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עמוד בית
Tue, 28.05.24

Search results

December 2019
Dror B Leviner MD, Guy Witberg MD, Amir Sharon MD, Yosif Boulos BsC, Alon Barsheshet MD, Erez Sharoni MD, Dan Spiegelstein MD, Hana Vaknin-Assa MD, Dan Aravot MD, Ran Kornowski MD and Abid Assali MD

Background: Current guidelines for choosing between revascularization modalities may not be appropriate for young patients.

Objectives: To compare outcomes and guide treatment options for patients < 40 years of age, who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2008 and 2018.

Methods: Outcomes were compared for 183 consecutive patients aged < 40 years who underwent PCI or CABG between 2008 and 2018, Outcomes were compared as time to first event and as cumulative events for non-fatal outcomes.

Results: Mean patient age was 36.3 years and 96% were male. Risk factors were similar for both groups. Drug eluting stents were implemented in 71% of PCI patients and total arterial revascularization in 74% of CABG patients. During a median follow-up of 6.5 years, 16 patients (8.6%) died. First cardiovascular events occurred in 35 (38.8%) of the PCI group vs. 29 (31.1%) of the CABG group (log rank P = 0.022), repeat events occurred in 96 vs. 51 (P < 0.01), respectively. After multivariate adjustment, CABG was associated with a significantly reduced risk for first adverse event (hazard ratio [HR] 0.305, P < 0.01) caused by a reduction in repeat revascularization. CABG was also associated with a reduction in overall repeat events (HR 0.293, P < 0.01). There was no difference in overall mortality between CABG and PCI.

Conclusions: Young patients with coronary disease treated by CABG showed a reduction in the risk for non-fatal cardiac events. Mortality was similar with CABG and PCI.

November 2019
Marcos Harel MD, Avshalom Shalom MD, Jacob Frand MD and Lior Leibou MD

Background: The use of oral midazolam as premedication to induce anxiolysis before surgical procedures under local anesthesia is widely accepted in plastic surgery. Rhinoplasty performed under local anesthesia is known to generate high levels of perioperative anxiety, thus the use of appropriate premedication is important. Oral midazolam has been shown to be safe in various procedures. However, the safety of oral midazolam before rhinoplasty has not been evaluated.

Objectives: To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events.

Methods: We retrospectively reviewed the anesthesia records of 62 patients who underwent rhinoplasty under local anesthesia and received premedication with oral midazolam for anxiolysis between March 2017 and December 2017. The median age of the patients was 25.4 years, and they were all classified as American Society of Anesthesiologists class 1. The patients received 10 mg midazolam hydrochloride orally 1 hour prior to the procedure. Oxygen blood saturation was monitored using a pulse oximeter and recorded every 15 minutes.

Results: All the patients maintained blood oxygen saturation levels above 95% (median peripheral capillary oxygen saturation 99%) on room air, and they did not require supplemental intraoperative oxygen. There were no transient hypoxemic events during and following the procedure.

Conclusions: Our study confirmed the safety of oral midazolam premedication to reduce perioperative anxiety when performing rhinoplasty under local anesthesia.


Aviv Mager MD, Yoav Hammer MD, Hadas Ofek MD, Ilana Kedmi PhD, Zaza Iakobishvili MD and Ran Kornowski MD

Background: The frequency of increased high-sensitivity C-reactive protein (hs-CRP) and the time course of evolution of their levels in patients with acute idiopathic pericarditis (AIP) are not well established.

Objective: To assess the time course of evolution of hs-CRP levels and the possible clinical significance of maximal hs-CRP levels in patients with AIP

Methods: We retrospectively reviewed the medical files of 241 patients admitted to the hospital with a diagnosis of AIP between March 2006 and March 2017. Data on demographics, time of symptom onset, laboratory and imaging findings, and outcome were collected.

Results: Data on serum hs-CRP levels were available for 225 patients (age 18–89 years, 181 men). Fever, pleural effusion, and age were independently associated with hs-CRP levels. Major cardiac complications (MCC) (death, cardiac tamponade, cardiogenic shock, large pericardial effusion, ventricular tachycardia, pericardiocentesis, or pericardiectomy) were more common in patients with hs-CRP levels above the median compared to those below (21.2% vs. 4.5%, respectively, P < 0.001). Hs-CRP levels were independently associated with MCC (odds ratio [OR] 1.071, 95% confidence interval [95%CI] 1.016–1.130, P = 0.011). Hs-CRP levels were elevated in 76.0%, 92.3% and 96.0% of the patients tested <6 hours, 7-12 hours, and >12 hours of symptom onset, respectively (P = 0.003). The frequency of elevated hs-CRP among patients tested > 24 hours was 98.1%.

Conclusions: Hs-CRP levels rise rapidly among patients with AIP. Maximal hs-CRP levels are associated with MCC. A normal hs-CRP level is rare among patients tested > 24 hours of symptom onset.

October 2019
Philip Lawson MD, Noam Nissan MD PhD, Renata Faermann MD, Osnat Halshtok MD, Anat Shalmon MD, Michael Gotleib MD, Merav Akiva Ben David MD and Miri Sklair Levy MD

Background: Male breast cancer (MBC) is a rare disease representing less than 1% of breast cancers. In the absence of a screening program, such as for females, the diagnostic workup is critical for early detection of MBC.

Objectives: To summarize our institutional experience in the workup of male patients referred for breast imaging, emphasizing the clinical, imaging, and histopathological characteristics of the MBC cohort.

Methods: All male patients who underwent breast imaging between 2011 and 2016 in our institution were retrospectively reviewed. Clinical, radiological, and histopathological data were collected and statistically evaluated. All images were reviewed using the American College of Radiology Breast Imaging Reporting and Data System.

Results: 178 male patients (average age 61 years, median age 64), underwent breast imaging in our institution. The most common indication for referral was palpable mass (49%) followed by gynecomastia (16%). Imaging included mostly mammography or ultrasound. Biopsies were performed on 56 patients, 38 (68%) were benign and 18 (32%) were malignant. In all, 13 patients had primary breast cancer and 5 had metastatic disease to the breast. Palpable mass at presentation was strongly associated with malignancy (P = 0.007).

Conclusion: Mammography and ultrasound remain the leading modalities in breast imaging among males for diagnostic workup of palpable mass, with gynecomastia being the predominant diagnosis. However, presentation with palpable mass was also associated with malignancy. Despite a notable MBC rate in our cohort, the likelihood of cancer is low in young patients and in cases of gynecomastia.

David Hakimian MD, Elliot Turvall MSc, Sarah Israel MD and Zvi Ackerman MD AGAF

Background: In developed countries, hepatitis A virus (HAV) infection occurs mainly in adults. It is usually symptomatic and may cause acute liver failure (ALF). In patients with chronic liver disease, serum ferritin levels (SFL) can predict short-term prognosis.

Objectives: To determine whether admission SFL can serve as a prognostic marker in patients with HAV infection.

Methods: A retrospective analysis of 33 adults with HAV infection was conducted. Because none of our patients presented with ALF, the parameter "length of hospital stay," was used as a surrogate marker of disease severity.

Results: The mean (± SD) at admission SFL was 2529 ± 4336 ng/ml. SFL correlated with the levels of international normalized ratio (INR), liver enzymes, and degree of hemolysis that occurred during the disease course. SFL did not correlate with the levels of either albumin or bilirubin or with the length of the hospital stay. The mean length of hospital stay was 5.1 ± 2.0 days, which correlated with the levels of INR, albumin, and bilirubin as well as the degree of hemolysis. However, in multivariate analysis only albumin and bilirubin predicted the length of the hospital stay. Follow-up SFL, which were available only in eight patients, decreased during the hospital stay.

Conclusions: In adults with acute HAV infection, SFL may be increased. SFL correlated with the degree of liver injury and hemolysis that occur during the disease. However, in our cohort of HAV patients, who had a relatively benign disease course, SFL were of no prognostic value.

Galina Goltzman MD, Sivan Perl MD, Lior Cohen Mendel MD, Eyal Avivi MD and Micha J Rapoport MD

Background: C-reactive protein (CRP) blood level is associated with clinical outcomes of several diseases. However, the independent predictive role of CRP in the heterogeneous population of patients admitted to internal medicine wards is not known. 

Objectives: To determine whether single CRP levels at admission independently predicts clinical outcome and flow of patients in general medicine wards.

Methods: This study comprised 275 patients (50.5% female) with a mean age of 68.25 ± 17.0 years, hospitalized with acute disease in a general internal medicine ward. The association between admission CRP levels and clinical outcomes including mortality, the need for mechanical ventilation, duration of hospitalization, and re-admission within 6 months was determined.

Results: A significant association was found between CRP increments of 80 mg/L and risk for the major clinical outcomes measured. The mortality odds ratio (OR) was 1.89 (95% confidence interval (95%CI, 1.37–2.61, P < 0.001), mechanical ventilation OR 1.67 (95%CI, 1.10–2.34, P = 0.006), re-admission within 6 months OR 2.29 (95%CI, 1.66–3.15 P < 0.001), and prolonged hospitalization >7 days OR 2.09 (95%CI, 1.59–2.74, P < 0.001). Lower increments of10 mg/L in CRP levels were associated with these outcomes although with lower ORs. Using a stepwise regression model for admission CRP levels resulted in area under the receiver operating characteristics curves between 0.70 and 0.76 for these outcomes.

Conclusions: A single admission CRP blood level is independently associated with major parameters of clinical outcomes in acute care patients hospitalized in internal medicine wards.

David Zahler MD, Elena Izkhakov MD PhD, Keren-Lee Rozenfeld MD, Dor Ravid MD, Shmuel Banai MD, Yan Topilsky MD and Yacov Shacham MD

Background: Data suggest that subclinical hypothyroidism (SCH) is associated with progression of chronic renal disease; however, no study to date has assessed the possible relation between SCH and acute deterioration of renal function.

Objectives: To investigate the possible relation between SCH and acute kidney injury (AKI) in a large cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary coronary intervention (PCI).

Methods: We evaluated thyroid stimulating hormone (TSH) and free T4 levels of 1591 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit (October 2007–August 2017). The presence of SCH was defined as TSH levels ≥ 5 mU/ml in the presence of normal free T4 levels. Patients were assessed for development of AKI ( 0.3 mg/dl increase in serum creatinine, according to the KDIGO criteria).

Results: The presence of SCH was demonstrated in 68/1593 (4.2%) STEMI patients. Patients presenting with SCH had more AKI complications during the course of STEMI (20.6% vs. 9.6 %; P = 0.003) and had significantly higher serum creatinine change throughout hospitalization (0.19 mg/dl vs. 0.08 mg/dl, P = 0.04). No significant difference was present in groups regarding baseline renal function and the amount of contrast volume delivered during coronary angiography. In multivariate logistic regression model, SCH was independently associated with AKI (odds ratio = 2.19, 95% confidence interval 1.05–4.54, P =0.04).

Conclusions: Among STEMI patients treated with PCI, the presence of SCH is common and may serve as a significant marker for AKI.

September 2019
Erez Marcusohn MD, Danny Epstein MD, Anees Musallam MD, Zohar Keidar MD PHD and Ariel Roguin MD PHD

Background: With the recent introduction of high-sensitivity troponin (hsTn), the incremental benefit of stress myocardial perfusion imaging (MPI) in the evaluation of patients who present to the emergency department (ED) with acute coronary syndrome (ACS) is unclear.

Objectives: To assess the added value of stress MPI in low-risk ACS patients with normal range hsTnI.

Methods: We analyzed all patients who were hospitalized at our medical center from February 2016 to November 2017, who presented with low-risk ACS and underwent stress MPI, and in whom hsTnI was in the normal range after the introduction of hsTnI.

Results: During the study period, 161 patients were admitted with a diagnosis of unstable angina (i.e., ACS with normal range hsTnI) and underwent stress MPI during index admission. The study population included 52/161 patients (31.7%) with low-risk ACS who had no indication for initial invasive strategy. No patients had positive MPI. One patient underwent coronary angiography due to suggestive history; however, he did not have a significant coronary artery disease and had no indication for percutaneous coronary intervention.

Conclusions: In patients with low-risk ACS and normal range hsTnI without additional high-risk features, stress MPI has little additional value for the correct diagnosis and management. Prospective studies are warranted to confirm whether resting hsTnI could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and thus, improve patient management.

August 2019
Michael J. Segel MD, Alexander Kogan MD, Sergey Preissman MD, Nancy Agmon-Levin MD, Aaron Lubetsky MD MSc, Paul Fefer MD, Hans-Joachim Schaefers MD and Ehud Raanani MD

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.

Yulia Treister-Goltzman MD and Roni Peleg MD

The Bedouins living in southern Israel are a Muslim-Arab population that is transitioning from a nomadic lifestyle to life in permanent settlements. The population has unique characteristics that could affect hemoglobin A1c (HbA1c) measurements. The objective of this study was to describe the socio-demographic and unique morbidity characteristics of this community and their effect on HbA1c measurements. Consanguinity, especially among cousins in the Bedouin population, results in a high prevalence of autosomal recessive genetic diseases such as thalassemia (underestimate of HbA1c), hemoglobinopathies (underestimate and overestimate), Gilbert’s disease, and glucose-6-phosphate dehydrogenase deficiency, an X-linked disorder, which can cause hyperbilirubinemia with an overestimate of HbA1c. Furthermore, nutritional deficiencies, autosomal recessive diseases, high birth rates, parasitic infections, and poverty can all cause high rates of anemia (iron and vitamin B12 deficiencies) that can raise HbA1c levels. Congenital dyserythropoietic anemia is found among Bedouin tribes in the Negev region and can lead to an underestimation of HbA1c levels. Pregnancy can also affect HbA1c levels. Medical teams working in the Bedouin community and in other Muslim populations with similar morbidity characteristics throughout the world should identify patients with medical conditions that can affect HbA1c measurements and be aware of possible measurement alternatives such as fructosamine and glycated albumin.

Levente Bodoki MD PhD, Edit Végh MD, Zoltán Szekanecz MD PhD and Gabriella Szűcs MD PhD
Baruch Levi PhD, Malke Borow JD, Leah Wapner JD LLM and Zeev Feldman MD

Global trends, such as the population aging, the increase of chronic morbidity, soaring costs of healthcare services, and work overload in hospitals raise the need to find innovative solutions for providing quality medical services. One solution adopted by healthcare systems around the world is "home hospitalization," that is, providing an array of necessary health services in the patient's home, instead of in the hospital department. The aim of this focus article is to explore the spread of home hospitalization worldwide and examine the challenges and pathways for its adoption and implementation. Many countries, including the United States, Canada, the United Kingdom, and Australia, operate home-based hospitalization programs. In Israel, the service is in its infancy, but in view of the extreme workload and the high mortality rate from infections in acute care hospitals, home hospitalization has recently gained public interest and political support, which may encourage its further development.

July 2019
Bar Davidov MD, Riva Shmulevich MSc, Ayelet Shabtay PhD, Tami Rubinek PhD and Ido Wolf MD

Background: Klotho is a transmembrane protein that can be shed and can act as a circulating hormone in three forms: soluble klotho (KL1 + KL2), KL1, and KL2. Klotho was discovered as a gene implicated in aging through inhibition of the IGF-I pathway. Our laboratory discovered the role of klotho as a tumor suppressor in breast cancer and other malignancies. Furthermore, we showed that the KL1 domain mediates this activity. Altered cancer cell metabolism is a hallmark of cancer and our lab demonstrated various effects of klotho on breast cancer cell metabolism. Thus, klotho inhibited glycolysis and activated adenosine monophosphate activating kinase (AMPK), an energy sensor pathway. Moreover, inhibition of AMPK reduced the tumor suppressor activity of klotho.

Objectives: To assess the effect of KL1 on breast tumor cells metabolism, as KL1 possesses the tumor suppressor activity of klotho.

Methods: We used MCF-7 breast cancer cells treated with soluble or over-expressed KL1 and klotho. Glycolysis was assessed by measuring mRNA levels of key glycolytic enzymes using reverse transcription polymerase chain reaction and by measuring lactate and glucose levels in media. The AMPK pathway was studied by monitoring AMPK phosphorylation as well as its down-stream target, acetyl-CoA carboxylase, using western blotting. Wound healing assay was used to assess cell migration.

Results: KL1 treatment reduced glycolytic enzymes mRNA levels and the activity of hexokinase, similar to klotho treatment. Furthermore, KL1 reduced glucose uptake and decreased lactate production. KL1 elevated phosphorylated acetyl-CoA carboxylase and phosphorylatedAMPK levels. Inhibition AMPK (using a mutant AMPK activator) stopped KL1 from inhibiting cell migration, suggesting AMPK underlies klotho’s tumor suppressor activity.

Conclusions: Our data indicate KL1 as a regulator of metabolic activity in breast cancer and suggest that metabolic alterations underlie KL1 tumor suppressor activities. Furthermore, as KL1 and klotho share a similar effect on cell metabolism, our results further support the central role KL1 domain plays in klotho’s tumor suppressor activity.

June 2019
Hagar Interator MSx RD, Avivit Brener MD, Moshe Hoshen PhD, Inbar Safra MD, Ran Balicer MD PhD MPH, Moshe Leshno MD PhD, Raanan Shamir MD and Yael Lebenthal MD

Background: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood.

Objectives: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents.

Methods: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations.

Results: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809–0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941–0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728–0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035–1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001).

Conclusions: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Ofer M. Kobo MD, Elit Vainer Evgrafov MD, Yuval Cohen MD, Yael Lerner MD, Alaa Khatib MD, Ron Hoffman MD, Ariel Roguin MD PhD and Inna Tzoran MD

Background: Malignancy is a known risk factor for venous thromboembolism; however, the association with arterial thromboembolic events remains unclear.

Objectives: To examine the association between non-ST-elevation myocardial infarction (NSTEMI) and non-significant coronary artery disease (CAD) and the presence of new or occult malignancy.

Methods: An observational cohort, single-center study was performed 2010–2015. Adult patients with NSTEMI, who underwent coronary angiography and had no significant coronary lesion, were included. Using propensity score matching, we created a 2:1 matched control group of adults with NSTEMI, and significant coronary artery disease. Risk factors for new or occult malignancy were assessed using multivariate backward stepwise logistic regression analysis. The primary outcome was new or occult malignancy, defined as any malignancy diagnosed in the 3 months prior and 6 months following the myocardial infarction (MI).

Results: During the study period, 174 patients who presented with MI with non-obstructive coronary arteries were identified. The matched control group included 348 patients. There was no significant difference in the group demographics, past medical history, or clinical presentation. The incidence of new or occult malignancy in the study group was significantly higher (7/174, 4% vs. 3/348, 0.9%, P = 0.019). NSTEMI with non-significant CAD was an independent risk factor for occult malignancy (odds ratio [OR] 4.6, 95% confidence interval [95%CI] 1.1–18.7). Other risk factors included active smoking (OR 11.2, 95%CI 2.5–49.1) and age (OR 1.1, 95%CI 1.03–1.17).

Conclusions: NSTEMI with non-significant CAD may be a presenting or early marker of malignancy and warrants further investigation.

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