Israel Medical Association Journal

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism. 

Objectives: To evaluate the retention of CPR skills and confidence in delivering CPR by preclinical medical students.

Methods: A questionnaire and the Objective Structured Clinical Examination (OSCE) were used to assess confidence and CPR skills among preclinical, second and third-year medical students who had passed a first-aid course during their first year but were not retrained since.

Results: The study group comprised 64 students: 35 were 1 year after training and 29 were 2 years after training. The groups were demographically similar. Preparedness, recollection and confidence in delivering CPR were significantly lower in the 2 years after training group compared to those 1 year after training (P < 0.05). The mean OSCE score was 19.8 ± 5.2 (of 27) lower in those 2 years post- training than those 1 year post-training (17.8 ± 6.35 vs. 21.4 ± 3.4 respectively, P = 0.009). Only 70% passed the OSCE, considerably less in students 2 years post-training than in those 1 year post-training (52% vs. 86%, P < 0.01). Lowest retention was found in checking safety, pulse check, airway opening, rescue breathing and ventilation technique skills. A 1 year interval was chosen by 81% of the participants as the optimal interval for retraining (91% vs. 71% in the 2 years post-training group vs. the 1 year post- training group respectively, P = 0.08).

Conclusions: Confidence and CPR skills of preclinical medical students deteriorate significantly within 1 year post-training, reaching an unacceptable level 2 years post-training. We recommend refresher training at least every year.

Objectives: To test vitamin D levels in kidney transplant recipients residing closer to the equator, compare them to levels in liver transplant recipients and hemodialysis patients, and identify possible risk factors.

Methods: In a cross-sectional study 103 kidney transplant recipients, 27 liver transplant recipients and 50 hemodialysis patients followed at our institute were tested for vitamin D levels. Demographic data, medical history and current treatment were recorded from the medical files.

Results: Inadequate vitamin D levels (< 30 ng/ml) were found in 75% of all patients and 75% of all kidney transplant recipients. Vitamin D levels were higher among dialysis patients than transplant recipients, though deficiency rates were similar. No association was found between kidney function and vitamin deficiency. Deficiency was associated with higher prednisone doses, use of mycophenolate sodium, tacrolimus, and iron supplements, or lower doses of vitamin D supplementation.

Conclusions: Despite potential higher ultraviolet B exposure, inadequate vitamin D levels were prevalent in our study group. Importantly, some immunosuppressive medications were associated with vitamin D deficiency and high doses of vitamin D were associated with less deficiency.

Objectives: To identify possible risk factors associated with a decreased level of care for osteoporosis among patients presenting acutely with the major types of fragility fractures, but also among patients who remain undertreated following their discharge.

Methods: We conducted a retrospective questionnaire-based cohort study. We searched our databases for patients admitted acutely with proximal humerus, distal forearm, thoracolumbar spine, and proximal femur fractures. A questionnaire was used to evaluate osteoporotic care including a referral to DEXA and any associated prescribed medication.

Results: The study group included 114 patients or their caregivers. The osteoporosis care rate rose from 56.1% (n=64) before admission to 71% (n=81) at follow-up. Significant risk factors associated with a decreased care rate prior to admission were the presence of fewer than three comorbidities, and a combination of male gender and young age. Continued neglect at follow-up was associated with the opposite risk factors, such as older age, multiple comorbidities, and polypharmacy. An additional finding was that treated patients had a significantly increased likelihood of presenting with vertebral fractures.

Conclusions: While the association of osteoporosis with the elderly may decrease its screening rates among younger and healthier patients, fragility fractures may be viewed as “end-stage” bone disease, rendering osteoporotic care inefficient.

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.

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.