Israel Medical Association Journal

Background: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms.

Objectives: To assess the effectiveness of climatotherapy at the Dead Sea on the production of vitamin D in Norwegian patients suffering from various rheumatic diseases and to investigate possible associations between increased vitamin D serum levels, musculoskeletal symptoms and disease severity.

Methods: Sixty Norwegian patients who came to the Dead Sea area for 21 days of medical rehabilitation were divided into three groups according to their diagnosis: chronic pain syndromes, i.e., low back pain or fibromyalgia (Group 1, n=33); rheumatoid arthritis (Group 2, n=16); and osteoarthritis (Group 3, n=11). Serum 25-hydroxyvitamin D (25-OH-D) levels were determined at arrival and prior to departure. The treatment protocol included daily sun exposure (climatotherapy), bathing in the Dead Sea and mineral spring water (balneotherapy), mud applications and fitness classes.

Results: 25-OH-D serum levels increased significantly from 71.3 ± 26.6 nM at arrival to 89.3 ± 23.2 nM prior to departure (P < 0.001). Adjusted for the initial levels of pain (assessed by a visual analog scale) and disease severity, a direct correlation was observed between increased 25-OH-D serum levels and pain reduction (P = 0.012) and reduction of disease severity (P = 0.02).

Conclusions: Climatotherapy at the Dead Sea induces significant changes in vitamin D. Increased 25-OH-D serum levels are associated with reduced musculoskeletal pain and disease severity.
 

Background: Rapid reperfusion of an infarct-related artery is crucial for the successful treatment of ST elevation myocardial infarction. Every effort should be made to shorten door-to-balloon time.

Objectives: To investigate whether bypassing the emergency room (ER) has a positive influence on door-to-balloon time in patients presenting with ST elevation myocardial infarction (STEMI) and whether the reduction in door-to-balloon time improves patients’ clinical outcome.

Methods: We analyzed data of 776 patients with STEMI[1] from the 2004 and the 2006 Acute Coronary Syndrome Israeli Survey (ACSIS) registry. The ACSIS[2] is a biennial survey on acute myocardial infarction performed in all 25 intensive cardiac care units in Israel during a 2-month period. Twenty-five percent of patients (193 of 776) arrived directly to the intensive cardiac care unit (ICCU) and 75% (583 of 776) were assessed first in the ER[3]. We compared door-to-balloon time, ejection fraction, 30 days MACE (major adverse cardiac and cerebrovascular events) and 30 days mortality in the two study groups.

Results: There was significantly shorter door-to-balloon time in the direct ICCU group as compared with the ER group (45 vs. 79 minutes, P < 0.002). Patients in the direct ICCU group were more likely to have door-to-balloon time of less than 90 minutes in accordance with ACC/AHA guidelines (88.7% vs. 59.2%, P < 0.0001). Moreover, patients in the direct ICCU group were less likely to have left ventricular ejection fraction < 30% (5.4% vs. 12.2%, P = 0.045) and less likely to have symptoms of overt congestive heart failure. Lastly, 30 days MACE[4] was significantly lower in the direct ICCU group (22 vs. 30%, P < 0.004).

Conclusions: There is significant reduction of the door-to-balloon time in the direct ICCU admission strategy. This reduction translates into improvement in clinical outcome of patients. It is reasonable to apply the direct ICCU strategy to patients with STEMI.

Background: Internet use by patients as a source of information on health and disease is expanding rapidly with obvious effects on the doctor-patient relationship. Many of these effects remain undocumented or are poorly understood.

Objectives: To assess the use of the internet  for health information by patients in primary care in Israel and their perception of the effects of internet use on their relationship with their doctor.

Methods: A cross-sectional survey was conducted among a convenience sample of patients visiting 10 primary care clinics in central Israel using a questionnaire developed for this survey. The survey examined attitudes to using the internet for health-related information and attitudes to sharing this information with doctors. Associations between demographic variables, internet use and patient satisfaction with the doctor’s response were tested using the chi-square statistic and t-tests.

Results: Completed questionnaires were received from 138 patients; the response rate was 69%. Patients in the study sample had a high rate of internet access (87%), with many using the internet as a source of health information (41%) although most patients using the internet never share this information with their doctor (81%). Among those who share information with the doctor, most felt that this has a positive effect on the relationship (87%). Few patients reported being referred to websites by the doctor (28%).

Conclusions: Internet use is prevalent in this population, though physicians may be unaware of this. Future study may examine the effects of doctors who ask patients actively about their internet use and inform them of relevant health information sources online.

Background: Community-acquired pneumonia requiring hospitalization is a severe illness with high mortality, especially if the appropriate treatment is delayed. Sometimes diagnosis is difficult due to an equivocal clinical picture or chest film, or to accompanying diseases that mask or simulate pneumonia.

Objectives: To assess the usefulness of certain inflammatory markers to differentiate pulmonary edema from pneumonia throughout the hospital stay in patients admitted for pneumonia or pulmonary edema of non-infectious origin and to monitor the response to treatment.

Methods: The study group comprised 50 patients admitted for pneumonia, 50 admitted for pulmonary edema and 30 healthy individuals. Blood samples for determination of leukocyte count, erythrocyte sedimentation rate (ESR), fibrinogen, C-reactive protein (CRP), albumin, sCD14 and oxidized fibrinogen were drawn upon admission, at 48 and 72 hours after admission, and at discharge from the intensive care unit.

Results: The levels of sCD14 were similar in both patient groups but higher than control levels during the first 48 hours (P < 0.03). They decreased gradually with hospital stay. The concentration of oxidized fibrinogen was similar in both patient groups and significantly lower than that of the healthy control group throughout the hospitalization period.

Conclusions: Oxidized fibrinogen and sCD14 are not reliable markers for the diagnosis of pneumonia, for its differential diagnosis from pulmonary edema, and for patient follow-up throughout hospitalization. The finding of elevated levels of oxidized fibrinogen in the group of healthy controls warrants further study to identify the factors responsible for altering fibrinogen oxidation. The other markers are more indicative.
 

Background: Intravitreal injections of the anti-vascular endothelial growth factor (VEGF) drugs bevacizumab (Avastin®) and ranibizumab (Lucentis®) became the mainstay of treatment for various retinal pathologies, but there is no consensus among ophthalmologists on the precise use of these drugs.

Objectives: To describe the current application of anti-VEGF[1] drugs among retinal specialists in Israel.

Methods: A questionnaire was sent via email to all 62 members of the Israeli Society of Retinal Specialists. The survey included 34 questions on various aspects of the use of anti-VEGF drugs: diagnosis, treatment, follow-up of different retinal pathologies, and the measures taken for ensuring sterile administration of the intravitreal injections.

Results: Fifty members (80%) completed the survey. Most of them (56%) offered both bevacizumab and ranibizumab to their patients for age-related macular degeneration, but 70% were influenced by the patient’s socioeconomic status. Three consecutive monthly injections were usually recommended (58%) for the first 3 months, and treatment was extended as long as subretinal or intraretinal fluids persisted (57%). Over two-thirds (68%) switched the drugs after the 3-monthly series if the first one yielded no improvement in fluid status. The routine practice for intravitreal injection (> 80%) involved the wearing of sterile gloves, using an eyelid speculum, and administering povidone-iodine pretreatment and topical antibiotics after treatment.

Conclusions: Intravitreal VEGF administration varies widely among Israeli retinal specialists. The current survey is intended to assist Israeli ophthalmologists in establishing their own treatment strategy for patients with retinal pathologies.  

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Tumor necrosis factor-alpha (TNFα) inhibitors may influence flow-mediated vasodilation (FMD) of the brachial artery, common carotid intima-media thickness (ccIMT) and arterial stiffness indicated by pulse-wave velocity (PWV) in RA.

Objectives: To assess the effects of adalimumab treatment on FMD[1], ccIMT[2] and PWV[3] in early RA[4].

Methods: Eight RA patients with a disease duration ≤ 1 year received 40 mg adalimumab subcutaneously every 2 weeks. Ultrasound was used to assess brachial FMD and ccIMT. PWV was determined by arteriograph. These parameters were correlated with C-reacive protein, vonWillebrand factor (vWF), immunoglobulin M (IgM)-rheumatoid factor (RF), anti-CCP levels and 28-joint Disease Activity Score (DAS28).

Results: Adalimumab therapy successfully ameliorated arthritis as it decreased CRP[5] levels (P = 0.04) and DAS28[6] (P < 0.0001). Endothelial function (FMD) improved in comparison to baseline (P < 0.05). ccIMT decreased after 24 weeks, indicating a mean 11.9% significant improvement (P = 0.002). Adalimumab relieved arterial stiffness (PWV) after 24 weeks. Although plasma vWF[7] levels decreased only non-significantly after 12 weeks of treatment, an inverse correlation was found between FMD and vWF (R = -0.643, P = 0.007). FMD also inversely correlated with CRP (R = -0.596, P = 0.015). CRP and vWF also correlated with each other (R = 0.598, P = 0.014). PWV and ccIMT showed a positive correlation (R = 0.735, P = 0.038).

Conclusions: Treatment with adalimumab exerted favorable effects on disease activity and endothelial dysfunction. It also ameliorated carotid atherosclerosis and arterial stiffness in patients with early RA. Early adalimumab therapy may have an important role in the prevention and management of vascular comorbidity in RA.

Background: Meningiomas are frequently detected incidentally. Their natural history has not yet been established because it is difficult to predict the growth pattern. Therefore, the management, after the radiological diagnosis, is still controversial.

Objectives: To evaluate the clinical outcome and growth rate of conservatively treated meningiomas at our tertiary center, identify prognostic factors of tumor growth, and suggest guidelines based on the available data and our experience.

Methods: We reviewed the clinical records of 56 patients with 63 untreated meningiomas. Most were diagnosed incidentally. Clinical features and imaging findings at diagnosis and during follow-up were compared between growing and non-growing tumors. Potential patient- and tumor-related predictive factors for growth were analyzed.

Results: The study group included 46 women (52 meningiomas) and 10 men (11 meningiomas) aged 39–83 years. Mean tumor size was 18 ± 11 mm (range 3–70 mm) at diagnosis and 22 ± 11 mm (range 8–70 mm) at last follow-up; mean follow-up time was 65 ± 34 months (range 15–152 months). During follow-up 24 tumors (38%) grew at a rate of 4 mm per year; none became symptomatic. Only two prognostic factors were statistically significantly associated with low growth rate: older age and tumor calcifications.

Conclusions: Given our finding of a low growth incidence of meningiomas in the elderly, we support conservative management in patients aged 70 years or older. Calcifications into the meningioma are also indicative of slow growth, suggesting a conservative strategy. Surgery is recommended in younger patients in whom tumor growth occurs more often and a longer follow-up is necessary.
 

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.

Background: One of the major concerns in performing nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) is the risk of tumor recurrence.

Objectives: To assess the rate, predictors and mechanisms of oncological failure in patients after NSS[1] for renal cancer.

Methods: Between 1993 and 2008 NSS was performed in 229 patients via flank incision. Only patients without metastases at diagnosis and minimal 12 months follow-up were included in the outcome analysis.

Results: During a mean follow-up of 45 ± 34 months (range 6–168 months) tumor recurrence was observed in 13 patients (5.6%). Mean follow-up time for detection of oncological failure was 51 months (range 6–132 months).  All patients with oncological failure were males, with a mean age of 61 years (median 58, range 51–74 years). The average size of the enucleated lesion was 5 cm (range 4–7 cm). Intraoperative frozen sections as well as postoperative final pathological examination of the surgical margins were negative in all recurrent cases. Mechanisms of recurrence were distant metastases (n=4), surgical scar implantation (n=2), perirenal fat recurrence (n=2), local renal recurrence at the surgical site (n=1), and new renal lesions (n=4). Predictors of oncological failure included warm ischemia time (P = 0.058), tumor size (P = 0.001), tumor location (central versus peripheral) (P = 0.015), and multifocality (P = 0.001).

Conclusions: Distant dissemination, seeding during surgery, residual disease and new growth are the mechanisms responsible for cancer relapse. Large central lesions, long warm ischemia time and multifocality were significant predictors of oncological failure.