Israel Medical Association Journal

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: Prolonged life expectancy has increased the number of elderly high risk patients referred for surgical aortic valve replacement (AVR). These referred high risk patients may benefit from sutureless bioprosthesis procedures which reduce mortality and morbidity.

Objectives: To present our initial experience with sutureless aortic bioprotheses, including clinical and echocardiographic results, in elderly high risk patients referred for AVR. 

Methods: Forty patients (15 males, mean age 78 ± 7 years) with symptomatic severe aortic stenosis underwent AVR with the 3F Enable™ or Perceval™ sutureless bioprosthesis during the period December 2012 to May 2014. Mean logistic EuroScore was 10 ± 3%. Echocardiography was performed preoperatively, intraoperatively, at discharge and at follow-up.

Results: There was no in-hospital mortality. Nine patients (22%) underwent minimally invasive AVR via a right anterior mini-thoracotomy and one patient via a J-incision. Four patients underwent concomitant coronary aortic bypass graft, two needed intraoperative repositioning of the valve, one underwent valve exchange due to inappropriate sizing, three (7.5%) had a perioperative stroke with complete resolution of neurologic symptoms, and one patient (2.5%) required permanent pacemaker implantation due to complete atrioventricular block. Mean preoperative and postoperative gradients were 44 ± 14 and 13 ± 5 mmHg, respectively. At follow-up, 82% of patients were in New York Heart Association functional class I and II.

Conclusions: Sutureless AVR can be used safely in elderly high risk patients with relatively low morbidity and mortality. The device can be safely implanted via a minimally invasive incision. Mid-term hemodynamic results are satisfactory, demonstrating significant clinical improvement.

 

Background: The rate of mitral bioprosthesis implantation in clinical practice is increasing. Transcatheter valve-in-valve implantation has been described for high risk patients requiring redo valve surgery. 

Objectives: To report our experience with transapical valve-in-valve implantation for failed mitral bioprosthesis.

Methods: Since 2010, 10 patients have undergone transapical valve-in-valve implantation for failed bioprosthesis in our center. Aortic valve-in-valve implantation was performed in one of them and mitral valve-in-valve implantation in nine. Mean age was 82 ± 4 years and 6 were female (67%). Mean time from original mitral valve (MV) replacement to valve-in-valve procedure was 10.5 ± 3.7 years. Follow-up was completed by all patients with a mean duration of 13 ± 12 months. 

Results: Preoperatively, all patients presented with significant mitral regurgitation; two with mitral stenosis due to structural valve failure. All nine patients underwent successful transapical valve-in-valve implantation with an Edwards Sapien™ balloon expandable valve. There was no in-hospital mortality. Mean and median hospital duration was 15 ± 18 and 7 days respectively. Valve implantation was successful in all patients and there were no major complications, except for major femoral access bleeding in one patient. At last follow-up, all patients were alive and in NYHA functional class I or II. Echocardiography follow-up demonstrated that mitral regurgitation was absent or trivial in seven patients and mild in two. At follow-up, peak and mean gradients changed from 26 ± 4 and 8 ± 2 at baseline to 16.7 ± 3 and 7.3 ± 1.5, respectively.

Conclusions: Transcatheter transapical mitral valve-in-valve implantation for failed bioprosthesis is feasible in selected high risk patients. Our early experience with this strategy is encouraging. Larger randomized trials with long-term clinical and echocardiographic follow-up are recommended.

 

Background: Selection of appropriate reference charts for fetal biometry is mandatory to ensure an accurate diagnosis. Most hospitals and clinics in Israel use growth curves from the United States. Charts developed in different populations do not perform well in the Israeli population.

Objectives: To construct new reference charts for fetal biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL), using a large sample of fetuses examined at 14–42 weeks gestational age in a medical center and a community ultrasound unit located in two different regions of Israel. 

Methods: Data from the medical center and the community clinic were pooled. The mean and standard error of each measure for each week was calculated. Based on these, reference charts were calculated using quantiles of the normal distribution. The performance of the reference charts was assessed by comparing the new values to empirical quantiles.

Results: Biometric measurements were obtained for 79,328 fetuses. Growth charts were established based on these measurements. The overall performance of the curves was very good, with only a few exceptions among the higher quantiles in the third trimester in the medical center subsample.

Conclusions: We present new local reference charts for fetal biometry, derived from a large and minimally selected Israeli population. We suggest using these new charts in routine daily obstetric practice.

 

Background: Trans-catheter valve implantation (TAVI) is a non-surgical alternative for patients with severe aortic stenosis (AS). Pre-procedural computed tomography angiography (CTA) allows accurate “road mapping,” aortic annulus sizing and the detection of incidental findings.

Objectives: To document the prevalence of non-valvular extra-cardiac findings on CTA prior to TAVI and the impact of these findings on the procedure.  

Methods: Ninety AS patients underwent CTA as part of pre-TAVI planning. Scans extended from the clavicles to the groin. Non-vascular non-valvular findings were documented and graded as follows: (A) significant findings causing TAVI cancellation or postponement, (B) significant findings leading to a change in the TAVI procedure approach, (C) non-significant findings not affecting the TAVI procedure. 

Results: TAVI was planned for 90 patients; their average age was 80.2 ± 7.5 years, 53% were females. Overall, non-valvular cardiac, extra-cardiac and extra-vascular significant and non-significant incidental findings were documented in 97% of scans (87/90). Significant pathologies causing TAVI cancellation or postponement (category A) were documented in 8%. Significant findings affecting the TAVI procedure (category B) were found in 16% of patients. 

Conclusions: Pre-TAVI CTA detected non-valvular extra-vascular pathologies leading to procedure cancellation/postponement or procedure modification in 8% and 16%, respectively. Comprehensive CTA evaluation that acknowledges the importance of such findings is of major importance since it might alter the TAVI procedure or even render it inappropriate. 

 

Background: Obesity causes specific sexual problems, including diminished sexual desire, poor performance and avoidance of sexual encounters.

Objectives: To systematically evaluate the effect of bariatric surgery on patients' sexual function as compared to their preoperative status.

Methods: Bariatric surgery candidates were given a validated sexual function questionnaire the day before surgery and again 1 year after surgery. Females were polled with the Female Sexual Function Index (FSFI) and males with the Brief Sexual Function Inventory (BSFI). Statistical analysis was performed to elucidate differences in response to the questionnaires.

Results: The study population included 34 females and 14 males. Mean age and body mass index (BMI) were 40.2 ± 10.2 years and 43.4 ± 5.3 kg/m2, respectively. Postoperative BMI was 31.4 ± 4.9 kg/m2 (P < 0.001). Laparoscopic sleeve gastrectomy was performed in 36 patients and laparoscopic Roux-y gastric bypass in 12. In females, the FSFI index rose significantly from 24 to 30 (P = 0.006), indicating increased sexual performance and satisfaction. In males the BSFI increased from 40.2 to 43.9 but did not reach statistical significance (P = 0.08). However, general satisfaction, desire and erection were each significantly improved within the BSFI.

Conclusions: In addition to the well-documented medical and quality-of-life benefits of bariatric surgery, there is also clear improvement in patients' sexual function, both physical and psychosexual.

 

Background: Isolation of methicillin-resistant Staphylococcus aureus (MRSA) in healthy individuals is not common in Israel. In our hospital, about 30% of MRSA isolates were SCCmec types IV and V.

Objectives: To identify the demographic and clinical characteristics of patients carrying MRSA SCCmec type IV or V, and to compare them with each other and with those of patients with SCCmec types I-III.

Methods: We conducted a case-control study that included 501 patients from whom MRSA was isolated: 254 with SCCmec type I, II, or III, and 243 isolates from SCCmec types IV or V. 

Results: MRSA was isolated from surveillance cultures in 75% of patients and from a clinical site in 25%. The majority of our study population was elderly, from nursing homes, and with extensive exposure to health care. First, we compared characteristics of patients identified through screening. Statistically significant predictors of SCCmec V vs. IV were Arab ethnicity (OR 7.44, 95%CI 1.5–37.9) and hospitalization in the year prior to study inclusion (OR 5.7, 95%CI 1.9–16.9). No differences were found between patients with SCCmec types I-III and patients with SCCmec type IV or V. Analysis of the subset of patients who had clinical cultures yielded similar results. 

Conclusions: SCCmec types IV and V were common in the hospital setting although rare in the community. It seems that in Israel, SCCmec IV and V are predominantly health care-associated MRSA. 

 

Background: Granulomatous lobular mastitis (GLM) is a rare disorder that can clinically mimic breast carcinoma. The recommendation for diagnosis and treatment of GLM has not yet been established. 

Objectives: To assess a series of GLM patients, including their clinical presentation, diagnosis, treatment and outcome. 

Methods: We retrospectively analyzed the clinical data and treatment of 17 female patients with biopsy-proven GLM. Breast tissue was obtained by a core needle biopsy (15 patients) or open biopsy (2 patients). Images were reviewed by an experienced radiologist.

Results: The mean age of the patients at diagnosis was 44.6 ± 12.6 years. Five patients (29%) presented with bilateral disease, and seven (41%) presented with a mass, suggesting the initial diagnosis of breast carcinoma. Treatment comprised observation alone (23%), antibiotics (58.8%) and/or corticosteroids (with or without methotrexate) (35%). At the end of the study 70.6% of the patients demonstrated complete remission. None of the patients developed any systemic (granulomatous) disease or breast carcinoma during the follow-up period (4.7 ± 3.8 years). 

Conclusions: Core needle biopsy is mandatory for the diagnosis of GLM and the exclusion of breast carcinoma. The recommended treatment modalities are observation alone or corticosteroids; surgery should be avoided. GLM is a benign disease with a high rate of resolution and complete remission.

 

Abstract

Background: Diabetes mellitus-related lower extremity amputation is a major complication severely affecting patient survival and quality of life.

Objectives: To analyze epidemiological and clinical trends in the incidence and survival of lower extremity amputations among diabetes patients.

Methods: We conducted a retrospective observational cohort study of 565 consecutive diabetes patients who underwent their first non-traumatic lower extremity amputation between January 2002 and December 2009.

Results: Major amputations were performed in 316 (55.9%) patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1 per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year mortality rates were lower among patients with minor amputations (31.7% vs. 39.6%, P = 0.569). First year mortality rates following below-knee amputation were somewhat lower than above-knee amputation (33.1 vs.45.1%, respectively). Cox regression model of survival at 1 year after the procedure found that age (HR 1.06 per year, 95% CI 1.04–1.07, P < 0.001), above-knee amputation (HR 1.36, 95% CI 1.01–1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26–2.24, P < 0.001) significantly increased one year mortality risk.

Conclusions: In this population-based study the incidence rate of non-traumatic amputations in diabetes patients between January 2002 and December 2009 decreased slightly. However, one year mortality rates after the surgery did not decline and remained high, stressing the need for a multidisciplinary effort to prevent amputations in diabetes patients.

Background: Most spine tumors are resistant to radiation and chemotherapy. Complete surgical removal provides the best chance for long-term control of the tumor. Total en bloc spondylectomy (TES) is a radical new technique that entails total removal of the tumor and affected vertebras with clean margins.

Objectives: To review our initial experience with TES, focusing on feasibility, surgical challenges and the short-term outcome.

Methods: We retrospectively reviewed the hospitalization charts and follow-up data of all patients treated with TES for spine tumors in the spine unit at Tel Aviv Medical Center.

Results: TES was performed in 12 patients aged 13–78 years. Nine patients had primary spinal tumors and three had metastasis. Total en bloc removal was achieved in all cases with spondylectomy of one to three affected vertebras. There was no perioperative mortality and only one major intraoperative complication of injury to a major blood vessel. Late complications were mainly related to hardware failure.

Conclusions: Total en bloc spondylectomy is feasible and effective for the management of selected patients with extradural spinal tumors. Since the surgical procedure is demanding and carries significant risk, careful preoperative evaluation and collaboration with colleagues from other specialties are crucial.

Background: The Syntax score (SS) is a helpful tool for determining the optimal revascularization strategy regarding coronary artery bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) in patients with complex coronary disease. While an association between higher SS and mortality was found for PCI patients, no such association was found for CABG patients.

Objectives: To assess whether the SS predicts late mortality in patients undergoing CABG in a real-world setting.

Methods: The study included 406 consecutive patients referred for CABG over a 2 year period. Baseline and clinical characteristics were collected. Angiographic data SS were interpreted by an experienced angiographer. Patients were divided into three groups based on SS tertiles: low ≤ 21 (n=205), intermediate 22–31 (n=138), and high ≥ 32 (n=63). Five year mortality was derived from the National Mortality Database.

Results: Compared with low SS, patients with intermediate and high scores were significantly older (P = 0.02), had lower left ventricular ejection fraction (64% vs. 52% and 48%, P < 0.001) and greater incidence of acute coronary syndrome, left main disease, presence of chronic total occlusion of the left anterior descending and/or right coronary artery, and a higher EuroSCORE (5% vs. 5% and 8%, P < 0.01). Patients with intermediate and high SS had higher 5 year mortality rates (18.1% and 19%, respectively) compared to patients with low score (9.8%, P = 0.04). On multivariate analysis, SS was not an independent predictor of late mortality.

Conclusion: Patients with lower SS had lower mortality after CABG, which is attributable to lower baseline risk. SS is not independently predictive of late mortality in patients with multi-vessel coronary artery disease undergoing CABG.

Background: Non-mobilized peripheral blood contains mostly committed cells with limited numbers of early progenitors. Objectives: To enrich functional progenitor cells from healthy donors and ischemic heart disease patients by short-term culture of mononuclear cells with defined culture conditions.

Methods: Mononuclear cells obtained from healthy donors and ischemic heart disease patients were cultured for 7 days in a cytokine cocktail. We tested the multilineage differentiation capacities and phenotype of cultured cells.

Results: The short-term culture (7 days) of all study groups with a defined cytokine cocktail resulted in two distinct cell populations (adherent and non-adherent) that differed in their differentiation capacities as well as their cell surface markers. Cultured adherent cells showed higher differentiation potential and expressed endothelial and mesenchymal fibroblast-like surface markers as compared to fresh non-cultured mononuclear cells. The non-adherent cell fraction demonstrated high numbers of colony-forming units, indicating a higher differentiation potential of hematopoietic lineage.

Conclusions: This study proved the feasibility of increasing limited numbers of multipotent progenitor cells obtained from the non-mobilized peripheral blood of healthy donors and ischemic patients. Moreover, we found that each of the two enriched subpopulations (adherent and non-adherent) has a different differentiation potential (mesenchymal, endothelial and hematopoietic).