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עמוד בית
Fri, 24.05.24

Search results

March 2023
Dorit Shitenberg MD, Barak Pertzov MD, Moshe Heching MD, Yael Shostak MD, Osnat Shtraichman MD, Dror Rosengarten MD, Moshe Yeshurun MD, Yury Peysakhovich MD, Yaron Barac MD, Mordechai R. Kramer MD

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

February 2023
Milton Saute MD, Ehud Raanani MD, Amir On MD, Ran Kramer MD, Liran Levy MD

Twenty years after being closed due to unfavorable results, a new lung transplant program was started at the Sheba Medical Center. The new team included an experienced lung transplant surgeon, an anesthesiologist, an intensive care specialist, and a pulmonologist with extensive experience in the field.

December 2020
Moshe Shai Amor, Dror Rosengarten, Dorit Shitenberg, Barak Pertzov, Yael Shostak, and Mordechai Reuven Kramer

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

July 2019
Adi Porat Rein MD, Uri Kramer MD and Alexis Mitelpunkt MD

Background: Benign rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes (BCECTS) is a common childhood epileptic syndrome. The syndrome resolves in adolescence, but 1–7% of patients have an atypical presentation, some of which require aggressive medical treatment. Early treatment may prevent complications and neurocognitive deterioration. Variants include Landau-Kleffner syndrome (LKS) and electrical status epilepticus during sleep (ESES).

Objectives: To determine data driven identification of risk factors and characterization of new subtypes of BCECTS based on anontology. To use data mining analysis and correlation between the identified groups and known clinical variants.

Methods: We conducted a retrospective cohort study comprised of 104 patients with a diagnosis of BCECTS and a minimum of 2 years of follow-up, between the years 2005 and 2017. The medical records were obtained from the epilepsy service unit of the pediatric neurology department at Dana–Dwek Hospital, Tel Aviv Sourasky Medical Center. We developed a BCECTS ontology and performed data preprocessing and analysis using the R Project for Statistical Computing (https://www.r-project.org/) and machine learning tools to identify risk factors and characterize subgroups.

Results: The ontology created a uniform and understandable infrastructure for research. With the ontology, a more precise characterization of clinical symptoms and EEG activity of BCECTS was possible. Risk factors for the development of severe atypical presentations were identified: electroencephalography (EEG) with spike wave (P < 0.05), EEG without evidence of left lateralization (P < 0.05), and EEG localization (centrotemporal, frontal, or frontotemporal) (P < 0.01).

Conclusions: Future use of the ontology infrastructure for expanding characterization for multicenter studies as well as future studies of the disease are needed. Identifying subgroups and adapting them to known clinical variants will enable identification of risk factors, improve prediction of disease progression, and facilitate adaptation of more accurate therapy. Early identification and frequent follow-up may have a significant impact on the prognosis of the atypical variants.

December 2018
Raviv Allon BsC, Yahav Levy MD, Idit Lavi MA, Aviv Kramer MD, Menashe Barzilai MD and Ronit Wollstein MD

Because fragility fractures have an enormous impact on the practice of medicine and global health systems, effective screening is imperative. Currently, dual-energy X-ray absorptiometry (DXA), which has limited ability to predict fractures, is being used. We evaluated the current literature for a method that may constitute a better screening method to predict fragility fractures. A systematic review of the literature was conducted on computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound to evaluate screening methods to predict fragility fractures. We found that ultrasound had sufficient data on fracture prediction to perform meta-analysis; therefore, we analyzed prospective ultrasound cohort studies. Six study populations, consisting of 29,299 individuals (87,296 person-years of observation) and including 992 fractures, were analyzed. MRI was found to be sensitive and specific for osteoporosis, but its use for screening has not been sufficiently evaluated and more research is needed on cost, accessibility, technical challenges, and sensitivity and specificity. CT could predict fracture occurrence; however, it may be problematic for screening due to cost, exposure to radiation, and availability. Ultrasound was found to predict fracture occurrence with an increased risk of 1.45 (95% confidence interval 1.21–1.73) to fracture. Ultrasound has not replaced DXA as a screening tool for osteoporosis, perhaps due to operator-dependency and difficulty in standardization of testing.

August 2016
Shimon Izhakian MD, Walter G. Wasser MD, Baruch Vainshelboim PhD, Benjamin D. Fox BM BS and Mordechai R. Kramer MD FCCP

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.


January 2015
Lior Leibou MD, Oscar Herman MD, Jacob Frand MD, Eyal Kramer MD and Shimonov Mordechai MD
April 2014
Eyal Kramer MD, Oscar Herman MD, Jacob Frand MD, Lior Leibou MD, Letizia Schreiber MD and Hananya Vaknine MD
 Background: Basal cell carcinoma (BCC) is the most common malignancy in humans. Several factors have been associated with the biological behavior of these tumors, including histopathologic type, depth of tumor invasion, perineural invasion, and the expression of several biologic markers including Ki67, a proliferative marker. Previous studies assessing the relationship between the proliferative fraction, as expressed by Ki67, and the histologic variants of BCC as well as its association with the tendency to recur, failed to illustrate significant statistical correlation.

Objectives: To examine the proliferative index, as expressed by Ki67, in various subtypes of basal cell carcinoma, and to assess its relationship to various histological and clinical variables.

Methods: In this retrospective study 51 lesions of BCC were examined. In each case, the following data were gathered: demographic (age and gender), anatomic location, size of the lesion, and clinical follow-up.  Each case was stained immunohistochemically with anti-Ki67 antigen (MIB-1), and the proliferative index was determined. Histologic analysis was performed for the following data: presence of an ulcer, intensity of inflammatory infiltrate, histologic subtype, mitotic count, and the presence of perineural invasion.

Results: Basal cell carcinoma exhibited a wide variation of proliferative indices, ranging from 1% to 61%. A significant statistical correlation was observed between the proliferative index and the mitotic activity, tumor ulceration and brisk tumor-infiltrating lymphocytes.

Conclusions: The wide variation in the degree of proliferation (from almost no activity to highly proliferative tumors) suggests that basal cell carcinoma exhibits a wide spectrum of biological characteristics. Ulcerated lesions were characterized by high proliferative index. No true correlation was demonstrated between the proliferative index and the aggressive histologic subtypes, implying that other factors were more biologically significant. The degree of proliferation also showed significant statistical correlation with the degree of tumor infiltration by lymphocytes. The significance of this proliferation-associated increased immunogenicity needs to be further studied.

September 2013
A. L. Schwartz, Y. Topilsky, G. Uretzky, N. Nesher, Y. Ben-Gal, S. Biner, G. Keren and A. Kramer

Background: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival.

Objectives: To report the outcomes of patients after aortic valve replacement with the Freestyle® stentless bioprosthesis in the Tel Aviv Medical Center followed for ≤ 15 years.

Methods and Results: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 ± 9.2 years, 4.2 ± 1.5 and 10.2 ± 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 ± 29.1 vs. 22.8 ± 9.6 mmHg, P < 0.0001; and 43.4 ± 17.2 vs. 12.1 ± 5.4 mmHg, P < 0.0001 respectively) in 3 months of follow-up. Mean overall follow-up was 4.9 ± 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 ± 2.5% and 57.2 ± 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 ± 2.3% vs. 76.0 ± 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 ± 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one.

Conclusions: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients. 

November 2011
D. Rosengarten, M.R. Kramer, G. Amir, L. Fuks and N. Berkman

Pulmonary epithelioid hemangioendothelioma (PEH), previously known as "intravascular bronchoalveolar tumor," is a rare vascular malignancy with an unpredictable prognosis. Treatment can vary from observation in asymptomatic patients to surgery in patients with resectable disease or chemotherapy in patients with disseminated disease. This report describes the clinical, radiological and pathological features of three cases of PEH and a review of the current literature.

November 2009
A. Amital, D. Shitrit, B.D. Fox, Y. Raviv, L.Fuks, I. Terner and M.R. Kramer

Background: Blunt chest trauma can cause severe acute pulmonary dysfunction due to hemo/pneumothorax, rib fractures and lung contusion.

Objectives: To study the long-term effects on lung function tests after patients' recovery from severe chest trauma.

Methods: We investigated the outcome and lung function tests in 13 patients with severe blunt chest trauma and lung contusion.

Results: The study group comprised 9 men and 4 women with an average age of 44.6 ± 13 years (median 45 years). Ten had been injured in motor vehicle accidents and 3 had fallen from a height. In addition to lung contusion most of them had fractures of more than three ribs and hemo/pneumothorax. Ten patients were treated with chest drains. Mean intensive care unit stay was 11 days (median 3) and mechanical ventilation 19 (0–60) days. Ten patients had other concomitant injuries. Mean forced expiratory volume in the first second was 81.2 ± 15.3%, mean forced vital capacity was 85 ± 13%, residual volume was 143 ± 33.4%, total lung capacity was 101 ± 14% and carbon monoxide diffusion capacity 87 ± 24. Post-exercise oxygen saturation was normal in all patients (97 ± 1.5%), and mean oxygen consumption max/kg was 18 ± 4.3 ml/kg/min (60.2 ± 15%). FEV1[1]. was significantly lower among smokers (71.1 ± 12.2 vs. 89.2 ± 13.6%, P = 0.017). There was a non-significant tendency towards lower FEV1 among patients who underwent mechanical ventilation.

Conclusions: Late after severe trauma involving lung contusion, substantial recovery is demonstrated with improved pulmonary function tests. These results encourage maximal intensive care in these patients. Further larger studies are required to investigate different factors affecting prognosis.



[1] FEV1 = forced expiratory volume in the first second

August 2009
G. Aviram, R. Mohr, R. Sharony, B. Medalion, A. Kramer and G. Uretzky

Background: Injury to patent grafts or cardiac chambers may occur during reoperation after coronary artery bypass grafting. Preoperative spatial localization of bypass grafts with computed tomography may improve the safety of these procedures.

Objectives: To characterize patients who undergo CT before repeat operations after previous coronary artery bypass grafting, and evaluate its benefit in terms of surgical outcome.

Methods: We compared 28 patients who underwent cardiac gated CT angiography before reoperation (CT group) to 45 re-do patients who were not evaluated with CT (no‑CT group).

Results: The two groups were similar in most preoperative and operative characteristics. The CT group, however, included more patients with patent saphenous vein grafts and fewer with emergency operations, acute myocardial infarction and need for intraaortic balloon pump support. During mid-sternotomy, there was no injury to grafts in the CT group, while there were two patent grafts and three right ventricular injuries in the no-CT group. There was no significant difference in perioperative mortality (3.6% vs. 8.9%). The overall complication rate in the CT group was 21.4% compared to 42.2% in the no‑CT group (P = 0.07). The only independent predictors of postoperative complications were diabetes mellitus, preoperative stroke and preoperative acute MI[1].

Conclusions: The patency and proximity of patent grafts to the sternum are well demonstrated by multidetector CT and may provide the surgeon with an important roadmap to avoid potential graft injury. A statistical trend towards reduced complications rate was demonstrated among patients who underwent CT angiography before their repeat cardiac operation. Larger series are required to demonstrate a statistically validated complication-free survival benefit of preoperative CT before repeat cardiac surgery.

[1] MI = myocardial infarction

September 2008
G. Izbicki, G. Fink, A. Algom, R. Hirsch, L. Blieden, E. Klainman, E. Picard, S. Goldberg and M. R. Kramer

Background: Since surgical repair of tetralogy of Fallot was introduced, follow-up studies have shown that the majority of patients lead actives lives and have no subjective exercise limitation.

Objectives: To examine lung function, cardiopulmonary functional capacity and echo-Doppler assessment of pulmonary pressure in adult patients 20 years after repair of TOF.

Methods: Unselected consecutive patients performed full lung function testing, progressive cardiopulmonary exercise, and echo-Doppler assessments of pulmonary pressure.

Results: Fifty consecutive patients (33 men, 17 women) aged 29 ± 11 years who underwent surgical repair of TOF at age 10.1 ± 10.9 years were enrolled in this study. Patients after TOF showed no restriction (forced expiratory vital capacity 80%, total lung capacity 91%) and had normal oxygen saturation (97%) and 6 minute walking distance (600 meters). Echocardiography showed normal pulmonary pressure and left ventricular ejection function (62%). Cardiopulmonary exercise testing showed mild limitation of exercise capacity with oxygen uptake at maximal effort of 75–78% predicted.

Conclusions: After corrections of TOF the study patients had normal lung function and pulmonary arterial pressure but mild limitation in their exercise capacity.

February 2008
A. Grubstein, O. Benjaminov, D. Ben Dayan, D. Shitrit, M. Cohen and M.R. Kramer

Background: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

[1] PHT = pulmonary arterial hypertension

[2] HRCT = high resolution computed tomography

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