Israel Medical Association Journal

Background: Bone maturation is currently assessed by subjective and automated radiography. 

Objectives: To evaluate the concordance and reproducibility of a quantitative ultrasound (QUS) based device versus X-ray based methods.

Methods: The study population comprised 150 children, 76 males, 4–17 years of age. X-ray scans were evaluated according to wrist, carpal and phalanx areas for bone age. QUS was performed by the the BAUS™ device (SonicBone, Rishon Lezion, Israel), using speed-of-sound (SOS) and distance attenuation factor (ATN) in similar areas. Data from 100 subjects were used to establish the device conversion equation, and 50 measurements were assigned to assess inter-modality agreement. 

Results: BAUS showed high repeatability performance, 0.73% relative standard deviation for SOS and 3.5% for ATN. R2 for the conversion equation, including gender, SOS, and ATN, was 0.80 for all methods (P < 0.001). There was no significant bias in bone age assessments.

Conclusions: Bone age assessment by SonicBone is comparable to the assessment by X-ray based methods. 

 

Background: Management of postoperative pain has become a growing concern, even for minor gynecological procedures. Proper postoperative pain management has been shown to lead to earlier mobilization, shortened hospital stay, and increased patient satisfaction. The optimal means of reducing the pain of pregnancy termination has not yet been determined.

Objectives: To compare the efficiency in pain management of two drugs, lornoxicam and paracetamol, given intravenously postoperatively to women who underwent abortion with dilation and curettage. 

Methods: The cohort comprised 80 women scheduled for dilation and curettage for pregnancy termination at 6–12 gestational weeks. The anesthesiologist gave 1000 mg paracetamol or 20 mg lornoxicam soon after starting the procedure, according to a randomization table. The medical staff and the patients were blinded to the drug that was administered. Pain levels were evaluated by a 10 cm visual analogue scale (VAS) at 15, 30, 60, 90, and 120 minutes following arrival at the postoperative care unit. 

Results: Mean levels of pain decreased from 60 minutes postoperative until the end of recording, reaching minimum levels at 120 minutes: 0.8 ± 0.19 and 1.5 ± 0.28, for lornoxicam and paracetamol, respectively. The differences between the groups were statistically significant (P < 0.05 from 60 minutes after the procedure until the time of discharge. 

Conclusions: Compared to women who received paracetamol, women who received lornoxicam after dilation and curettage for termination of pregnancy reported lower levels of pain, from 30 minutes postoperative until the time of discharge following the procedure. 

Background: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. 

Objectives: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. 

Methods: In March 2013 the authors launched a seven-component intervention program: 

1. Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory


2. Education program for the emergency department staff


3. Dissemination of information regarding the urgency of the PPCI decision


4. Activation of the catheterization team by a single phone call


5. Reimbursement for transportation costs to on-call staff who use their own cars


6. Improvement in the quality of medical records


7. Investigation of failed cases and feedback 

Results: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. 

Conclusions: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival. 

 

Background: Strategies aimed at expanding the organ donor pool have been sought, which has resulted in renewed interest in donation after cardio-circulatory death (DCCD), also known as non-heart beating donors (NHBDs).

Objectives: To describe the derivation and implementation of a protocol for DCCD in Israel and report on the results with the first six cases. 

Methods: After receiving approval from an extraordinary ethics committee, Ministry of Health, the steering committee of the National Transplant Center defined and reached consensus on the unique challenges presented by a DCCD program. These protocol included medical aspects (construction of a clinical pathway), social and ethical aspects (presentation of the protocol at a public gathering(, legal/ethical aspects (consent for organ preservation procedures being either implied if the donor had signed an organ donor card or received directly from a surrogate decision maker), and logistical aspects (pilot study confined to kidney retrieval and to four medical centers). Data regarding organ donors and recipients were recorded.

Results: The protocol was implemented at four medical centers. Consent for organ donation was received from four of the six potential donors meeting criteria for inclusion, in all cases, from a surrogate decision maker. Of the eight kidneys retrieved, only four were suitable for transplantation, which was carried out successfully for four recipients. Graft function remained normal in all cases in 6–12 months follow-up. 

Conclusions: The DCCD program was successfully implemented and initial results are encouraging, suggesting that expansion of the program might further aid in decreasing the gap between needs and availability of organs.

 

Background: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure.

Objectives: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation.

Methods: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis.

Results: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2.

Conclusions: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

 

Background: Cytomegalovirus (CMV) infection during pregnancy is the most common cause of intrauterine infection, and is a common cause of sensorineural hearing loss and mental retardation. 

Objectives: To evaluate trends in amniocentesis and pregnancy outcome in women with suspected cytomegalovirus (CMV) infection during the first trimester.

Methods: All blood tests for CMV immunoglobulin M (IgM) done between 2008 and 2009 on pregnant women who were enrolled in the Maccabi Healthcare Services were retrieved from laboratory database. Immunoglobulin G (IgG) avidity was measured and women were classified according to the risk of acquiring CMV infection. For each patient, performance of amniocentesis and whether pregnancy came to term were recorded.

Results: Of 109,439 pregnant women evaluated during the study period, 76,712 (70.1%) were tested for CMV IgM, and 792 (1.03%) were found to be positive. Among women with positive IgM, only 205 (25.9%) underwent amniocentesis. When compared with women with negative CMV IgM, the rate of pregnancy cessation was doubled in women with positive CMV IgM (28.3% vs. 14.3%, P < 0.05) and mostly elevated in women with a high risk of acquiring CMV (42.3% pregnancy cessation). Among women with positive CMV IgM, those who did not undergo amniocentesis were more likely to abort than those who performed amniocentesis (35.6% vs. 7.3%, P < 0.05). 

Conclusions: More women with suspected CMV infection during the first trimester of pregnancy aborted before all means of detection were utilized to rule out or confirm fetal infection with CMV.

 

Background: Patients with giant cell arteritis (GCA) suffer from inflammatory diseases often treated by large amounts of corticosteroids. Whether this inflammatory burden also carries an increased risk for cardiovascular morbidity, and especially ischemic heart disease, is not clearly established.

Objectives: To clarify the linkage between GCA and ischemic heart disease. 

Methods: In a cross-sectional study, we assessed the association between GCA and ischemic heart disease, adjusting for cardiovascular risk factors, among GCA patients and matched controls using the database of the largest healthcare provider in Israel.

Results: The study group was comprised of 5659 GCA patients and 28,261 age and gender matched controls. The proportion of ischemic heart disease was higher in the GCA group (27.5% vs. 12.5% among controls, odds ratio 2.65). Diabetes mellitus, hypertension, hyperlipidemia and smoking were also found to have higher concurrency in GCA. After stratifying for those cardiovascular co-morbidities using logistic regression, GCA remained independently associated with ischemic heart disease with an odds ratio of 1.247 (1.146–1.357 P < 0.001).

Conclusions: GCA is associated with both cardiovascular risk factors and ischemic heart disease. Healthcare professionals should not overlook this aspect of the disease when managing GCA patients. 

 

Background: Common variable immunodeficiency (CVID) is the most common symptomatic primary immune deficiency of adulthood. Besides recurrent infections, autoimmune disorders–mainly cytopenias–affect 30% of patients with CVID.

Objectives: To describe the efficacy and safety of facilitated subcutaneous immunoglobulin (fSCIg), which is a combination of 10% [human] SCIg with recombinant human hyaluronidase for the treatment of CVID-linked cytopenias. 

Methods: We describe four women (mean age 54 years) with CVID associated with idiopathic thrombocytopenic purpura (ITP) (n=3) and autoimmune hemolytic anemia (AIHA) (n=1). Diagnosis of CVID was made according to the European Society of Immune Deficiencies / Pan-American Group for Immune Deficiency criteria. All were treated with fSCIg (bi-monthly, 20 g).

Results: After a median follow-up of 22 months, all patients achieved a stable remission from the cytopenias, characterized by increased platelet values in ITP (mean values 93000/mmc), and resolution of anemia. A reduction of the daily prednisone dose was documented in the patient with AIHA. No systemic adverse drug reactions were observed. 

Conclusions: Our preliminary data documented the efficacy and safety of fSCIg in the treatment of CVID associated with autoimmune cytopenias, with a good tolerability. We also noted the role of fSCIg as a steroid sparing agent. It is thus possible to suppose an immunomodulatory role for fSCIg, but linked to different mechanisms than IVIg, due to the peculiar pharmacokinetic and administration route of fSCIg. 

 

Fevers recurring at a nearly predictable rate every 3–8 weeks are the signature symptom of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome, an acquired autoinflammatory disorder which recurs in association with at least one sign among aphthous stomatitis, pharyngitis, and/or cervical lymph node enlargement without clinical signs related to upper respiratory airways or other localized infections. The disease usually has a rather benign course, although it might relapse during adulthood after a spontaneous or treatment-induced resolution in childhood. The number of treatment choices currently available for PFAPA syndrome has grown in recent years, but data from clinical trials dedicated to this disorder are limited to small cohorts of patients or single case reports. The response of PFAPA patients to a single dose of corticosteroids is usually striking, while little data exist for treatment with cimetidine and colchicine. Preliminary interesting results have been published with regard to vitamin D supplementation in PFAPA syndrome, while inhibition of interleukin-1 might represent an intriguing treatment for PFAPA patients who have not responded to standard therapies. Tonsillectomy has been proven curative in many studies related to PFAPA syndrome, although the evidence of its efficacy is not widely shared by different specialists, including pediatricians, rheumatologists and otorhynolaryngologists.

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: Trials have shown superiority of primary percutaneous intervention (PPCI) over in-hospital thrombolysis in ST-elevation myocardial infarction (STEMI) patients treated within 6-12 hours from symptom onset. These studies also included high-risk patients not all of whom underwent a therapeutic intervention. 

Objectives: To compare the outcome of early-arriving stable STEMI patients treated by thrombolysis with or without coronary angiography to the outcome of PPCI-treated STEMI patients.

Methods: Based on six biannual Acute Coronary Syndrome Israeli Surveys comprising 5474 STEMI patients, we analyzed the outcome of 1464 hemodynamically stable STEMI patients treated within 3 hours of onset. Of these, 899 patients underwent PPCI, 383 received in-hospital thrombolysis followed by angiography (TFA), and 182 were treated by thrombolysis only.

Results: Median time intervals from symptom onset to admission were similar while door-to-reperfusion intervals were 63, 45 and 52.5 minutes for PPCI, TFA and thrombolysis only, respectively (P < 0.001). The 30-day composite endpoint of death, post-infarction angina and myocardial infarction occurred in 77 patients of the PPCI group (8.6%), 64 patients treated by TFA (16.7%), and 36 patients of the thrombolysis only group (19.8%, P < 0.001), with differences mostly due to post-infarction angina. One-year mortality rate was 27 (3%), 13 (3.4%) and 11 (6.1%) for PPCI, TFA and thrombolysis only, respectively (P = 0.12).

Conclusions: PPCI was superior to thrombolysis in early-arriving stable STEMI patients with regard to 30-day composite endpoint driven by a decreased incidence of post-infarction angina. No 1 year survival benefit for PPCI over thrombolysis was observed in early-arriving stable STEMI patients.

 

Background: While patients presenting to emergency departments (ER) with chest pain are increasingly managed in chest pain units (CPU) that utilize accelerated diagnostic protocols for risk stratification, such as single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), data are lacking regarding the prognostic implications of mildly abnormal scans in this population.

Objectives: To evaluate the prognostic implications of mildly abnormal SPECT MPI results in patients with acute chest pain.

Methods: Of the 3753 chest pain patients admitted to the CPU at the Leviev Heart Center, Sheba Medical Center 1593 were further evaluated by SPECT MPI. Scans were scored by extent and severity of stress-induced perfusion defects, with 1221 patients classified as normal, 82 with myocardial infarction without ischemia, 236 with mild ischemia, and 54 with more than mild ischemia. Mild ischemia patients were further classified to those who did and did not undergo coronary angiography within 7 days.

Results: Mild ischemia patients who underwent coronary angiography were more likely to be male (92% vs. 81%, P = 0.01) and to have left anterior descending ischemia (67% vs. 42%, P = 0.004). After 50 months, these patients returned less often to the ER with chest pain (53% vs. 87%, P < 0.001) and had a lower combined endpoint of acute coronary syndrome and death (8% vs. 16%, P < 0.001).

Conclusions: Compared to patients with chronic stable angina, patients presenting with acute chest pain exhibiting mildly abnormal SPECT MPI findings should perhaps undergo a more aggressive diagnostic and therapeutic approach.

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.