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עמוד בית Wed, 26.06.19

September 2013

Original Articles
A. Elizur, A. Maliar, I. Shpirer, A. E. Buchs, E. Shiloah and M. J. Rapoport
 Background: Obstructive sleep apnea has been shown to be associated with impaired glucose metabolism and overt diabetes mellitus. However, the effect of hypoxic episodes on nocturnal glucose regulation in non-diabetic patients is unknown.

Objectives: To investigate the effect of hypoxemia and nocturnal glucose homeosatsis in non-diabetic patients with sleep apnea.

Methods: Seven non-diabetic patients with moderate to severe sleep apnea were connected to a continuous glucose-monitoring sensor while undergoing overnight polysomnography. Mean SpO2 and percentage of time spent at SpO2 < 90% were recorded. The correlation between mean glucose levels, the difference between consecutive mean glucose measurements (glucose variability) and the corresponding oxygen saturation variables were determined in each patient during REM[1] and non-REM sleep.

Results: No consistent correlation was found for the individual patient between oxygen saturation variables and glucose levels during sleep. However, a lower mean SpO2 correlated with decreased glucose variability during sleep (r = 0.79, P = 0.034). This effect was primarily evident during REM sleep in patients with significant, compared to those with mild, oxygen desaturations during sleep (> 30% vs. < 10% of sleeping time spent with SpO2 < 90%) (P = 0.03).

Conclusions: Severe nocturnal hypoxemia in non-diabetic patients with moderate to severe sleep apnea might affect glucose regulation primarily during REM sleep.


[1] REM = rapid eye movement

A. L. Schwartz, Y. Topilsky, G. Uretzky, N. Nesher, Y. Ben-Gal, S. Biner, G. Keren and A. Kramer

Background: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival.

Objectives: To report the outcomes of patients after aortic valve replacement with the Freestyle® stentless bioprosthesis in the Tel Aviv Medical Center followed for ≤ 15 years.

Methods and Results: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 ± 9.2 years, 4.2 ± 1.5 and 10.2 ± 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 ± 29.1 vs. 22.8 ± 9.6 mmHg, P < 0.0001; and 43.4 ± 17.2 vs. 12.1 ± 5.4 mmHg, P < 0.0001 respectively) in 3 months of follow-up. Mean overall follow-up was 4.9 ± 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 ± 2.5% and 57.2 ± 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 ± 2.3% vs. 76.0 ± 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 ± 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one.

Conclusions: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients. 

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.





S. Shiber and Y. Molad
 Background: Antiphospholipid syndrome (APS) is an autoimmune disease with clinical manifestations of arterial and venous thrombosis, obstetric manifestations, and the presence of antiphospholipid antibodies or lupus anticoagulant. Catastrophic APS is a rare variant of APS defined as acute failure of at least three tissues, organs or systems caused predominantly by small vessel thrombosis confirmed by histopathologic evidence. Catastrophic APS develops rapidly and leads to death in 30% of cases.

Methods: We evaluated 11 patients with catastrophic APS – 8 of them with a probable diagnosis of catastrophic APS and 3 with a definite diagnosis – admitted to Beilinson hospital during the period 2003–2011.

Results: Overall venous events numbered 18 and overall arterial events 10. The event duration per patient was 2.6 ± 1.2 weeks (mean ± SD). Deep vein thrombosis of the legs was quite common (7 events), as was venous intraabdominal thrombosis (10 events). Eight patients had microangiopathic anemia with schizocytes seen in the blood smear. The mean ± SD hemoglobin level was 10.3 ± 3.6 g/dl and the mean ± SD creatinine level 0.98 ± 0.78 mg/dl. All our patients had high acute-phase reactant and all had lupus anticoagulant positivity, The most common positive antibodies were immunoglobulin G anticardiolipin (8 patients) and IgG[1] β2-glycoprotein (7 patients). During the events warfarin was stopped and the patients were given intravenous heparin. All the patients received steroids in variable doses. Five patients underwent plasma exchange, two patients received rituximab and two patients intravenous immunoglobulin.

Conclusions: Catastrophic APS, a rare syndrome, is important because of its major morbidity and mortality among young patients.


[1] IgG = immunoglobulin G

T. Fuchs, A. Torjman, L. Galitzkaya, M. Leitman and R. Pilz-Burstein

Background: Sudden death in athletes can occur during sport activities and is presumably related to ventricular arrhythmias.

Objectives: To investigate the long-term follow-up of athletes with ventricular arrhythmias during an exercise test.

Methods: From a database of 56,462 athletes we identified 192 athletes < 35 years old who had ventricular arrhythmias during an exercise test. Ninety athletes had ≥ 3 ventricular premature beats (VPB) (group A) and 102 athletes had ventricular couplets or non-sustained ventricular tachycardia (NSVT) during an exercise test (group B). A control group of 92 athletes without ventricular arrhythmias was randomly selected from the database (group C). Of the 192 athletes 39 returned for a repeat exercise test after a mean follow-up period of 70 ± 25 months and they constitute the study population.

Results: Twelve athletes from group A, 21 from group B and 6 from group C returned for a repeat exercise test. The athletes reached a significantly lower peak heart rate during their follow-up exercise test (P = 0.001). More athletes were engaged in competitive sports during their initial exercise test than in the follow-up test (P = 0.021). Most of the athletes who had VPB and/or ventricular couplets and/or NSVT during their initial exercise test had far fewer ventricular arrhythmias in the follow-up exercise test (P = 0.001).

Conclusions: Athletes engaged in competitive sports are more likely to develop ventricular arrhythmias during exercise. These arrhythmias subside over time when athletes are engaged in non-competitive sports. 

S. Harnof, M. Hadani, A. Ziv and H. Berkenstadt
 Background: Communication skills are an important component of the neurosurgery residency training program. We developed a simulation-based training module for neurosurgery residents in which medical, communication and ethical dilemmas are presented by role-playing actors.

Objectives: To assess the first national simulation-based communication skills training for neurosurgical residents.

Methods: Eight scenarios covering different aspects of neurosurgery were developed by our team: 1) obtaining informed consent for an elective surgery, 2) discharge of a patient following elective surgery, 3) dealing with an unsatisfied patient, 4) delivering news of intraoperative complications, 5) delivering news of a brain tumor to parents of a 5 year old boy, 6) delivering news of brain death to a family member, 7) obtaining informed consent for urgent surgery from the grandfather of a 7 year old boy with an epidural hematoma, and 8) dealing with a case of child abuse. Fifteen neurosurgery residents from all major medical centers in Israel participated in the training. The session was recorded on video and was followed by videotaped debriefing by a senior neurosurgeon and communication expert and by feedback questionnaires.

Results: All trainees participated in two scenarios and observed another two. Participants largely agreed that the actors simulating patients represented real patients and family members and that the videotaped debriefing contributed to the teaching of professional skills.

Conclusions: Simulation-based communication skill training is effective, and together with thorough debriefing is an excellent learning and practical method for imparting communication skills to neurosurgery residents. Such simulation-based training will ultimately be part of the national residency program.

I. Strauss, N. Carmi-Oren, A. Hassner, M. Shapiro, M. Giladi and Z. Lidar

Background: Spinal epidural abscess (SEA) is a rare disease with a potentially devastating outcome, and a reported incidence traditionally estimated at 0.2–2 cases/10,000 hospital admissions. Since the implementation in October 2007 of a program to increase medical personnel’s awareness of SEA, we have documented a sharp increase in the incidence of SEA at our medical center

Objectives: To investigate the cause of the increased incidence of SEA.

Methods: All cases diagnosed with SEA during the period 1998–2010 were retrospectively reviewed. Cases diagnosed before 2007 were compared with those diagnosed thereafter.

Results: From January 1998 to October 2007 SEA was diagnosed in 22 patients (group A), giving an annual incidence of 0.14–0.6 cases per 10,000 admissions. During the period November 2007 to April 2010, 26 additional patients were diagnosed (group B), yielding an incidence of 0.81–1.7 cases per 10,000 admissions (P < 0.01). The two groups did not differ significantly in epidemiological, clinical or laboratory characteristics, or in the causative bacteria isolated.

Conclusions: The threefold rise in the incidence of SEA observed at a tertiary medical center in Tel Aviv since November 2007 was not explained by different host characteristics or by more virulent bacterial isolates. We suggest that heightened awareness of the clinical presentation and timely utilization of MR imaging has resulted in more cases being identified. 

D. Guttman, A. Mizrachi, T. Hadar, G. Bachar, Y. Hamzani, S. Marx and J. Shvero
 Background: Voice restoration following total laryngectomy is an important part of patients’ rehabilitation and long-term quality of life.

Objectives: To evaluate the long-term outcome of indwelling voice prostheses inserted during (primary procedure) or after (secondary procedure) total laryngectomy.

Methods: The study group included 90 patients who underwent total laryngectomy and tracheoesophageal puncture (TEP) with placement of voice prosthesis at a tertiary medical center during the period 1990–2008. Background, clinical and outcome data were collected by medical file review. Findings were compared between patients in whom TEP was performed as a primary or a secondary procedure.

Results: TEP was performed as a primary procedure in 64 patients and a secondary procedure in 26. Corresponding rates of satisfactory voice rehabilitation were 84.4% and 88.5% respectively. There was no association of voice quality with either receipt of adjuvant radiation/chemoradiation or patient age. The average lifetime of the voice prosthesis was 4.2 months for primary TEP and 9.06 months for secondary TEP (p = 0.025).

Conclusions: Primary TEP provides almost immediate and satisfactory voice rehabilitation. However, it is associated with a significantly shorter average prosthesis lifetime than secondary TEP. Chemoradiotherapy and patient age do not affect voice quality with either procedure.

S. Schwartzenberg, V. Meledin, L. Zilberman, S. Goland, J. George and S. Shimoni

Background: The pathophysiology of aortic stenosis (AS) involves inflammatory features including infiltration of the aortic valve (AV) by activated macrophages and T cells, deposition of lipids, and heterotopic calcification.

Objectives: To evaluate the correlation between white blood cell (WBC) differential count and the occurrence and progression of AS.

Methods: We identified in our institutional registry 150 patients with AS who underwent two repeated echo studies at least 6 months apart. We evaluated the association between the average of repeated WBC differential counts sampled during the previous 3 years and subsequent echocardiographic AS indices.

Results: There was no significant difference in total WBC, lymphocyte or eosinophil count among mild, moderate or severe AS groups. There was a progressive decrease in monocyte count with increasing AS severity (P = 0.046), more prominent when comparing the mild and severe groups. There was a negative correlation between AV peak velocity or peak or mean gradient and monocyte count in the entire group (r = -0.31, -0.24, and -0.25 respectively, all P ≤ 0.01). Similar partial correlations controlling for age, gender, hypertension, smoking, dyslipidemia and ejection fraction remained significant. The median changes over time in peak velocity and peak gradients in AS patients were 0.44 (0–1.3) m/sec/year and 12 (0–39) mmHg/year, respectively. There was no correlation between any of the WBC differential counts and the change in peak velocity or peak gradient per year.

Conclusions: Severe AS is associated with decreased total monocyte count. These findings may provide further clues to the mechanism underlying the pathogenesis of aortic stenosis.

A. Kadar MD, R. Ankory, H. Sherman, I. Eshed, N. Shasha, A. Gold, M. Aharon and M. Salai

Background: The articular surface replacement (ASR) total hip arthroplasty (THA) was recently recalled from the market due to high failure rates. This modality was used frequently by surgeons at our medical center.

Objectives: To assess the clinical and radiographic outcomes in patients following the surgery and determine the revision rate in our cohort.

Methods: Between 2007 and 2010 139 hips were operated on and evaluated in our clinic. All patients underwent a clinical interview, function and pain evaluation, as well as physical examination and radiographic evaluation. When necessary, patients were sent for further tests, such as measuring cobalt-chromium levels and magnetic resonance hip imaging. Results: With an average follow-up of 42 months the revision rate was 2% (3/139). Patients reported alleviation of pain (from 8.8 to 1.7 on the Visual Analog Scale, P < 0.001), good functional outcomes on the Harris Hip Score, and improved quality of life. Overall satisfaction was 7.86 on the reversed VAS[1]. For patients who required further tests, clinical and radiographic outcomes were significantly poorer than for the rest of the cohort. Average blood ion levels were high above the normal (cobalt 31.39 ppb, chromium 13.32 ppb), and the rate of inflammatory collection compatible with pseudotumors on MRI was 57%.

Discussion: While our study favors the use of the ASR implant both clinically and radiographically, some patients with abnormal ion levels and inflammatory collections on MRI might require revision in the future. 

[1] VAS = Visual Analogue Scale

 The issue of professional responsibility for the treatment and care of the patient with pressure ulcers (PU) is crucial as it impacts on mortality, financial costs and the patient’s quality of life. Pressure ulcers in the elderly present a complicated health problem with multifactorial etiologies. Since the pressure ulcer is the final common pathway of multiple underlying factors and medical conditions, the approach when dealing with the elderly is not only local wound management but systemic – i.e., it relates to the patient's overall condition, comorbidities, nutritional status, and disabilities. With the increase in longevity and disability, the prevalence of PU is higher and has concomitant severity and complications. For treatment to be effective it must be comprehensive and multidisciplinary. The traditional, and pivotal, role of the nurse in coordinating treatment has expanded and now includes collaborating more actively with the physician and the multidisciplinary team on the development and course of the wound. Physicians are required to be knowledgeable, actively involved, and alert to reversible multifactorial etiologies, in order to determine the goal and level of aggressive treatment during the course of PU.

K. Goldman, S.Gertel and H. Amital
 Anti-citrullinated peptide antibodies (ACPA) are detected in the sera of rheumatoid arthritis (RA) patients and have a profound role in diagnosis of the disease. In this review we discuss the different cohorts of RA patients in whom the presence, sensitivity and specificity of ACPA were evaluated. The significance of ACPA in the pathogenesis and prognosis RA is also interpreted. Recent advances in the understanding of molecular pathways involved in the pathogenesis of RA have led to the identification of novel biologic agents that are now widely used in patients with RA


Case Communications
From Botswana
הבהרה משפטית: כל נושא המופיע באתר זה נועד להשכלה בלבד ואין לראות בו ייעוץ רפואי או משפטי. אין הר"י אחראית לתוכן המתפרסם באתר זה ולכל נזק שעלול להיגרם. כל הזכויות על המידע באתר שייכות להסתדרות הרפואית בישראל. מדיניות פרטיות
ז'בוטינסקי 35 רמת גן, בניין התאומים 2 קומות 10-11, ת.ד. 3566, מיקוד 5213604. טלפון: 03-6100444, פקס: 03-5753303