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עמוד בית
Mon, 26.02.24

Search results


June 2023
Yael Laitman MSc, Rinat Bernstein-Molho MD, Talia Golan MD, Eitan Friedman MD PhD

Germline pathogenic variants (PVs) in the RET proto-oncogene (OMIM 164761) are associated with a diverse phenotype based on the type of PV. Gain-of-function (GOF) PVs are associated with the highly penetrant multiple endocrine neoplasia type 2 (MEN2-OMIM 171400), which are hallmarked by an increased risk for developing medullary thyroid cancer (MTC), pheochromocytoma, and parathyroid adenomas. Loss-of-function (LOF) RET PVs are associated with incompletely penetrant Hirschsprung's disease (HSCR OMIM 142623), which are pathologically characterized by the absence of enteric ganglia affecting the distal colon and clinically manifest as neonatal intestinal obstruction. Despite anecdotal reports of familial clustering of neoplasms in HSCR families, mostly MEN2-associated tumors [1,2], HSCR is not considered to be associated with an increased risk for developing cancer [3]. We report on a family with an unusual multigenerational solid tumor phenotype and severe HSCR phenotype with a LOF RET PV.

January 2023
Naama Hermann MD, Pnina Mor CNM PhD, Orit Kaidar-Person MD, Rinat Bernstein-Molho MD, Mali Brodsky RN MSc, Dana Madorsky Feldman MD, Anath A. Flugelman MD MPH MA, Hadar Aboody Nevo MD, Danna Meshoulam Avital MD, Miri Sklair-Levy MD, Eitan Friedman MD PhD, Tanir M. Allweis MD

Background: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

March 2020
Eyal Lotan MD PhD, Kent P. Friedman MD, Tima Davidson MD and Timothy M. Shepherd MD PhD

The authors reviewed the two most common current uses of brain 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer’s disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.

April 2019
Or Friedman MD, Ehud Fliss MD, Amir Inbal MD, Ehud Arad MD, Jacob Frand MD and Yoav Barnea MD

Background: There are several methods for primary breast reconstruction following oncologic resection, including alloplastic and autologous-based reconstruction. Major complications that can lead to re-operation and reconstruction failure occur in up to 25% of the patients and necessitate salvage procedures.

Objectives: To present the authors' experience using a pedicled latissimus dorsi (LD) flap for the salvage of complicated and impending failed breast reconstruction.

Methods: A retrospective cohort study was conducted of all patients who underwent breast reconstruction salvage by means of an LD flap in our institution during a 5-year period. Demographic, oncologic, surgical, and postoperative data were collected and analyzed.

Results: Seventeen patients underwent breast reconstruction salvage with the LD flap. Fourteen patients had alloplastic reconstruction and three patients had autologous reconstruction. Postoperative complications included wound infection in three patients, minor wound dehiscence in two, and donor site seroma in two. One case of postoperative infection required re-operation with exchange of the implant with a tissue expander. All breast reconstructions were salvaged using the LD flap. Only one patient complained of functional limitations in using the arm of the harvested LD.

Conclusions: The LD flap is a valuable and reliable flap for alloplastic or autologous breast reconstruction salvage and has a high rate of salvage success despite the challenging surgical environment. This flap offers a good cosmetic reconstruction outcome with relatively low donor-site morbidity and high patient satisfaction.

February 2019
Shirley Friedman MD, Lilach Zac MD, Anat Cattan MsC, Dror Ovadia MD, David E. Lebel MD and Idit Matot MD PhD

Background: Hyperchloremia is frequent in adult surgical patients and is associated with renal dysfunction. Studies in surgical pediatric patients are lacking.

Objectives: To identify both the incidence of postoperative hyperchloremia in children undergoing surgery for idiopathic and non-idiopathic scoliosis, and the association of postoperative hyperchloremia with intraoperative fluid management and postoperative diuresis.

Methods: The records of 74 children and adolescents who underwent elective scoliosis surgery were retrospectively evaluated. The primary endpoint was the incidence of serum chloride level ≥ 110 mEq/L at the end of surgery and 12 hours postoperatively. Secondary endpoints were the type and volume of administered fluids, 12 hours postoperative diuresis, and the incidence of postoperative oliguria.

Results: Hyperchloremia occurred in 55% of the patients at the end of surgery and in 52% 12 hours postoperatively. Hyperchloremic patients received larger intraoperative volume of 0.9% NaCl diluted cell-saver blood and 10% HAES than did normochloremic patients [median (interquartile range) 6.8 (2.5–11.0) ml/kg vs. 0 (0–7.3), P = 0.003 and 10.0 (0–12.8) vs. 4.4 (0–9.8), P = 0.02, respectively]. Additionally, when compared with normochloremic patients, diuresis during the first 12 hours postoperatively was lower in hyperchloremic patients. Postoperative oliguria (urine output < 0.5 ml/kg/hr for 12 hours) was diagnosed in 7 children (9%), of whom 6 were hyperchloremic at the end of surgery.

Conclusions: Early postoperative hyperchloremia is common in children undergoing scoliosis repair surgery and may be attributed to the administration of 0.9% NaCl diluted cell-saver blood and 10% HAES. Postoperative hyperchloremia might be associated with postoperative oliguria.

January 2019
Moran Livne Margolin MD, Nona Zeitlin MD, Yehudit Eden Friedman MD, Opher Globus MD and Meir Mouallem MD
May 2018
Yehudit Eden Friedman MD, Gabriela Gayer MD, Moran Livne Margolin MD, Abraham Kneller MD and Meir Mouallem MD
April 2018
Mahmoud Abu–Shakra MD, Devy Zisman MD, Alexandra Balbir-Gurman MD, Howard Amital MD, Yair Levy MD, Pnina Langevitz MD, Moshe Tishler MD, Yair Molad MD, Suhail Aamar MD, Itzhak Roser MD, Nina Avshovich MD, Daphna Paran MD, Tatiana Reitblat MD, Reuven Mader MD, Hillel Savin MD, Joshua Friedman MD, Nicky Lieberman MD and Sharon Ehrlich MD

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

June 2017
Hagit Schayek PhD, Yael Laitman MSc, Lior H Katz MD, Elon Pras MD, Liat Ries-Levavi PhD, Frida Barak MD and Eitan Friedman MD PhD

Background: Biallelic BLM gene mutation carriers are at an increased risk for cancer, including colorectal cancer (CRC). Whether heterozygous BLM gene mutations confer an increased cancer risk remains controversial.

Objectives: To evaluate CRC and endometrial cancer risk in BLM heterozygous mutation carriers.

Methods:
Jewish Ashkenazim at high risk for colon or endometrial cancer and endometrial cancer cases unselected for family history were genotyped for the BLMAsh predominant mutation.

Results: Overall, 243 high-risk individuals were included: 97 men CRC patients (55.12 ± 12.3 years at diagnosis), 109 women with CRC (56.5 ± 13.7 years), 32 women with endometrial cancer (58.25 ± 13.4 years) and 5 women with both CRC and endometrial cancer. In addition, 120 unselected Ashkenazi women with endometrial cancer (64.2 ± 11.58 years) were genotyped. The BLMAsh mutation was present in 4/243 (1.65%) high-risk patients; 2 CRC (0.97%) 2 endometrial cancer (5.4%), and 1/120 unselected endometrial cancer patients (0.84%). Notably, in high-risk cases, BLMAsh mutation carriers were diagnosed at a younger age (for CRC 47.5 ± 7.8 years; P = 0.32 ; endometrial cancer 49.5 ± 7.7 years; P = 0.36) compared with non-carriers.

Conclusions: Ashkenazi high risk CRC/endometrial cancer, and women with endometrial cancer have a higher rate of BLMAsh heterozygous mutation compared with the general population. BLMAsh heterozygous mutation carriers are diagnosed with CRC and endometrial cancer at a younger age compared with non-carriers. These observations should be validated and the possible clinical implications assessed.

May 2017
Dvora S. Shapiro MD, Reuven Friedmann MD, Ashraf Husseini MD, Hefziba Ivgi PhD, Amos M. Yinnon MD and Marc V. Assous MD PhD

Background: It is a challenge to diagnosis Clostridium difficile colitis.

Objectives: To determine, among patients who developed nosocomial diarrhea, whether serum procalcitonin (PCT) can distinguish between C. difficile toxin (CDT)-positive and CDT-negative patients.

Methods: This prospective study included 50 adults (>18 years) who developed diarrhea during hospitalization, 25 with a positive fecal test for CDT (study group) and 25 CDT negative (control group).

Results: Baseline demographic and underlying illnesses were similar in both groups. Duration of diarrhea was 6 ± 4 days and 3 ± 1 in the study and control groups, respectively (P = 0.001). Mean blood count was 20 ± 15 and 9.9 ± 4, respectively (P = 0.04). CRP level was higher in the study than in the control group (10.9 ± 7.4 and 6.6 ± 4.8, P = 0.028). PCT level was higher in the study group (4.4 ± 4.9) than the control group (0.3 ± 0.5, P = 0.102). A PCT level > 2 ng/ml was found in 7/25 patients (28%) and 1/25 (4%), respectively [odds ratio 9.33, 95% confidence interval (0.98 to 220), P = 0.049]. Multivariate analysis showed that only duration of diarrhea and left shift of peripheral leucocytes were significant indicators of CDT (P = 0.014 and P = 0.019, respectively). The mortality rate was 12/25 (48%) vs. 5/25 (20%), respectively (P = 0.04).

Conclusions: We found a non-significant tendency to higher PCT levels in patients with CDT-positive vs. CDT-negative nosocomial diarrhea. However, a PCT level > 2 ng/ml may help distinguish between these patients.

October 2016
Osnat Halshtok Neiman MD, Zippy Erlich PhD, Eitan Friedman M PhD, Arie Rundstein MD, Anat Shalmon MD, Yael Servadio MD and Miri Sklair Levy MD

Background: Automated breast volumetric sonography (ABVS) is a new technology with various possible applications.

Objectives: To compare ABVS and breast magnetic resonance imaging (MRI) in the surveillance of women with BRCA1/2 gene mutation carriers.

Methods: We conducted a prospective study in Jewish female BRCA1/2 mutation carriers who underwent breast MRI and ABVS. The results of both exams performed 6 months apart or less, and relevant clinical data, were reviewed. The BIRADS results were divided into three subgroups according to subsequent expected management: BIRADS 1-2 (normal study), BIRADS 3 (probably benign finding), and BIRADS 4 and 5 (suspicious findings). BIRADS 0 and 6 scores were excluded from the study. Distribution of ABVS and MRI BIRADS scores were compared using McNemar's test, and concordance was calculated using the Cohen kappa test.

Results: Overall, 68 women, 40 BRCA1 and 28 BRCA2 mutation carriers, age range 26–69 (mean 44.55 ± 12.1 years), underwent 79 paired ABVS and MRI examinations. McNemar's test calculations showed no significant difference between MRI and ABVS BIRADS score distribution. Cohen’s kappa test resulted in k = 0.158, an agreement that can be described as only "slight agreement" between both modalities. Of 14 discordant cases there was one cancer, revealed by MRI and not by ABVS performed 6 months prior to MRI.

Conclusions: ABVS showed slight agreement with MRI in BRCA1/2 mutation carriers. These preliminary results on a small group of healthy high risk patients suggest that the diagnostic abilities of ABVS are inferior to MRI. Further studies encompassing larger groups are needed.

 

November 2015
Oren Gordon MD PhD, Sinan Abu-Leil MD, Yotam Almagor MD, Elite Cohen MD, Alexander Margulis MD, Dan Arbell MD, Benjamin Bar-Oz and Smadar Eventov-Friedman MD PhD
July 2015
Smadar Eventov-Friedman MD PhD, Ayala Frumkin PhD, Benjamin Bar-Oz MD and Annick Raas-Rothschild MD
October 2012
T. Friedman, D.J. Lurie and A. Shalom

The Dutch painter Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. Although about 40 of his oil paintings could be considered “self-portraits,” controversy still exists regarding 14 of them. We undertook to determine the identity of the painter or the subject. Our work was based on the generally accepted premise that these portraits represent a “realistic” rendering of the subject. Self-portraits on which there is consensus regarding the authenticity were chosen as the basis for our measurements. Using a computerized technique we measured the brow ptosis. We also subjectively analyzed Rembrandt's facial aging and the unique asymmetrical elements in his face. We could not add any useful information on 6 of the 14 portraits and suggest that 8 should be considered authentic. Facial aging analysis and the unique surface anatomy allowed us to confirm Rembrandt as the painter in four of six self-portraits. We confirmed Rembrandt as the subject and painter in three more paintings. Of the two paintings in which the subject’s identity was controversial, we determined Rembrandt as the subject in one. We were able to date Rembrandt’s age in two other works and considered another portrait to be a copy. Our methodology may serve as an additional tool for the authentication of self-portraits.
 

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