Israel Medical Association Journal

Background: Exposure to air pollution in the form of particulate matter smaller than 10 µm in diameter (PM10) has been associated with increased morbidity and mortality. However, since air pollution is correlated with confounding factors that might otherwise affect health, identifying the causal link has proven challenging. 

Objectives: To identify the effect of PM10 on hospital admissions due to respiratory illnesses. 

Methods: We used the Instrumental Variable (IV) methodology to control for confounding factors affecting hospital admissions. Exploiting the timing of sandstorms as an instrumental variable allows for a better estimate of the relationship between PM10 and hospital admissions. Data on PM concentrations and hospital admissions rates were compiled for Israel’s two largest cities, Jerusalem and Tel Aviv, for 2007–2009. We compared our IV estimates to those derived from a Poisson regression, which is commonly used in the existing literature. 

Results: Sandstorms led to an increase of 307 µg/m3 of PM10 concentrations. A 10 µg/m3 increase in PM10 is associated with a 0.8% increase in hospital admissions due to respiratory conditions, using Poisson regression. The same finding was noted using the IV methodology. 

Conclusions: The association between PM10 and hospital admission reflects a primarily causal relationship. Instrumental variable methodology could be applied to analysis of the effect of air pollution on hospital admissions. 

 

Background: Gastric bezoars in children are infrequent. Most are trichobezoars. Surgical intervention is sometimes necessary.

Objectives: To describe the clinical findings and radiological workup, as well as treatment and outcome of patients with complicated gastric bezoars who underwent surgery in our institution.

Methods: We conducted a retrospective review of all cases of surgery for gastric bezoars performed in our institution between 2000 and 2010. Data collected included gender and age of the patients, composition and extent of the bezoar, presenting signs and symptoms, imaging studies used, performance of endoscopy, and surgical approach. Outcome was measured by the presence of postoperative complications.

Results: We identified seven patients with gastric bezoars who underwent surgery. All were females aged 4–19 years. Six had trichobezoars and one had a mass composed of latex gloves. Presenting symptoms included abdominal pain, vomiting, weight loss, and halitosis. All patients had a palpable epigastric mass. A large variety of imaging modalities was used. Endoscopic removal was attempted in three patients but failed, and the laparoscopic approach was attempted in one patient and failed. All patients eventually underwent laparotomy with gastrotomy and recovered without complications. 

Conclusions: The presence of gastric bezoars should be suspected in any child with unexplained abdominal pain, vomiting, weight loss, or halitosis, or with a palpable abdominal mass, especially in girls. A variety of imaging modalities can aid in diagnosis. Endoscopic removal might be attempted, although failure of this approach is frequent and must prompt surgical intervention, preferably laparotomy and gastrotomy, which has an excellent outcome.

 

Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other pro-inflammatory cytokines play an important role in pathogenesis. 

Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls.

Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. 

Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SSc variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score.

Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.

 

Background: Evidence suggests that prolonged bisphosphonate (BP) treatment predisposes to atypical fractures (AF), but the etiology has yet to be determined. Addressing causality begins with case identification, which requires radiological adjudication. However, many trials based their case findings on coded diagnoses. 

Objectives: To investigate the feasibility of case findings by the coding system and the reproducibility of radiological evaluations in two hospitals in Israel, and to compare BP exposure of AF patients to a control group with typical (intertrochanteric of femoral neck) fractures. 

Methods: Diagnostic databases from 2007–2010 were reviewed and admission X-rays of patients were examined in two steps by two radiologists. Fractures were classified as atypical or not atypical according to published criteria. A 2:1 control group was created. Ambulatory drug acquisition was reviewed. 

Results: Of the 198 patients who fulfilled the search criteria, 38 were classified by initial radiological opinion as AF. Subsequent radiological opinion judged 16 as not atypical. Of the AF patients, 80% were exposed to BP. Of those, 81% continued to receive BP treatment for 2.4 years after AF. Only one AF patient was discharged with suspected AF diagnosis. In the control group, 27% were exposed to BP prior to fracture (P < 0.001). 

Conclusions: Thorough radiological revision is mandatory for proper classification of AF, and even when performed there is significant inconsistency in interpretation. Conclusions drawn from trials based solely on coded diagnoses lead to significant bias. BP exposure was significantly higher in the AF group. Caregiver unawareness of AF leads to improper management. 

 

Background: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. 

Objectives: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS.

Methods: Using the BioPlex™ 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls. 

Results: Three non-classic aPL were significantly more prevalent among MS patients in comparison to the control group. These antibodies included IgM and IgG against phosphatidylserine-β2GPI (PS-B2), IgG prothrombin complex (PT-PT) and IgM prothrombin (PT). The positive results according to Bonferroni correction are PS-B2 IgG and PT-PT IgG. The remaining aPL profiles did not differ significantly between the two groups.

Conclusions: An association between certain non-classic aPL and MS has been established. The specific role of these autoantibodies in the pathogenesis of the condition remains uncertain.  

 

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: 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: In Israel, where the "Do not resuscitate code" and "advanced directives" are not yet universally practiced, physicians are frequently ‘forced’ to mechanically ventilate patients despite an upfront unfavorable prognosis. Due to the shortage of intensive care unit (ICU) beds, patients are mostly hospitalized in general medicine wards. 

Objectives: To differentiate between patients with particularly grim prognoses and those with good prognoses, in order to inform the potential decision-making process regarding whether or not to offer aggressive medical care.  

Methods: This retrospective study included all mechanically ventilated patients hospitalized exclusively in one of the six general internal medicine wards at the Assaf Harofeh Medical Center during 2009–2010. Demographic and ventilation-related data, laboratory values and main medical diagnoses were correlated to in-hospital mortality. 

Results: The study group comprised 437 patients with a median age of 83 years. Mortality was 72%. Initiation of mechanical ventilation out of the hospital or in the emergency room improved outcome. Age, anemia, leukocytosis and renal failure correlated negatively to outcome. In-hospital mortality was 80% in patients after in-hospital resuscitation, 90% in patients ventilated due to infections, but 50% in patients ventilated for cardiac or respiratory failure.

Conclusions: The prognosis of mechanically ventilated patients can be foreseen, which could help in deciding whether aggressive life support would be in the interest of the patient. 

 

Clostridium difficile-associated diarrhea is a problem most hospital-based physicians will face in their career. This review aims to refresh current knowledge with regard to Clostridium difficile infection and bring physicians up to date with the latest developments in the growing field of fecal microbiota transplantation, the benefits it offers, and the promise this and other developments hold for the future.