Israel Medical Association Journal

Background: Acute kidney injury remains a common significant clinical problem. Yet there are scant data in Israel on the incidence of hospital-acquired AKI[1] and on diagnosis validity.

Objectives: To describe the epidemiology of AKI among hospitalized patients in the Western Galilee Hospital, Nahariya, compare discharge summaries to laboratory diagnosis, and investigate the impact of AKI on mortality and length of stay.

Methods: Computerized medical and laboratory data of 34,802 hospitalized subjects were collected. AKI was diagnosed according to three different definitions. We calculated the sensitivity and specificity of AKI based on ICD-9 diagnosis compared to patient's laboratory data as the gold standard.

Results: The overall AKI annual incidence rate was 1–5.1%, depending on the AKI definition used. The incidence of AKI based on ICD-9 diagnosis was significantly lower compared to the laboratory-based diagnosis. Average in-hospital length of stay was 2.4 times longer among patients with AKI compared to subjects without this condition. Furthermore, the in-hospital death rate among AKI patients was 14 times higher than among non-AKI hospitalized subjects, with a positive association between AKI severity and risk of death.

Conclusions: Using AKI laboratory diagnosis as the gold standard revealed ICD-9 diagnosis to be 9.1% sensitive and 99.4% specific. Hospital-acquired AKI is a major contributor to prolonged length of stay and high mortality rates; therefore, interventions to reduce in-hospital disease incidence are required.

Background: Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University ocular oncology clinic has become a referral center for uveal melanoma patients.

Objectives: To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988–2007.

Methods: Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software.

Results: Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 ± 7.1 new cases per year (mean ± standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 ± 16.5 years (range 5–95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma.

Conclusions: Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Background: The causative role of diffuse macular edema in various etiologies is often undetermined.

Objectives: To describe an association between extrafoveal vitreous traction and non-diabetic diffuse macular edema secondary to various ocular entities.

Methods: In a retrospective study of eyes with non-diabetic diffuse macular edema, charts and optical coherence tomography scans demonstrating extrafoveal vitreous traction were analyzed. Excluded were diabetic patients and eyes that had vitreofoveal traction. A control group (n=12) allowed for mapping of normal macular thickness.

Results: Five eyes with macular edema were associated with extrafoveal traction, each secondary to and representing a different etiology. The causes were penetrating injury, cataract extraction, branch retinal vein occlusion, central retinal vein occlusion, and idiopathic. Vitreous traction was detected either at the papillomacular bundle (n=3), superonasally to the fovea (n=1), and at the optic nerve head (n=1). The associated retinal edema (all eyes) and serous retinal detachment (four eyes) at the traction sites were in continuum with the foveal edema in each eye, manifesting as diffuse macular edema. Of the two modalities, the OCT[1]-Line group program and the OCT-Automatic central program, only the former enabled detection of extrafoveal traction in each.

Conclusions: Diffuse macular edema secondary to various ocular diseases may be associated with extrafoveal vitreous traction. The OCT-Automatic central program may omit some of these extrafoveal traction sites. Further studies are required to validate these findings and to assess whether early vitrectomy may improve visual prognosis in these eyes.

Background: Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules.

Objectives: To correlate FNA[1] cytology results with surgical pathological findings in two teaching medical centers across the Atlantic.

Methods: We retrospectively identified 484 patients at Hadassah University Hospital, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only).

Results: The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P p <0.05).

Conclusion: The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.

Head and neck cancer is the sixth most common cancer worldwide. HNCs[1] can originate in the skin or soft tissue, in the upper aerodigestive tracts (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, salivary glands), or in the thyroid. In each of these sites, tumors vary not only by the primary site but also by pathophysiology, biological behavior and sensitivity to radiotherapy or chemotherapy. Management should be planned according to the tumor's characteristics, patient factors and expertise of the medical team. The main goals of therapy are ablation of the cancer while minimizing morbidity and preserving function and cosmesis. A multidisciplinary team is needed to achieve these goals. Early-stage HNC (stage I and II) should be managed with a single modality, and advanced tumors (stage III and IV) with multimodality therapy. Treatment should be directed to the primary tumor and the area of its lymphatic drainage – the neck lymph nodes. Evidence of metastases in the neck necessitates comprehensive clearance of regional lymphatic basins. However, even if there is no evidence of lymph nodes metastases, when the risk for positive neck lymph nodes exceeds 15–20% elective neck dissection is indicated. Advances in minimally invasive techniques now enable reliable microscopic and endoscopic procedures that mimic the open approaches. Development of contemporary surgical techniques and reconstructive means will help improve the quality of life of patients and prolong survival.

There are isolated cases of physicians who murdered their patients. However, never had a single physician personally supervised the mass murder of hundreds of thousands of individuals, until Dr. Irmfried Eberl. Commander of the Nazi death camp Treblinka, he killed both the ill and those he considered "a disease to his nation." At age 32 Dr. Eberl established Treblinka, where he was responsible for the killing of approximately 280,000 individuals within a few weeks. The position of camp commandant was earned following his success as head of two psychiatric hospitals in Germany where he coordinated the murder of thousands of mentally ill Jews and non-Jews within the context of the euthanasia program. However, few in medicine have heard of him or the harm he caused to the ethical practice of the profession and to human rights.

Background: Despite progress in medical and surgical care the mortality rate of congenital diaphragmatic hernia remains high. Assessment of short-term outcome is important for comparison between different medical centers.

Objectives: To evaluate the short-term outcome of infants born with symptomatic CDH[1] and to correlate demographic and clinical parameters with short-term outcome.

Methods: We performed a retrospective cohort study in which demographic, obstetric and perinatal characteristics were extracted from infants' files. For comparison of categorical variables chi-square test and Fisher's exact test were used and for continuous variables with categorical variables the Mann-Whitney test was used. Sensitivity and specificity were estimated by receiver operator curve.

Results: The study group comprised 54 infants with CDH, of whom 20 (37%) survived the neonatal period. Demographic characteristics were not associated with survival. Regarding antenatal characteristics, absence of polyhydramnion and postnatal diagnosis were correlated with better survival. Apgar scores (above 5 at 1 minute and 7 at 5 minutes), first arterial pH after delivery (above 7.135) and presence of pulmonary hypertension were significantly correlated with survival. Also, infants surviving up to 6 days were 10.71 times more likely to survive the neonatal period.

Conclusions: The survival rate of symptomatic newborns with CDH at our center was 37% for the period 1988–2006. Prenatal diagnosis, Apgar score at 5 minutes and first pH after delivery were found to be the most significant predictors of survival. Prospective work is needed to evaluate the long-term outcome of infants with CDH.

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: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

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.

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.