Israel Medical Association Journal

Background: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic.

Objectives: To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy.

Methods: We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed.

Results: In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF< 25% was 64% (95% CI 41%–79%) and of NYHA class > 2 was 53% (95% CI 36–69%). A logistic model incorporating these three variables incorrectly classified 29% of patients.

Conclusions: IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.
 

Background: There is a striking increase in the number of people with metabolic syndrome (MetS) as a result of the global epidemic of obesity and diabetes. Increasing evidence suggests that uric acid may play a role in MetS.

Objectives: To assess the prevalence of MetS in a large cohort from Israel and its association with hyperuricemia using the latest three definitions of MetS.

Methods: We conducted a retrospective analysis of the database from a screening center in Israel, using the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the Harmonizing definitions of MetS, to assess 12,036 subjects with an age range of 20–80 years.

Results: The mean age of the study sample was 46.1 ± 10.2 years and 69.8% were male. The prevalence of MetS was 10.6%, 18.2% and 20.2% in the revised NCEP ATP III, the IDF and the Harmonizing definitions respectively. The prevalence of hyperuricemia in subjects with MetS, for all three MetS definitions, was similar: 20.0%, 19.9% and 19.1% respectively. There was a graded increase in the prevalence of MetS among subjects with increasing levels of uric acid. The increasing trend persisted after stratifying for age and gender and after multivariate analysis (P for trend < 0.001).

Conclusions: This large cohort shows a high prevalence of MetS in Israel, but is still lower than the prevalence in western countries. Hyperuricemia is common in those subjects and might be considered a potential clinical parameter in the definition of MetS.
 

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.

Current treatments for systemic lupus erythematosus (SLE) are effective in reducing morbidity and mortality but are not specific and have severe adverse effects. Based on understanding of the different dysregulated immunological pathways involved in SLE pathogenesis, specific targeted therapies were developed. This review presents the current and the near-future novel biological immune targeted treatments, such as B cell-targeted therapy, cytokine blockade, peptide-based treatments and other novel treatments for SLE.
 

Background: Gastric stump cancer is often described as a tumor with a poor prognosis and low resectability rates.

Objectives: To compare the pathological characteristics of gastric stump cancer patients with those of patients with proximal gastric cancer.

Methods: This retrospective study was based on the demographic and pathological data of patients diagnosed with gastric cancer and treated at Assaf Harofeh Medical Center during an 11 year period. The patients were divided into two groups: those undergoing proximal gastrectomy for proximal gastric cancer and those undergoing total gastrectomy for gastric stump cancer.

Results: Patients with gastric stump cancer were predominantly male, older (P = 0.202, not significant), and had a lower T stage with less signet-ring type histology, fewer harvested and fewer involved lymph nodes (P = 0.03, statistically significant) and less vascular/lymphatic involvement than patients with proximal gastric cancer.

Conclusions: The lower incidence of involved lymph nodes and lymphovascular invasion in gastric stump cancer as compared to proximal gastric cancer in this study may imply that the prognosis of gastric stump cancer may be better than that of proximal gastric cancer. However, to verify this assumption a study comparing patient survival is required.
 

Background: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change, imposed by this mutation on pyrin structure, may help to understand the role of this mutation

Objectives: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein.

Methods: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined.

Results: The E148Q mutation caused deviation from the wild-type pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%.

Conclusions: A quantum-chemistry based model suggests that the structural effect of the E148Q mutation is indeed low, but not zero.