Israel Medical Association Journal

Background: Post-pericardiotomy syndrome (PPS) is a major cause of pericarditis, yet data on the risk of recurrence are limited, and the impact of steroids and colchicine in this context is unknown.

Objectives: To examine the effect of prednisone and colchicine on the rate of recurrence of PPS.

Methods: Medical files of patients diagnosed with PPS were reviewed to extract demographic, echocardiographic, X-ray imaging, and follow-up data.

Results: The study comprised 132 patients (57% men), aged 27–86 years. Medical treatment included prednisone in 80 patients, non-steroidal anti-inflammatory agents in 41 patients, colchicine monotherapy in 2 patients, and no anti-inflammatory therapy in 9 patients. Fifty-nine patients were given colchicine for prevention of recurrence. The patients were followed for 5–110 months (median 64 months). Recurrent episodes occurred in 15 patients (11.4%), 10 patients had a single episode, 4 patients had two episodes, and one patient had three episodes. The rate of recurrence was lower in patients receiving colchicine compared to patients who did not (8.5% vs. 13.7%), and in patients not receiving vs. receiving prednisone (7.7% vs. 13.8%) but the differences were non-significant. Twenty-three patients died and there were no recurrence-related deaths.

Conclusions: The rate of recurrence after PPS is low and multiple recurrences are rare. The survival of patients with recurrent PPS is excellent. Prednisone pre-treatment was associated with a numerically higher rate of recurrence and colchicine treatment with a numerically lower rate, but the differences were non-significant.

Background: Endothelial progenitor cells may have a role in ongoing endothelial repair. Impaired mobilization or depletion of these cells may contribute to progression of vascular disease. Our hypothesis was that endothelial progenitor cells would be suppressed in patients with acute cerebrovascular event based on our previous study that found severe endothelial dysfunction in those patients.

Objectives: To study the ability of patients with acute stroke to build colonies of endothelial progenitor cells.

Methods: We studied the number of colony-forming units of endothelial progenitor cells (CFU-EPCs) from the peripheral blood of 22 male patients with a first-time acute stroke (age 58.09 ± 9.8 years) and 13 healthy men (34 ± 6.7 years), 8 female patients with a first-time acute stroke (54.6 ± 10.3 years) and 6 healthy women (38.3 ± 11.6 years). Endothelium-dependent function was assessed by high-resolution ultrasonography of the brachial artery that measured the change in diameter of the artery by flow-mediated diameter percent change (FMD%). All patients had strokes demonstrated by a brain computed tomography (CT) scan done on admission. Peripheral blood was drawn soon after admission and was processed for endothelial progenitor cells in culture.

Results: Thirty patients without known cardiovascular risk factors and who did not take any medications were admitted with a first-time acute stroke. All demonstrated a strong correlation between CFU-EPCs grown in culture and endothelial dysfunction (r = 0.827, P < 0.01). Endothelial dysfunction with an FMD% of -2.2 ± 9.7% was noted in male patients vs. 17.5 ± 6.8% in healthy males (P = 0.0001), and -7.2 ± 10.1% in female patients vs. 25.1 ± 7.1% in healthy females (P = 0.0001). CFU-EPCs were 5.5 ± 6.3 in men with stroke vs. 23.75 ± 5.3 in healthy males (P = 0.0001), and 7.6 ± 4.9 in women with stroke vs. 22.25 ± 6.7 in healthy females (P = 0.0004).

Conclusions: Patients with acute stroke had an impaired ability to grow CFU-EPCs in culture and exhibited endothelial dysfunction. The novelty of this study was the discovery of the phenomenon of depressed numbers of EPCs and the poor ability to grow colonies of EPCs in the first 24 hours of the cerebrovascular event.

Background: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. 

Objectives: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. 

Methods: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.

Results: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. 

Conclusions: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

Background: Israel is a country with a sunny climate; however, vitamin D deficiency and insufficiency are common findings in certain populations whose exposure to sunlight is limited. Medical residency is known for long indoor working hours, thus theoretically limiting the opportunities for sun exposure.

Objectives: To evaluate whether the vitamin D status among residents in a single medical center in Tel Aviv is below the normal range.

Methods: Forty-six residents (28 females, 18 males, average age 33.9 ± 2.8 years) in three residency programs (internal medicine, general surgery/obstetrics and gynecology, pediatrics) were recruited. Demographic data, personal lifestyle, physical activity details and sun exposure duration were obtained by a questionnaire. Serum levels for 25(OH)D were analyzed by a radioimmunoassay.

Results: The mean serum 25(OH)D concentration was 29.8 ± 5.8 ng/ml. According to Institute of Medicine definitions, none of the residents were vitamin D deficient and only two residents (4%) were vitamin D insufficient (15 ng/ml each). The level of 25(OH)D was similar among the various medical specialties. The 25(OH)D levels correlated with the duration of sun exposure and the number of offspring (regression analysis: R2 = 9.2%, P < 0.04 and R2 = 8.9%, P < 0.04, respectively), but not with nutritional data, blood chemistry, or extent of physical activity. 

Conclusions: Most of the residents maintained normal or near normal 25(OH)D levels, indicating that the residency program itself did not pose a significant risk for vitamin D deficiency. 

 

Background: More than 90% of all thyroid cancers are differentiated thyroid carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used risk stratification systems for DTC include: European Organization for Research and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor, Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion). Other systems are also utilized. Several new factors that may be involved in DTC risk stratification have emerged in recent studies, with other "traditional" factors being challenged. 

Objectives: To present recent updates in the literature on new potential prognostic factors for DTC.

Methods: We conducted a literature review and analysis of publications regarding DTC prognostic factors or risk stratification published in the last 10 years. 

Results: Several new factors with potential prognostic implications for DTC were noted, including family history, lymph node involvement parameters, positive PET-CT findings, multifocal disease, thyroglobulin level and several molecular markers including BRAF. Increasing age is associated with poorer outcome in DTC; however, recent studies suggest that the cutoff point of 45 years may be contested. Furthermore, several studies have shown contradictory results regarding male gender as a negative prognostic factor, thus questioning its prognostic significance. 

Conclusions: A number of new factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined.

 

Background: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. 

Objectives: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. 

Methods: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7–128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64–83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. 

Results: Five year progression-free survival was 68% (95%CI 59.8–74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3–0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). 

Conclusions: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.

 

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Concomitant carotid artery disease (CaAD) in patients with coronary artery disease (CAD) is associated with worse cardiac and neurologic outcomes. The reported prevalence and risk factors for concomitant CaAD in CAD patients varied among previous studies. 

Objectives: To examine these factors in ambulatory patients with CAD and well-documented cholesterol levels treated with cholesterol-lowering medications. 

Methods: We retrospectively analyzed prospectively collected data from 325 unselected patients with CAD (89 women, mean age 68.8 ± 9.9 years) undergoing routine evaluation at the coronary clinic of our hospital. 

Results: The low density lipoprotein-cholesterol (LDL-C) was < 100 mg/dl in 292 patients (90%). Age at onset of CAD symptoms was 59.4 ± 10.8 years. Carotid stenosis ≥ 50% was seen in 83 patients (25.5%) and between 30% and 49% in 55 patients (17%) (duplex method). Carotid stenosis was significantly associated with hypertension (P = 0.032), peripheral arterial disease (P = 0.002) and number of coronary arteries with ≥ 50% stenosis (P = 0.002), and showed a borderline association with age at CAD onset (P = 0.062) and diabetes mellitus (P = 0.053). On linear regression analysis, independent predictors of CaAD were peripheral vascular disease (OR 3.186, 95%CI 1.403–7.236, P = 0.006), number of coronary arteries with ≥ 50% stenosis (OR 1.543, 95%CI 1.136–2.095, P = 0.005), and age at CAD onset (OR 1.028, 95%CI 1.002–1.054, P = 0.003). None of the variables studied predicted freedom from CaAD. 

Conclusions: Carotid atherosclerosis is very common in stable ambulatory patients with CAD regularly taking statins. The risk is higher in patients with peripheral arterial disease, a greater number of involved coronary arteries, and older age at onset of CAD. 

 

Background: Several studies have identified associations between low vitamin D concentrations and risk of upper respiratory infections (URI). T lymphocytes have a major anti-viral role, are affected by vitamin D metabolism, and may mediate the link between vitamin D and URIs. Competitive swimmers have a relatively high rate of URIs, alongside a high prevalence of low vitamin D concentration. 

Objectives: To examine the associations linking T cell receptor excision circles (TREC, markers of thymus activity), circulating 25(OH)D concentrations and the effect of vitamin D supplementation, and URI symptoms in young competitive swimmers.

Methods: We tested 82 adolescent swimmers for serum 25(OH)D and TREC concentrations and found that 55 had vitamin D insufficiency. Randomized supplementation of either vitamin D3 or placebo was given for 12 winter weeks. URI symptoms were recorded weekly. The associations between TREC copy numbers, vitamin D and URI burden were examined.

Results: TREC concentrations decreased with the participants’ age (r = -0.346, P = 0.003), with no significant between-gender difference. TREC concentrations did not materially differ among subjects with normal, insufficient or deficient vitamin D status, and were not affected by vitamin D supplementation. No significant correlations were found between TREC levels or their changes during the study period, and mean URI severity or duration. 

Conclusions: Thymus activity, represented by higher TREC levels, was not related to vitamin D concentrations or status, and was not affected by vitamin D supplementation in adolescent swimmers. TREC concentrations were not associated with URI severity or duration in this population.

 

Background: Several trials support the trans-radial route of percutaneous coronary intervention (PCI) since it reduces access site vascular complications and bleeding. 

Objectives: To examine the effects of trans-radial interventions (TRI) on clinical outcomes in a 'real world' cohort of patients undergoing PCI.

Methods: We analyzed 4873 consecutive patients who underwent PCI at a tertiary center and identified 373 patients who underwent TRI. Patients (radial vs. femoral) were compared using a propensity score analysis to best match between groups. Outcome parameters included total mortality, myocardial infarction (MI), repeat target vessel revascularization (TVR) rates, length of hospitalization and ∆Ht/Hb/creatinine values during hospitalization. These were evaluated at 6 months and 1 to 3 years after PCI.

Results: The rates of major adverse cardiovascular event (MACE) and its constituents were similar in the trans-radial vs. trans-femoral groups at all time intervals: 6.7% vs. 5.5% at 6 months, 10.3% vs. 10% at 1 year, 15.7% vs. 15% at 2 years, 15.7% vs. 16% at 3 years, respectively (P = 0.6). The length of hospitalization was shorter in the TRI group (2.87 days ± 2.04 vs. 3.3 days ± 3.12, P = 0.023). We did not find significant differences between the groups in the mean ∆Ht/Hb/creatinine values during the hospitalization course.

Conclusions: In a 'real-world' setting of PCI, the TRI route of PCI is as safe and efficient as the femoral approach. TRI is associated with shorter duration of hospitalization.