Israel Medical Association Journal

Background: Fracture of the scaphoid is the most common fracture of a carpal bone. Nevertheless, the diagnosis of SF[1] might be challenging. Plain X-rays that fail to demonstrate a fracture line while clinical findings suggest the existence of such a fracture is not uncommon. Currently there is no consensus in the literature as to how a clinically suspected SF should be diagnosed, immobilized and treated.

Objectives: To assess the current status of diagnosis and treatment of clinically suspected scaphoid fractures in Israeli emergency departments

Methods: We conducted a telephonic survey among orthopedic surgeons working in Israeli EDs[2] as to their approach to the diagnosis and treatment of occult SF.

Results: A total of 42 orthopedic surgeons in 6 hospital EDs participated in the survey. They reported performing a mean of 2.45 ± 0.85 clinical tests, with tenderness over the snuffbox area being the sign most commonly used.  A mean of 4.38 ± 0.76 X-ray views were ordered for patients with a clinically suspected SF. The most common combination included posterior-anterior, lateral, semipronated and semisupinated oblique views. All participating surgeons reported immobilizing the wrists of patients with occult fractures in a thumb spica cast based on their clinical findings. Upon discharge from the ED patients were advised to have another diagnostic examination as follows: 29 (69%) repeated X-rays series, 18 (43%) were referred to bone scintigraphy and 2 (5%) to computed tomography; none were referred to magnetic resonance imaging.

Conclusions: No consensus was found among Israeli orthopedic surgeons working in EDs regarding the right algorithm for assessment of clinically suspected SF. There is a need for better guidelines to uniformly dictate the order and set of tests to be used in the assessment of occult fractures.

Background: The incidence of cardiovascular disease increases with age, and visits by elderly patients to the outpatient cardiac clinic are becoming more frequent.

Objectives: To characterize cardiovascular pathologies of patients 70 years of age and over who visit the outpatient cardiac clinic.

Methods: We investigated cardiovascular pathologies, risk factors, and medications in new patients over a 2 month period.

Results: The study population comprised 290 patients: 139 (47.9%) were older than 70 years. Among the cardiovascular pathologies, aortic stenosis, angina pectoris, congestive heart failure, s/p coronary artery bypass graft, and stroke were more frequent in the elderly patients than in those under age 70. Among the risk factors for ischemic heart disease, only hypertension was more frequent in the elderly population, whereas fewer in this group were active smokers. The mean number of medications administered was 3.51 ± 1.63 among the elderly patients compared to 1.99 ± 1.71 among the younger ones (P = 0.0001). Beta-blockers were the most frequently used cardiovascular drugs both in the elderly (59.7%) and in the younger patients (43%) (P = 0.0046).

Conclusions: Patients over age 70 represent about half the visits in our outpatient clinic. Their multiple cardiovascular pathologies and therapeutic requirements raise the issue of developing the cardiology service to meet the special needs of geriatric patients.
 

Background: The forced oscillation technique is a non-invasive and effort-independent technique and is well suited for lung function measurement in young children. FOT[1] employs small-amplitude pressure oscillations superimposed on normal breathing. Therefore, it has the advantage over conventional lung function techniques in that it does not require patient cooperation for conducting respiratory maneuvers.

Objectives: To test the feasibility of the FOT test in preschool children and to compare the results to the commonly used spirometry before and after the administration of bronchodilator therapy.

Methods: Forty-six children (median age 4.9 years, range 1.8–18.3) attending the Pulmonary Clinic at Schneider Children's Medical Center tried to perform FOT and routine spirometry. Results were retrospectively analyzed. 

Results: Of the 46 children 40 succeeded in performing FOT and only 29 succeeded in performing simple spirometry. All but one of the 32 children aged 4 years and above (97%) could perform both tests. Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%) could perform spirometry. Baseline values of respiratory resistance measured at 6 Hz (R6) negatively correlated with body length (r² = 0.68, P < 0.005). Twenty-four children performed both tests before and after bronchodilator therapy. A significant concordance was found between the measured responses to bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative response by FOT but a positive response by spirometry.

Conclusions: The FOT is a simple, non-invasive technique that does not require subject cooperation and thus can be utilized for measuring lung function in children as young as 2 years of age. Furthermore, the FOT was shown to reliably measure response to bronchodilator therapy.

Background: Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).

Objectives: To evaluate the migratory capacity and efficacy of NTF-SC[1] in animal models of Parkinson's disease and Huntington's disease.

Methods: MSCs[2] underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were transplanted on the day of 6-OHDA[3] administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acid-induced striatal lesion, a rat model for Huntington's disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology.

Results: NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington's disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA[4]-induced lesion.

Conclusions: The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue.

Background: The TANTALUS^™ System (MetaCure Ltd.) is a minimally invasive implantable device for the treatment of type 2 diabetes. The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. The system is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date.

Objectives: To re-analyze previously reported data from different studies. This retrospective analysis of the type 2 diabetes subpopulation analyzed the expected benefit and characterize the significance of baseline A1c in the determination of the expected clinical outcome.

Methods: From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the U.S., 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM[1] on a stable regime of oral medication for 3 months prior to implant were identified. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline.

Results: Data after 24 weeks demonstrate a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 ± 0.1%. The average weight loss was 5.5 ± 0.7 kg.

Conclusions: The results suggest that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

The incidence of aortic valve stenosis is growing rapidly in the elderly. Nonetheless, many symptomatic patients are not referred for surgery usually because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues were the first to describe percutaneous aortic valve implantation, opening a new era of aortic stenosis management. In the present review we report a patient treated by this novel method, discuss and assess how it is implanated, report the findings of studies conducted to date, and suggest future directions for percutaneous treatment of aortic valve disease.
 

Background: Monitoring the rate of infections in individual centers that treat patients with hematological malignancies is of major importance. However, there are no uniform guidelines for infection surveillance.

Objectives: To describe the epidemiology of bacterial and fungal infections in a single hematology ward and to compare methods for reporting surveillance and infection rates in other centers in Israel.

Methods: We conducted a prospective surveillance of all patients admitted to our hematology ward, applying standard definitions for invasive fungal infections and adapting definitions for non-fungal infections. Incidence rates were calculated using patients, admissions, hospital days and neutropenia days. We performed a search for other reported surveillance studies in Israel.

Results: We detected 79 infectious episodes among 159 patients admitted to the hematology ward during 1 year. Using neutropenia days as the denominator for calculation of incidence discriminated best between patients at high and low risk for infection. The incidence of invasive fungal infections was 7, 10 and 18 per 1000 neutropenia days, among all patients, those with acute leukemia and those with acute leukemia undergoing induction therapy, respectively. Only 10 reports from Israel were identified, 6 of which were prospective. Our data could not be compared to these reports because of the varying definitions and denominators used.

Conclusions: Hematology centers should monitor infection rates and report them in a uniform methodology.
 

Background: Aural cholesteatoma is an epidermal cyst of the middle ear or mastoid that can only be eradicated by surgical resection. It is usually managed with radical or modified radical mastoidectomy. Clinical diagnosis of recurrent cholesteatoma in a closed postoperative cavity is difficult. Thus, the accepted protocol in most otologic centers for suspected recurrence consists of second-look procedures performed approximately 1 year after the initial surgery. Brain herniation into a post-mastoidectomy cavity is not rare and can be radiologically confused with cholesteatoma on the high resolution computed tomographic images of temporal bones that are carried out before second-look surgery.

Objectives: To present our experience with meningoceles that were confused with recurrent disease in patients who had undergone primary mastoidectomy for cholesteatoma and to support the use of magnetic resonance imaging as more suitable than CT in postoperative follow-up protocols for cholesteatoma.

Methods: We conducted a retrospective chart review of four patients.

Results: Axial CT sections demonstrated a soft tissue mass in the middle ear and mastoid in all four patients. Coronal reconstructions of CT scans showed a tympanic tegmen defect in two patients. CT failed to exclude cholesteatoma in any patient. Each underwent a second-look mastoidectomy and the only finding at surgery was meningocele in all four patients.

Conclusions: Echo-planar diffusion-weighted MRI can differentiate between brain tissue and cholesteatoma more accurately than CT. We recommend that otolaryngologists avoid unnecessary revision procedures by using the newest imaging modalities for more precise diagnosis of the patients who had undergone mastoidectomy for cholesteatoma in the past.
 

Background: Although unprotected left main coronary artery disease is considered by contemporary guidelines to be an indication for surgery, percutaneous coronary intervention may be necessary in patients at high surgical risk.

Objectives: To assess the outcome of angioplasty in the treatment of unprotected LMCA[1] disease.

Methods: Angiographic and clinical data were collected prospectively for all patients who underwent emergent or non-emergent (planned) therapeutic PCI[2] for unprotected LMCA disease at our center from 2003 to 2007. Baseline values were compared with findings at 1, 6 and 12 months after the procedure.

Results: The study group comprised 71 consecutive patients with a mean age of 74 ± 12 years; 63% were men, and 31% had diabetes. Forty-three patients had a planned procedure and 28 an emergent procedure. Mean EuroScore was 7.3 ± 3.6 (range 5–12). Forty-nine percent of the procedures were performed with bare metal stents and 51% with drug-eluting stents. Procedural success was achieved in 100% of cases. The overall mortality rate was 11.3% at 1 month, 18.3% at 6 months and 19.7% at 12 months. Elective PCI was associated with significantly lower mortality (2.3% vs. 25% at 1 month, 4.6% vs. 39% at 6 months and 6.9% vs. 39% at 12 months), and the use of drug-eluting stents was associated with lower rates of target vessel revascularization and major adverse cardiac events than use of bare metal stents (2.8% vs. 14% at 1 month, 8.3% vs. 43% at 6 and 12 months). Variables that correlated with increased mortality or MACE[3] at 6 and 12 months were cardiogenic shock, emergent PCI, ejection fraction < 35%, renal failure, distal left main stenosis location, and reference diameter < 3 mm.

Conclusions: PCI is a feasible and relatively safe therapeutic option for unprotected LMCA. The less favorable outcome of emergent compared to planned PCI is probably attributable to the overwhelming acute myocardial ischemic injury in emergent cases. The use of drug-eluting stents may improve the intermediate-term restenosis rate.

[1] LMCA = left main coronary artery

[2] PCI = percutaneous coronary intervention

Background: Venous thromboembolism is a well-recognized and relatively frequent complication of malignancy, whereas tumor thrombosis is a rare complication of solid cancers. Correct diagnosis of tumor thrombosis and its differentiation from VTE[1] can alter patient management and prevent unnecessary long-term anticoagulation treatment.

Objectives: To evaluate the contribution of 18F-fluorodeoxyglucose positron emission tomography/computed tomography to the diagnosis of tumor thrombosis and its differentiation from VTE.

Methods: PET/CT[2] scans from 11 patients with suspected tumor thrombosis were retrospectively evaluated. Suspicion arose from positive PET/CT in eight cases, or from findings on contrast-enhanced CT in three patients. Criteria for positivity of PET/CT included increased focal or linear uptake of 18F-FDG[3] in the involved vessel. Findings were categorized as PET/CT positive, or PET/CT negative and compared to contrast-enhanced or ultrasound Doppler, pathology where available, and clinical follow-up.

Results: Eight occult tumor thromboses were identified by PET/CT-positive scans. Underlying pathologies included pancreatic, colorectal, renal cell, and head-neck squamous cell carcinoma, as well as lymphoma (4 patients). Three thrombotic lesions on contrast-enhanced CT were PET/CT negative, due to VTE (2 patients) and leiomyomatosis. Accuracy of PET/CT to differentiate between tumor thrombosis and benign VTE was 100% in this small study.

Conclusions: Contrast-enhanced CT defines the extent of thrombotic lesions, while the functional information from PET/CT characterizes the lesions. It appears that PET/CT may be helpful in the diagnosis of occult tumor thrombosis and its differentiation from VTE.