Israel Medical Association Journal

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: 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: Several studies have identified associations between low vitamin D concentrations and risk of upper respiratory infections (URI). T lymphocytes have a major anti-viral role, are affected by vitamin D metabolism, and may mediate the link between vitamin D and URIs. Competitive swimmers have a relatively high rate of URIs, alongside a high prevalence of low vitamin D concentration. 

Objectives: To examine the associations linking T cell receptor excision circles (TREC, markers of thymus activity), circulating 25(OH)D concentrations and the effect of vitamin D supplementation, and URI symptoms in young competitive swimmers.

Methods: We tested 82 adolescent swimmers for serum 25(OH)D and TREC concentrations and found that 55 had vitamin D insufficiency. Randomized supplementation of either vitamin D3 or placebo was given for 12 winter weeks. URI symptoms were recorded weekly. The associations between TREC copy numbers, vitamin D and URI burden were examined.

Results: TREC concentrations decreased with the participants’ age (r = -0.346, P = 0.003), with no significant between-gender difference. TREC concentrations did not materially differ among subjects with normal, insufficient or deficient vitamin D status, and were not affected by vitamin D supplementation. No significant correlations were found between TREC levels or their changes during the study period, and mean URI severity or duration. 

Conclusions: Thymus activity, represented by higher TREC levels, was not related to vitamin D concentrations or status, and was not affected by vitamin D supplementation in adolescent swimmers. TREC concentrations were not associated with URI severity or duration in this population.

 

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: Childhood attention deficit hyperactivity disorder (ADHD) is a chronic health problem with significant risk for long-term morbidity in adulthood.

Objectives: We examined long-term outcomes of ADHD in a population-based sample of childhood ADHD cases prospectively assessed as adults.

Methods: Long-term outcomes for 70 adults who were diagnosed with ADHD during childhood were examined and compared with data on the general population.

Results: Most subjects admitted to persistence of ADHD-related symptoms in adulthood, despite discontinuation of regular medical treatment and follow-up. Areas most severely affected by past and ongoing symptoms included driving performance and incidence of motor vehicle accidents, and rates of marriage stability over time. Relatively unaffected were occupational and academic achievements and military service. 

Conclusions: There is a need for outreach and better services for adults who were previously diagnosed with ADHD. 

 

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: Obstructive sleep apnea (OSA) is a common health problem with an estimated prevalence of 4% among men, many of whom are undiagnosed and untreated. 

Objectives: To compare demographic characteristics, health profiles, risk factors, and disease severity in Arab and Jewish men with OSA syndrome.

Methods: In this cross-sectional study we retrospectively analyzed clinical data from the medical files of men ≥ 22 years old who were referred to the Rambam Medical Center sleep clinic during the period 2001–2009 with a suspected diagnosis of OSA. OSA severity was measured using the apnea-hypopnea index (AHI). Categorical variables were compared using the chi-square test. Relations between OSA severity and a set of independent risk factors were assessed by linear regression analysis.

Results: A total of 207 men were included (39 Arabs, 19%; 168 Jews, 81%). Arab participants were younger than their Jewish counterparts (45.5 ± 8.9 years vs. 49.8 ± 11.8, P = 0.04) and their body mass index (BMI) was higher (33.1 ± 5.1 vs. 30.0 ± 4.4, P = 0.001). OSA severity (AHI score) was higher among Arab men, with low, medium and high severity scores seen in 10%, 33% and 56% of Arab men vs 35%, 29% and 37% of Jewish men, respectively [T(198)=2.39, P = 0.02]. Mean blood oxygen saturation was comparable.

Conclusions: Arab men presenting for evaluation of sleep apnea harbored more severe OSA symptoms, were younger, and had higher BMI compared to Jewish men. Since OSA syndrome evolves for several years until it becomes severe, these findings suggest that Arab men seek medical assistance later than Jewish men with OSA.

 

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. 

 

Background: Anemia confers an adverse prognosis in patients with ST-elevation myocardial infarction (STEMI). Several mechanisms have been implicated in the etiology of anemia in this setting, including inflammation, blood loss, and the presence of comorbidities such as renal failure.

Objectives: To evaluate the adequacy of bone marrow response as potentially reflected by elevation in blood and reticulocyte counts.

Methods: Consecutive men with STEMI who underwent primary percutaneous intervention within 6 hours of symptom onset and who presented to our catheterization laboratory during a 36 month period were included in the study. The cohort was divided into quartiles according to hemoglobin concentration, and differences in clinical and laboratory characteristics between the groups were evaluated.

Results: A total of 258 men with STEMI were recruited, 22% of whom suffered from anemia according to the World Health Organization classification (hemoglobin < 13 g/dl). Men in the lowest quartile of hemoglobin concentration presented with significantly lower white blood cell and platelet counts (9.6 ± 2.9 vs. 12.6 ± 3.6 x103/µl, P < 0.001) and (231 ± 79 vs. 263 ± 8 x103/µl, P < 0.01), respectively, despite higher inflammatory biomarkers (C-reactive protein and fibrinogen) compared with patients in the upper hemoglobin concentration quartile. Reticulocyte production index was not significantly higher in anemic patients with a value of 1.8, 1.4, 1.5 and 1.6 in the ascending hemoglobin quartiles, respectively (P = 0.292). 

Conclusions: Anemic men with STEMI have relatively lower leukocyte and platelet counts as well as a reduced reticulocyte count despite higher inflammatory biomarkers. These findings might suggest inadequate bone marrow response. 

 

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.