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עמוד בית
Fri, 30.09.22

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August 2022
Tavor Ben-Zeev MS, Yehuda Shoenfeld MD FRCP MaACR, and Jay R. Hoffman PhD

The connection between physical exercise and the brain has long been studied. The evidence showing that physical exercise plays a significant role on neurogenesis and cognitive function has primarily been based on research examining aerobic exercise. In this review, we described three exercise modalities: aerobic, anaerobic, and resistance exercise and their impact on brain plasticity and cognitive function. While each of these exercise modalities have been demonstrated to positively influence brain plasticity and cognitive function, the specific mechanism that stimulates these changes appear to differ to some degree between these training modalities. The effect of aerobic and anaerobic exercise appears to be primarily mediated by changes in expression of brain-derived neurotrophic factor (BDNF), lactate, vascular endothelial growth factor (VEGF), and several additional proteins within the brain. However, resistance exercise appears to influence brain plasticity by myokines such as irisin, insulin-growth factor-1 (IGF1), and BDNF that are secreted from skeletal tissue and stimulate neurogenesis within the brain. In addition to the various training modes, manipulation of various acute program variables such as intensity, volume, and rest intervals leads to numerous possible training paradigms that can provide a different stimulus for neurogenesis. This review focuses on the three primary training modes and their connection to neurogenesis and cognitive function.

October 2021
Amir Krivoy MD, Shai Shrot MD, Matan Avrahami MD, Tsvi Fischel MD, Abraham Weizman MD, Yael Mardor PhD, David Guez PhD, Dianne Daniels PhD, Athos Katelaris BSc, David Last PhD, and Chen Hoffmann MD

Background: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce.

Objectives: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia.

Methods: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level.

Results: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas.

Conclusions: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

March 2020
Aviad Hoffman MD, Ofir Ben Ishay MD, Nir Horesh MD, Moshe Shabtai MD, Eyal Forschmidt MD, Danny Rosin MD, Mordechai Gutman MD FACS and Edward Ram MD

Background: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women.

Objectives: To review the experience with MBC of a single center in Israel over a period of 22 years.

Methods: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993–2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes.

Results: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A–2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2–178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival.

Conclusions: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.

January 2020
Alina Weissmann-Brenner MD, Anna Mitlin MD, Chen Hoffman MD, Reuven Achiron MD, Yishai Salem MD and Eldad Katorza MD

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

November 2019
Nir Horesh MD, Aviad Hoffman MD, Yaniv Zager MD, Mordechai Cordoba MD, Marat Haikin MD, Danny Rosin MD, Mordechai Gutman MD and Alexander Lebedeyev MD

Background: Evaluation of low rectal anastomosis is often recommended prior to ostomy closure, but the efficacy of such evaluations is uncertain.

Objectives: To assess whether routine colonic preoperative evaluation has an effect on postoperative ileostomy closure results.

Methods: We performed a retrospective study evaluating all patients who underwent ileostomy closure over 9 years. Patient demographics, clinical, surgical details, and surgical outcomes were recorded and analyzed.

Results: The study comprised 116 patients who underwent ileostomy closure, of them 65 were male (56%) with a mean age of 61 years (range 20–91). Overall, 98 patients (84.4%) underwent colonic preoperative evaluation prior to ileostomy closure. A contrast enema was performed on 61 patients (62.2%). Abnormal preoperative results were observed in 12 patients (12.2%). The overall complication rate was 35.3% (41 patients). No differences in postoperative outcome was observed in patient gender (P = 1), age (P = 0.96), body mass index (P = 0.24), American Society of Anesthesiologists score (P = 0.21), and the Charlson Comorbidity Index score (P = 0.93). Among patients who had postoperative complications, we did not observe a difference between patients who underwent preoperative evaluation compared to those who did not (P = 0.42). No differences were observed among patients with preoperative findings interpreted as normal or abnormal (P = 1). The time difference between ileostomy creation and closure had no effect on the ileostomy closure outcome (P = 0.34).

Conclusions: Abnormal findings in preoperative colonic evaluation prior to ileostomy closure were not associated with worse postoperative outcome.

June 2019
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.

September 2017
Jonathan Cohen MD, Ruth Rahamimov MD, Aaron Hoffman MD, Eyal Katvan PhD, Kyril Grozovski RN and Tamar Ashkenazi PhD

Background: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs).

Objectives: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. 

Methods: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded.

Results: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6–12 months follow-up. 

Conclusions: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.


September 2016
Rotem Sivan-Hoffmann MD, Benjamin Gory MD MSc, Muriel Rabilloud MD PhD, Dorin N. Gherasim MD, Xavier Armoiry PharmD PhD, Roberto Riva MD, Paul-Emile Labeyrie MD MSc, Udi Gonike-Sadeh MD, Islam Eldesouky MD and Francis Turjman MD PhD

Mechanical thrombectomy with stent retrievers is now the reference therapy for acute ischemic stroke (AIS) in the anterior circulation in association with thrombolysis. We conducted an extensive systematic review and meta-analysis to evaluate the clinical and angiographic outcomes of stent-retriever thrombectomy in patients with acute anterior circulation stroke. Available literature published to date on observational studies and three randomized trials (MR CLEAN, ESCAPE, and EXTEND-IA) involving the stent-retriever device were reviewed. Successful recanalization and favorable clinical outcome were defined by a TICI ≥ 2b and modified Rankin Scale score of ≤ 2 at 90 days following AIS, respectively. A total of 2067 patients harboring an anterior circulation stroke were treated with a stent retriever: 433 patients from 3 randomized trials involving the device and 1634 patients from observational studies. Mean NIH Stroke Scale score on admission was 16.6, and mean time from onset to recanalization was 300 minutes. Successful recanalization was achieved in 82% (95%CI 77–86, 31 studies). The 90 day favorable outcome was achieved in 47% (95%CI 42–5.2, 34 studies) with an overall mortality rate of 17% (95%CI 13–20, 31 studies). Symptomatic intracerebral hemorrhage was identified in 6% (95%CI 4–8, 32 studies). In patients with AIS caused by a proximal intracranial occlusion of the anterior circulation, stent-retriever thrombectomy is safe and restores brain reperfusion in four of five treated patients, allowing favorable clinical outcome in one of two AIS patients with large vessel occlusion. 

January 2016
Avinoam Nevler MD, Esther Shabtai MD, Danny Rosin MD, Aviad Hoffman MD, Mordechai Gutman MD and Moshe Shabtai MD

Background: High density breast mammography has been associated with a greater risk for breast cancer and an increased likelihood of false negative results. 

Objectives: To assess whether the degree of mammographic breast density correlates with an increased risk for the presence of radiographic findings requiring further histological investigation. 

Methods: Included in the study were 2760 consecutive screening mammograms performed in a large volume, early detection mammography unit. All mammograms were complemented by high resolution ultrasound and interpreted by a single expert radiologist. Breast density (BD) was evaluated using a semi-quantitative 5 grade scale and grouped into low breast density (LBD) and high breast density (HBD) mammograms. Demographic and all relevant obstetric, personal and family history of breast cancer data were recorded. 

Results: Of the 2760 mammograms 2096 (76%) were LBD and 664 (24%) were HBD. Mean age of the LBD and HBD groups was 59 ± 10.5 and 50.9 ± 9.3 years respectively (P = 0.001). Breast density significantly correlated with presence of mammographic findings requiring further histological assessment (8.7% and 12.3% for LBD and HBD respectively, P < 0.01). In women younger than 60 years in whom histological assessment was required due to these findings, malignant pathology was significantly more prevalent in the HBD group (2.3% and 4.1% respectively, P = 0.03). Age, parity, patient history and HBD were identified as independent risk factors for any pathological mammographic finding. 

Conclusions: Highly dense mammography, aside from being an indicator of higher risk for breast cancer, appears to be associated with a significantly higher incidence of findings that will prompt further investigation to achieve a definite diagnosis. 


December 2013
Nir Samuel, Anat K. Politansky, Ron Hoffman, Shlomit Itzkovich and Hanna Mandel
July 2013
H.S. Oster, M. Benderly, M. Hoffman, E. Cohen, A. Shotan and M. Mittelman
 Background: Anemia is common in heart failure (HF), but there is controversy regarding its contribution to morbidity and mortality.

Objective: To examine the association of mild and severe anemia with acute HF severity and mortality.

Methods: Data were prospectively collected for patients admitted to all departments of medicine and cardiology throughout the country during 2 months in 2003 as part of the Heart Failure Survey in Israel. Anemia was defined as hemoglobin (Hb) < 12 g/dl for women and < 13 g/dl for men; Hb < 10 g/dl was considered as severe anemia. Mortality data were obtained from the Israel population registry. Median follow-up was 33.6 months.

Results: Of 4102 HF patients, 2332 had acute HF and available hemoglobin data. Anemia was common (55%) and correlated with worse baseline HF. Most signs and symptoms of acute HF were similar among all groups, but mortality was greater in anemic patients. Mortality rates at 6 months were 14.9%, 23.7% and 26.3% for patients with no anemia, mild anemia, and severe anemia, respectively (P < 0.0001), and 22.2%, 33.6% and 39.9% at one year, respectively (P < 0.0001). Compared to patients without anemia, multivariable adjusted hazard ratio was 1.35 for mild anemia and 1.50 for severe anemia (confidence interval 1.20–1.52 and 1.27–1.77 respectively).

Conclusions: Anemia is common in patients with acute HF and is associated with increased mortality correlated with the degree of anemia.

G. Yaniv, G. Twig, O. Mozes, G. Greenberg, C. Hoffmann and Y. Shoenfeld
 Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving multiple organs. One of the main sites of SLE morbidity is the central nervous system (CNS), specifically the brain. In this article we review several imaging modalities used for CNS examination in SLE patients. These modalities are categorized as morphological and functional. Special attention is given to magnetic resonance imaging (MRI) and its specific sequences such as diffusion-weighted imaging (DWI), diffuse tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). These modalities allow us to better understand CNS involvement in SLE patients, its pathophysiology and consequences.


May 2013
G. Yaniv, O. Mozes, G. Greenberg, M. Bakon and C. Hoffmann
 Background: Misinterpretation of head computerized tomographic (CT) scans by radiology residents in the emergency department (ED) can result in delayed and even erroneous radiology diagnosis. Better knowledge of pitfalls and environmental factors may decrease the occurrence of these errors.

Objectives: To evaluate common misinterpretations of head CT scans by radiology residents in a level I trauma center ED.

Methods: We studied 960 head CT scans of patients admitted to our ED from January 2010 to May 2011. They were reviewed separately by two senior neuroradiologists and graded as being unimportant (score of 1), important but not requiring emergent treatment (score of 2), and important requiring urgent treatment (score of 3). We recorded the time of day the examination was performed, the year of residency, the site, subsite and side of the lesion, the pathology, the anatomical mistake, false-positive findings, and the attending neuroradiologists' score.

Results: A total of 955 examinations were interpreted of which 398 had misinterpreted findings that were entered into the database, with the possibility of multiple errors per examination. The overall misinterpretation rate was 41%. The most commonly missed pathologies were chronic infarcts, hypodense lesions, and mucosal thickening in the paranasal sinuses. The most common sites for misdiagnosis were brain lobes, sinuses and deep brain structures. The highest percentage of misinterpretation occurred between 14:30 and 20:00, and the lowest between 00:00 and 08:00 (P < 0.05). The overall percentage of errors involving pathologies with a score of 3 by at least one of the neuroradiologists was 4.7%. Third-year residents had an overall higher error rate and first-year residents had significantly more false-positive misinterpretations compared to the other residents.

Conclusions: The percentage of errors made by our residents in cases that required urgent treatment was comparable to the published data. We believe that the intense workload of radiology residents contributes to their misinterpretation of head CT findings.


February 2013
O. Halshtok Neiman, S. Sadetzki, A. Chetrit, S. Raskin, G. Yaniv and C. Hoffmann
 Background: MRI differentiation between metastases and high grade gliomas is a challenging task. Contrast enhancement and size of edema do not provide clear-cut differentiators. The differences in the properties of the peritumoral edema between these tumor types may be exploited to distinguish between them, using MRI perfusion sequences, which are capable of imaging edema in the clinical setting and may be a reliable method to make this differentiation.

Objectives: To assess the ability of perfusion-weighted imaging to differentiate between high grade gliomas and brain metastases.

Methods: During 5 months, 21 patients (age 40–85, median age 61, 16 males and 5 females) with either glioblastoma multiforme (GBM) or metastasis (pathology proven), underwent MRI for assessment of the tumor prior to surgery. Most of the scans were done at 3 Tesla. The scans included perfusion-weighted imaging sequences. Perfusion in the tumor, in the peritumoral edema and in normal tissue were assessed using Functool® software. The ratios of tumor perfusion and peritumoral edema perfusion to normal tissue perfusion were calculated and compared.

Results: Bleeding artifact precluded perfusion assessment in four patients. There was no statistically significant difference between the tumor perfusion ratios of high grade gliomas and those of metastases. The edema perfusion ratios were higher in GBM than in metastases (P = 0.007).

Conclusions: Perfusion-weighted imaging of peritumoral edema can help to differentiate between GBM and metastases.

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