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עמוד בית
Mon, 22.07.24

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May 2024
Ron Dabby MD, Diana Paleacu Kertesz MD, Ilia Demurchev MD, Oded Hershkovich MD, Mira Ginsberg MD, Menachem Sadeh MD

Background: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy.

Objectives: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel.

Methods: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments.

Results: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections.

Conclusions: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.

March 2024
Eiman Shalabna MD, Nir Haya MD, Ariel Zilberlicht MD, Rotem Sadeh MD, Yoram Abramov MD

Background: Obliterative vaginal procedures may offer lower perioperative morbidity and equal success rates as reconstructive procedures for frail and elderly women who no longer desire future coital function. The combination of vaginal hysterectomy with either reconstructive or obliterative vaginal procedures has not yet been investigated.

Objectives: To compare peri- and postoperative outcomes of vaginal hysterectomy with pelvic floor reconstruction (VHR) vs. vaginal hysterectomy with colpocleisis (VHC).

Methods: We conducted a retrospective study comparing medical and surgical data of patients undergoing either VHR or VHC between 2006 and 2015. Data were obtained from inpatient and outpatient medical records including peri- and postoperative course, as well as long-term (24 months) follow-up data.

Results: We identified 172 patients who underwent VHR and 44 who underwent VHC. Patients in the VHC group were significantly older (71.3 ± 4.5 vs. 68.6 ± 6.5 years, P = 0.01), and more likely to have medical co-morbidities (P = 0.001 and P = 0.029, respectively). Patients in the VHC group experienced shorter operative time (2.3 ± 0.58 vs. 2.7 ± 1.02 hours, P = 0.007), lower perioperative blood loss (P < 0.0001), shorter hospital stay (P < 0.0001), and lower rates of postoperative urinary retention. Long-term pelvic organ prolapse (POP) recurrence rates were significantly higher among the VHR group. Postoperative resolution of both stress urinary incontinence and overactive bladder were common in both groups.

Conclusions: VHC is associated with lower perioperative blood loss, shorter operative time, shorter hospital stay, shorter time with an indwelling catheter, and lower long-term objective POP recurrence rates.

December 2022
Rotem Sadeh MD, Meirav Schmidt MD, Yael Hod, Ariel Zilberlicht MD, Ido Feferkorn MD, Nir Haya MD, Yoram Abramov MD

Background: Vaginal hysterectomy (VH) and colpocleisis are both used for the treatment of advanced pelvic organ prolapse (POP).

Objective: To compare short- and long-term outcomes of vaginal hysterectomy vs. colpocleisis for advanced POP.

Methods: Hospital and outpatient charts of patients who underwent VH or colpocleisis at our institution between January 2006 and December 2015 were reviewed. Clinical data were obtained and analyzed.

Results: In this study, 188 patients underwent VH and 32 patients underwent colpocleisis. The colpocleisis group was significantly older than the VH group (79.5 ± 4.5 vs. 69 ± 6.1 years respectively, P < 0.0001) and presented with significantly higher co-morbidity rates and a higher degree of POP. Perioperative blood loss was significantly lower (250 ± 7.6 ml vs. 300 ± 115 ml, P < 0.0001) and postoperative hospitalization was significantly shorter (2 ± 2.7 vs. 3 ± 2.2 days, P = 0.015) among the colpocleisis group. None of the patients from the colpocleisis group required an indwelling urethral catheter after discharge, compared to 27.5% of the patients from the VH group (P = 0.001). Total postoperative complication rate was significantly lower among the colpocleisis group (25% vs. 31% P < 0.0001). Objective recurrence of POP was significantly more common among the VH group (7% vs. 0% and 21% vs. 0% for the anterior and posterior compartments, respectively, P = 0.04).

Conclusions: Colpocleisis is associated with faster recovery, lower perioperative morbidity, and higher success rates than VH and should be considered for frail and elderly patients.

December 2021
Ben Sadeh MD, Tamar Itach MD, Ilan Merdler MD MHA, Shir Frydman MD, Samuel Morgan BSc, David Zahler MD, Yogev Peri MD, Aviram Hochstadt MD MPH, Yotam Pasternak MD MSc, Yan Topilsky MD,Shmuel Banai MD, and Yacov Shacham MD

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06–5.62; P = 0.036) for patients with moderate-severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate

July 2021
Ben Sadeh MD, Tamar Itach MD, Ilan Merdler MD MHA, Shir Frydman MD, Samuel Morgan BSc, David Zahler MD, Yogev Peri MD, Aviram Hochstadt MD, Yotam Pasternak MD MSc, Yan Topilsky MD, Shmuel Banai MD, and Yacov Shacham MD

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients.

Objectives: To investigate the possible implication of TR among STEMI patients.

Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded.

Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06–5.6, P = .036) for patients with moderate to severe TR.

Conclusions: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate

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. 

June 2016
Tzippora Shalem MD, Akiva Fradkin MD, Marguerite Dunitz-Scheer MD, Tal Sadeh-Kon Dsc RD, Tali Goz-Gulik MD, Yael Fishler MD and Batia Weiss MD

Background: Children dependent on gastrostomy tube feeding and those with extremely selective eating comprise the most challenging groups of early childhood eating disorders. We established, for the first time in Israel, a 3 week intensive weaning and treatment program for these patients based on the "Graz model."

Objectives: To investigate the Graz model for tube weaning and for treating severe selective eating disorders in one center in Israel. 

Methods: Pre-program assessment of patients’ suitability to participate was performed 3 months prior to the study, and a treatment goal was set for each patient. The program included a multidisciplinary outpatient or inpatient 3 week treatment course. The major outcome measures were achievement of the target goal of complete or partial tube weaning for those with tube dependency, and expansion of the child's nutritional diversity for those with selective eating. 

Results: Thirty-four children, 28 with tube dependency and 6 with selective eating, participated in four programs conducted over 24 months. Their mean age was 4.3 ± 0.37 years. Of all patients, 29 (85%) achieved the target goal (24 who were tube-dependent and 5 selective eaters). One patient was excluded due to aspiration pneumonia. After 6 months follow-up, 24 of 26 available patients (92%) maintained their target or improved. 

Conclusions: This intensive 3 week program was highly effective in weaning children with gastrostomy tube dependency and ameliorating severe selective eating. Preliminary evaluation of the family is necessary for completion of the program and achieving the child’s personal goal, as are an experienced multidisciplinary team and the appropriate hospital setup, i.e., inpatient or outpatient. 

 

December 2013
Sergiu C. Blumen, Anat Kesler, Ron Dabby, Stavit Shalev, Chaiat Morad, Yechoshua Almog, Joseph Zoldan, Felix Benninger, Vivian E. Drory, Michael Gurevich, Menachem Sadeh, Bernard Brais and Itzhak Braverman
 Background: Oculopharyngeal muscular dystrophy (OPMD) produced by the (GCG)13 expansion mutation in the PABPN1 gene is frequent among Uzbek Jews in Israel.

Objectives: To describe the phenotypic and genotypic features in five Bulgarian Jewish patients, from different families, with autosomal dominant OPMD.

Methods: We performed clinical follow-up, electrodiagnostic tests and mutation detection. Blood samples were obtained after informed consent and DNA was extracted; measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD mutations were performed according to standard techniques.

Results: We identified five patients (four females), aged 58 to 71 years, with bilateral ptosis, dysphagia, dysphonia (n=3) and myopathic motor units by electromyography. In all patients we noticed proximal weakness of the upper limbs with winging scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.

Conclusions: OPMD among Bulgarian Jews is produced by a (GCG)13 expansion, identical to the mutation in Uzbek Jews and French Canadians. In addition to the classical neurological and neuro-ophthalmological features, early shoulder girdle weakness is common in Bulgarian Jewish patients; this is an unusual feature during the early stages of OPMD produced by the same mutation in other populations. We suggest that besides the disease-producing GCG expansion, additional ethnicity-related genetic factors may influence the OPMD phenotype. OPMD is a rare disease, and the identification of five affected families in the rather small Bulgarian Jewish community in Israel probably represents a new cluster; future haplotype studies may elucidate whether a founder effect occurred. 

September 2013
M. Sadeh, B. Glazer, Z. Landau, J. Wainstein, T. Bezaleli, R. Dabby, A. Hanukoglu, M. Boaz and E. Leshinsky-Silver

Background: Type 1 diabetes in humans is an autoimmune disease in which T cells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulin-producing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potential vanilloid receptor-1 (TRPV1) gene.


Objectives: To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes.

Methods: We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M315I), rs224534 (T469I) and rs8065080 (I585V) variants of the TRPV1 gene.

Results: There was a significant increase in the rs222747 (M315I) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M315I) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type1 diabetes was significantly associated with rs222747 (M315I), such that having diabetes increased the odds of rs222747 homozygosity (M315I) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08–2.57, P < 0.02. No difference was found in the rs224534 (T469I) and rs8065080 (I585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases.

Conclusions: Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.

 

 

 

 

November 2012
L. Leibou, J. Frand, M. Sadeh, A. Lossos, E. Kremer, A. Livneh, D. Yarnitsky, O. Herman and R. Dabby

Background: Transthyretin (TTR)-associated familial amyloid polyneuropathy (FAP) is an autosomal dominant multisystem disease with neurological and extra-neurological manifestations. It is caused by various mutations in the TTR gene leading to the formation of insoluble amyloid.

Objectives: To describe the clinical and genetic findings in patients with TTR-associated FAP in Israel.

Methods: We evaluated eight patients clinically and genetically during the years 2006 to 2011.

Results: At onset, all the patients exhibited sensory loss of the lower and upper limbs, five patients experienced muscle pain, and one patient had lower limb weakness. Five patients had autonomic nervous system manifestations, and four demonstrated evidence of amyloid cardiomyopathy. Nerve conduction studies showed sensorimotor axonal neuropathy in all patients. Sural nerve biopsies were obtained in five patients; only three biopsies revealed amyloid deposit. In four patients of Yemenite descent, genetic analysis of the TTR gene demonstrated ser77tyr mutation. One patient of Tunisian descent and one Ashkenazi patient harbored the val30met mutation. One patient of Iranian descent showed val32ala mutation, and another Ashkenazi patient showed phe33leu mutation.

Conclusions: TTR-associated FAP is a progressive and fatal disease that exists in the Israeli population and is unproportionally common among Yemenite Jews. This disease may be under-diagnosed and should be considered in the differential diagnosis of any patient with rapidly progressive neuropathy, especially with autonomic involvement or extra-neural features. The absence of amyloid in nerve biopsy should not rule out the diagnosis.  
 

December 2011
R. Dabby, M. Sadeh, O. Herman, L. Leibou, E. Kremer, S. Mordechai, N. Watemberg and J. Frand

Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.

Objectives: To describe the clinical, electrophysiologic and pathologic findings in patients with myotonic dystrophy 2.

Methods: We evaluated 10 patients genetically, clinically and electrophysiologically during the years 2007 to 2008.

Results: All patients were of Jewish European ancestry. Among affected individuals, eight patients had symptoms of proximal muscle weakness, two had muscle pain, and two exhibited myotonia. On physical examination six patients had severe weakness of hip flexor muscles. Seven individuals underwent cataract surgery, and cardiac involvement was seen in one case. On the initial electromyographic (EMG) examination five patients demonstrated myotonic discharges; repeated studies showed these discharges in nine cases. Six muscle biopsies showed non-specific pathological changes. Seven patients had an affected first-degree relative with either a diagnosed or an undiagnosed muscular disorder, consistent with an autosomal dominant trait.

Conclusions: DM2 may often present with proximal muscle weakness without myotonia. EMG may initially fail to show myotonic discharges, but these discharges may eventually show in most cases on repeated EMG. Thus, DM2 may be underdiagnosed and should be included in the differential diagnosis of adult patients of Jewish European ancestry presenting with proximal lower limb weakness.
 

October 2008
A. Kesler, L. Berkner, M. Sadeh, R. Levite and D. Varssano

Background: Ocular hypotony is a common unexplained feature of myotonic dystrophy type 1. Spuriously low applanation tonometric readings can be caused by thin corneas, flat corneal curvature and corneal edema.

Objectives: To determine whether structure abnormalities of the cornea cause spuriously low readings in applanation tonometry.

Methods: We utilized a TMS-2N corneal topographer, a NonconRobo SP-6000 Specular microscope and a Corneo-Gage Plus 1A Pachymeter to examine seven patients with DM1[1] and eight healthy controls. Intraocular pressure, central corneal thickness, and endothelial cell density were measured, and simulated keratometry readings were made. Cornea guttata and irregularity of corneal topography patterns were also sought.

Results: The mean intraocular pressure was 9.86 ± 1.29 mmHg for all patients (intraocular operated and non‑operated eyes) and 12.88 ± 1.89 mmHg for the controls (P = 0.000021, two-tailed t-test). Central corneal thickness was 530.57 ± 35.30 micron for all patients and 535.00 ± 39.62 micron for the controls (P = 0.75, two-tailed t-test). Endothelial cell density was 3164 ± 761 cells/mm2 for all patients and 3148 ± 395 cells/mm2 for the controls (P = 0.94, two-tailed t-test). Simulated keratometry readings were similar in both groups when the operated eyes were excluded. Cornea guttata and irregularity of corneal topography patterns were also noted in the study group.

Conclusions: Corneal thickness, corneal curvature and corneal hydration were within normal limits and thus were not the cause for the low applanation tonometry reading in DM1. The presence of cornea guttata and irregularity of corneal topography patterns in DM1 warrants further investigation. 






[1] DM1 = myotonic dystrophy type 1


February 2006
R. Dabby, M. Sadeh, O. Herman, E. Berger, N. Watemberg, S. Hayek, J. Jossiphov and Y. Nevo

Background: Persistent creatine kinase elevation is occasionally encountered in subjects without any clinical manifestation of a neuromuscular disorder or any condition known to be associated with increased serum CK[1] levels. It is still unresolved whether extensive investigations and specifically a muscle biopsy should be performed in clinically normal individuals with elevated CK levels.

Objective: To study the muscle pathology of patients with asymptomatic or minimally symptomatic hyperCKemia.

Methods: The clinical and laboratory data of patients with persistent hyperCKemia and normal neurologic examination were reviewed and their muscle biopsies evaluated.

Results: The study group included 40 patients aged 7–67 years; the male to female ratio was 3:1. Nineteen patients were completely asymptomatic, 20 had mild non-specific myalgia, and 1 had muscle cramps. Electromyography was performed in 27 patients and showed myopathic changes in 7 (26%). Abnormal muscle biopsy findings (e.g., increased variation in fiber size, increased number of central nuclei and occasional degenerating fibers) were detected in 22 of the 40 patients (55%). No fat or glycogen accumulation was detected. Immunohistochemistry demonstrated abnormal dystrophin staining in 3 patients (8%), resembling the pathologic changes of Becker muscular dystrophy. No abnormal findings were detected on immunohistochemical staining for merosin, dysferlin, caveolin 3, or alpha and gamma sarcoglycans. The EMG[2] findings did not correlate with the pathologic findings.

Conclusions: Abnormal muscle biopsies were found in 55% of patients with asymptomatic or minimally symptomatic hyperCKemia. Specific diagnosis of muscular dystrophy, however, was possible in only 8% of the patients.






[1] CK = creatine kinase

[2] EMG = electromyography


April 2002
Sigal Korem, PhD, Zaki Kraiem, PhD, Eitan Shiloni, MD, Oved Yehezkel, BSc, Orit Sadeh, MSc and Murray B. Resnick, MD, PhD

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.






[1] MMPs = matrix metalloproteinases


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