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עמוד בית
Fri, 30.09.22

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May 2020
Yolanda Braun-Moscovici MD, Yonit Tavor MD, Doron Markovits MD PhD, Kohava Toledano MD, Alexander Rozin MD, Menahem A. Nahir MD PhD and Alexandra Balbir-Gurman MD

Background: Behçet's disease is a multi-systemic chronic relapsing inflammatory disease, classified among the vasculitides. The heterogeneity of clinical manifestations challenges the disease management.

Objectives: To assess efficacy and safety of adalimumab in patients with active persistent Behçet's arthritis who did not respond to disease-modifying anti-rheumatic drugs and to assess the impact of treatment on the cytokine milieu.

Methods: Our cohort comprised 10 patients with active arthritis who received adalimumab in a 24-week investigator-initiated prospective open-label study. Patients who relapsed within 12 weeks following adalimumab discontinuation could enter a 3-year extension study. The patients underwent a comprehensive assessment including questionnaires and measurement of inflammatory cytokines, adalimumab serum levels, and anti-drug antibodies.

Results: A significant improvement was observed in arthritis, disease activity visual analogue scales, Behçet's disease current activity form, and interleukin-6 (IL-6) levels, but not in health assessment questionnaire and functional assessment of chronic illness therapy fatigue scale questionnaire. Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. The disease relapsed in 9 of 10 patients, within 2–6 weeks following adalimumab discontinuation. Of the 7 patients who continued the study, arthritis was resolved in 5. Two patients with high neutralizing antidrug antibodies titer relapsed.

Conclusions: Adalimumab treatment achieved a significant improvement in arthritis, mucocutaneous manifestations, and IL-6 levels in all study patients but only 40% reported significant pain reduction. The arthritis relapsed in 90% of patients following adalimumab discontinuation and long-term treatment was required.

November 2017
Einat Slonimsky MD, Tammar Kushnir PhD, Assaf Kadar MD, Aharon Menahem MD, Alon Grundshtein MD, Steven Velekes MD, Merav Lidar MD, Shmuel Dekel MD and Iris Eshed MD

Background: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs).

Objectives: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs.

Methods: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files.

Results: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm3. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N.

Conclusions: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

March 2015
Alexandra Balbir-Gurman MD, Mordechai Yigla MD, Ludmila Guralnik MD, Emilia Hardak MD, Anna Solomonov MD, Alexander P. Rozin MD, Kohava Toledano MD, Amir Dagan MD, Rema Bishara MD, Doron Markovits MD PhD, Menahem A. Nahir MD and Yolanda Braun-Moscovici MD


Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.


February 2011
M. Papoulas, N. Lubezky, Y. Goykhman, I. Kori, E. Santo, R. Nakache, J. Klausner and M. Ben-Haim

Background: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar  cholangiocarcinoma  presents a complex surgical challenge.

Objectives: To assess the outcome of the radical approach for the management of types III and IV hilar  cholangiocarcinoma.

Methods: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepatico-jejunostomy.

Results: Fifteen patients (mean age 49 years, range 24–72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (R0) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6–72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively.

Conclusions: In selected patients, the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.

November 2010
Y. Goykhman, M. Ben-Haim, G. Rosen, M. Carmiel-Haggai, R. Oren, R. Nakache, O. Szold, J. Klausner and I. Kori

Background: Inserting a transjugular intrahepatic portosystemic shunt by means of interventional radiology has become the procedure of choice for decompression of portal hypertension. The indications and criteria for patient selection have been expanded and refined accordingly.

Objectives: To review our experience with TIPS[1] and analyze the results with emphasis on patient selection and indication (conventional vs. atypical).

Methods: In this retrospective analysis in a single center all cases were managed by a multidisciplinary team (comprising liver surgery and transplantation, hepatology, imaging, interventional radiology and intensive care).

Results: Between August 2003 and December 2009, 34 patients (mean age 51, range 27–76 years) were treated with TIPS. The cause of portal hypertension was cirrhosis (23 cases), hypercoagulabilty complicated by Budd-Chiari syndrome (n=6), and acute portal vein thrombosis (n=5). Clinical indications for TIPS included treatment or secondary prevention of variceal bleeding (10 cases), refractory ascites (n=18), mesenteric ischemia due to acute portal vein thrombosis (n=5), and acute liver failure (n=1). TIPS was urgent in 18 cases (53%) and elective in 16. Three deaths occurred following urgent TIPS. The overall related complication rate was 32%: transient encephalopathy (6 cases), ischemic hepatitis (n=2), acute renal failure (n=2) and bleeding (n=1). Long-term results of TIPS were defined as good in 25 cases (73%), fair in 4 (12%) and failure in 5 (15%). In three of five patients with mesenteric ischemia following acute portal vein thrombosis, surgery was obviated. Revision of TIPS due to stenosis or thrombosis was needed in 7 cases (20%).

Conclusions: TIPS is safe and effective. While its benefit for patients with portal hypertension is clear, the role of TIPS in treatment of portal-mesenteric venous thrombosis needs further evaluation. Patient selection, establishing the indication and performing TIPS should be done by a multidisciplinary dedicated team.

[1] TIPS = transjugular intrahepatic portosystemic shunt

April 2008
Y. Braun-Moscovici, D.n Markovits, A. Rozin, K. Toledano, A. M. Nahir and Alexandra Balbir-Gurman

Background: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and increased dosage is not allowed. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease.

Objectives: To describe our experience with anti-TNF[1] therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results.

Methods: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects.

Results: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n=108), juvenile idiopathic arthritis (n=11), psoriatic arthritis (n=37), ankylosing spondylitis (n=29), adult Still's disease (n=4), overlap disease (RA[2] and scleroderma or polymyositis, n=6), temporal arteritis (n=1), polyarteritis nodosa (n=1), dermatomyositis (n=1), amyloidosis secondary to RA (n=1) and Wegener's granulomatosis (n=1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS[3] and PS[4] patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease.

Conclusion: Our daily practice data are generally in agreement with worldwide experience. The ‘deviations’ might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.

[1] TNF = tumor necrosis factor

[2] RA = rheumatoid arthritis

[3] AS = ankylosing spondylitis

[4] PS = psoriatic arthritis

October 2007
R. Small, N. Lubezky and M. Ben-Haim

Surgical resection offers the best opportunity for cure in patients with colorectal cancer metastasis to the liver, with 5 year survival rates of up to 58% following resection. However, only a small percentage of patients are eligible for resection at the time of diagnosis and the average recurrence rate is still high. Consequently, research endeavors have focused on methods aimed to increase the number of patients eligible for surgical resection, refine the selection criteria for surgery, and improve the disease-free and overall survival time in these patients. Improvements in imaging techniques and the increasing use of FDG-PET allow more accurate preoperative staging and superior identification of patients likely to benefit from surgical resection. Advances in the use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Many reports have critically evaluated the surgical techniques applied to liver resection, the concurrent or alternative use of local ablative therapies, such as radiofrequency ablation, and the subsequent utilization of adjuvant chemotherapy in patients undergoing surgical resection for hepatic metastases.

D. Ergas, A. Abdul-Hai. Z. Sthoeger, B-H. Menahem and R. Miller
July 2007
T.Naftali, D.Novick, G.Gabay, M.Rubinstein, and B.Novis

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases with an unknown etiology. Interleukin-18 is a pro-inflammatory cytokine that is up-regulated in Crohn’s disease. IL-18[1] binding protein neutralizes IL-18. The relationship of IL-18 and IL-18BP[2] and disease activity in these diseases is not fully understood.

Objectives: To investigate the correlation of IL-18 and IL-18BP with disease activity and other disease parameters in inflammatory bowel disease.

Methods: IL-18 and IL-18BP isoform α were measured in 129 patients and 10 healthy individuals. Patients' mean age was 40.5 (range 15–70 years) and 43 were women; 58 Crohn's and 28 colitis patients were in remission and 52 and 14, respectively, were in exacerbation. Twenty-three (19 and 4 respectively) were studied in both remission and exacerbation.

Results: The mean level of free IL-18 was significantly different between healthy individuals and Crohn's patients, and between Crohn's patients during exacerbation and remission (167 ± 32 vs. 471 ± 88 and 325 ± 24 pg/ml, respectively, P < 0.05). Mean level of IL-18BP was significantly different between healthy individuals and Crohn patients, and between Crohn patients during exacerbation and remission (2.1 ± 1.1, 7.5 ± 4 and 5.23 ± 2.8 ng/ml, respectively, P < 0.01). In the colitis patients, mean free IL-18 level and IL-18BP were significantly different between healthy individuals and patients, but not between disease remission and exacerbation (167 ± 32, 492 ± 247 and 451± 69 pg/ml for IL-18, and 2.1 ± 1.1, 7.69 ± 4 and 6.8 ± 7 ng/ml for IL-18BP, respectively, P = 0.05).

Conclusions: IL-18 and IL-18BP levels are higher in patients with inflammatory bowel disease compared to healthy individuals. In Crohn's disease, but not in ulcerative colitis, IL-18 (but not free IL-18) and IL-18BP levels are significantly higher during exacerbation compared to remission. This observation highlights the importance of IL-18 in the pathogenesis of inflammatory bowel diseases, especially in Crohn's disease.

[1] IL = interleukin

[2] IL-18BP = IL-18 binding protein

September 2006
M. Ben-Haim, M. Carmiel, P. Katz, E. Shabtai, R. Oren and R. Nakache

Background: The model for end-stage liver disease is the best available predictor of waiting list mortality among liver transplant candidates.

Objectives: To validate the applicability of MELD[1] in Israel.

Methods: All candidates awaiting liver transplantation in our institution were followed prospectively since 2002. We measured the concordance (c-statistic) equivalent to the area under the receiver operating characteristic curve in order to assess the predictive power of MELD. Other independent mortality risk factors were identified by a separate multivariate analysis. Mortality rates within different MELD and Child‑Pugh‑Turcotte scores were compared to the original (United States) MELD data.

Results: Of 86 patients listed for transplantation, 40 were transplanted (36 in Israel and 4 abroad). Of the other 46 patients, 24 are alive and still listed, and 22 died (25%, ~7%/year). The area under the ROC[2] curve for MELD score was 0.79 (0.83 USA) compared to a CPT[3] score of 0.71 (O.76 USA). High MELD scores, occurrence of spontaneous bacterial peritonitis, and diagnosis of hepatocellular carcinoma were independent risk factors of mortality. Death rates per mid MELD score (20–29) were significantly higher than the USA results.

Conclusions: MELD is valid in Israel and superior to CPT in predicting waiting list mortality. Although longer waiting time due to organ scarcity is a key factor, death rates in the mid-range (10–29) MELD groups indicate further audit of the care of patients with end‑stage liver disease.

[1] MELD = model for end-stage liver disease

[2] ROC = receiver operating characteristic

[3] CPT = Child‑Pugh‑Turcotte

August 2005
A. Balbir-Gurman, D. Markovits, A.M. Nahir, A. Rozin and Y. Braun-Moscovici
March 2005
M. Ben-Haim, M. Carmiel, N. Lubezky, R. Keidar, P. Katz, A. Blachar, A. Nomrod, P. Sorkine, R. Oren, J.M. Klausner and R. Nakache
Background: Adult-to-adult living donor liver transplantation is becoming an alternative to cadaveric transplantation in urgent and elective settings. Donor selection crucially affects donor safety and recipient outcome.

Objective: To present our algorithm of urgent and elective donor selection.

Methods: Urgent selection is expeditious and protocol‑based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases.

Results: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n=5; chronic end-stage liver disease, n=6); primary graft non-function, n=1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n=14, 42%), incompatible anatomy (n=8, 24%) – including problematic volume distribution (n=2) or vascular anatomy (n=6) – psychosocial issues (n=4, 12%), or medical co-morbidity (n=7, 22%). Five recipients (FHF[1], n=4; chronic ESLD[2], n=1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF[3]) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates.

Conclusions: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.


[1] FHF = fulminant hepatic failure

[2] ESLD = chronic end-stage liver disease

[3] PGNF = primary graft non-function

August 2004
N. Lubezky, R. Nakache, M. Carmiel, R. Oren, P. Sorkin, J. Klausner and M. Ben-Haim

Background: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living-donor segmental liver transplantation may be the only alternative.

Objectives: To report our initial experience with urgent lifesaving LDLT[1] in this unique scenario.

Methods: Three adult patients with FHF[2] (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography.

Results: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications.

Conclusions: Urgent adult-to-adult living-donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

[1] LDLT = living-donor liver transplantation

[2] FHF = fulminant hepatic failure

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