Israel Medical Association Journal

Background: The use of oral midazolam as premedication to induce anxiolysis before surgical procedures under local anesthesia is widely accepted in plastic surgery. Rhinoplasty performed under local anesthesia is known to generate high levels of perioperative anxiety, thus the use of appropriate premedication is important. Oral midazolam has been shown to be safe in various procedures. However, the safety of oral midazolam before rhinoplasty has not been evaluated.

Objectives: To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events.

Methods: We retrospectively reviewed the anesthesia records of 62 patients who underwent rhinoplasty under local anesthesia and received premedication with oral midazolam for anxiolysis between March 2017 and December 2017. The median age of the patients was 25.4 years, and they were all classified as American Society of Anesthesiologists class 1. The patients received 10 mg midazolam hydrochloride orally 1 hour prior to the procedure. Oxygen blood saturation was monitored using a pulse oximeter and recorded every 15 minutes.

Results: All the patients maintained blood oxygen saturation levels above 95% (median peripheral capillary oxygen saturation 99%) on room air, and they did not require supplemental intraoperative oxygen. There were no transient hypoxemic events during and following the procedure.

Conclusions: Our study confirmed the safety of oral midazolam premedication to reduce perioperative anxiety when performing rhinoplasty under local anesthesia.

Background: Congenital factor VII deficiency is a rare recessive autosomal bleeding disorder with a wide spectrum of clinical manifestations.

Objectives: To compare the clinical and laboratory findings in Jewish and Bedouin patients with factor VII deficiency.

Methods: The clinical and laboratory findings of patients with factor VII deficiency treated at Soroka Medical Center, a tertiary hospital in Israel, from 2005 to 2015 were analyzed regarding blood factor levels, illness severity, treatment administration, and disease outcome.

Results: Seventy-eight patients were enrolled (1:13,000 of the population in southern Israel) of whom 26 were diagnosed with severe factor VII deficiency (1:40,000). Sixty (76.9%) patients were Jewish and 18 (23.1%) were Bedouin. In univariable analysis, Bedouin patients exhibited a more severe illness, with significantly higher complication and fatality rates, and required more preventive treatment than the Jewish patients.

Conclusions: The prevalence of congenital factor VII deficiency (including severe deficiency) in the Jewish and Bedouin populations of southern Israel is higher than previously reported. The clinical spectrum of the disease was found to be more severe in the Bedouin population.

Background: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs).

Objectives: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs.

Methods: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files.

Results: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm³. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N.

Conclusions: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

Background: Computed tomography (CT) brain perfusion is a relatively new imaging method that can be used to differentiate patients following epileptic seizures in the setting of acute neurological deficits (e.g., hemiparesis, hemiplegia, hemianopsia, aphasia) who arrive at the emergency room with a suspected stroke.

Objectives: To evaluate brain perfusion changes in patients who had an epileptic seizure.

Methods: We retrospectively identified 721 patients who presented at our stroke center between 2012 and 2015 with a suspected acute stroke and underwent examination thorough a stroke protocol, including cerebral CT perfusion (CTP) and CT angiography (CTA) within 8 hours from the onset of symptoms. 

Results: Out of 721 patients, 25 presented with ictal electroencephalography (EEG) findings within 24–72 hours from symptom onset without evidence of vascular occlusion on CTA. While 15 patients had to be excluded from the study due to concomitant brain pathology, we found a specific reduction in cerebral blood volume and cerebral blood flow occurring at the ictal zone, which was identified by a post hoc EEG investigation. 

Conclusions: Our study shows that CTP is an easily accessible tool in emergency department setting for the detection of changes in blood flow dynamics among postictal patients. Thus, we propose the use of CTP in emergency settings to discriminate between postictal changes and acute vascular events. 

 

Background: Once a well-recognized entity, occult bacteremia (OB) is no longer a significant or serious bacterial infection. First following the introduction of the Haemophilus influenzae type B vaccine and now with the implementation of the conjugate pneumococcal vaccine (PCV), the number of cases has declined significantly. This has led to a change in many published guidelines to avoid taking blood cultures in fully vaccinated children presenting with fever. In Israel, the introduction of the PCV13 is now widespread. 

Objectives: To assess the incidence and outcome of OB, specifically by Streptococcus pneumoniae, in a single large pediatric medical center. 

Methods: We conducted a retrospective review of all cases of pneumococcal bacteremias in the years 2008–2013 and specifically those considered occult. 

Results: Of 355 cases of bacteremia diagnosed during the study period, 164 were caused by S. pneumoniae and 20 (12.8%) were considered occult. None of the OB cases had any complications. OB was not found in children over the age of 36 months. There was a change in the serotypes involving pneumococcal OB. 

Conclusions: OB is uncommon in the PCV-vaccinated population and the serotypes involved have changed.

 

Background: Approximately 80% of patients with myelodysplastic syndromes (MDS) receive multiple red blood cells (RBC), often multiple transfusions, and are therefore prone to develop alloantibodies against RBC. Because of increasing evidence for the role of immune dysregulation in the pathobiology of MDS, we hypothesized that in patients with MDS there is an increase in alloantibody formation beyond that expected by multiple transfusions.

Objectives: To determine the prevalence rates of alloantibodies in patients with MDS who are transfusion dependent and compare them to those of non-MDS patients matched for number of RBC units they received. 

Methods: The blood bank database was screened to identify non-MDS patients matched for age and number of units transfused. Logistic regression analysis was applied to determine factors affecting alloantibody formation. 

Results: Of 60 patients with MDS, 18 (30%) developed alloantibodies against RBC. Transfusion-dependent MDS and non-MDS patients (N=56 each), matched for number of RBC units and age, were compared. Fifteen MDS patients (27%) but only 12 non-MDS patients (12%) developed alloantibodies (P = 0.057). The relative risk for developing antibodies in MDS patients was 2.14, and MDS was the strongest predictor for formation of alloantibodies during transfusion therapy (odds ratio 3.66, confidence interval 1.4–9.3). 

Conclusions: Patients with MDS are at increased risk to develop RBC alloantibodies, partly because these patients receive multiple RBC transfusions. Whether matching for RH and KEL would lead to lower rates of RBC alloantibodies remains to be determined.

 

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. 

 

Background: Non-mobilized peripheral blood contains mostly committed cells with limited numbers of early progenitors. Objectives: To enrich functional progenitor cells from healthy donors and ischemic heart disease patients by short-term culture of mononuclear cells with defined culture conditions.

Methods: Mononuclear cells obtained from healthy donors and ischemic heart disease patients were cultured for 7 days in a cytokine cocktail. We tested the multilineage differentiation capacities and phenotype of cultured cells.

Results: The short-term culture (7 days) of all study groups with a defined cytokine cocktail resulted in two distinct cell populations (adherent and non-adherent) that differed in their differentiation capacities as well as their cell surface markers. Cultured adherent cells showed higher differentiation potential and expressed endothelial and mesenchymal fibroblast-like surface markers as compared to fresh non-cultured mononuclear cells. The non-adherent cell fraction demonstrated high numbers of colony-forming units, indicating a higher differentiation potential of hematopoietic lineage.

Conclusions: This study proved the feasibility of increasing limited numbers of multipotent progenitor cells obtained from the non-mobilized peripheral blood of healthy donors and ischemic patients. Moreover, we found that each of the two enriched subpopulations (adherent and non-adherent) has a different differentiation potential (mesenchymal, endothelial and hematopoietic).

Background: Claudication is one of the sequelae of peripheral arterial disease (PAD). To date, no effective treatment has been found for this condition.

Objectives: To investigate a new device to treat PAD. The device administers pre-programmed protocols of oscillations to the foot.

Methods: Fifteen patients aged 40–70 years who suffered from intermittent claudication secondary to PAD were recruited to an open prospective study. Each patient was treated once for 30 minutes. The following parameters were evaluated: pain-free and maximal walking distances, skin blood flux by laser-Doppler, skin temperature, ankle-brachial and toe-brachial indices, transcutaneous oxygen pressure (tcpO₂) and transcutaneous carbon dioxide pressure (tcpCO₂). Non-parametric signed-rank test was applied for testing differences between baseline assessment and post-treatment assessments for quantitative parameters.

Results: Mean pain-free walking distance was 122 ± 33 m and increased to 277 ± 67 m, after the treatment session (P = 0.004). Mean maximal walking distance was 213 ± 37 m and it increased to 603 ± 77 m (P < 0.001). Foot skin perfusion also improved, as demonstrated by an increase in tcpO₂ by 28.6 ± 4.1 mmHg (P < 0.001), a decrease in tcpCO₂ by 2.8 ± 1.3 (P = 0.032), and up to twofold improvement in blood flux parameters, and an increase in skin temperature by 1.9 ± 0.5°C (P < 0.001). Ankle-brachial index increased by 0.06 ± 0.01 (P = 0.003) and toe-brachial index by 0.17 ± 0.02 (P < 0.001).

Conclusions: Preprogrammed oscillations applied to the foot had a positive effect on microcirculation, tissue oxygenation and CO₂ clearance; they had a smaller though significant effect on arterial blood pressure indices, and the change in the arterial-brachial index correlated with the change in the pain-free walking distance. 

Objectives: To investigate the prevalence of hypertension and its relation to body mass index (BMI) in obese children aged 9–17 years in Israel.

Methods: Weight, height, BMI, and systolic and diastolic blood pressure (BP) (twice) were measured in children attending general and pediatric endocrine clinics. Obesity was defined as BMI ≥ 95th percentile and overweight as BMI ≥ 85th percentile. Pre-hypertension and hypertension were defined as systolic and/or diastolic BP ≥ 90th percentile for age, gender and height and BP ≥ 95th percentile respectively. In children with pre-hypertension or hypertension, repeated measurements were performed.

Results: We evaluated 264 children of whom 152 had BMI ≥ 85th percentile (study group). Their mean age was 12.5 years. The prevalence of elevated BP (both pre-hypertension and hypertension) in the study group was 44.1% and 31% at the first and second measurements respectively, compared to 11.6% and 1.9% in the normal-weight group. Hypertension was documented in 17.2% of the study group at the second measurement.

Conclusions: Elevated BP was diagnosed in 31% of overweight and obese children and adolescents. Increased awareness and early diagnosis and treatment are essential.

Background: Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN.

Objectives: To evaluate the prevalence of mutated JAK2 (JAK2-V617F) among patients with major intraabdominal vein thrombosis who had normal blood counts at diagnosis of the initial event.

Methods: The medical records of patients who presented with a major intraabdominal venous thrombosis and normal peripheral blood counts were obtained. JAK2-V617F mutation status was determined by real-time polymerase chain reaction.

Results: Twenty-two patients were available for this analysis and 9 (41%) were found to have JAK2-V617F. Patients with positive JAK2-V617F were younger and had more frequent clinical splenomegaly than those with wild-type JAK2.

Conclusions: A high proportion of patients presenting with “idiopathic” major intraabdominal vein thrombosis and normal blood counts carry JAK2-V617F. We recommend searching for the mutation in this clinical setting to detect patients with occult MPN.

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism. 

Background: The pathophysiology of aortic stenosis (AS) involves inflammatory features including infiltration of the aortic valve (AV) by activated macrophages and T cells, deposition of lipids, and heterotopic calcification.

Objectives: To evaluate the correlation between white blood cell (WBC) differential count and the occurrence and progression of AS.

Methods: We identified in our institutional registry 150 patients with AS who underwent two repeated echo studies at least 6 months apart. We evaluated the association between the average of repeated WBC differential counts sampled during the previous 3 years and subsequent echocardiographic AS indices.

Results: There was no significant difference in total WBC, lymphocyte or eosinophil count among mild, moderate or severe AS groups. There was a progressive decrease in monocyte count with increasing AS severity (P = 0.046), more prominent when comparing the mild and severe groups. There was a negative correlation between AV peak velocity or peak or mean gradient and monocyte count in the entire group (r = -0.31, -0.24, and -0.25 respectively, all P ≤ 0.01). Similar partial correlations controlling for age, gender, hypertension, smoking, dyslipidemia and ejection fraction remained significant. The median changes over time in peak velocity and peak gradients in AS patients were 0.44 (0–1.3) m/sec/year and 12 (0–39) mmHg/year, respectively. There was no correlation between any of the WBC differential counts and the change in peak velocity or peak gradient per year.

Conclusions: Severe AS is associated with decreased total monocyte count. These findings may provide further clues to the mechanism underlying the pathogenesis of aortic stenosis.

Objectives: To retrospectively analyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood.

Methods: CMV DNA was detected by rt-PCR performed on infants’ cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation.

Results: During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen (82%) infants would not otherwise have been diagnosed.

Conclusions: The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.