Background: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study.

Objectives: To determine the efficacy and safety of Xolair® as an add-on treatment in patients with severe persistent asthma.

Methods: Asthma patients (age 12–75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair® or placebo for 28 weeks in a double-blind study in two Israeli centers.

Results: Thirty-three patients, 20 females and 13 males, mean age 54 ± 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair® (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction).
Conclusions: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA[1] and inhaled corticosteroids (GINA 2002 step 4), Xolair® is a safe and effective treatment

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia.

Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel.

Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm³) and clinically significant bacteremia or fungemia during the period 1988–2004.

Results: Among adults (462 episodes) the most common bloodstream isolate was Esherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3 throughout the study period. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital.
Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients’ risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment

Background: Asthma control and treatment compliance are widely investigated issues around the world. Studies have demonstrated relatively low asthma compliance and control in 40–90% of asthma patients in different countries. There are no available data on the Israeli adult asthmatic population

Objectives: To investigate the level of asthma control and compliance in adult asthmatic patients.

Methods: This cross-sectional study of consecutive adult asthmatic patients visiting the pulmonary clinic used a combined questionnaire that included demographics, data on asthma severity and management, and asthma control and compliance scores. Each patient was interviewed and questionnaires were filled out during a routine visit.

Results: The study group comprised 142 males (35.4%) and 259 females (64.6%). Compliance was found optimal in 8 patients (2%), fair in 146 (36%), partial in 156 (39%) and poor in 92 (23%) of the participating asthmatic patients. Asthma control was found optimal in 26 (7%), fair in 124 (31%), partial in 122 (30%) and poor in 129 (32%) patients. Sephardic and Ashkenazi Jewish origin, higher level of education, and treatment protocol including either single fixed-dose inhalers or short-acting beta-agonist bronchodilators significantly improved compliance in our cohort. Socioeconomic status and compliance were found to positively affect asthma control, whereas active smoking negatively affected asthma control in the study patients.

Conclusions: The figures of optimal asthma control and compliance to treatment in Israeli adult asthmatics are low and worse than reported in other studies abroad.
 

Background: Pain following brain surgery is a significant problem. Infiltration of the scalp with local intradermal anesthetics was suggested for postoperative pain control but was assessed only in the first hour postoperatively.

Objectives: To evaluate wound infiltration with a single dose of metamizol (dipyrone) for postoperative pain control in patients undergoing awake craniotomy.

Methods: This open, prospective, non-randomized observational study, conducted in anesthesiology and neurosurgical departments of a teaching hospital, included 40 patients undergoing awake craniotomy for the removal of brain tumor. Intraoperative anesthesia included wound infiltration with lidocaine and bupivacaine, conscious sedation using remifentanil and propofol, and a single dose of metamizol (dipyrone) for postoperative pain control. Outcome was assessed by the Numerical Pain Scale on arrival at the postoperative care unit, and 2, 4 and 12 hours after the end of surgery.

Results: On arrival at the postoperative care unit, patients reported NPS[1] scores of 1.2 ± 1.1 in a scale of 0–10 (mean ± SD) (median = 1, range 0–4). The scores were 0.8 ± 0.9, 0.9 ± 0.9, and 1 ± 0.9 at 2 hours, 4 hours, and 12 hours after the end of surgery, respectively. Based on patients' complaints and NPS lower then 3, 27 patients did not require any supplementary analgesia during the first 12 postoperative hours, 11 patients required a single dose of oral metamizol or intramuscular diclofenac, one patient was given 2 mg of intravenous morphine, and one patient required two separate doses of metamizol.

Conclusions: Although the clinical setup prevents the use of placebo local analgesia as a control group, the results suggest the possible role of local intradermal infiltration of the scalp combined with a single dose of metamizol to control postoperative pain in patients undergoing craniotomy.

Background: Spontaneous coronary reperfusion occurs in 7–27% of patients with ST elevation myocardial infarction, and is an independent predictor of myocardial salvage, percutaneous coronary intervention success, and improved outcome.

Objectives: To determine the optimal PCI[1] time for patients admitted to the hospital due to STEMI[2] with SCR[3].

Methods: We performed a retrospective analysis of all patients admitted to the coronary care unit between July 2002 and November 2004 with a diagnosis of STEMI with SCR.

Results: The study group comprised 86 patients. There was not a single reinfarction episode during an observation period of 6579 patient hours. Cardiac catheterization was executed early (< 24 hours from pain onset) in 26 patients and late (> 24 hours) in 55. Pre-PCI angiographic TIMI flow 2–3 was seen in > 95% in both groups. PCI was performed more frequently in the “early” group (P = 0.024), while multi-vessel coronary artery disease (P = 0.094) requiring coronary bypass surgery (P = 0.056) was observed more frequently in the “late catheterization” group. Myocardial infarction and angina pectoris at 30 days occurred more frequently in the early catheterization group (P = 0.039), however no difference in any major adverse cardiac events was detected during long-term follow-up (491 ± 245 days).

Conclusions: Reinfarction after STEMI with SCR is a rare event. Early PCI in patients with STEMI and SCR, even when executed with aggressive anti-platelet therapy, seems to result in an excess of early MACE, without any long-term advantage. Prospective randomized trials should determine the optimal PCI timing for these patients.

Background: The decision to perform primary percutaneous coronary intervention in unconscious patients resuscitated after out-of-hospital cardiac arrest is challenging because of uncertainty regarding the prognosis of recovery of anoxic brain damage and difficulties in interpretation of ST segment deviations. In ST elevation myocardial infarction patients after OHCA[1], primary PCI[2] is generally considered the only option for reperfusion. There are few published studies and no randomized trial has yet been performed in this specific group of patients.

Objectives: To define the demographic, clinical and angiographic characteristics, and the prognosis of STEMI[3] patients undergoing primary PCI after out-of-hospital cardiac arrest.

Methods: We performed a retrospective analysis of medical records and used the prospectively acquired information from the Rambam Primary Angioplasty Registry (PARR) and the Rambam Intensive Cardiac Care (RICCa) databases.

Results: During the period March1998 to June 2006, 25 STEMI patients (21 men and 4 women, mean age 56 ± 11years) after out-of-hospital cardiac arrest were treated with primary PCI. The location of myocardial infarction was anterior in 13 patients (52%) and non-anterior in 12 (48%). Cardiac arrest was witnessed in 23 patients (92%), but bystander resuscitation was performed in only 2 patients (8%). Eighteen patients (72%) were unconscious on admission, and Glasgow Coma Scale > 5 was noted in 2 patients (8%). Cardiogenic shock on admission was diagnosed in 4 patients (16%). PCI procedure was successful in 22 patients (88%). In-hospital, 30 day, 6 month and 1 year survival was 76%, 76%, 76% and 72%, respectively. In-hospital, 30 day, 6 month and 1 year survival without severe neurological disability was 68%, 68%, 68% and 64%, respectively.

Conclusions: In a selected group of STEMI patients after out-of-hospital cardiac arrest, primary PCI can be performed with a high success rate and provides reasonably good results in terms of short and longer term survival.

Background: Radiofrequency ablation has been suggested as first-line therapy in the management of accessory pathways. There are limited data on the results of ablation over years of experience.

Objectives: To assess the results and complications following RFA[1] of APs[2] performed in our institution over a 14 year period.

Methods: RFA was performed using deflectable electrode catheters positioned at the mitral or tricuspid annulus. The site of the AP was localized by electrophysiological study and radiofrequency energy was applied via the tip of the catheter

Results: The study cohort comprised 508 consecutive patients (64.2% males, mean age 33.6 ± 15.1 years) who underwent 572 RFA procedures for ablating 534 APs. A single AP was found in 485 (95.5%) patients while multiple APs were noted in 23 patients (4.5%). The APs were manifest, concealed or intermittent in 46.8%, 44.4% and 8.8% of cases, respectively. AP distribution was as follows: left free wall (56.6%), posteroseptal (23%), right anteroseptal (7.9%), right free wall (6.2%), midseptal (3.4%) and right atriofascicular (3.0%). Acute successful rates for a first or multiple ablation attempts were 93.1% and 95.3%, respectively. At a first ablation attempt, acute success and failure rates were the highest for midseptal (100%) and right atriofascicular (12.5%) APs respectively. Right anteroseptal APs were associated with the highest rate (23.9%) of discontinued or non-attempted procedures. Recurrent conduction in an AP after an initial successful ablation was observed in 9.9% of cases; it was the highest (24.2%) for right free wall APs and the lowest (5.0%) for left free wall APs. During follow-up (85 ± 43 months), definite cure of the AP was achieved in 94.9% of cases following a single or multiple procedures: midseptal (100%), left free wall (98%), right free wall (97%), posteroseptal (92.7%), right atriofascicular (87.5%) and right anteroseptal (78.5%). A non-fatal complication occurred in 18 patients (3.5%), more frequently in females (6.6%) than in males (1.8%) (P < 0.01). The two major complications (pericardial effusion and myocardial ischemic events) mainly occurred during RFA of a left free wall AP using a retrograde aortic approach. Catheter-induced mechanical trauma to APs was observed in 56 cases (10.5%). Mechanical trauma mainly involved right atriofascicular (43.8%) and right anteroseptal (38.1%) APs and contributed to the low success rate of RFA at these AP locations. During the 14 year period, our learning curve was achieved quickly in terms of success rate, although the most significant complications were observed at the beginning of our experience.

Conclusions: The results of this study confirm the efficacy and safety of RFA and suggest that it is a reasonable first-line therapy for the management of APs at any location.

Background: Endothelial dysfunction is recognized as a major factor in the development of atherosclerosis and it has a prognostic value.

Objectives: To detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects and patients with cardiovascular disease.

Methods: We prospectively assessed brachial artery flow-mediated dilation in 110 consecutive subjects (46 CVD[1] patients and 64 healthy controls), mean age 57 ± 11 years; 68 were men. After an overnight fast and discontinuation of all medications for ≥ 12 hours, percent improvement in FMD and nitroglycerin-mediated vasodilatation were assessed using high resolution ultrasound.

Results: %FMD[2] but not %NTG[3] was significantly lower in CVD patients (9.5 ± 8.0% vs. 13.5 ± 8.0%, P = 0.012) compared to healthy controls (13.4 ± 8.0% vs. 16.7 ± 11.0%, P = 0.084; respectively). In addition, an inverse correlation between %FMD and the number of traditional CVD risk factors was found among all study participants (r = -0.23, P = 0.015) and healthy controls (r = -0.23, P = 0.036). In a mean follow-up of 15 ± 2 months, the composite CVD endpoints (all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with FMD < 6% compared to subjects with FMD > 6% (33.3% vs. 12.1%, P < 0.03, respectively).
Conclusions: Thus, brachial artery %FMD provides important prognostic information in addition to that derived from traditional risk factor assessment

Background: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia.

Objectives: To assess the added diagnostic value of a new cardiac performance index (dP/dt^ejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-nduced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia.

Methods: The study group comprised 40 patients undergoing Sestamibi-SPECT[1]/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dt^ejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dt^ejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dt^ejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone.

Results: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%.
Conclusions: If ECG alone is used for specificity, the combination with dP/dt^ejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise

Background: The use of the bilateral internal mammary arteries has been reserved mainly for younger and low risk patients.

Aim: To assess the safety and efficacy of BIMA[1] grafting in older patients (≥ 70 years).

Methods: We reviewed the records of all consecutive patients ≥ 70 years old who underwent coronary artery bypass surgery with a BIMA graft in our institute over a 2 year period. Demographic data, operative data, perioperative morbidity and mortality were recorded. Findings were compared with a matched-size group of patients who underwent CABG[2] with a left internal mammary artery graft to left anterior descending artery.

Results: The study sample included 136 patients, of whom 68 underwent BIMA grafting and 68 LIMA[3] grafting. Baseline demographic and clinical characteristics were similar in the two groups. There was no significant difference in operative mortality between the BIMA and LIMA groups (1.5% vs. 0%, P = 0.3) or in mortality during follow-up at a mean of 16 months (4.4% vs. 2.9%, P = 0.4, respectively). There was no difference between the groups in the incidence of perioperative complications, re-admission and re-intervention rates during follow-up. Significant between-group differences were noted for mean cardiopulmonary bypass time (93.2 ± 34.7 BIMA vs. 108.8 ± 40.7 LIMA min, P = 0.02) and for red blood cell transfusion (1.9 ± 1.9 vs. 4.3 ± 2.8 packed cells/patient, P < 0.001).

Conclusions: The performance of mainly arterial revascularization with BIMA grafting in patients 70 years or older is as safe as LIMA grafting, with the added advantage of being a better conduit than saphenous vein graft, requiring fewer blood transfusions, and shorter cardiopulmonary bypass time.

Backgound: The use of intraoperative transesophageal echocardiogram in patients with infective endocarditis is usually reserved for cases of inadequate preoperative testing or suspected extension to perivalvular tissue.

Objectives: To explore the impact of routine intraoperative TEE[1] in patients with infective endocarditis.

Methods: The impact of intraoperative TEE on the operative plan, anatomic-physiologic results, and hemodynamic assessment or de-airing was analyzed in 59 patients (38 males, 21 females, mean age 57.7 ± 16.8 years, range 20–82) operated for active infective endocarditis over 56 months.

Results: Immediate pre-pump echocardiography was available in 52 operations (86.7%), and changed the operative plan in 6 of them (11.5%). Immediate post-pump study was available in 59 patients (98.3%) and accounted for second pump-run in 6 (10.2%): perivalvular leak (3 cases), and immobilized leaflet, significant mitral regurgitation following vegetectomy, and failing right ventricle requiring addition of vein graft (1 case each). Prolonged de-airing was necessary in 6 patients (10.2%). In 5 patients (8.5%) the postoperative study aided in the evaluation and treatment of difficult weaning from the cardiopulmonary bypass pump. In 21 patients (35.6%) the application of intraoperative TEE affected at least one of the four pre-specified parameters.
Conclusions: Intraoperative TEE has an important role in surgery for infective endocarditis and should be routinely implemented