treatment in the field of emergency medicine, as well as in various other departments in the hospital setting. Currently, the main methods of diagnosis of ADHF using POCUS are pleural B-lines and inferior vena cava (IVC) width and respiratory variation.

Objectives: To examine the potential use and benefits of bedside ultrasound of the jugular veins in the evaluation of dyspneic patients for identification of ADHF.

Methods: A blood BNP level was drawn from each participant at time of recruitment. The area and size of the internal jugular vein (IJV) during inspiration and expiration were examined.

Results: Our results showed that the respiratory area change of the IJVs had a specificity and sensitivity of nearly 70% accuracy rate in indentifying ADHF in our ED.

Conclusions: Ultrasound of the IJV may be a useful tool for the diagnosis of ADHF because it is easy to measure and requires little skill. It is also not affected by patient body habitus.

Background: Gender-related differences (GRD) exist in the outcome of patients with cardiac resynchronization therapy (CRT).

Objectives: To assess GRD in patients who underwent CRT.

Methods: A retrospective cohort of 178 patients who were implanted with a CRT in a tertiary center 2005–2009 was analyzed. Primary outcome was 1 year mortality. Secondary endpoints were readmission and complication rates.

Results: No statistically significant difference was found in 1 year mortality rates (14.6% males vs. 11.8% females, P = 0.7) or in readmission rate (50.7% vs. 41.2%, P = 0.3). The complication rate was only numerically higher in women (14.7% vs. 5.6%, P = 0.09). Men more often had CRT-defibrillator (CRT-D) implants (63.2% vs. 35.3%, P = 0.003) and had a higher rate of ischemic cardiomyopathy (79.2% vs. 38.2%, P < 0.001). There was a trend to higher incidence of ventricular fibrillation/ventricular tachycardia in men before CRT implantation (29.9% vs. 14.7%, P = 0.07%). A higher proportion of men upgraded from implantable cardioverter defibrillator (ICD) to CRT-D, 20.8% vs. 8.8%, P = 0.047. On multivariate model, chronic renal failure was an independent predictor of 1 year mortality (hazard ratio [HR] 3.6; 95% confidence interval [95%CI] 1.4–9.5), CRT-D had a protective effect compared to CRT-pacemaker (HR 0.3, 95%CI 0.12–0.81).

Conclusions: No GRD was found in 1 year mortality or readmission rates in patients treated with CRT. There was a trend toward a higher complication rate in females. Men were implanted more often with CRT-D and more frequently underwent upgrading of ICD to CRT-D.