Israel Medical Association Journal

Background: Several murine models are susceptible to atherosclerosis, such as low density-lipoprotein receptor-deficient (LDLR^-/-) and apolipoprotein E-deficient (apoE^-/-) mice, and are used for studying pathophysiological mechanisms. Atherosclerotic lesions in the aortic valve and thoracic/abdominal aorta are commonly associated with hyperlipidemia. We recently demonstrated the development of large atherosclerotic plaques in Helicobacter pylori-infected heterozygous LDLR^+/- apoE^+/- mice.

Objectives: To measure novel biomarkers related to atherosclerosis, blood coagulation, and oxidative stress in order to investigate their possible pathogenic roles in atherosclerosis-prone mice.

Methods: Mice were fed with a normal chow diet or high-fat diet and sacrificed at different age intervals to measure aortic plaque size. Plasma cholesterol was enzymatically measured. Enzyme-linked immunosorbent assay was used to measure oxidized LDL (oxLDL)/beta-2-glycoprotein I (β2GPI) complexes, immunoglobulin M (IgM) antibodies against native LDL, oxLDL, or oxLDL/β2GPI, and urine 11-dehydro-thromboxane B₂ (11-dhTxB₂) or 8-hydroxy-deoxyguanosine.

Results: There was a parallel increase in plaque size, plasma cholesterol, and urinary 11-dhTxB₂ in atherosclerosis-prone mice. In contrast to atherosclerosis-prone strains, an elevation of urinary 11-dhTxB₂ with no significant plaque generation was observed in LDLR^+/- apoE^+/- mice. The atherogenic autoantigen oxLDL/β2GPI complex was detected only in LDLR^-/- mice. These levels seem to depend on plaque size. IgM antibodies against oxLDL in apoE^-/- mice were found, accompanied by atherosclerotic progression.

Conclusions: Progression of atherosclerotic lesions was associated not only with cholesterolemia but also with platelet activation and natural autoimmune-mediated regulatory mechanism(s) in murine models.
 

Background: Total cholesterol is significantly associated with increased risk of ischemic stroke. Patients with ischemic stroke and high cholesterol levels may show better functional outcome after rehabilitation.

Objectives: To study the possible interrelations between hypercholesterolemia and functional outcome in elderly survivors of ischemic stroke.

Methods: We conducted a retrospective chart review study of consecutive patients (age ≥ 60 years) with acute stroke admitted to a geriatric rehabilitation ward in a university-affiliated hospital. The presence or absence of hypercholesterolemia was based on registry data positive for hypercholesterolemia, defined as total cholesterol ≥ 200 mg/dl (5.17 mmol/L). Functional outcome of patients with hypercholesterolemia (Hchol) and without (NHchol) was assessed by the Functional Independence Measurement scale (FIM^TM) at admission and discharge. Data were analyzed by t-test and chi-square test, as well as linear regression analysis.

Results: The complete data for 551 patients (age range 60–96 years)w ere available for final analysis; 26.7% were diagnosed as having hypercholesterolemia. Admission total FIM[1] scores were significantly higher in patients with Hchol[2] (72.1 ± 24.8) compared with NHchol[3] patients (62.2 ± 24.7) (P < 0.001). A similar difference was found at discharge (Hchol 90.8 ± 27.9 vs. NHchol 79.7 ± 29.2, P < 0.001). However, total FIM change upon discharge was similar in both groups (18.7 ± 13.7 vs. 17.6 ± 13.7, P = 0.4). Regression analyses showed that high Mini Mental State Examination scores (β = 0.13, P = 0.01) and younger age (β = -0.12, P = 0.02) were associated with higher total FIM change scores upon discharge. Total cholesterol was not associated with better total FIM change on discharge (β = -0.012, P = 0.82).

Conclusions: Elderly survivors of stroke with Hchol who were admitted for rehabilitation showed higher admission and discharge FIM scores but similar functional FIM gains as compared to NHchol patients. High cholesterol levels may be useful in identifying older individuals with a better rehabilitation potential.

Background: Major changes in the evaluation and treatment of curable colorectal cancer (CRC) have emerged in the last two decades. These changes have led to better patient outcome over time.

Objectives: To evaluate the impact of these changes as reflected in the difference in long-term outcome of a consecutive group of recently laparoscopically operated curable CRC[1] patients and a consecutive group of patients operated 20 years earlier in the same department.

Methods: Data of the new group were taken from our prospectively collected data of patients who underwent elective laparoscopic surgery for CRC in recent years. Data regarding patients operated on 20 years ago were retrieved from previous prospectively collected data on the long-term survival of CRC patients operated in the same department.

Results: The recently operated group comprised 203 patients and the previous group 199 patients. Perioperative mortality was 0.5% in the new group versus 1.5% in the old group (not significant). There were more early-stage and more proximal tumors in the recently operated group. A Kaplan-Meier 5-year survival analysis revealed no difference between stage I patients of the two groups. However, there was a significant increase in 5-year survival in the new group for stage II (85% vs. 63%, P = 0.004) and for stage III patients (57% vs. 39%, P = 0.01). This trend was maintained after removing the rectal cancer patients from the calculated data.

Conclusions: We have demonstrated improved survival for stage II and III CRC patients over a 20-year period in the same medical center. This change most likely reflects advances both in imaging techniques leading to more accurate staging and in adjuvant treatments.

Intussuception is the most common cause of intestinal obstruction in early childhood. The cause of most intussusceptions is unknown but it can complicate the course of Henoch-Schonlein purpura (HSP) as a result of the vasculitic process. Familial Mediterranean fever (FMF), a most common disease in Israel is also associated with HSP. In a few patients, particularly in children, HSP has been reported to precede the diagnosis of FMF. We describe two patients with an unusual clinical course of severe abdominal pain as a result of intusucception. The correlation between intusucception, HSP and FMF are discussed.
 

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: Esophageal perforations and postoperative esophageal leaks are associated with substantial morbidity and mortality and pose a difficult therapeutic challenge. 

Objectives: To evaluate the outcome of removable self-expanding metallic stents (SEMS) as a treatment for postoperative leaks and perforations of the esophagus and stomach.

Methods: We conducted a retrospective study of all patients in one medical center who underwent temporary insertion of a covered plastic stent for postoperative leaks and perforations of the esophagus and stomach from June 2009 to February 2010. Data were retrieved from hospital and outpatient clinical data charts. Data included indication for insertion, post-insertion outcome including stent complications, and follow-up after stent removal.

Results: The indications for stent insertion were postoperative leak in four patients and postoperative esophagopleural fistula in one patient. Three of the patients had a leak at the gastro-esophageal junction following laparoscopic sleeve gastrectomy. In all cases the stent insertion was completed successfully. In three patients the stent migrated distally. In two of these three it was repositioned or replaced endoscopically, and in the third it was excreted in the feces. Stents were removed electively after 6 to 7 weeks. All patients recovered fully and were discharged from the hospital.

Conclusions: SEMS insertion may have an important role in the management of postoperative leaks and perforations of the esophagus and stomach and should be considered in such cases.
 

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: 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: 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.

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.