Israel Medical Association Journal

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.

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.

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. 

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.

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. 

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.

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.

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. 

Background: Trans-catheter aortic valve implantation (TAVI) has emerged as a novel therapeutic approach for patients with severe tricuspid aortic stenosis (AS) not suitable for aortic valve replacement.

Objectives: To describe our initial single-center experience with TAVI in patients with "off-label" indications.

Methods: Between August 2008 and December 2011 we performed TAVI in 186 patients using trans-femoral, trans-axillary, trans-apical and trans-aortic approaches. In 11 patients (5.9%) TAVI was undertaken due to: a) pure severe aortic regurgitation (AR) (n=2), b) prosthetic aortic valve (AV) failure (n=5), c) bicuspid AV stenosis (n=2), and d) prosthetic valve severe mitral regurgitation (MR) (n=2).

Results: Implantation was successful in all: six patients received a CoreValve and five patients an Edwards-Sapien valve. In-hospital mortality was 0%. Valve hemodynamics and function were excellent in all patients except for one who received an Edwards-Sapien that was inside a Mitroflow prosthetic AV and led to consistently high trans-aortic gradients. No significant residual regurgitation in AR and MR cases was observed.
Conclusions: TAVI is a good alternative to surgical AV replacement in high risk or inoperable patients with severe AS. TAVI for non-classical indications such as pure AR, bicuspid AV, and failed prosthetic aortic and mitral valves is feasible and safe and may be considered in selected patients. 

Objective: To assess the ability of TREC and KREC counts to identify patients with combined T and B cell immunodeficiency in a pilot study in Israel.

Methods: We studied seven children born in Israel during the years 2010–2011 and later diagnosed with SCID, and an additional patient with pure B cell immunodeficiency. TREC and KREC in peripheral blood upon diagnosis and in their neonatal Guthrie cards were analyzed using real-time quantitative polymerase chain reaction, as were Guthrie cards with dried blood spots from healthy newborns and from normal and SCID-like controls.

Results: The first features suggestive of SCID presented at age 3.1 ± 2.4 months in all patients. Yet, the diagnosis was made 4.1 ± 2.9 months later. Their TREC were undetectable or significantly low at their clinical diagnosis and in their originally stored Guthrie cards, irrespective of the amount of their circulating T cells. KREC were undetectable in six SCID patients who displayed B cell lymphopenia in addition to T cell lymphopenia. KREC were also undetectable in one patient with pure B cell immunodeficiency.

Conclusions: TREC and KREC quantification are useful screening tests for severe T and B cell immunodeficiency. Implementation of these tests is highly important especially in countries such as Israel where a high frequency of consanguinity is known to exist.