Israel Medical Association Journal

Background: Silicone breast augmentation is a common cosmetic surgery. Previous case reports demonstrated lymphadenopathy in the presence of implant ruptures.

Objectives: To investigate the association between enlarged axillary lymph nodes and silicone implant ruptures as seen on breast magnetic resonance imaging (MRI).

Methods: Two groups were derived retrospectively from breast MRI reports in our institution for the period December 2011–May 2014. A search of our hospital records for "silicone" and "lymph node" was performed (group A), and the relationship between the presence of enlarged nodes and ruptures was evaluated. The prevalence of ruptures in the presence of nodes was calculated and the association between MRI imaging features and ruptures evaluated. A search for "silicone" and "implant rupture" was performed (group B) and, as for group A, the relationship between the presence of ruptures and nodes was evaluated and the prevalence of enlarged nodes in the presence of ruptures calculated.

Results: Group A comprised 45 women with enlarged nodes. Intracapsular ruptures were associated with nodes (P = 0.005), while extracapsular ruptures showed a trend of association with nodes (P = 0.08). The prevalence of ruptures in the presence of nodes was 31.4%. Nodes associated with ruptures showed a strong silicone signal (P = 0.008) and absent enhancement (P = 0.005). Group B comprised 73 women with ruptures. Enlarged nodes were associated with both intra- and extracapsular ruptures (P < 0.001 and P = 0.002 respectively). The prevalence of nodes in the presence of ruptures was 22.2%.

Conclusions: Enlarged axillary nodes were associated with ruptures in two groups of patients. This finding can guide clinical decisions when either enlarged nodes or ruptures are encountered in patients with silicone implants. The association between silicone lymphadenopathy and implant rupture raises concerns regarding the role of rupture in silicone-induced systemic disease.

 

Background: Legg-Calvé-Perthes disease (LCPD) is an idiopathic hip osteonecrosis prevalent in children < age 15 years. The etiology remains incompletely understood, partly because of multiple potential environmental risk factors and partly because of lack of genetic markers. It has been hypothesized that hyperactivity may induce mechanical stress and/or vascular damage at a fragile joint. 

Objectives: To assess children with LCPD for markers of attention deficit hyperactivity disorder (ADHD) relative to their unaffected comparably aged siblings to exclude the contribution of hyperactive behavior versus environmental and/or genetic factors in LCPD. 

Methods: All children followed in the Pediatric Orthopedic Clinic, and their comparably aged siblings, were recruited. ADHD was assessed using the TOVA computerized test and DSM-IV criteria. Quality of life and sleep disorders as ancillary tests were assessed using the Child Health Questionnaire (Parent Form 50), Pediatric Outcomes Data Collection Instrument, and Pediatric Daytime Sleepiness Scale.

Results: Sixteen children with LCPD (age 9.1 ± 3.3, 75% males) were compared with their closest-aged siblings (age 9.3 ± 2.6, 30% males). Mean TOVA scores of children with LCPD (-3.79 ± 2.6) and of their non-LCPD siblings (-3.6 ± 4.04) were lower relative to the general population (0 ± 1.8, P < 0.0001). Both group means were in the ADHD range (≤ -1.8) implying that 73% of this LCPD cohort and 53% of their non-LCPD siblings performed in the ADHD range, relative to 3.6% incidence expected in the general population (P < 0.0001). Other test results were similar in both groups. 

Conclusions: Our findings in a small cohort of children with LCPD and their comparably aged siblings do not support an association between LCPD and ADHD. ADHD markers were equally high in the LCPD children and siblings. 

 

Autoimmune diseases are classic examples of multifactorial disorders in which a large number of genes interact with environmental factors to form the final phenotype. Identification of the genes involved in these diseases is a daunting challenge. Initially the search involved the candidate approach where polymorphisms in suspected genes were tested for association in large cohorts of patients and controls. Today, the most widely used method is genome-wide association studies (GWAS), a method based on screening large panels of patients and controls with hundreds of thousands of single nucleotide polymorphisms (SNPs), with microarray-based technology. Unique families in which autoimmune diseases are caused by single genes are another alternative. The identification of candidate genes is often followed by studies that provide biologic plausibility for the findings. The widely expanding list of genes involved in autoimmune conditions show that the same genes frequently underlie the pathogenesis of different autoimmune diseases. Despite all available resources, the main void of heritability in autoimmune conditions is yet to be discovered. Identification of these genes will help define new biological pathways and identify novel targets for the development of new therapeutic drugs.

Background: Stroke is a leading cause of death and disability worldwide. The risk factors for stroke overlap those for cardiovascular disease. Atrial fibrillation (AF) is a particularly strong risk factor and is common, particularly in the elderly. Maccabi Healthcare Services (MHS) has maintained a vascular registry of clinical information for over 100,000 members, among them patients with heart disease and stroke. 

Objectives: To determine the prevalence of stroke in MHS, and whether the association of AF and stroke, along with other risk factors, in the Maccabi population is similar to that in published studies.

Methods: Data on stroke and AF patients aged 45 and older were collected from the database for the year 2010, including age, previous transient ischemic attack (TIA), body mass index (BMI), prior myocardial infarction (MI), diabetes, hypertension, anticoagulation and dyslipidemia. A cross-sectional analysis was used to estimate stroke prevalence by AF status. A case-control analysis was also performed comparing a sample of stroke and non-stroke patients. This permitted estimation of the strength of associations for atrial fibrillation and various other combinations of risk factors with stroke. 

Results: Stroke prevalence ranged from 3.5 (females, age 45–54 years) to 74.1 (males, age 85+) per thousand in non-AF members, and from 29 (males, age 45–54) to 165 (males, age 85+) per thousand for patients with AF. AF patients had significantly more strokes than non-AF patients in all age groups. Stroke prevalence increased with age and was significantly higher in males. Multivariable analysis revealed that male gender, increasing age, AF, hypertension, diabetes, and history of TIA were highly significant risk factors for stroke. In addition, for males, dyslipidemia and prior MI were moderately strong risk factors. 

Conclusions: Analysis of the MHS vascular database yielded useful information on stroke prevalence and association of known risk factors with stroke, which is consistent with the epidemiological literature elsewhere. Further analysis of health fund data could potentially provide useful information in the future. 

 

Background: Cardiac resynchronization therapy (CRT) is a non-pharmacological option for patients with heart failure and interventricular dyssynchrony. Elevated red cell distribution width (RDW) reflects higher size and heterogeneity of erythrocytes and is associated with poor outcome in patients with chronic heart failure. 

Objectives: To examine the association between RDW levels and outcomes after CRT implantation.

Methods: We conducted a cohort analysis of 156 patients (126 men, median age 69.0 years) who underwent CRT implantation in our institution during 2004–2008. RDW was measured at three time points before and after implantation. Primary outcome was defined as all-cause mortality, and secondary outcome as hospital re-admissions. We investigated the association between RDW levels and primary outcome during a median follow-up of 61 months.

Results: Ninety-five patients (60.9%) died during follow-up. Higher baseline RDW levels were associated with all-cause mortality (unadjusted HR 1.35, 95%CI 1.20–1.52, P < 0.001). On multivariate analysis adjusted for clinical, electrocardiographic and laboratory variables, baseline RDW levels were associated with mortality (HR 1.33, 95%CI 1.16–1.53). RDW levels 6 months and 12 months post-implantation were also associated with mortality (HR 1.22, 95%CI 1.08–1.38, P = 0.001; and HR 1.15, 95%CI 1.01–1.32, P = 0.02, respectively). Patients who were re-admitted to hospital during follow-up (n=78) had higher baseline RDW levels as compared to those who were not (14.9%, IQR 14.0, 16.0% vs. 14.3%, IQR 13.7, 15.0%, respectively, P = 0.03). 

Conclusion: An elevated RDW level before and after CRT implantation is independently associated with all-cause mortality. 

 

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Background: Ethiopian immigration to Israel was initiated in 1981. Most immigrants were rural dwellers who migrated first to Addis Ababa or Gondar, where they waited for eligibility status from Israel to leave Ethiopia. Soon after arriving in Israel, all immigrants were offered screening tests for human immunodeficiency virus (HIV) and syphilis.

Objectives: To evaluate the association of age, gender, marital status and length of time spent in urban areas in Ethiopia with the prevalence of HIV and syphilis seropositivity.

Methods: All adult Ethiopian immigrants who arrived at the Jerusalem immigration center between 1999 and 2002 and consented to HIV and syphilis screening tests were interviewed.

Results: Altogether, 678 immigrants (51% females) were screened; 39 (5.8 %) were seropositive for HIV and 33 (4.9%) for syphilis. The length of time the immigrants spent in Ethiopian cities before leaving for Israel was significantly associated with HIV: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.13–6.71, and syphilis seropositivity  OR 3.87, 95%CI  1.56–9.62.

Conclusions: The length of transit time Ethiopian immigrants from rural areas spend in Ethiopian cities is significantly associated with HIV and syphilis seropositivity. Efforts should be made to shorten this time in order to reduce the risk of infection

Objectives: To investigate the association between CAD and H. pylori infection using MPI.

Methods: This prospective study evaluated CAD positivity among consecutive patients referred to a tertiary medical center for a stress/rest MPI. All patients were tested for serum anti-H. pylori and CagA protein immunoglobulin G antibodies. The CAD-positive group included patients with ischemia and/or myocardial infarctions (MI) on a stress MPI, coronary artery bypass graft surgery (CABG) or percutaneous coronary interventions (PCI). CAD-negative subjects were defined as participants with a normal MPI, no pathological Q waves in resting ECG tracing, and no history of CAD. Both groups were compared for H. pylori and CagA seropositivity. Patients’ demographic data, risk factors for CAD, and childhood socioeconomic status were recorded.

Results: The study group consisted of 300 consecutive patients, 170 men and 130 women; 64% (110/173) CAD-positive patients and 47% (60/127) CAD-negative participants were found seropositive for H. pylori infection (P = 0.005). In the adjusted analysis, H. pylori infection was found to be associated with CAD- positive (odds ratio 1.83, 95% confidence interval 1.06–3.17, P = 0.031), and MI (fixed perfusion defects on MPI) (OR 3.36, 95%CI 1.44–7.84, P = 0.005). No association was noted with CagA positivity.

Conclusions: In patients undergoing a stress MPI, serum anti-H. pylori antibodies positivity was found to be associated with CAD, independent of traditional cardiovascular risk factors. 

Background: Alopecia areata (AA) is an autoimmune disease, based on the response to local and/or systemic corticosteroid treatment. The role of vitamin D in the pathogenesis of immune/autoimmune mediated diseases has been widely investigated.

Objectives: To investigate a possible association between serum 25-hydroxyvitamin D levels and alopecia areata.

Methods: The study included 23 patients diagnosed with AA followed at our outpatient clinic during the period March 2010 to May 2011, as well as a control group matched for age and gender. All subjects underwent a complete work-up and medical examination, anthropometric measurements and laboratory tests. Laboratory tests included complete blood count, C-reactive protein (CRP), and vitamin D levels.

Results: Mean CRP values were significantly higher in the AA group than the control group (1.1 ± 0.7 mg/dl vs. 0.4 ± 0.8 mg/dl, P < 0.05). Vitamin D levels were significantly decreased in the AA group (11.32 ± 10.18 ng/ml vs. 21.55 ± 13.62 ng/ml in the control group, P < 0.05). Multivariate analysis showed that CRP (odds ratio 3.1, 95% confidence interval 2.6–4.2, P = 0.04) and serum vitamin D levels < 30 ng/ml (OR 2.3, 95%CI 2.2–3.1, P = 0.02) were associated with AA. 

Conclusions: We found a significant correlation between AA and vitamin D deficiency. Vitamin D deficiency can be significant risk factor for AA occurrence.

Objectives: To report the first results from the Serbian National Cohort study, which was started in January 2000.

Methods: Our study included 374 patients: 260 primary APS patients and 114 SLE patients with secondary APS. Antiphospholipid antibody (aPL) analysis included detection of anticardiolipin antibodies (aCL) (immunoglobulin G and M), ß₂-glycoprotein 1, and lupus anticoagulant. Echocardiography was performed in all patients, and data on myocardial infarction, unstable angina, chronic cardiomyopathy and acute heart failure were collected.

Results: There were 30.7% secondary APS patients and 9.2% primary APS patients with pseudo-infective endocarditis (P = 0.0001). Cardiac manifestations were observed in 28.7% of patients who had more than one type of antibody (category I), in 24.1% with category IIa, in 23.1% with category IIb, and in 27.8% with category IIc (P = 0.78). Age was confirmed as a significant factor for cardiac manifestations in APS patients (52.3 and 43.3 years, respectively, P = 0.001). aCL IgG and IgM positivity was related to valvular changes in all APS patients and high levels of those antibodies increased the risk of these manifestations.

Conclusions: Patients with secondary APS had a higher prevalence of valvular lesions, and some aPL types and high levels of aPL were risk factors for specific cardiac manifestations in APS 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.

Objective: To examine the association of mild and severe anemia with acute HF severity and mortality.

Methods: Data were prospectively collected for patients admitted to all departments of medicine and cardiology throughout the country during 2 months in 2003 as part of the Heart Failure Survey in Israel. Anemia was defined as hemoglobin (Hb) < 12 g/dl for women and < 13 g/dl for men; Hb < 10 g/dl was considered as severe anemia. Mortality data were obtained from the Israel population registry. Median follow-up was 33.6 months.

Results: Of 4102 HF patients, 2332 had acute HF and available hemoglobin data. Anemia was common (55%) and correlated with worse baseline HF. Most signs and symptoms of acute HF were similar among all groups, but mortality was greater in anemic patients. Mortality rates at 6 months were 14.9%, 23.7% and 26.3% for patients with no anemia, mild anemia, and severe anemia, respectively (P < 0.0001), and 22.2%, 33.6% and 39.9% at one year, respectively (P < 0.0001). Compared to patients without anemia, multivariable adjusted hazard ratio was 1.35 for mild anemia and 1.50 for severe anemia (confidence interval 1.20–1.52 and 1.27–1.77 respectively).

Conclusions: Anemia is common in patients with acute HF and is associated with increased mortality correlated with the degree of anemia.

Objectives: To review positive temporal artery biopsiese of GCA in an attempt to correlate various histological parameters with clinical features, disease complications and outcome.

Methods: Positive biopsies from 65 GCA patients were randomly selected for review by a single pathologist. In each biopsy the following parameters were scored: intensity and location of the inflammatory infiltrate, presence of giant cells and other cell types, fragmentation and calcification of the internal elastic lamina, intimal thickening, and presence of luminal thrombus. Clinical data were obtained from the patients’ charts. Intensity of the initial systemic inflammatory reaction (ISIR) at the time of diagnosis was scored by the presence of five parameters: fever, anemia, thrombocytosis, leukocytosis, and sedimentation rate > 100 mm/hr.

Results: In cases with bilateral positive biopsy (n=27), there was good correlation between the two sides regarding intensity of inflammation (r = 0.65, P < 0.001), location of the infiltrate (r = 0.7, P < 0.001), degree of intimal thickening (r = 0.54, P < 0.001), and presence of giant cells (r = 0.83, P < 0.001). The rate of corticosteroid discontinuation tended to be quicker in patients with inflammatory infiltrates confined mainly to the adventitia, but other histological parameters did not affect this rate.

Conclusions: Inflammatory infiltrates confined to the adventitia were associated with more neuro-ophthalmic ischemic manifestations, weak/moderate ISIR at the time of diagnosis, and faster rate of corticosteroid discontinuation. No association was found between other temporal artery biopsy histological parameters and clinical features of GCA patients.