Israel Medical Association Journal

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.

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. 

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: 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. 

Objectives: To assess whether a new herbal-based potentially wake-promoting beverage is effective in counteracting somnolence and reduced post-lunch performance.

Methods: Thirty healthy volunteers were studied on three different days at the sleep clinic. On each visit they ate a standard lunch at noontime, followed by a drink of "Wake up®," 50 mg caffeine, or a placebo in a cross-over double-blind regimen. At 30 and 120 minutes post-drinking, they underwent a battery of tests to determine the effects of the beverage. These included: a) a subjective assessment of alertness and performance based on a visual analog scale, and b) objective function tests: the immediate word recall test, the digit symbol substitution test (DSST), and hemodynamic measurements. The results of the three visits were compared using one-way analysis of variance, with P < 0.05 considered statistically significant.

Results: In all performance tests, subjective vigilance and effectiveness assessment, both Wake up® and caffeine were significantly superior to placebo 30 minutes after lunch. However, at 2 hours after lunch, performance had deteriorated in those who drank the caffeine-containing drink, while Wake up® was superior to both caffeine and placebo. Blood pressure and pulse were higher 2 hours after caffeine ingestion, compared to both Wake up® and placebo.

Conclusions: These results suggest that a single dose of Wake up® is effective in counteracting the somnolence and reduced performance during the post-lunch hours. In the current study it had no adverse hemodynamic consequences.

Objectives: To examine the files of patients hospitalized in a tertiary hospital in Israel following a serious suicide attempt. Their mental conditions were determined and their unique demographic and clinical characteristics and needs compared to the other patients examined by the psychiatric service.

Methods: The study focused on 49 consecutive patients admitted after performing a life-threatening suicide attempt. They were compared to 389 non-suicidal patients assessed by the same psychiatric service during one year.

Results: Nearly half the patients hospitalized following a serious suicide attempt had only an axis II diagnosis (personality disorder). Non-violent methods of suicide were used predominantly by females, and violent methods mainly by males. All suicide attempts by Muslims used violent methods, while less than half the attempts by Jews were violent. Compared to the non-suicidal patients, the suicide-attempters group was younger, had greater representation of Jewish females and Muslim males. Compared to the non-suicidal patients, these patients required more intense psychiatric care, earlier commencement of treatment in the course of hospitalization, more psychiatric visits and treatment hours, and more referrals for further care. Several risk factors appear to be associated with a need for more intense in-hospital care and a greater need for referral: male gender, religion, method of suicide attempt (violent vs. non-violent), and the existence of a psychiatric diagnosis.

Conclusions: Suicide-attempt patients who are in need of hospitalization for further medical treatment have unique clinical characteristics and require more intense treatment provided by the Consultation-Liaison Unit. 

Methods: We assessed 25 patients with insomnia who were enrolled in a hypnotic study but prior to the study were asked to undergo two full nights in lab polysomnography studies: with and without a placebo. Although they were not explicitly told that they were receiving a placebo, the participants knew that the results of these studies would determine whether they met the criteria to participate in the pharmaceutical study.

Results: Although the participants acknowledged that they were given a placebo, almost all measures of their sleep improved. With placebo, sleep latency was shortened from 55.8 ± 43.5 to 39.8 ± 58.5 minutes (P < 0.05); total sleep time was extended from 283 ± 72.5 to 362.9 ± 56.3 minutes, and sleep efficiency improved from 59.57 ± 14.78 to 75.5 ± 11.70% (P < 0.05). Interestingly, placebo had no effect on the relative sleep stage distribution (percentage of total sleep time), except for a trend toward increased percentage of REM[1] sleep.

Conclusions: Our findings how a clear and significant beneficial effect of placebo on insomnia, despite participants' understanding that they were receiving placebo. These results emphasize the importance of the patients' perception and belief in insomnia treatment, and suggest that in some cases placebo may serve as a treatment.