The Chaim Sheba Medical Center

Tel Aviv, Israel

The Chaim Sheba Medical Center

Tel Aviv, Israel

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Bangalore S.,New York University | Kumar S.,University of Nebraska Medical Center | Kjeldsen S.E.,University of Oslo | Makani H.,Columbia University | And 6 more authors.
The Lancet Oncology | Year: 2011

Background: The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical trials. Methods: We undertook traditional direct comparison meta-analyses, multiple comparisons (network) meta-analyses, and trial sequential analyses. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from 1950, to August, 2010, for randomised clinical trials of antihypertensive therapy (ARBs, angiotensin-converting-enzyme inhibitors [ACEi], β blockers, calcium-channel blockers [CCBs], or diuretics) with follow-up of at least 1 year. Our primary outcomes were cancer and cancer-related deaths. Findings: We identified 70 randomised controlled trials (148 comparator groups) with 324 168 participants. In the network meta-analysis (fixed-effect model), we recorded no difference in the risk of cancer with ARBs (proportion with cancer 2·04%; odds ratio 1·01, 95% CI 0·93-1·09), ACEi (2·03%; 1·00, 0·92-1·09), β blockers (1·97%; 0·97, 0·88-1·07), CCBs (2·11%; 1·05, 0·96-1·13), diuretics (2·02%; 1·00, 0·90-1·11), or other controls (1·95%, 0·97, 0·74-1·24) versus placebo (2·02%). There was an increased risk with the combination of ACEi plus ARBs (2·30%, 1·14, 1·02-1·28); however, this risk was not apparent in the random-effects model (odds ratio 1·15, 95% CI 0·92-1·38). No differences were detected in cancer-related mortality for ARBs (death rate 1·33%; odds ratio 1·00, 95% CI 0·87-1·15), ACEi (1·25%; 0·95, 0·81-1·10), β blockers (1·23%; 0·93, 0·80-1·08), CCBs (1·27%; 0·96, 0·82-1·11), diuretics (1·30%; 0·98, 0·84-1·13), other controls (1·43%; 1·08, 0·78-1·46), and ACEi plus ARBs (1·45%; 1·10, 0·90-1·32). In direct comparison meta-analyses, similar results were recorded for all antihypertensive classes, except for an increased risk of cancer with ACEi and ARB combination (OR 1·14, 95% CI 1·04-1·24; p=0·004) and with CCBs (1·06, 1·01-1·12; p=0·02). However, we noted no significant differences in cancer-related mortality. On the basis of trial sequential analysis, our results suggest no evidence of even a 5-10% relative risk (RR) increase of cancer and cancer-related deaths with any individual class of antihypertensive drugs studied. However, for the ACEi and ARB combination, the cumulative Z curve crossed the trial sequential monitoring boundary, suggesting firm evidence for at least a 10% RR increase in cancer risk. Interpretation: Our analysis refutes a 5·0-10·0% relative increase in the risk of cancer or cancer-related death with the use of ARBs, ACEi, β blockers, diuretics, and CCBs. However, increased risk of cancer with the combination of ACEi and ARBs cannot be ruled out. Funding: None. © 2011 Elsevier Ltd.


Monteith S.J.,University of Virginia | Bakon M.,The Chaim Sheba Medical Center | Bakon M.,Tel Aviv University
Neurosurgical Focus | Year: 2013

This paper reviews the current intraoperative imaging tools that are available to assist neurosurgeons in the treatment of intracerebral hemorrhage (ICH). This review shares the authors' experience with each modality and discusses the advantages, potential limitations, and disadvantages of each. Surgery for ICH is directed at blood clot removal, reduction of intracranial pressure, and minimization of secondary damage associated with hematoma breakdown products. For effective occlusion and safe obliteration of vascular anomalies associated with ICH, vascular neurosurgeons today require a thorough understanding of the various intraoperative imaging modalities available for obtaining real-time information. Use of one or more of these modalities may improve the surgeon's confidence during the procedure, the patient's safety during surgery, and surgical outcome. The modern techniques discussed include 1) indocyanine green-based video angiography, which provides realtime information based on high-quality images showing the residual filling of vascular pathological entities and the patency of blood vessels of any size in the surgical field; and 2) intraoperative angiography, which remains the gold standard intraoperative diagnostic test in the surgical management of cerebral aneurysms and arteriovenous malformations. Hybrid procedures, providing multimodality image-guided surgeries and combining endovascular with microsurgical strategies within the same surgical session, have become feasible and safe. Microdoppler is a safe, noninvasive, and reliable technique for evaluation of hemodynamics of vessels in the surgical field, with the advantage of ease of use. Intraoperative MRI provides an effective navigation tool for cavernoma surgery, in addition to assessing the extent of resection during the procedure. Intraoperative CT scanning has the advantage of very high sensitivity to acute bleeding, thereby assisting in the confirmation of the extent of hematoma evacuation and the extent of vascular anomaly resection. Intraoperative ultrasound aids navigation and evacuation assessment during intracerebral hematoma evacuation surgeries. It supports the concept of minimally invasive surgery and has undergone extensive development in recent years, with the quality of ultrasound imaging having improved considerably. Image-guided therapy, combined with modern intraoperative imaging modalities, has changed the fundamentals of conventional vascular neurosurgery by presenting real-time visualization of both normal tissue and pathological entities. These imaging techniques are important adjuncts to the surgeon's standard surgical armamentarium. Familiarity with these imaging modalities may help the surgeon complete procedures with improved safety, efficiency, and clinical outcome. © AANS, 2013.


Otahal J.,Academy of Sciences of the Czech Republic | Folbergrova J.,Academy of Sciences of the Czech Republic | Kovacs R.,Charité - Medical University of Berlin | Kunz W.S.,University of Bonn | And 2 more authors.
International Review of Neurobiology | Year: 2014

Epilepsy is one of the most common neurologic disorders affecting a substantial part of the population worldwide. Epileptic seizures represent the situation of increased neuronal activity associated with the enhanced demands for sufficient energy supply. For that purpose, very efficient regulatory mechanisms have to operate to ensure that cerebral blood flow, delivery of oxygen, and nutrients are continuously adapted to the local metabolic needs. The sophisticated regulation has to function in concert at several levels (systemic, tissue, cellular, and subcellular). Particularly, mitochondria play a key role not only in the energy production, but they are also central to many other processes including those leading to neuronal death. Impairment of any of the involved pathways can result in serious functional alterations, neurodegeneration, and potentially in epileptogenesis. The present review will address some of the important issues concerning vascular and metabolic changes in pathophysiology of epilepsy. © 2014 Elsevier Inc.


Kopel E.,The Chaim Sheba Medical Center | Kopel E.,Ministry of Health | Oren G.,The Chaim Sheba Medical Center | Sidi Y.,The Chaim Sheba Medical Center | And 2 more authors.
Emerging Infectious Diseases | Year: 2012

We describe an inadequate antibody response to rabies vaccine in an immunocompromised patient. A literature search revealed 15 additional immunocompromised patients, of whom 7 did not exhibit the minimum acceptable level of antibodies after a complete postexposure prophylaxis regimen. An international rabies registry is needed to provide a basis for determining appropriate vaccination protocols.


Kivity S.,Sheba Medical Center | Kivity S.,Tel Aviv University | Agmon-Levin N.,Sheba Medical Center | Agmon-Levin N.,Tel Aviv University | And 7 more authors.
BMC Medicine | Year: 2015

Neuropsychiatric symptoms affect nearly half of the patients with systemic lupus erythematosus; however, the effect on disease severity, quality of life, and prognosis is tremendous. Symptoms of neuropsychiatric systemic lupus erythematosus may range from mild diffuse ones, to acute life threatening events. Although the underlying mechanisms are still largely unraveled, several pathogenic pathways are identified, such as antibody-mediated neurotoxicity, vasculopathy due to anti-phospholipid antibodies and other mechanisms, and cytokine-induced neurotoxicity. In the current review, we describe the old and the new regarding epidemiology, pathophysiology, diagnosis, and management of neuropsychiatric systemic lupus erythematosus. The possible link between neuropsychiatric symptoms and specific mechanisms may help to facilitate our understanding of the disease in the future, thus allowing for better treatment strategies. © Kivity et al.


Silverberg D.,The Chaim Sheba Medical Center
Vascular and endovascular surgery | Year: 2010

We report a single-center experience with the endovascular management of mycotic aortic aneurysms. Four cases of mycotic aortic aneurysms are described; all treated with endovascular stent graft with variable configurations. All patients underwent successful placement of stent grafts for their aneurysms. No 30-day perioperative mortality was observed. One patient died during the follow-up period from a cause unrelated to the aneurysm. Repair of mycotic aneurysms can be accomplished with endovascular repair. This may be a valid alternative to open repair particularly in patients who are not candidates for conventional open repair.


Shemesh D.,Shaare Zedek Medical Center | Raikhinstein Y.,Shaare Zedek Medical Center | Orkin D.,The Chaim Sheba Medical Center | Goldin I.,Shaare Zedek Medical Center | Olsha O.,Shaare Zedek Medical Center
Journal of Vascular Access | Year: 2014

The type of anesthesia chosen is an integral part of the decision-making process for arteriovenous access construction. We discuss the different types of anesthesia used, with emphasis on brachial plexus block, which is potentially safer than general anesthesia in this fragile patient population with end-stage renal disease. Brachial plexus block is superior to local anesthesia and enables the use of a tourniquet to minimize potential damage to the blood vessels during anastomosis using microsurgery techniques, and does not lead to the vasospasm that may be seen with local anesthesia. Regional anesthesia has a beneficial sympathectomy-like effect that causes vasodilation with increased blood flow during surgery and in the fistula postoperatively that may prevent early thrombosis and potentially improve outcome. © 2014 Wichtig Publishing.


Hajdu S.D.,The Chaim Sheba Medical Center | Agmon-Levin N.,The Chaim Sheba Medical Center | Shoenfeld Y.,The Chaim Sheba Medical Center | Shoenfeld Y.,Tel Aviv University
European Journal of Clinical Investigation | Year: 2011

Eur J Clin Invest 2011; 41 (2): 203-211Background Since the 1960s, silicone implants have been successfully used for breast augmentation and reconstruction. However, safety issues regarding the use of silicone have led to a moratorium by the US Food and Drug Administration between 1992 and 2006.Design To date, although the moratorium has been removed and women overwhelmingly prefer silicone over saline implants, local and systemic adverse effects still remain a concern.Results Silicone-elicited inflammatory fibro-proliferative response and capsular contracture is irrefutable. Studies on silicone breast implants have not supported a relationship to carcinogenesis, whereas that to autoimmunity mainly to nondefined autoimmune phenomena seems very plausible. These silicone-related autoimmune adverse events termed 'siliconosis' are probably limited to a small minority of implanted patients.Conclusions Risk factors, such as characteristic environmental exposure and/or genetic predisposition, still require further elucidation. Similarly to antibacterial agents, texturized implants and Zafirlukast that were found to be beneficial in inhibiting fibro-proliferative response and capsular contracture, elucidating autoimmune-related risk factors might subsequently enable physicians to accurately predict long-term health status of silicone implant recipients. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.


Grossman E.,The Chaim Sheba Medical Center | Grossman E.,Tel Aviv University | Laudon M.,Neurim Pharmaceuticals Ltd | Zisapel N.,Neurim Pharmaceuticals Ltd | Zisapel N.,Tel Aviv University
Vascular Health and Risk Management | Year: 2011

Background: Patients with nocturnal hypertension are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. Published studies inconsistently reported decreases in nocturnal blood pressure with melatonin. Methods: A meta-analysis of the efficacy and safety of exogenous melatonin in ameliorating nocturnal blood pressure was performed using a random effects model of all studies fitting the inclusion criteria, with subgroup analysis of fast-release versus controlled-release preparations. Results: Seven trials (three of controlled-release and four of fast-release melatonin) with 221 participants were included. Meta-analysis of all seven studies did not reveal significant effects of melatonin versus placebo on nocturnal blood pressure. However, subgroup analysis revealed that controlled-release melatonin significantly reduced nocturnal blood pressure whereas fastrelease melatonin had no effect. Systolic blood pressure decreased significantly with controlledrelease melatonin (-6.1 mmHg; 95% confidence interval [CI] -10.7 to -1.5; P = 0.009) but not fast-release melatonin (-0.3 mmHg; 95% CI -5.9 to 5.30; P = 0.92). Diastolic blood pressure also decreased significantly with controlled-release melatonin (-3.5 mmHg; 95% CI -6.1 to -0.9; P = 0.009) but not fast-release melatonin (-0.2 mmHg; 95% CI -3.8 to 3.3; P = 0.89). No safety concerns were raised. Conclusion: Add-on controlled-release melatonin to antihypertensive therapy is effective and safe in ameliorating nocturnal hypertension, whereas fast-release melatonin is ineffective. It is necessary that larger trials of longer duration be conducted in order to determine the long-term beneficial effects of controlled-release melatonin in patients with nocturnal hypertension. © 2011 Grossman et al, publisher and licensee Dove Medical Press Ltd.


Gelkopf M.,Haifa University | Hasson-Ohayon I.,Bar - Ilan University | Bikman M.,The Chaim Sheba Medical Center | Kravetz S.,Bar - Ilan University
Psychiatry Research | Year: 2013

Chronic combat-related posttraumatic stress disorder (CR-PTSD) is a condition with many treatment barriers. Nature Adventure Rehabilitation (NAR) as a second line or as a supplemental intervention has the potential to overcome some of these barriers and incorporate aspects of successful treatment modalities for PTSD within an experiential learning paradigm. In a pre-post controlled trial, CR-PTSD veterans (n=22) underwent a 1-year NAR intervention compared to a waiting list (WL) control group (n=20). Posttraumatic symptoms (PTS), depression, functional problems, quality of life, perceived control over illness (PCI) and hope were measured by self report measures. PTS, emotional and social quality of life, PCI, hope and functioning improved significantly. Change in PTS was contingent upon change in PCI. The current study is the first to present NAR as a promising supplemental intervention for chronic CR-PTSD. NAR seems to work through a process of behavioral activation, desensitization, gradual exposure to anxiety evoking situations and gaining control over symptomatology. © 2013 Elsevier Ireland Ltd.

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