Israel Medical Association Journal

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Background: Intravenous tissue plasminogen activator has been approved treatment for acute (≤ 3 hours) ischemic stroke in Israel since late 2004. The Israeli experience with IV tPA[1] is still limited. Several factors may influence the response to IV thrombolysis, including time-to-treatment parameters and tandem internal carotid artery/middle cerebral artery stenosis/occlusion.

Objectives: To compare our experience with IV tPA treatment of patients with acute ischemic stroke to the findings of the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy, international data) and of the Sheba Medical Center (national data) and to compare the early outcome among patients with ischemic stroke in the MCA[2] with and without severe ICA[3] stenosis.

Methods: We obtained demographic data, timing details, stroke severity, hemorrhagic complications, mortality, and early outcome from the records of IV tPA-treated acute ischemic stroke patients.

Results: Fifty-eight patients (median age 69 years, 26 females) with acute ischemic stroke were treated by IV tPA at the Tel Aviv Sourasky Medical Center in 2006–2007. Median time between stroke onset and IV tPA administration was 148 minutes for the Sourasky center, 150 minutes for the Sheba center, and 140 minutes for SITS-MOST. The Sourasky mortality rate was 10.5%. Of the 31 patients who suffered MCA stroke, 8 had severe ipsilateral ICA stenosis. These 8 had significantly lower neurological improvement than the 23 without ipsilateral ICA stenosis (1/8 versus 15/23, P <0.001).

Conclusions: Our data demonstrate fairly similar parameters of IV tPA treatment compared to other centers and suggest that patients with severe ICA stenosis might be less likely to benefit from IV tPA.

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

Background: The Israel National Poison Information Center, Rambam Health Care Campus, provides telephone consultations on clinical toxicology as well as drug and teratogen information around the clock. The Center participates in research, teaching and regulatory activities, and also provides laboratory services.

Objectives: To analyze data on the epidemiology of poisonings and poison exposures in Israel.

Methods: We conducted computerized queries and a descriptive analysis of the medical records database of the IPIC[1] during 2007.

Results: Overall, 26,738 poison exposure cases were recorded, a 118.5% increase compared to 1995. Children under 6 years old were involved in 45% of cases; 73% of the calls were made by the public and 25.5% by physicians; 74.4% of exposures were unintentional and 9.2% intentional. Chemicals were involved in 37.9% of cases, pharmaceuticals in 44.2%, bites and stings in 4.3% and poisonous plants in 1.2%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.5%. Substances most frequently involved in moderate/major exposures were insecticides, drugs of abuse and corrosives. Eight fatalities were recorded – three unintentional exposures (all chemicals) and five intentional (chemicals, medications, drugs of abuse).

Conclusions: The rates of poison exposures and poisonings in Israel have increased significantly, contributing substantially to morbidity and mortality. The IPIC database is a valuable national resource for collecting and monitoring cases of poison exposure and can be used as a real-time surveillance system. It is recommended that reporting to the IPIC become mandatory and that its activities be adequately supported by national resources.

Background: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and increased dosage is not allowed. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease.

Objectives: To describe our experience with anti-TNF[1] therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results.

Methods: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects.

Results: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n=108), juvenile idiopathic arthritis (n=11), psoriatic arthritis (n=37), ankylosing spondylitis (n=29), adult Still's disease (n=4), overlap disease (RA[2] and scleroderma or polymyositis, n=6), temporal arteritis (n=1), polyarteritis nodosa (n=1), dermatomyositis (n=1), amyloidosis secondary to RA (n=1) and Wegener's granulomatosis (n=1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS[3] and PS[4] patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease.

Conclusion: Our daily practice data are generally in agreement with worldwide experience. The ‘deviations’ might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.

Background: Surgical repair of tetralogy of Fallot may leave the patient with pulmonary regurgitation causing eventual right ventricle dilatation and dysfunction. Predicting clinical deterioration may help to determine the best timing for intervention.

Objectives: To assess whether the clinical and humoral status of patients in the second decade after repair of ToF[1] is worse than that of patients in the first decade after repair.

Methods: Twenty-one patients with repaired ToF underwent clinical assessment, electrocardiogram, echocardiogram and measurement of plasma B-type natriuretic peptide and N-terminal pro-BNP[2] as well as the 6 minute walk distance test. Patients were divided into two groups: group A – less than 10 years after repair (n=10, age < 12 years old), and group B – more than 10 years after repair (n=11, age > 12 years old). The age at repair was similar in both groups.

Results: In all but one patient the distance in the 6 min walk test was less than the minimum for age. RV[3] end-diastolic volume and the 6 min walk test correlated with age. NT-proBNP[4] levels were significantly higher in the ToF group compared to 26 healthy controls (P < 0.0001) and were inversely correlated with RV ejection fraction. Comparison of the two groups showed no difference in RV end-diastolic volume indexed for body surface area, pulmonary regurgitation severity, right or left ventricular myocardial performance index, RV ejection fraction, QRS duration, or 6 min walk indexed to minimum for age.

Conclusions: In this group of patients with similar age at operation and pulmonary regurgitation severity, most clinical, echocardiographic and humoral parameters were not worse in the second decade after repair of ToF. These data suggest that very early pulmonary valve replacement may not be of benefit.

Background: Babies born with extreme prematurity and low birth weight (< 1000 g) present a unique treatment challenge. In addition to the complexity of achieving survival, they may require surgical interventions for abdominal emergencies. Usually, these infants are transferred to a referral center for surgery treatment. Since 2000 our approach is bedside abdominal surgery at the referring center.

Objectives: To evaluate whether the approach of bedside abdominal surgery at the referring center is safe and perhaps even beneficial for the baby.

Methods: We retrospectively reviewed our data since 2000 and included only babies weighing < 1000 g who were ventilated, suffered from hemodynamic instability and underwent surgery for perforated bowel at the referring neonatal unit. Results were analyzed according to survival from the acute event (> 1 week), survival from the abdominal disease (> 30 days) and survival to discharge.

Results: Twelve babies met the inclusion criteria. Median weight at operation was 850 g (range 620–1000 g) and median age at birth was 25 weeks (range 23–27). Eleven infants survived the acute event (91.7%), 9 survived more than 30 days (81.8%), and 5 survived to discharge.

Conclusions: Our results show that bedside laparotomy at the referring hospital is safe and feasible. A larger randomized study is indicated to prove the validity of this approach.

Background: Echocardiographic assessment of left ventricular function includes calculation of ejection fraction and regional wall motion analysis. Recently, speckle imaging was introduced for quantification of left ventricular function.

Objectives: To assess LVEF[1] by speckle imaging and compare it with Simpson’s method, and to assess the regional LV strain obtained by speckle imaging in relation to conventional echocardiographic scores.

Methods: Thirty consecutive patients, 28 with regional LV dysfunction, underwent standard echocardiographic evaluation. LV end-diastolic volume, LV end-systolic volume and EF were calculated independently by speckle imaging and Simpson’s rule. The regional peak systolic strain presented by speckle imaging as a bull's-eye map was compared with the conventional visual estimate of echo score.

Results: Average EDV[2] obtained by speckle imaging and by Simpson’s method were 85.1 vs. 92.7 ml (P = 0.38), average ESV[3] was 49.4 vs. 48.8 ml (P = 0.94), calculated EF was 43.9 vs. 50.5% (P = 0.08). The correlation rate with Simpson’s rule was high: 0.92 for EDV, 0.96 for ESV, and 0.89 for EF. The peak systolic strain in two patients without wall motion abnormality was 17.3 ± 4.7; in normal segments of patients with regional dysfunction, peak systolic strain (13.4 ± 4.9) was significantly higher than in hypokinetic segments  (10.5 ± 4.5) (P < 0.000001). The strain in hypokinetic segments was significantly higher than in akinetic segments (6.2 ± 3.6) (P < 0.000001).

Conclusions: Speckle imaging can be successfully used for the assessment of LV volumes and EF. Bull's-eye strain map, created by speckle imaging, can achieve an accurate real-time segmental wall motion analysis.

Objective: To report our experience with terlipressin treatment for facilitation of transport to distant facilities for diagnostic or therapeutic procedures in septic patients treated with norepinephrine.

Methods:  We conducted a retrospective analysis of the records of our ICU[1], identifying the patients with septic shock who required norepinephrine for hemodynamic support.

Results: Terlipressin was given to 30 septic shock patients (15 females and 15 males) who were on high dose norepinephrine (10 μg/min or more) in order to facilitate their transport outside the ICU. The dose of terlipressin ranged from 1 to 4 mg, with a mean of 2.13 ± 0.68 mg. The dose of norepinephrine needed to maintain systolic blood pressure above 100 mmHg decreased following terlipressin administration, from 21.9 ± 10.4 μg/min (range 5–52 μg/min) to 1.0 ± 1.95 (range 0–10) (P < 0.001). No patients required norepinephrine dose adjustment during transport. No serious complications or overshoot in blood pressure values were observed following terlipressin administration. Acrocyanosis occurred only in eight patients receiving more than 1 mg of the drug. The overall mortality rate was 50%.

Conclusions: Our data suggest that terlipressin is effective in septic shock. Because it is long-acting and necessitates less titration it might be indicated for patient transportation.

Objectives: To report 3 years national experience with orthotopic liver transplantation, and to evaluate patient and perioperative risk factors that could affect 1 year graft survival.

Methods: The study related to all 124 isolated adult liver transplantations performed in Israel between October 1997 and October 2000. Data were abstracted from the medical records. One-year graft survival was described using the Kaplan-Meier survival curve and three multivariate logistic regression models were performed: one with preoperative case-mix factors alone, and the other two with the addition of donor and operative factors respectively.

Results: Of the 124 liver transplantations performed, 32 failed (25.8%). The 1 year survival was lower than rates reported from both the United States and Europe, but the difference was not significant. Of the preoperative risk factors, recipient age ≥ 60 years, critical condition prior to surgery, high serum bilirubin and serum hemoglobin ≤ 10 g/dl were independently associated with graft failure, adjusting for all the other factors that entered the logistic regression equation. Extending the model to include donor and operative factors raised the C-statistic from 0.79 to 0.87. Donor age ≥ 40, cold ischemic time > 10 hours and a prolonged operation (> 10 hours) were the additional predictors for graft survival. A MELD score of over 18 was associated with a sixfold increased risk for graft failure (odds ratio = 6.5, P = 0.001).

Conclusions: Graft survival in Israel is slightly lower than that reported from the U.S. and Europe. Adding donor and operative factors to recipient characteristics significantly increased our understanding of 1 year survival of liver grafts.