Israel Medical Association Journal

Background: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken.

Objectives: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease.

Methods: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of co-morbidities, fasting lipid profile and anti-LPL antibodies.

Results: Mean patient age was 55 ± 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 ± 3.6 kg/m²; 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 ± 111 mg/dl. High-density lipoprotein was 42.6 ± 15.4 mg/dl, low-density lipoprotein 110.7 ± 42.4 mg/dl and very low-density lipoprotein 48 ± 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels.

Conclusions: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.
 

Background: Fractures of the humerus in neonates can pose a diagnostic challenge, especially when the fracture occurs in the proximal or distal epiphysis.

Objectives: To review our experience in the diagnosis and treatment of birth-related humeral fractures.

Methods: Between the years 2001 and 2009, seven newborn patients and two patients treated in the neonatal intensive care unit sustained a fracture of the humerus. Four of the fractures occurred in the humeral shaft, three in the proximal epiphysis and two in the distal epiphysis. In all the newborn patients the diagnosis was made on the first day of life using radiography and ultrasonography. The fractures of the shaft and of the distal epiphysis were treated by gentle manipulation and casting, and the fractures of the proximal epiphysis were treated by swaddling.

Results: All of the patients demonstrated fracture union within 2 weeks, and radiographs at the age of 6 months demonstrated complete remodeling of the fracture.

Conclusions: Ultrasonography is a simple, readily available and inexpensive modality for the diagnosis of birth-related fractures of the humerus, especially in the yet unossified epiphyses.

Hypercholesterolemia is one of the main factors in the development of atherosclerotic cardiovascular disease. The advent of statins led to huge progress in the treatment of hypercholesterolemia, yet the proportion of patients with prohibitive lipid values and the high incidence of cardiovascular events despite treatment are still very high. Niacin, one of the older drugs used to treat hyperlipidemia, was shown to reduce low-density lipoprotein-cholesterol (LDL-C) and triglycerides and to markedly increase high-density lipoprotein-cholesterol (HDL-C) levels. This drug came into disuse owing to frequent side effects, mainly flushing, but in recent years a reemergence of its application has occurred, and multiple clinical trials have shown its effectiveness in the treatment of hyperlipidemia and in the reduction in cardiovascular events. New formulations such as extended-release niacin (ERN) have been developed with the purpose of reducing side effects. Lately, a new compound, laropiprant, which selectively antagonizes the prostaglandin 2 (PGD2) receptor responsible for flushing, has been developed. Laropiprant, when combined with ERN,[1] significantly reduces the incidence of flushing. New and ongoing trials will definitively prove in the long term whether this drug combination significantly reduces the severity of flushing and the incidence of cardiovascular events.

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: Glioblastoma multiforme (GBM) is an ultimately fatal disease that affects patients of all ages. Elderly patients (65 years and older) constitute a special subgroup of patients characterized by a worse prognosis and frequent comorbidities.

Objectives: To assess the efficacy of different treatment modalities in terms of survival in elderly patients with GBM¹.

Methods: Using retrospective analysis, we extracted, anonymized and analyzed the files of 74 deceased patients (aged 65 or older) treated for GBM in a single institution.

Results: Mean survival time was 8.97 months and median survival time 7.68 months. Patients who underwent tumor resection had a mean survival of 11.83 months, as compared to patients who underwent no surgical intervention or only biopsy and had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full radiation treatment had a mean survival of 11.31 months, compared to patients who received only partial radiotherapy or none at all and had a mean survival of 4.09 months (P < 0.0001). Patients who underwent chemotherapy had a mean survival 12.4 months, compared to patients who did not receive any chemotherapy and had a mean survival of 5.89 months (P < 0.001).

Conclusions: Age alone should not be a factor in the decision on which treatment should be given. Treatment should be individualized to match the patient’s overall condition and his or wishes, while taking into consideration the better overall prognosis expected with aggressive treatment.
 

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.