Israel Medical Association Journal

Background: Coronary computed tomography angiography (CCTA) is an established modality for ruling out coronary artery disease. However, it has been suggested that CCTA may be a source of non-negligible radiation exposure.

Objectives: To evaluate the potential degradation in coronary image quality when using prospective gated (PG) CCTA as compared with retrospective gated (RG) CCTA in chest pain evaluation.

Methods: The study cohort comprised 216 patients: 108 consecutive patients in the PG CCTA arm and 108 patients matched for age, gender and heart rate in the RG CCTA arm. Scans were performed using a 64-slice multidetector CT scanner. All 15 coronary segments were evaluated subjectively for image quality using a 5-point visual scale. Dose-length product was recorded for each patient and the effective radiation dose was calculated

Results: The PG CCTA technique demonstrated a significantly higher incidence of step artifacts in the middle and distal right coronary artery, the distal left anterior descending artery, the second diagonal, the distal left circumflex artery, and the second marginal branches. Nevertheless, the diagnostic performance of these scans was not adversely affected. The mean effective radiation doses were 3.8 ± 0.9 mSv vs.17.2 ± 3 mSv for PG CCTA and RG CCTA, respectively (P < 0.0001).

Conclusions: Artifacts caused by the PG CCTA technique (64 MDCT) scanners tended to appear in specific coronary segments but did not impair the overall diagnostic quality of CCTA and there was a marked reduction in radiation exposure. We conclude that 64-slice PG CCTA is suitable for clinical use, especially for acute chest pain "fast track" evaluation targeted at relatively young subjects in a chest pain unit.
 

Background: Uterine sarcoma constitutes a highly malignant group of uterine tumors. It accounts for 2–6% of uterine malignancies and its incidence is 1.7 in 100,000 women. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma. Based on relatively small case series, the literature provides little information on the risk factors, the natural course of the disease and the preferred treatment.

Objectives: To evaluate uterine sarcoma patients treated in a tertiary referral center in Israel over a 20 year period (1980–2005).

Methods: We conducted a retrospective review of the charts of 40 uterine sarcoma patients, including their tumor characteristics, stage at diagnosis, treatment modalities, follow-up and survival.

Results: The patients’ mean age was 53 years (range 32–76); 30% of the patients had carcinosarcoma, 55% had leiomyosarcoma and 15% had ESS[1]. Half of the patients presented with stage I disease, 23% stage II, 10% stage III and 15% stage IV. Thirty-nine patients were treated by surgery. Adjuvant radiotherapy was administered to 39% of the patients, adjuvant chemotherapy to 21% and combined radiotherapy and chemotherapy to 9%. The mean follow-up period was 44 months, at which time disease had recurred in 44% of the patients. The disease stage was correlated with the 5-year survival rate, which was 73.1% for stages I-II and 22.2% for stages III- IV.

Conclusions: In accordance with other larger studies our data show that the only prognostic factor that was significantly correlated with prognosis was the stage of the disease at diagnosis. Despite advances in diagnosis and treatment, survival has not improved over the last 25 years.

Background: Patients with multiple (< 100) colorectal adenomatous polyps are at increased risk for colorectal cancer. Genetic evaluation of those patients who test negative for APC gene mutation is both a clinical and economic burden but is critical for counseling and surveillance. In Israel, this is confounded by the fact that national health insurance does not fully cover genetic evaluation of APC gene exon 16.

Objectives: To perform a comprehensive genetic evaluation of APC gene mutation-negative polyposis patients with the aim of developing a future evaluation protocol.

Methods: Genetic analyses were performed in 29 APC gene mutation-negative Jewish individuals with 5 to ≥ 40 colonic adenomas who did not fulfill Amsterdam (clinical) criteria for Lynch syndrome. Analyses included completion of APC gene exon 16 sequencing, analysis for APC gene copy number variations (deletions or duplications), MUTYH gene sequencing, and microsatellite instability in CRC[1] patients fulfilling “Bethesda” (laboratory investigation) criteria for Lynch syndrome.

Results: Completion of APC gene exon 16 sequencing revealed one patient with the E1317Q polymorphism. All were normal by APC multiplex ligation-dependent probe amplification analysis. Pathogenic MUTYH mutations were found in three patients, all of North African origin; two additional patients had variants of unknown significance. One of six patients with Bethesda-positive criteria was MSI²-High with immunohistology consistent with MLH1 mutation.

Conclusions: Based on this small but well-characterized cohort with multiple colorectal adenomas, Lynch syndrome needs to be excluded if there are compatible criteria; otherwise MUTYH sequencing is probably the first step in evaluating APC-negative patients, especially for Jews of North African descent. Completing APC exon 16 sequencing and copy number variations analysis should probably be the last evaluations.

Background: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness.

Objectives: To assess the routine evaluation of patients presenting to the ED[1] with acute chest pain via the utilization of a cardiologist-based chest pain unit using different non-invasive imaging modalities.

Methods: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU[2]. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography.

Results: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 445 patients underwent MDCT[3], 444 MPS[4], and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 ± 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event.

Conclusions: Utilization of the CPU enabled a rapid and thorough evaluation of the patients’ primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.
 

[1] ED = emergency department

[2] CPU = chest pain unit

[3] MDCT = multidetector computed tomography

[4] MPS = myocardial perfusion scintigraphy

Background: In many hospitals a chest X-ray is performed routinely at each patient’s admission. There are scant data regarding its usefulness in contemporary patient populations, which are characterized by patients’ increasing age, severity of illness, and different comorbidities.

Methods: We studied consecutive patients admitted during a 2 month period to a single department of medicine, where hospital policy mandates performing a CXR[1] on admission or soon after. Two senior clinicians who were not involved in the care of these patients assessed the discharge summaries for a clinical indication to perform CXR on admission, as well as its contribution to patient management (major positive, major negative, minor positive, or no contribution). Logistic regression analysis was performed with the SPSS 12 software program.

Results: The study population comprised 675 patients whose mean age was 64.5 ± 17.2 years. Their presenting complaints included chest pain (18%), dyspnea (12%), weakness (10.5%), fever (9%), abdominal pain (8%) and neurologic complaints (7.5%). Physical examination of the chest was normal in 585 (87%) of the cases and abnormal in 87 (13%). Examination of the heart was normal in 518 (77%) and abnormal in 129 (19%). In 19.6% (130 cases) CXR was not performed. Of the 545 CXRs done, 260 (48%) were normal. In only 128 (23.5%) did the admission CXR make a major positive contribution to diagnosis or treatment. In 61 (11.2%) it provided a minor positive contribution and in 153 (28.1%) a major negative contribution. In 184 patients (33.8%) the CXR did not affect either diagnosis or management. It made a major positive contribution to management in patients for whom there was an indication for performing the X-ray (odds ratio 10.3, P < 0.0005) and in those with a relevant finding on physical examination (OR[2] 1.63, P = 0.110). For a major negative contribution of the CXR to management (i.e., ruling out clinically important possibilities), the clinical indication was also very important (OR 72.9, P < 0.005). When patients with either a clinical indication for performing a CXR or an abnormal chest examination were excluded, 329 patients remained (60% of the 545 who had a CXR) in only 12 of them (3.6%) did the routine admission CXR contribute to patient management.

Conclusions: A routine admission CXR has a significant impact on patient management only in those patients in whom there are relevant findings on physical examination or a clear clinical indication for performing the test. There is no need to routinely order CXR on admission to hospital.

[1] CXR = chest X-ray

[2] OR = odds ratio

Background: Normal-tension glaucoma is a chronic progressive optic neuropathy of unknown etiology. Neuroimaging workup in these patients is controversial.

Objectives: To determine the value of routine neurologic and neuro-ophthalmologic evaluations in patients with NTG[1].

Methods: We conducted a retrospective review of all patients diagnosed with NTG in our institution between 2001 and 2006. Neurologic and neuro-ophthalmologic data were evaluated.

Results: Sixty-eight patients were considered suitable for the study (35 males, 33 females age range 43–90 years). Neurologic and neuro-ophthalmologic findings were normal in all of them. The computed tomography brain scan was normal in 88% and duplex carotid Doppler scan was normal in 92%.

Conclusions: Pathologic findings in neurologic and neuro-ophthalmologic assessments were uncommon in NTG. Therefore, contrary to earlier suggestions, neurologic and neuro-ophthalmologic evaluations in typical normal-tension glaucoma patients appear to have no added value.

Background: Although febrile urinary tract infections are very common in young children, the need for antimicrobial prophylaxis and evaluation following a first event is controversial.

Objectives: To assess the approach of leading pediatric specialists throughout Israel.

Methods: A questionnaire regarding the approach to antibiotic prophylaxis and diagnostic evaluation following a first event of febrile UTI[1], according to age and underlying renal abnormality, was sent to all 58 directors of departments of pediatrics, units of pediatric infectious diseases and pediatric nephrology in Israel.

Results: Fifty-six directors (96%) responded. Most prescribed prophylactic antibiotics after UTI. Heads of infectious disease departments prescribed less prophylaxis following UTI at the age of 18 months than heads of pediatrics or heads of pediatric nephrology units (34% vs. 72–75%, P = 0.018), but more often in cases of severe vesico-ureteral reflux without UTI. Cephalosporins were used prophylactically more often by directors of pediatrics compared to heads of pediatric nephrology units (71% vs. 38%, P = 0.048); the latter used non-beta-lactam prophylaxis (61% vs. 23%, P = 0.013) more often. Most pediatricians used renal sonography for evaluation; renal scan was used more commonly by pediatric nephrologists.

Conclusions: The administration of prophylactic antibiotics after UTI is still common practice among pediatric opinion leaders, although the specific approach differs by subspecialty. According to up-to-date evidence-based data, educational efforts are needed to formulate and implement judicious guidelines.

Background: Familial dysautonomia is a genetic disease that affects the sensory and autonomic nervous systems with varying severity. The deep breath test is one of several measures used to assess the severity of autonomic diseases, but its value in familial dysautonomia has not yet been investigated.

Objectives: To determine the diagnostic value of the DBT[1] in patients with familial dysautonomia.

Methods: Eight patients with familial dysautonomia and eight healthy volunteers were examined by electrocardiography for 1 minute at rest and during forced deep breathing. The following values were recorded: maximum expiratory and minimum inspiratory heart rate and the difference between them (ΔE/I), standard deviation of the heart rate values, interbeat intervals, and E/I[2] ratio. Spectral power analysis of heart rate variability was also performed.

Results: The patients with familial dysautonomia showed a lesser change in heart rate in response to the change in breathing pattern than the controls. Mean values in the study group were significantly higher for minimal inspiratory heart rate and significantly lower for ΔE/I, heart rate standard deviation and E/I ratio, indicating a non-flexible heart response and abnormal parasympathetic function. These findings were supported by power spectral analysis.

Conclusions: Patients with familial dysautonomia have a significantly disturbed response to physiological stimuli. The DBT may serve as a reliable means to quantify autonomic dysfunction in this patient population.

Background: Anti-ribosomal-P antibodies have been associated with central nervous manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn, or the different methods used for antibodies detection.

Objectives: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs[1] in patients with SLE[2] and normal controls.

Methods: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA[3] kits: Kit-1, which uses synthetic peptide comprising the 22 C-terminal amino-acids; Kit-2, which uses native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions.

Results: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS[4] manifestations and anti-Rib-P Abs was observed.

Conclusions: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future that enable a better assessment of anti-Rib-P Abs presence and clinical correlation. 

Background: Heart rate variability is a sensitive marker of cardiac sympathetic activity.

Objectives: To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV[1].

Methods: Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled. Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups. The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing.

Results:  One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls (25.6 ± 10.5 vs. 34.3 ± 12.6 beats/min, P < 0.05). There were no significant differences in mean, maximal and minimal heart rate between the groups

Conclusions: Thyroxine therapy administered for epithelial thyroid cancer resulted in subclinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate.

Chronic disease management has been a rapidly growing entity in the 21st century as a strategy for managing chronic illnesses in large populations. However, experience has shown that disease management programs have not been able to demonstrate their financial value. The objectives of disease management programs are to create quality benchmarks, such as principles and guidelines, and to establish a uniform set of metrics and a standardized methodology for evaluating them. In order to illuminate the essence of disease management and its components, as well as the complexity and the problematic nature of performing economic calculations of their profitability and value, we collected data from several reports that dealt with the economic intervention of disease management programs. The disease management economic evaluation is composed of a series of steps, including the following major categories: Data/information technology, information generation, assessment/recommendations, actionable customer plans, and program assessment/reassessment. We demonstrate the elements necessary for economic analysis. Disease management is one of the most innovative tools in the managed care environment and is still in the process of being defined. Therefore, objectives should include the creation of quality benchmarks, such as principles and guidelines, and the establishment of a uniform set of metrics and a standardized methodology for evaluating them.