Tel Hashomer Medical Center

Tel Aviv, Israel

Tel Hashomer Medical Center

Tel Aviv, Israel

Time filter

Source Type

PubMed | University of Michigan, Oregon Health And Science University, wkc, California Pediatric Surgery Group and 4 more.
Type: Clinical Trial | Journal: Human molecular genetics | Year: 2015

Congenital diaphragmatic hernia (CDH) is a serious birth defect that accounts for 8% of all major birth anomalies. Approximately 40% of cases occur in association with other anomalies. As sporadic complex CDH likely has a significant impact on reproductive fitness, we hypothesized that de novo variants would account for the etiology in a significant fraction of cases. We performed exome sequencing in 39 CDH trios and compared the frequency of de novo variants with 787 unaffected controls from the Simons Simplex Collection. We found no significant difference in overall frequency of de novo variants between cases and controls. However, among genes that are highly expressed during diaphragm development, there was a significant burden of likely gene disrupting (LGD) and predicted deleterious missense variants in cases (fold enrichment = 3.2, P-value = 0.003), and these genes are more likely to be haploinsufficient (P-value = 0.01) than the ones with benign missense or synonymous de novo variants in cases. After accounting for the frequency of de novo variants in the control population, we estimate that 15% of sporadic complex CDH patients are attributable to de novo LGD or deleterious missense variants. We identified several genes with predicted deleterious de novo variants that fall into common categories of genes related to transcription factors and cell migration that we believe are related to the pathogenesis of CDH. These data provide supportive evidence for novel genes in the pathogenesis of CDH associated with other anomalies and suggest that de novo variants play a significant role in complex CDH cases.


Arnson Y.,Meir Medical Canter | Suleiman M.,Rambam Medical Center | Glikson M.,Tel Hashomer Medical Center | Sela R.,Naharia Medical Center | And 10 more authors.
Heart Rhythm | Year: 2014

Background Defibrillation threshold (DFT) testing during placement of an implantable cardioverter-defibrillator (ICD) has been considered mandatory. Accumulating data suggest a more limited role for DFT. Objective The purpose of this study was to compare the outcome of ICD recipients who underwent DFT testing compared with those who did not. Methods In this prospective cohort analysis of patients who received an ICD between July 2010 and March 2013, we compared patients who underwent DFT testing and those who did not. Primary end-points were death and malignant ventricular arrhythmias. Secondary end-points included the composite end-points and inappropriate ICD discharges. Results Of the 3596 patients in the registry, 614 patients (17%) underwent DFT testing during ICD placement vs 2982 (83%) who did not. Variables associated with ICD testing were implantation for secondary prevention (relative risk [RR] 1.87), prior ventricular arrhythmias (RR 1.81), use of antiarrhythmic medication (RR 1.59), and sinus rhythm (RR 2.05). Factors predisposing against testing were cardiac resynchronization therapy defibrillator implantation (RR 0.56) and concomitant diuretic use (RR 0.71). ICD testing was not associated with 1-year mortality (5.3% vs 5.1%, P =.74), delivery of appropriate shocks (8.6% vs 5.6%, P =.16), combined outcomes of ventricular arrhythmias and death (12.9% vs 11.3%, P =.45), or inappropriate ICD discharges (3.9% vs 2.1%, P =.2) compared to no DFT testing. Conclusion No significant differences in the incidence of mortality, malignant ventricular arrhythmias, or inappropriate ICD discharges were observed between patients who underwent DFT testing compared to those who did not. Our results may support avoiding DFT testing during ICD placement, but this requires confirmation by additional prospective studies. © 2014 Heart Rhythm Society.


Yu L.,Columbia University | Wynn J.,Columbia University | Cheung Y.H.,Columbia University | Shen Y.,Columbia University | And 12 more authors.
Human Genetics | Year: 2013

Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of the diaphragm occurring as either an isolated defect or in association with other anomalies. Genetic factors including aneuploidies and copy number variants are important in the pathogenesis of many cases of CDH, but few single genes have been definitively implicated in human CDH. In this study, we used whole exome sequencing (WES) to identify a paternally inherited novel missense GATA4 variant (c.754C>T; p.R252W) in a familial case of CDH with incomplete penetrance. Phenotypic characterization of the family included magnetic resonance imaging of the chest and abdomen demonstrating asymptomatic defects in the diaphragm in the two "unaffected" missense variant carriers. Screening 96 additional CDH patients identified a de novo heterozygous GATA4 variant (c.848G>A; p.R283H) in a non-isolated CDH patient. In summary, GATA4 is implicated in both familial and sporadic CDH, and our data suggests that WES may be a powerful tool to discover rare variants for CDH. © 2012 Springer-Verlag Berlin Heidelberg.


Meydan C.,Tel Hashomer Medical Center | Haklai Z.,Ministry of Health | Gordon B.,Israel Defense Forces | Gordon B.,Tel Aviv University | And 3 more authors.
Journal of Evaluation in Clinical Practice | Year: 2015

Rationale, aims and objectives Israel's healthcare system has been facing increasing hospital bed shortage over the last few decades. Community-based services and shortening length of stay have helped to ease this problem, but hospitals continue to suffer from serious overload and saturation. The objective of this study is to present hospitalization trends in Israel's internal medicine departments. Methods The data is based on the National Hospital Discharges database (NHDR) in the Israeli Health Ministry, pertaining to hospitalizations in all internal medicine departments nationwide between 2000 and 2012. Results Total yearly hospitalization days, representing healthcare burden, had increased by 4.2% during the study period, driven mainly by the most advanced age groups. The rate of total hospitalization days per 100,000 people for all the age groups has decreased by 17.6%, but the oldest patient group had a modest reduction in comparison (7.5%). The parameter of age correlated with length of stay and readmission rates, and neither decreased during the surveyed years. Conclusions These results demonstrated that the healthcare burden on acute internal medicine services has been reduced mostly for middle-Aged populations but only modestly for elderly populations. The length of hospital stay and the readmission rates have reached and maintained a plateau in recent years, regardless of age. The findings of this study call for planning specific to elderly populations in light of changing demographics. Possible directions may include renewed emphasis on internal medicine and geriatric medicine, and efforts to shorten hospitalization time by extended utilization of multidisciplinary primary care. © 2014 John Wiley & Sons, Ltd.


PubMed | Hebrew University of Jerusalem, Soroka Medical Center, Wolfson Medical Center, Rabin Medical Center and 6 more.
Type: Comparative Study | Journal: Heart rhythm | Year: 2014

Defibrillation threshold (DFT) testing during placement of an implantable cardioverter-defibrillator (ICD) has been considered mandatory. Accumulating data suggest a more limited role for DFT.The purpose of this study was to compare the outcome of ICD recipients who underwent DFT testing compared with those who did not.In this prospective cohort analysis of patients who received an ICD between July 2010 and March 2013, we compared patients who underwent DFT testing and those who did not. Primary end-points were death and malignant ventricular arrhythmias. Secondary end-points included the composite end-points and inappropriate ICD discharges.Of the 3596 patients in the registry, 614 patients (17%) underwent DFT testing during ICD placement vs 2982 (83%) who did not. Variables associated with ICD testing were implantation for secondary prevention (relative risk [RR] 1.87), prior ventricular arrhythmias (RR 1.81), use of antiarrhythmic medication (RR 1.59), and sinus rhythm (RR 2.05). Factors predisposing against testing were cardiac resynchronization therapy defibrillator implantation (RR 0.56) and concomitant diuretic use (RR 0.71). ICD testing was not associated with 1-year mortality (5.3% vs 5.1%, P = .74), delivery of appropriate shocks (8.6% vs 5.6%, P = .16), combined outcomes of ventricular arrhythmias and death (12.9% vs 11.3%, P = .45), or inappropriate ICD discharges (3.9% vs 2.1%, P = .2) compared to no DFT testing.No significant differences in the incidence of mortality, malignant ventricular arrhythmias, or inappropriate ICD discharges were observed between patients who underwent DFT testing compared to those who did not. Our results may support avoiding DFT testing during ICD placement, but this requires confirmation by additional prospective studies.


Yu L.,Columbia University | Sawle A.D.,Columbia University | Wynn J.,Columbia University | Aspelund G.,Columbia University | And 7 more authors.
Human Molecular Genetics | Year: 2015

Congenital diaphragmatic hernia (CDH) is a serious birth defect that accounts for 8% of all major birth anomalies. Approximately 40% of cases occur in association with other anomalies. As sporadic complex CDH likely has a significant impact on reproductive fitness, we hypothesized that de novo variants would account for the etiology in a significant fraction of cases. We performed exome sequencing in 39 CDH trios and compared the frequency of de novo variants with 787 unaffected controls from the Simons Simplex Collection. We found no significant difference in overall frequency of de novo variants between cases and controls. However, among genes that are highly expressed during diaphragm development, there was a significant burden of likely gene disrupting (LGD) and predicted deleterious missense variants in cases (fold enrichment = 3.2, P-value = 0.003), and these genes are more likely to be haploinsufficient (P-value = 0.01) than the ones with benign missense or synonymous de novo variants in cases. After accounting for the frequency of de novo variants in the control population, we estimate that 15% of sporadic complex CDH patients are attributable to de novo LGD or deleterious missense variants. We identified several genes with predicted deleterious de novo variants that fall into common categories of genes related to transcription factors and cell migration that we believe are related to the pathogenesis of CDH. These data provide supportive evidence for novel genes in the pathogenesis of CDH associated with other anomalies and suggest that de novo variants play a significant role in complex CDH cases. © The Author 2015. Published by Oxford University Press. All rights reserved.


Fujita H.,Rockefeller University | Shemer A.,Tel Hashomer Medical Center | Suarez-Farinas M.,Rockefeller University | Johnson-Huang L.M.,Rockefeller University | And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2011

Background: Atopic dermatitis (AD) and psoriasis represent polar immune diseases. AD is a TH2/TH22-dominant disease, whereas psoriasis is considered a TH1/TH17 disease. Local immune deviation is suggested to be regulated by dendritic cell (DC)-induced T-cell polarization and recruitment of specific T-cell subsets by chemokines. Although the role of chemokines is well documented, the actual contribution of DCs to activate polar T-cell subsets in human subjects is still a matter of speculation. Objective: We sought to elucidate the significance of each cutaneous DC subset in disease-specific T-cell immune deviation. Methods: We performed a comprehensive analysis of major cutaneous resident (Langerhans cells and blood dendritic cell antigen 1-positive dermal DCs) and inflammatory (inflammatory dendritic epidermal cells and blood dendritic cell antigen 1-negative dermal DCs) DC subsets directly isolated from the lesional skin of patients with AD and those with psoriasis. Results: The ability of each DC subset to expand TH1, TH2, TH17, and T H22 subsets was similar between the 2 diseases, despite the association of both with accumulation of resident and inflammatory DCs. We also confirmed differential upregulation of chemokine expression in patients with AD (CCL17, CCL18, and CCL22) and psoriasis (CXCL1, IL-8, and CCL20). The expression of CCL17 and CCL22 was higher in Langerhans cells from patients with AD than from patients with psoriasis, whereas the opposite was observed for CXCL9 and CXCL10. Conclusion: Our results suggest that DC polarity does not directly drive differential T-cell subset responses. Alternatively, disease-specific chemokines might recruit specific memory T-cell subsets into the skin, which in turn might be activated and expanded by DCs at the site of inflammation, maintaining differential immune polarity in these diseases. © 2011 American Academy of Allergy, Asthma & Immunology.


Wynn J.,Columbia University | Krishnan U.,Columbia University | Aspelund G.,Columbia University | Zhang Y.,Columbia University | And 23 more authors.
Journal of Pediatrics | Year: 2013

Objective: To identify clinical factors associated with pulmonary hypertension (PH) and mortality in patients with congenital diaphragmatic hernia (CDH). Study design: A prospective cohort of neonates with a diaphragm defect identified at 1 of 7 collaborating medical centers was studied. Echocardiograms were performed at 1 month and 3 months of age and analyzed at a central core by 2 cardiologists independently. Degree of PH and survival were tested for association with clinical variables using Fischer exact test, χ2, and regression analysis. Results: Two hundred twenty patients met inclusion criteria. Worse PH measured at 1 month of life was associated with higher mortality. Other factors associated with mortality were need for extracorporeal membrane oxygenation, patients inborn at the treating center, and patients with a prenatal diagnosis of CDH. Interestingly, patients with right sided CDH did not have worse outcomes. Conclusions: Severity of PH is associated with mortality in CDH. Other factors associated with mortality were birth weight, gestational age at birth, inborn status, and need for extracorporeal membrane oxygenation. © 2013 Mosby Inc. All rights reserved.


Meydan C.,Assia Medical Group | Meydan C.,Tel Aviv University | Raziel A.,Assia Medical Group | Sakran N.,Assia Medical Group | And 6 more authors.
Obesity Surgery | Year: 2016

Background: Single anastomosis gastric bypass (SAGB) has been established as a safe and effective bariatric procedure. SAGB has also been suggested as a conversion option from other procedures, but so far not extensively explored in that direction. Methods: The study retrospectively reviewed and analyzed 154 consecutive SAGB procedures, including 48 conversional SAGB (cSAGB) and 106 primary SAGB (pSAGB). Preoperative physical dimensions and perioperative complications were obtained. Patients were followed 1, 3, and 6 months postoperatively, with weight measurements compared between groups. Results: Operative times were longer in the cSAGB group but length of hospital stay was the same for both groups. Sixty-five percent of the cSAGB group had adjustable banding as a primary operation, and 94 % opted for conversion due to insufficient weight loss or regain thereof. Follow-up data availability was 98, 82, and 79 % for the three checkpoints. Three and 6 months postoperatively, cSAGB had inferior mean excess weight loss (EWL) compared to pSAGB, though both groups were successful after 6 months (mean EWL >50 %). Body mass index loss was significantly higher for pSAGB for the first postoperative 3 months. Low complication rates in both groups precluded statistical comparison in that respect. Discussion: Initial weight loss after conversional SAGB is inferior to primary SAGB after 6 months. The observed safety of cSAGB is comparable to previous evidence for this procedure in the conversional settings. Conclusion: SAGB may be considered as a safe and effective conversional procedure, but not as effective as pSAGB for initial weight loss. © 2016 Springer Science+Business Media New York


PubMed | Tel Hashomer Medical Center
Type: Journal Article | Journal: Journal of evaluation in clinical practice | Year: 2015

Israels healthcare system has been facing increasing hospital bed shortage over the last few decades. Community-based services and shortening length of stay have helped to ease this problem, but hospitals continue to suffer from serious overload and saturation. The objective of this study is to present hospitalization trends in Israels internal medicine departments.The data is based on the National Hospital Discharges database (NHDR) in the Israeli Health Ministry, pertaining to hospitalizations in all internal medicine departments nationwide between 2000 and 2012.Total yearly hospitalization days, representing healthcare burden, had increased by 4.2% during the study period, driven mainly by the most advanced age groups. The rate of total hospitalization days per 100,000 people for all the age groups has decreased by 17.6%, but the oldest patient group had a modest reduction in comparison (7.5%). The parameter of age correlated with length of stay and readmission rates, and neither decreased during the surveyed years.These results demonstrated that the healthcare burden on acute internal medicine services has been reduced mostly for middle-aged populations but only modestly for elderly populations. The length of hospital stay and the readmission rates have reached and maintained a plateau in recent years, regardless of age. The findings of this study call for planning specific to elderly populations in light of changing demographics. Possible directions may include renewed emphasis on internal medicine and geriatric medicine, and efforts to shorten hospitalization time by extended utilization of multidisciplinary primary care.

Loading Tel Hashomer Medical Center collaborators
Loading Tel Hashomer Medical Center collaborators