Israel Medical Association Journal

We present a literature review of collaborative enterprises between psychiatrists and primary care physicians in Israel and other countries. Also described are local psychiatric liaison initiatives in Israel, as well as landmark studies of collaborative psychiatric care. These studies demonstrate the superiority of community psychiatric liaison models in the treatment of patients suffering from depressive anxiety disorders and somatization disorder. In light of the mental health reform process currently underway in Israel, it is important to develop, implement and assess such liaison models. 

Background: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable.

Objectives: To evaluate the association of biomarkers with coronary and carotid disease.

Methods: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery. Biochemical markers of cardiovascular disease risk were obtained at the time of coronary angiography, including serum lipid levels, hemoglobin A1C (HbA1c), white blood cell count, fibrinogen and high sensitivity C-reactive protein (hs-CRP).

Results: The mean age of the patients was 66 ± 11; 73% were males. Significant carotid stenosis was associated with higher hs-CRP (9.4 ± 17 vs. 6.3 ± 13 mg/L, P = 0.001), while high HbA1c (6.7 ± 1.6 vs. 5.8 ± 0.8%, P < 0.001) and low high density lipoprotein levels (40 ± 9 vs. 47 ± 14 mg/dl, P < 0.001) were linked with advanced coronary artery disease severity. In contrast, CIMT was not related to any of the biomarkers evaluated.

Conclusions: Although atherosclerosis is considered a systemic disease, different biomarkers are associated with coronary and carotid artery disease. Identifying the specific biomarkers for each disease is important for both prevention and for exposing the underlying pathophysiologic mechanism.

 

Background: Granulomatous lobular mastitis (GLM) is a rare disorder that can clinically mimic breast carcinoma. The recommendation for diagnosis and treatment of GLM has not yet been established. 

Objectives: To assess a series of GLM patients, including their clinical presentation, diagnosis, treatment and outcome. 

Methods: We retrospectively analyzed the clinical data and treatment of 17 female patients with biopsy-proven GLM. Breast tissue was obtained by a core needle biopsy (15 patients) or open biopsy (2 patients). Images were reviewed by an experienced radiologist.

Results: The mean age of the patients at diagnosis was 44.6 ± 12.6 years. Five patients (29%) presented with bilateral disease, and seven (41%) presented with a mass, suggesting the initial diagnosis of breast carcinoma. Treatment comprised observation alone (23%), antibiotics (58.8%) and/or corticosteroids (with or without methotrexate) (35%). At the end of the study 70.6% of the patients demonstrated complete remission. None of the patients developed any systemic (granulomatous) disease or breast carcinoma during the follow-up period (4.7 ± 3.8 years). 

Conclusions: Core needle biopsy is mandatory for the diagnosis of GLM and the exclusion of breast carcinoma. The recommended treatment modalities are observation alone or corticosteroids; surgery should be avoided. GLM is a benign disease with a high rate of resolution and complete remission.

 

Background: Anemia confers an adverse prognosis in patients with ST-elevation myocardial infarction (STEMI). Several mechanisms have been implicated in the etiology of anemia in this setting, including inflammation, blood loss, and the presence of comorbidities such as renal failure.

Objectives: To evaluate the adequacy of bone marrow response as potentially reflected by elevation in blood and reticulocyte counts.

Methods: Consecutive men with STEMI who underwent primary percutaneous intervention within 6 hours of symptom onset and who presented to our catheterization laboratory during a 36 month period were included in the study. The cohort was divided into quartiles according to hemoglobin concentration, and differences in clinical and laboratory characteristics between the groups were evaluated.

Results: A total of 258 men with STEMI were recruited, 22% of whom suffered from anemia according to the World Health Organization classification (hemoglobin < 13 g/dl). Men in the lowest quartile of hemoglobin concentration presented with significantly lower white blood cell and platelet counts (9.6 ± 2.9 vs. 12.6 ± 3.6 x103/µl, P < 0.001) and (231 ± 79 vs. 263 ± 8 x103/µl, P < 0.01), respectively, despite higher inflammatory biomarkers (C-reactive protein and fibrinogen) compared with patients in the upper hemoglobin concentration quartile. Reticulocyte production index was not significantly higher in anemic patients with a value of 1.8, 1.4, 1.5 and 1.6 in the ascending hemoglobin quartiles, respectively (P = 0.292). 

Conclusions: Anemic men with STEMI have relatively lower leukocyte and platelet counts as well as a reduced reticulocyte count despite higher inflammatory biomarkers. These findings might suggest inadequate bone marrow response. 

 

Abstract

Background: In the era of primary percutaneous coronary intervention (PPCI), information on the incidence and prognostic significance of high degree atrioventricular block (AVB) in ST elevation myocardial infarction (STEMI) patients is limited.

Objectives: To assess the incidence, time of onset, predictors and prognostic significance of high degree AVB in a large cohort of consecutive STEMI patients undergoing PPCI.

Methods: We retrospectively studied 1244 consecutive STEMI patients undergoing PPCI. Patient records were reviewed for the presence of high degree AVB, its time of occurrence and relation to in-hospital complications, as well as long-term mortality over a 5 year period.

Results: High degree AVB was present in 33 patients (3.0%), in 25 (76%) of whom the conduction disorder occurred prior to PPCI. Twelve patients (36%) required temporary pacing, all prior to or during coronary intervention, and all AVB resolved spontaneously before hospital discharge. AVB was associated with a significantly higher 30 day (15 % vs. 2.0%, P = 0.001) and long-term mortality rate (30% vs. 6.0%, P < 0.001). Time of AVB had no effect on mortality. In a multivariate regression model, AVB emerged as an independent predictor for long-term mortality (hazard ratio 2.8, 95% confidence interval 1.20–6.44, P = 0.001).

Conclusions: High degree AVB remains a significant prognostic marker in STEMI patients in the PPCI era, albeit transient.

Abstract

Background: Renal hemangiomas are rare benign tumors seldom distinguished from malignant tumors preoperatively.

Objectives: To describe the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with diagnosing and treating renal hemangiomas, and to explore possible clinical and radiologic features that can aid in diagnosing renal hemangiomas preoperatively.

Methods: Patients with renal hemangiomas treated at MSKCC were identified in our prospectively collected renal tumor database. Descriptive statistics were used to describe the patient characteristics and the tumor characteristics. All available preoperative imaging studies were reviewed to assess common findings and explore possible characteristics distinguishing benign hemangiomas from malignant renal tumors preoperatively.

Results: Of 6341 patients in our database 15 were identified. Eleven (73%) were males, median age at diagnosis was 53.3 years, and the affected side was evenly distributed. All but two patients were treated surgically. The mean decrease in estimated glomerular filtration rate (eGFR) after surgery was 36.3%; one patient had an abnormal presurgical eGFR and only two patients had a normal eGFR after surgery. We could not identify radiographic features that would make preoperative diagnosis certain, but we did identify features characteristic of hepatic hemangiomas that were also present in some of the renal hemangiomas.

Conclusions: Most renal hemangiomas cannot be distinguished from other common renal cortical tumors preoperatively. In select cases a renal biopsy can identify this benign lesion and the deleterious effects of extirpative surgery can be avoided.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of the innate and adaptive immune systems with the production of autoantibodies by stimulated B lymphocytes. The BLyS protein (B lymphocyte stimulator) is secreted mainly by monocytes and activated T cells and is responsible for the proliferation, maturation and survival of B cells.

Objectivs: To study sera BLyS level and its clinical significance in Israeli lupus patients over time.

Methods: The study population included 41 lupus patients (8 males, 33 females; mean age 35.56 ± 15.35 years) and 50 healthy controls. The patients were followed for 5.02 ± 1.95 years. We tested 221 lupus sera (mean 5.4 samples/patient) and 50 normal sera for BLyS levels by a capture ELISA. Disease activity was determined by the SLEDAI score.

Results: Sera BLyS levels were significantly higher in SLE patients than in controls (3.37 ± 3.73 vs. 0.32 ± 0.96 ng/ml, P < 0.05). BLyS levels were high in at least one sera sample in 80.5% of the patients but were normal in all sera in the control group. There was no correlation between sera BLyS and anti-ds-DNA autoantibody levels. BLyS levels fluctuated over time in sera of lupus patients with no significant correlation to disease activity.

Conclusions: Most of our lupus patients had high sera BLyS levels, suggesting a role for BLyS in the pathogenesis and course of SLE. Our results support the current novel approach of targeting BLyS (neutralization by antibodies or soluble receptors) in the treatment of active lupus patients.

Background: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008 for the treatment of metastatic renal cell carcinoma (mRCC), based on an international trial. However, the efficacy of sunitinib treatment in Israeli mRCC patients has not been previously reported.

Objectives: To report the outcome and associated factors of sunitinib treatment in a large cohort of Israeli mRCC patients.

Methods: We conducted a retrospective study of an unselected cohort of mRCC patients who were treated with sunitinib during the period 2006–2013 in six Israeli hospitals. Univariate and multivariate analyses were performed to determine the association between treatment outcome and clinicopathologic factors.

Results: We identified 145 patients; the median age was 65 years, 63% were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy-nine percent (n=115) had clinical benefit (complete response 5%, n=7; partial response 33%, n= 48; stable disease 41%, n=60); 21% (n=30) were refractory to treatment. Median progression-free survival (PFS) was 12 months and median overall survival 21 months. Factors associated with clinical benefit were sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated with PFS were female gender [hazard ratio (HR) 2, P = 0.004], pre-sunitinib treatment neutrophil to lymphocyte ratio ≤ 3 (HR 2.19, P = 0.002), and active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR 0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment interrupted in 39% (n=57). 

Conclusions: The efficacy of sunitinib treatment for mRCC among Israeli patients is similar to that of international data.

Objectives: To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome.

Methods: Unilateral nephrectomy was performed and myocardial infarction induced in rats. Rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests.

Results: After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling.

Conclusions: Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome. 

Objectives: To investigate the 30 day clinical outcome of the first 300 consecutive patients treated with transfemoral TAVI at the Tel Aviv Medical Center.

Methods: The CoreValve was used in 250 patients and the Edwards-Sapien valve in 50 patients. The mean age of the patients was 83 ± 5.3 years (range 63–98 years) and the mean valve area 0.69 ± 0.18 cm² (range 0.3–0.9 cm²); 62% were women.

Results: The procedural success rate was 100%, and 30 day follow-up was done in all the patients. The average Euro-score for the cohort was 26 ± 13 (range 1.5–67). Total in-hospital mortality and 30 day mortality were both 2.3% (7 patients). Sixty-seven patients (22%) underwent permanent pacemaker implantation after the TAVI procedure, mostly due to new onset of left bundle brunch block and prolonged PR interval or to high degree atrioventricular block. The rate of stroke was 1.7% (5 patients). Forty-one patients (13.7%) had vascular complications, of whom 9 (3%) were defined as major vascular complications (according to the VARC definition).

Conclusions: The 30 day clinical outcome in the first 300 consecutive TAVI patients in our center was favorable, with a mortality rate of 2.3% and low rates of stroke (1.7%) and major vascular complications (3%).