Israel Medical Association Journal

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

Objectives: To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings.

Methods: The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan.

Results: Median age was 28 ± 88 days and mean weight 3.7 ± 1.5 kg. Diagnostic quality was good or excellent (visual image score 3–4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information regarding extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 ± 0.07 mSv (range 1.014–2.3 mSv).

Conclusions: ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE regarding extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose. 

Objectives: To test vitamin D levels in kidney transplant recipients residing closer to the equator, compare them to levels in liver transplant recipients and hemodialysis patients, and identify possible risk factors.

Methods: In a cross-sectional study 103 kidney transplant recipients, 27 liver transplant recipients and 50 hemodialysis patients followed at our institute were tested for vitamin D levels. Demographic data, medical history and current treatment were recorded from the medical files.

Results: Inadequate vitamin D levels (< 30 ng/ml) were found in 75% of all patients and 75% of all kidney transplant recipients. Vitamin D levels were higher among dialysis patients than transplant recipients, though deficiency rates were similar. No association was found between kidney function and vitamin deficiency. Deficiency was associated with higher prednisone doses, use of mycophenolate sodium, tacrolimus, and iron supplements, or lower doses of vitamin D supplementation.

Conclusions: Despite potential higher ultraviolet B exposure, inadequate vitamin D levels were prevalent in our study group. Importantly, some immunosuppressive medications were associated with vitamin D deficiency and high doses of vitamin D were associated with less deficiency.

Objectives: To compare the incidence rate of overall and site-specific cancers among Israeli Arabs with T2DM to that of Israeli Arabs without.

Methods: A retrospective cohort study of all adult Arab members of Clalit Healthcare Services in northern Israel was conducted over a 10 year period (1999–2008).

Results: During the study period 752 and 2045 incident cases of cancer were diagnosed among 13,450 adults with diabetes and 74,484 without, respectively. The follow-up time involved 817,506 person-years. Diabetes was associated with a standard incidence ratio (SIR) of 3.27 (95%CI 1.49–5.05) and 2.87 (95%CI 1.25–4.50) for pancreatic cancer in men and women, respectively. A significantly reduced SIR (0.67, 95%CI 0.36–0.99) was observed for esophageal, stomach and intestinal cancers in men.

Conclusions: Our findings support an association between T2DM and increased risk of cancer of the pancreas in Arab men and women. A significantly reduced risk of all other cancers was observed only in Arab men. Our findings underscore the need for effective diabetes and cancer prevention and intervention programs. 

Objectives: To describe the exposures experienced by emergency responders to smoke, fire retardants and stress; the utilization of protective equipment; and the frequency of corresponding symptoms during and following the Carmel Forest fire.

Methods: A cohort of 204 firefighters and 68 police who took part in rescue and fire-abating activities during the Carmel Forest fire were recruited from a representative sample of participating stations throughout the country and interviewed regarding their activities during the fire and their coinciding symptoms. Unpaired two-sample t-test compared mean exposures and symptom frequency for firefighters and police. Chi-square estimates of OR and 95% CI are provided for odds of reporting symptoms, incurring injury or being hospitalized for various risk factors.

Results: Of the study participants, 87% reported having at least one symptom during rescue work at the Carmel Forest fire, with eye irritation (77%) and fatigue (71%) being the most common. Occupational stress was extremely high during the fire; the average length of time working without rest was 18.4 hours among firefighters.

Conclusions: Firefighters and police were exposed to smoke and occupational stress for prolonged periods during the fire. Further research is needed on the residual health effects from exposure to forest fires among emergency responders, and to identify areas for improvement in health preparedness.  

Background: Establishing the etiology of a large pericardial effusion is of crucial importance since it is likely the result of a serious underlying disease. However, there is a paucity of literature on the diagnostic management of patients with large hemorrhagic effusions.

Objectives: To analyze the management of patients with large hemorrhagic pericardial effusion.

Methods: We reviewed seven cases of large hemorrhagic pericardial effusions hospitalized in Soroka University Medical Center in 2010.

Results: All seven patients underwent a comprehensive evaluation followed by pericardiocentesis. Six of the seven cases demonstrated echocardiographic signs of tamponade. Large amounts of hemorrhagic pericardial effusion (> 600 ml) were aspirated from each patient. A pericardial window was performed in two of the seven patients. The causes for the hemorrhagic effusions were malignancy, streptococcal infection, familial Mediterranean fever exacerbation, and idiopathic. Four patients completely recovered. The condition of one patient improved after initiation of chemotherapy for lung cancer, and two patients with progressive malignancies passed away shortly after discharge. Two cases of massive pulmonary embolism were diagnosed which resolved spontaneously without anticoagulation therapy after the effusion was treated.

Conclusions: All cases of pericardial effusion resolved after rapid diagnosis and initiation of specific treatment. Pulmonary embolism in situ may be a complication of large pericardial effusions that does not require anticoagulation treatment after the effusion resolves.
 

Background: Coronary computed tomography angiography (CCTA) is an established modality for ruling out coronary artery disease. However, it has been suggested that CCTA may be a source of non-negligible radiation exposure.

Objectives: To evaluate the potential degradation in coronary image quality when using prospective gated (PG) CCTA as compared with retrospective gated (RG) CCTA in chest pain evaluation.

Methods: The study cohort comprised 216 patients: 108 consecutive patients in the PG CCTA arm and 108 patients matched for age, gender and heart rate in the RG CCTA arm. Scans were performed using a 64-slice multidetector CT scanner. All 15 coronary segments were evaluated subjectively for image quality using a 5-point visual scale. Dose-length product was recorded for each patient and the effective radiation dose was calculated

Results: The PG CCTA technique demonstrated a significantly higher incidence of step artifacts in the middle and distal right coronary artery, the distal left anterior descending artery, the second diagonal, the distal left circumflex artery, and the second marginal branches. Nevertheless, the diagnostic performance of these scans was not adversely affected. The mean effective radiation doses were 3.8 ± 0.9 mSv vs.17.2 ± 3 mSv for PG CCTA and RG CCTA, respectively (P < 0.0001).

Conclusions: Artifacts caused by the PG CCTA technique (64 MDCT) scanners tended to appear in specific coronary segments but did not impair the overall diagnostic quality of CCTA and there was a marked reduction in radiation exposure. We conclude that 64-slice PG CCTA is suitable for clinical use, especially for acute chest pain "fast track" evaluation targeted at relatively young subjects in a chest pain unit.
 

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI[1] the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction.

Objectives: To determine the added value of thrombus aspiration prior to primary PCI[2] by comparing AMI[3] patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI.

Methods: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups.

Results: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P = 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although P was not significant). Long-term follow-up total MACE[4] showed a non-significant positive trend in the extraction group (12.96% vs. 24.71%, P = 0.26).

Conclusions: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.