Israel Medical Association Journal

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: Several trials support the trans-radial route of percutaneous coronary intervention (PCI) since it reduces access site vascular complications and bleeding. 

Objectives: To examine the effects of trans-radial interventions (TRI) on clinical outcomes in a 'real world' cohort of patients undergoing PCI.

Methods: We analyzed 4873 consecutive patients who underwent PCI at a tertiary center and identified 373 patients who underwent TRI. Patients (radial vs. femoral) were compared using a propensity score analysis to best match between groups. Outcome parameters included total mortality, myocardial infarction (MI), repeat target vessel revascularization (TVR) rates, length of hospitalization and ∆Ht/Hb/creatinine values during hospitalization. These were evaluated at 6 months and 1 to 3 years after PCI.

Results: The rates of major adverse cardiovascular event (MACE) and its constituents were similar in the trans-radial vs. trans-femoral groups at all time intervals: 6.7% vs. 5.5% at 6 months, 10.3% vs. 10% at 1 year, 15.7% vs. 15% at 2 years, 15.7% vs. 16% at 3 years, respectively (P = 0.6). The length of hospitalization was shorter in the TRI group (2.87 days ± 2.04 vs. 3.3 days ± 3.12, P = 0.023). We did not find significant differences between the groups in the mean ∆Ht/Hb/creatinine values during the hospitalization course.

Conclusions: In a 'real-world' setting of PCI, the TRI route of PCI is as safe and efficient as the femoral approach. TRI is associated with shorter duration of hospitalization.

 

Abstract

Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.

Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine.

Methods: We reanalyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants without worsening of the sixth criterion).

Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept.

Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study. 

Abstract

Background: Gaucher disease is the most common lysosomal storage disorder and is caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads to the accumulation of undegraded substrates, mainly in cells of the monocyte/macrophage lineage, which is responsible for the clinical manifestations of the disease. To date, no study has attempted to identify the mutation spectrum of the glucocerebrosidase gene (GBA) in Slovak patients

Objectives: To identify mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.

Methods: Using molecular genetics methods PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and direct sequencing of coding region GBA we identified the spectrum of mutations in our patients.

Results: Five mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the mutant alleles. The remaining 25% were rare and probably individual mutations.

Conclusions: The mutational spectrum in our patients is similar to that observed in other European countries and corresponds to a Caucasian population, with N370S, L444P, RecNciI being the most common mutation. Interestingly, mutation G377S was more frequent in our patients as compared to other published data. The C4W, L96P, H311N, 745delG and 1127_1128delTT mutations are described here for the first time in Gaucher disease, contributing to the panel of published GBA mutations.  

Smoking is a risk factor for thromboangiitis obliterans (TAO, Buerger’s disease) and arteriosclerosis, but there are few cases of coronary heart disease (CAD)-associated Buerger's disease. A literature search for articles in English, Spanish and French published between 1966 and 2012 on patients with coronary involvement and TAO revealed 12 patients. We describe an additional case with involvement of the central nervous system, myocardium and large-diameter proximal arteries. The main clinical manifestations in these 13 cases were lower limb claudication and acute thoracic pain. The histologic findings showed thrombosis with unbroken internal elastic lamina and intimal clusters of granulocytes; coronary angiography revealed predominant involvement of the left anterior descending and right coronary artery. Treatment included coronary bypass procedures, coronary angioplasty, smoking cessation, and anticoagulant therapy. A complete therapeutic response was observed in half the patients. This review of all published cases of TAO patients with coronary symptoms, together with our patient, demonstrates the rarity of this clinical association. Patients under age 40 with CAD but no prominent cardiovascular risk factors besides smoking should be evaluated for the presence of Buerger's disease.

Objectives: To investigate whether the change in protocols over the years resulted in an outcome difference at two hospitals in Israel.

Methods: We thoroughly reviewed the records of 153 patients from Sheba Medical Center and Soroka Medical Center, of whom 106 comprised the study group. The patients were divided into two groups according to the treatment protocol used: 40 patients with the 1989/93 protocol and 66 with the 1999/2003 protocol. Outcome was analyzed for the two groups.

Results: We found a significant difference in disease-free survival (DFS) between the two groups for B cell-ALL (B-ALL) patients who achieved complete remission after induction. There was no difference in overall survival. We did not find any difference in outcome for T cell-ALL patients or for CD20-positive patients.

Conclusions: In our retrospective analysis, GMALL 99/2003 led to a better DFS for B-ALL patients who were in complete remission after induction. This is possibly related to the differences in medications between the protocols, but may also be due to better supportive care. Despite the proven advantage of the newer protocols regarding overall survival, in our experience there was no other significant difference between the two regimens. 

The Dutch painter Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. Although about 40 of his oil paintings could be considered “self-portraits,” controversy still exists regarding 14 of them. We undertook to determine the identity of the painter or the subject. Our work was based on the generally accepted premise that these portraits represent a “realistic” rendering of the subject. Self-portraits on which there is consensus regarding the authenticity were chosen as the basis for our measurements. Using a computerized technique we measured the brow ptosis. We also subjectively analyzed Rembrandt's facial aging and the unique asymmetrical elements in his face. We could not add any useful information on 6 of the 14 portraits and suggest that 8 should be considered authentic. Facial aging analysis and the unique surface anatomy allowed us to confirm Rembrandt as the painter in four of six self-portraits. We confirmed Rembrandt as the subject and painter in three more paintings. Of the two paintings in which the subject’s identity was controversial, we determined Rembrandt as the subject in one. We were able to date Rembrandt’s age in two other works and considered another portrait to be a copy. Our methodology may serve as an additional tool for the authentication of self-portraits.
 

Background: Understanding the mechanism and the main components involved in rheumatic mitral regurgitation (MR) associated with dominant pliable mitral stenosis (MS) may improve our ability to repair some mixed rheumatic mitral valve pathologies.

Objectives: To assess mitral valve structural components in pure mitral stenosis versus mitral stenosis associated with mild regurgitation

Methods: Using two-dimensional echocardiography, we performed mitral valve structural analysis in two groups of patients prior to balloon mitral valvuloplasty (BMV). The first group, consisting of 13 females and 2 males (mean age 39 ± 5 years), suffered from pure pliable mitral stenosis (PPMS), while the second group, with 22 females and 2 males (mean age 44 ± 5 years), had mixed mitral valve disease (MMVD) characterized by mild MR in the presence of dominant pliable MS. All echocardiographic measurements relating to the mechanism of MR were undertaken during the systolic phase.

Results: The mean Wilkins scores of the PPMS and MMVD groups were 7 ± 1 and 8 ± 1 respectively (P = 0.004). No significant differences were found between the MMVD group and the PPMS group regarding annular circumference (15.5 ± 1.4 cm vs. 15.4 ± 1.6 cm, P = 0.84), annular diameter (36 ± 4 mm vs. 38 ± 5 mm, P = 0.18), and chordae tendinae length directed to the anterior mitral leaflet (AML) (10 ± 2 mm vs. 11 ± 2 mm, P = 0.137). However, anterior vs. posterior mitral leaflet length during systole was significantly lower in the MMVD than in the PPMS group (2.2 ± 0.5 vs. 2.8 ± 0.4, P = 0.02), whereas the AML thickness at the co-aptation point was greater in the MMVD than in the PPMS group (7 ± 1 vs. 5 ± 1 mm, P = 0.0004).

Conclusions: In rheumatic valves, thickening and shortening of the AML are the main factors determining the appearance of mild MR in the presence of dominant pliable MS.

Background: Studies suggest that global semen quality is declining, but the debate remains open owing to geographic variation.

Objectives: To evaluate temporal trends of sperm parameters – namely concentration, motility and total motile sperm count – in sperm donated during the period 1995–2009.

Methods: In a retrospective longitudinal cohort study we analyzed the sperm count and motility of 2182 semen samples provided on a weekly basis by 58 young, healthy, fertile, university-educated, paid donors.

Results: Despite the lowering of criteria for sperm parameters satisfactory for donation that were implemented in 2004, 38% of applicants for sperm donation are now rejected based on semen quality as compared to a third of applicants 10–15 years ago (P < 0.001). If the old strict criteria were in place 88% of candidates would be rejected today (P < 0.0001). Over the study period, the average sperm parameters dropped from a concentration of 106 ± 25 million spermatozoa/ml with 79% ± 4.3% motility to 68 ± 14 million/ml with 66% ± 4.5% motile sperm (P < 0.0001, P < 0.0001, respectively). The total motile sperm count per ejaculate also decreased, from 66.4 ± 18.2 million to 48.7 ± 12 million (P < 0.005). When the previous criteria were implemented for the analysis of the latest group of sperm donors, only 18% of donors had an acceptable sperm quality, with an average concentration of 87 ± 12 million spermatozoa/ml, 73% ± 2.6% motile sperm and total motile sperm count of 53.1 ± 3.8 million per ejaculate – still significantly lower than 15 years ago (P = 0.01, P = 0.003, P = 0.058 respectively).

Conclusions: The rapid deterioration of sperm quality among fertile semen donors is alarming and may lead to cessation of sperm donation programs.

Background: Glioblastoma multiforme (GBM) is an ultimately fatal disease that affects patients of all ages. Elderly patients (65 years and older) constitute a special subgroup of patients characterized by a worse prognosis and frequent comorbidities.

Objectives: To assess the efficacy of different treatment modalities in terms of survival in elderly patients with GBM¹.

Methods: Using retrospective analysis, we extracted, anonymized and analyzed the files of 74 deceased patients (aged 65 or older) treated for GBM in a single institution.

Results: Mean survival time was 8.97 months and median survival time 7.68 months. Patients who underwent tumor resection had a mean survival of 11.83 months, as compared to patients who underwent no surgical intervention or only biopsy and had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full radiation treatment had a mean survival of 11.31 months, compared to patients who received only partial radiotherapy or none at all and had a mean survival of 4.09 months (P < 0.0001). Patients who underwent chemotherapy had a mean survival 12.4 months, compared to patients who did not receive any chemotherapy and had a mean survival of 5.89 months (P < 0.001).

Conclusions: Age alone should not be a factor in the decision on which treatment should be given. Treatment should be individualized to match the patient’s overall condition and his or wishes, while taking into consideration the better overall prognosis expected with aggressive treatment.
 

Background: Routine histopathological analysis of bone extracted during total joint replacement is controversial.

Objectives: To evaluate the utility of routine histopathological analysis in total joint replacement.

Methods: We calculated the risk for discrepant diagnosis between the pre- and postoperative histopathological results by performing a meta-analysis of 11 studies (including our data). We also calculated the risk for significant discrepancies.

Results: The discrepant diagnoses analysis showed a random effect of 3% discrepancies (95% confidence interval 1.2–3.7%). Funnel plot indicates a publication bias; consequently, the conclusions from this analysis should be interpreted with caution. Regarding the significant discrepancy in diagnosis, we performed a meta-analysis of nine studies. Fixed-effects analysis of all the studies resulted in 0.16% significant discrepancies (95% CI[1] 0.02–0.30%) with no heterogeneity (Q = 3.93, degrees of freedom = 9, P = 0.14, I² = 49.2%), and appropriate fixed-effects models.

Conclusions: We recommend no further routine histological examination, reserving this tool for cases with a controversial primary diagnosis and unexpected findings during the operation.

Objectives: To assess our experience with perichondritis in a large group of patients hospitalized with this entity.

Methods: We retrospectively studied 114 patients who were admitted with perichondritis during 1987–2004, including their demographic details, medical history, current illness, etiology, pathogens and treatments. 

Results: The patients’ mean age was 41.8 ± 20.7 years. In more than half of the patients the etiology could not be determined. Forty-seven patients (41%) were treated prior to hospitalization for an average of 2.5 ± 1.9 days. Eight patients (7%) required surgical intervention. Pseudomonas aeruginosa was found to be the predominant organism (69% of available isolates) and was associated with a more advanced clinical presentation and longer hospitalization (P = 0.008). 

Conclusions:  Perichondritis develops in many cases after apparent minor trauma. Since P. aeruginosa is probably the predominant pathogen, initial treatment should include anti-pseudomonal antibiotics.