Israel Medical Association Journal

Background: Atrial fibrillation (AF) is a common complication of coronary artery bypass graft (CABG) surgery, occurring in 20%–40% of patients, mostly during the first week after surgery. It is associated with increased morbidity and mortality, but data are limited. 

Objectives: To assess the correlation between new-onset in-hospital AF following CABG and long-term AF, cerebrovascular accident (CVA), or death.

Methods: We conducted an analysis of 161 consecutive patients who underwent isolated CABG surgery in a tertiary center during the period 2002–2003. 

Results: Patients’ mean age was 72 years, and the majority were males (77%). Approximately half of the patients experienced prior myocardial infarction, and 14% had left ventricular ejection fraction < 40%. Postoperative AF (POAF) occurred in 27% of the patients. Patients were older and had larger left atrium diameter. POAF was strongly correlated with late AF (OR 4.34, 95%CI 1.44–13.1, P = 0.01) during a mean follow-up of 8.5 years. It was also correlated with long-term stroke but was not associated with long-term mortality. 

Conclusions: POAF is a common complication of CABG surgery, which is correlated with late AF and stroke. Patients with POAF should be closely monitored to facilitate early administration of anticoagulant therapy in a high risk population upon recurrence of AF. 

 

Background: Prophylaxis for hospitalized venous-thromboembolic events (VTEs) is frequently underutilized, in part due to lack of a simple risk assessment model (RAM). 

Objectives: To compare patient selection and administration of VTE prophylaxis according to the American College of Chest Physicians (ACCP) 2008 guidelines versus the newer 2012 guidelines, and assess the feasibility of developing simpler local RAMs.

Methods: We conducted a prospective assessment of VTE risk among 300 unselected consecutive patients admitted to a medical hospital ward, using the 2008 and 2012 ACCP guidelines. The frequency and relative weight of each risk factor in the 2012 ACCP guidelines were used to develop a local VTE RAM.

Results: VTE prophylaxis was indicated by the 2008 and 2012 ACCP guidelines in 40% and 42% of the cohort respectively, and was administered in 28% and 26% of eligible patients, respectively. Contraindication to VTE prophylaxis was found in 29% of patients according to both guidelines. In comparison to the 2008 guidelines, sensitivity and specificity of the 2012 guidelines were 96% and 88%, respectively. A local RAM based on the following concise score, comprising age, malignancy and immobility, correctly identified 99% of at-risk patients based on the 2012 guidelines, with a sensitivity and specificity of 98% and 95%, respectively.

Conclusions: Both guidelines performed to a similar degree and were poorly implemented in daily practice. A simplified RAM accurately identified the vast majority of these eligible patients. The development of local RAMs is feasible and may result in higher utilization rates.

 

Background: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect on outcome of age at initial exposure have yet to be determined. 

Objectives: To identify the characteristics of radiation-induced thyroid carcinoma.

Methods: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. 

Results: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS).

Conclusions: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

 

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: In recent years several reports have been published describing dogs’ ability to detect, by scent, patients with cancer. This ability is based on the sniffing of volatile organic elements that are secreted by malignant cells, react to them. 

Objectives: To evaluate the ability of trained dogs to detect (i) breast cancer cell cultures (MCF7) compared to the control pseudo-normal keratinocyte cell line (HaCaT), and then (ii) melanoma (BG) and (iii) type 2 epithelial lung carcinoma (A549) malignant cell cultures to which they were not previously exposed in the course of their training.

Methods: Cell cultures were prepared in a standard manner. Two Belgian Shepherd dogs were trained and then tested in a single-blind test (for dogs and trainers) on their ability to detect the "target specimen," a MCF7 breast cancer cell culture. Following this, the ability of the dogs to detect cancer cell cultures that they were not previously exposed to (i.e., A549, BG) was tested. In each test round, four specimens placed in identical blocks were arranged in a line with one meter between them: one target specimen (MCF7, A549, BG), two control specimens (HaCaT), and a sample containing cell culture medium only.

Results: The two dogs picked out all the target specimens of MCF7 breast cancer cell cultures that they were trained to detect (10/10) as well as all the target specimens that they were not previously exposed to [A549 (5/5) and BG (5/5)], but did not pick out the control specimens or the cell culture medium. Thus, the sensitivity, specificity, and positive and negative predictive values for both dogs were 100%.

Conclusions: The results of this study support the assumption that cancer cells have a unique odor pattern, and that this odor pattern is common to different types of cancer.

 

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.

 

Background: Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. 

Objectives: To implement a policy change to improve asthma treatment in pediatric wards and the pediatric emergency department.

Methods: The study was performed in the emergency department and pediatric wards of a university medical center. The study group comprised all children admitted with a diagnosis of asthma necessitating treatment. The medical and nursing staff of both the pediatric emergency department and the pediatric wards was trained how to use metered dose inhalers attached to spacers on a regular basis in asthmatic pediatric patients. At a preset date nebulizers were replaced by spacers and their use was monitored by the supervising physician. Salbutamol was administered by metered dose inhaler (100 μg/puff) attached to a spacer device. The number of puffs was determined by severity of disease according to GINA recommendations. After 2 years the outcome and cost analysis were examined.

Results: During 3 years since the initial policy change 92.5% patients were treated with spacers throughout their hospital stay (emergency department and pediatric ward). Costs were reduced by an estimated 63%. 

Conclusions: In view of its many advantages the replacement of nebulizers by MDI+S for the treatment of acute asthma is feasible, if performed in collaboration with the staff, hospital authority and patients.

 

Background: Elevated serum levels of the epithelial marker CA125 are occasionally observed in leiomyosarcoma (LMS) patients.

Objectives: To assess the immunohistochemical expression of this marker in the tissue of LMS.

Methods: The consecutive unselected records of all patients with LMS diagnosed during the period 1995–2012 were located and abstracted. After verification of the diagnosis, 4 µm unstained slides were prepared from each case for immunohistochemical staining for CA125. Sections of ovarian carcinoma known to express CA125 were used as positive controls.

Results: We located 17 LMS patients from the period under study. Bleeding was the presenting symptom in 9 patients; the diagnosis was established prior to treatment in 11 patients. The tumor was in an advanced stage in 6 patients, and in 7 unstaged patients it was grossly confined to the uterus. Ten patients died within 14 months after the diagnosis. Serum CA125 levels prior to treatment were assessed in only 8 patients and were above normal limits (> 35 U/ml) in 3 of them. Two of the three with elevated serum levels were in stage III, and the third was an unstaged apparent stage I patient. None of the LMS tissue specimens demonstrated immunohistochemical expression of CA125.

Conclusions: CA125 was not immunohistochemically expressed in the tissue of any LMS tumors examined by us. The origin of elevated serum CA125 in some of these tumors is therefore not in its tissue and remains unknown. 

Background: The role of routine active surveillance cultures (ASCs) in predicting consequent blood stream infections is unclear.

Objectives: To determine prospectively whether routine screening ASCs obtained on admission to the intensive care unit (ICU) can predict the causative agent of subsequent bloodstream infections.

Methods: We prospectively studied a cohort of 100 mechanically ventilated patients admitted consecutively to a 16-bed ICU. On admission, ASCs were obtained from four sites: skin cultures (swabs) from the axillary region, rectal swabs, nasal swabs, and deep tracheal aspirates. Thereafter, cultures were obtained from all four sites daily for the next 5 days of the ICU stay.

Results: Of the 100 recruited patients 31 (31%) had culture-proven bacteremia; the median time to development of bacteremia was 5 days (range 1–18). Patients with bacteremia had a longer median ICU stay than patients without bacteremia: 14 days (range 2–45) vs. 5 days (1–41) (P < 0.001). ICU and 28 day mortality were similar in patients with and without bacteremia. Most ASCs grew multiple organisms. However, there was no association between pathogens growing on ASCs and eventual development of bacteremia.

Conclusions: ASCs obtained on ICU admission did not identify the causative agents of most subsequent bacteremia events. Therefore, bloodstream infections could not be related to ASCs.

Objectives: To evaluate if fetal reduction of triplets to twins improves outcome.

Methods: We analyzed the outcome of 80 triplet gestations cared for at Rambam Health Care Campus in the last decade; 34 families decided to continue the pregnancy as triplets and 46 opted for MFPR to twins.

Results: The mean gestational age at delivery was 32.3 weeks for triplets and 35.6 weeks for twins after MFPR. Severe prematurity (delivery before 32 gestational weeks) was experienced in 37.5% of triplets and in 7% of twins. Consequently, the rate of severe neonatal morbidity (respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage) and of neonatal death was significantly higher in unreduced triplets, as was the length of hospitalization in the neonatal intensive care unit (31.4 vs. 15.7, respectively). Overall, the likelihood of a family with triplets to take home all three neonates was 80%; the likelihood to take home three healthy babies was 71.5%.

Conclusions: MFPR reduces the risk of severe prematurity and the neonatal morbidity of triplets. A secondary benefit is the reduction of cost of care per survivor. Our results indicate that MFPR should be offered in triplet gestations.

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.