Israel Medical Association Journal

Background: Fetal alcohol spectrum disorder (FASD) may be under-recognized and under-diagnosed in Israel. Fewer than 10 FASD diagnoses were reported between 1998 and 2007; however, several hundred diagnoses have been made since. Furthermore, less than 10% of surveyed Israeli pediatricians reported adequate knowledge of FASD.

Objectives: To determine the prevalence of suspected FASD, to establish a database as a starting point for epidemiological studies, and to develop FASD awareness for health, social, and educational services.

Methods: A chart review was conducted at an educational facility for children and adolescents with behavioral and learning challenges. The following information was extracted: adoption status, history of alcohol/drug abuse in the biological mother, medical diagnoses, medication use, and information regarding impairment in 14 published neurobehavioral categories. Subjects were classified as: category 1 (highly likely FASD) – impairment in three or more neurobehavioral categories and evidence of maternal alcohol abuse was available; category 2 (possible FASD) – impairment in three or more neurobehavioral categories and evidence to support maternal substance abuse (type/time unspecified); and category 3 (unconfirmed likelihood of FASD) – impairment in three or more neurobehavioral categories and no information regarding the biological family.

Results: Of 237 files analyzed, 38 subjects (16%) had suspected FASD: 10 subjects (4%) in category 1, 5 (2%) in category 2, and 23 (10%) in category 3. Twenty-seven subjects with suspected FASD (69%) had been adopted.

Conclusions: This study is the most comprehensive review of FASD among Israeli children and adolescents in a population with learning and behavior challenges.

Background: Pneumonia is a major cause of morbidity and mortality in burn patients with inhalation injuries. An increased risk of pneumonia has been demonstrated in trauma and burn patients urgently intubated in the field vs. emergency departments (EDs).

Objectives: To compare intubation setting (field vs. ED) and subsequent development of pneumonia in burn patients and to evaluate the indication for urgent intubation outside the hospital setting.

Methods: A retrospective medical records review was conducted on all intubated patients presenting with thermal (study group, 118 patients) or trauma (control group A, 74 patients) injuries and admitted to the intensive care unit of a level I trauma and burn center at a single institution during a 15 year period. Control group B (50 patients) included non-intubated facial burn patients hospitalized in the plastic surgery department.

Results: Field intubation was less frequent (37% field vs. 63% ED), although it was more frequent in larger burns (total body surface area > 50%; 43% field vs. 27% ED). More field intubated patients developed pneumonia during hospitalization (65% field vs. 36% ED [burns]; 81% field vs. 45% ED [multi-trauma]; 2% non-intubated, P < 0.05), with a significantly higher all-cause mortality (49% field vs. 24% ED, P < 0.05) and dramatically lower rates of extubation within 3 days (7% field vs. 27% ED, P < 0.05).

Conclusions: Field intubation is associated with a higher risk of subsequent development of pneumonia in burn and multi-trauma patients and should be applied with caution, only when airway patency is at immediate risk.

Background: The salutary effects of statin therapy in patients with cardiovascular disease (CVD) are well established. Although generally considered safe, statin therapy has been reported to contribute to induction of diabetes mellitus (DM).

Objectives: To assess the risk-benefit of statin therapy, prescribed for the prevention of CVD, in the development of DM.

Methods: In a population-based real-life study, the incidence of DM and CVD were assessed retrospectively among 265,414 subjects aged 40–70 years, 17.9% of whom were treated with statins. Outcomes were evaluated according to retrospectively determined baseline 10 year cardiovascular (CV) mortality risks as defined by the European Systematic COronary Risk Evaluation, statin dose-intensity regimen, and level of drug adherence.

Results: From 2010 to 2014, 5157 (1.9%) new cases of CVD and 11,637 (4.4%) of DM were observed. Low-intensity statin therapy with over 50% adherence was associated with increased DM incidence in patients at low or intermediate baseline CV risk, but not in patients at high CV risk. In patients at low CV risk, no CV protective benefit was obtained. The number needed to harm (NNH; incident DM) for low-intensity dose regimens with above 50% adherence was 40. In patients at intermediate and high CV risk, the number needed to treat was 125 and 29; NNH was 50 and 200, respectively.

Conclusions: Prescribing low-dose statins for primary prevention of CVD is beneficial in patients at high risk and may be detrimental in patients at low CV risk. In patients with intermediate CV risk, our data support current recommendations of individualizing treatment decisions.

Background: Risk factors for bleeding complications after percutaneous kidney biopsy (PKB) and the role of primary hemostasis screening are not well established.

Objectives: To determine the role of primary hemostasis screening and complication outcomes among individuals who underwent PKB.

Methods: We reviewed data of 456 patients who underwent PKB from 2010 to 2016 in a large university hospital. In 2015, bleeding time (BT) testing was replaced by light transmission aggregometry (LTA) as a pre-PKB screening test.

Results: Of the 370 patients who underwent pre-PKB hemostasis screening by BT testing, prolonged BT was observed in 42 (11.3%). Of the 86 who underwent LTA, an abnormal response was observed in 14 (16.3%). Overall, 155 (34.0%) patients experienced bleeding: 145 (31.8%) had minor events (hemoglobin fall of 1–2 g/dl, macroscopic hematuria, perinephric hematoma without the need for transfusion or intervention) and 17 (3.7%) had major events (hemoglobin fall > 2 g/dl, blood transfusion or further intervention). Abnormal LTA response did not correlate with bleeding (P = 0.80). In multivariate analysis, only prolonged BT (P = 0.0001) and larger needle size (P = 0.005) were identified as independent predictors of bleeding.

Conclusions: Bleeding complications following PKB were common and mostly minor, and the risk of major bleeding was low. Larger needle size and prolonged BT were associated with a higher bleeding risk. Due to the relatively low risk of major bleeding and lack of benefit of prophylactic intervention, the use of pre-PKB hemostasis screening remains unestablished.

Background: Abnormal gestational weight gain (GWG) has been associated with adverse outcomes for mothers and their offspring.

Objectives: To compare the achievement of recommended GWG and lifestyle factors in women with high-risk versus normal-risk pregnancies.

Methods: Pregnant women hospitalized in a gynecological and obstetrics department and pregnant women who arrived at a community clinic for a routine checkup were interviewed and completed questionnaires relating to weight gain and lifestyle factors (e.g., smoking, diet, exercise). Recommended GWG was defined by the American Congress of Obstetricians and Gynecologists (ACOG).

Results: GWG higher than ACOG recommendations was reported by 52/92 women (57%) with normal pregnancies and by 43/86 (50%) with high-risk pregnancies. On univariate analysis, characteristics associated with greater GWG were: current or past smoking, age > 40 years, pre-gestational body mass index (BMI) > 25 kg/m², low fruit intake, and high snack intake. High-risk pregnancies were associated with pre-gestational BMI > 25 kg/m² (48% vs. 27%, P = 0.012), consumption of vitamins (84% vs. 63%, P = 0.001), avoidance of certain foods (54% vs. 21%, P = 0.015), receiving professional nutritionist consultation (65% vs. 11%, P = 0.001), and less physical activity (9% vs. 24%, P = 0.01).

Conclusions: A minority of pregnant women met the recommended GWG. No difference was noted between normal and high-risk pregnancies. High-risk population tended to have a less healthy lifestyle. Counseling to follow a healthy, balanced diet should be recommended, regardless of pregnancy risk, with particular attention to women at high risk of extra weight gain.

Background: A patient`s individual chance of being diagnosed with cardiovascular disease can be determined by risk scores.

Objectives: To determine the risk score profiles of patients presenting with a first acute coronary event according to pre-admission risk factors and to evaluate its association with long-term mortality.

Methods: The research was based on a retrospective study of a cohort from the 2010 and 2013 Acute Coronary Syndrome Israeli Surveys (ACSIS). Inclusion criteria included first event and no history of coronary heart disease or cardiovascular disease risk equivalent. The Framingham Risk Score, the European Systematic COronary Risk Evaluation (SCORE), and the American College of Cardiology/American Heart Association/ (ACC/AHA) risk calculator were computed for each patient. The risk profile of each patients was determined by the three scores. The prognostic value of each score for 5 year survival was evaluated.

Results: The study population comprised 1338 patients enrolled in the prospective ACSIS survey. The ACC/AHA score was the most accurate in identifying patients as high risk based on pre-admission risk factors (73% of the subjects). The Framingham algorithm identified 53%, whereas SCORE recognized only 4%. After multivariate adjustment for clinical factors at presentation, we found that no scores were independently associated with 5 year mortality following the first acute coronary event.

Conclusions: Patients with first acute coronary event had a higher pre-admission risk scores according to the ACC/AHA risk algorithm. No risk scores were independently associated with 5 year survival after an event.

Background: Skin colonization of microorganisms in blood cultures (BCs) are generally considered clinically non-significant and can be the source of a true infection, particularly in immunosuppressed patients.

Objectives: To study the epidemiology and risk factors for bacteremia caused by contaminants.

Methods: This retrospective, descriptive study is based on adult BCs collected (2004–2013) and categorized as positive (True bacteremia [TrueB] or contamination) or negative. Clinical, demographic, and laboratory characteristics of BCs positive for the six most common potential contaminant pathogens (PCPs) that can cause TrueB and contamination (Coagulase-negative Staphylococcus [CoNS], Streptococcus viridans, Propionibacterium acnes, Corynebacterium spp., Bacillus spp., Clostridium spp.) were assessed. Ninety-two TrueB were identified vs. 196 contaminations (1:2 ratio).

Results: From 74,014 BCs, PCPs were found in 3735 samples, of which 3643 (97.5%) were contaminations and 92 (2.5%) were TrueB. The overall rate of BC contamination decreased during the study period from 6.7% to 3.8%. CoNS was the most common PCP. Bacillus spp. were only contaminants. Clostridium spp. and Streptococcus viridans were more often TrueB. In a multivariate model, predictors of TrueB included high creatinine levels, Streptococcus viridans in BC, and multiple positive BCs. A single culture of CoNS was strongly predictive of contamination.

Conclusions: Ten years of data on BCs, focusing on six PCPs, demonstrates a significant, yet insufficient reduction in the rate of contamination. High creatinine level, isolation of Streptococcus viridans, and multiple positive BCs were predictors of TrueB, while growth of CoNS was strongly predictive of contamination. This model could assist in diagnostic and therapeutic decision making.

Background: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.

Objectives: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.

Methods: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.

Results: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958–2.682, respectively) with ESBL colonization.

Conclusions: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Background: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean).

Objectives: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications.

Methods: We analyzed all gastrectomies for gastric cancer performed 2009–2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification.

Results: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05).

Conclusions: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

Background: Coronary artery disease (CAD) has known risk factors. Individual risks related to specific ethnicities are complex and depend on genetic predisposition and lifestyle.

Objectives: To compare the nature and prevalence of risk factors in Arab and non-Arab ethnic patients with symptomatic obstructive CAD referred for coronary angiography.

Methods: CAD, defined as coronary angiography with a ≥ 50% narrowing in ≥ 1 vessel, was diagnosed in 1029 patients admitted to a medical center between April 2014 and October 2015. Patients were divided into two groups according to ethnic origin: Arab vs. non-Arab. Demographics, clinical presentation, and coronary risk profiles were compared.

Results: The diagnosis of CAD was made during ST-elevation myocardial infarction (STEMI) in 198 patients (19%) who arrived at the clinic, 620 (60%) with unstable angina/non-STEMI, and 211 (21%) with stable angina. Patients with symptomatic CAD and Arab ethnicity were 47% more prevalent than non-Arab patients presenting with CAD. The Arab patients were appoximately 5 years younger, 50% more likely to be active smokers, 25% more likely to be obese, and more likely to have a family history of CAD. Other coronary risk factors were similar between the two groups.

Conclusions: Smoking and obesity, which are potentially modifiable CAD risk factors, stood out as major risk factors, in addition to genetic disposition, among Arab and non-Arab patients with symptomatic CAD. Screening and educational interventions for smoking cessation, obesity control, and compliance to treatment of co-morbidities should be attempted in order to decrease CAD in the Arab population.

Background: Diabetic ketoacidosis (DKA) as the first presentation of type 1 diabetes mellitus (T1DM) is a serious complication that is preventable.

Objectives: To identify risk factors for DKA at presentation of T1DM to delineate high-risk Israeli populations that could benefit from preventative measures.

Methods: Data for this multicenter retrospective study were collected from the medical files of three pediatric diabetes centers representing three districts in Israel. Inclusion criteria were diagnosis of T1DM, age at diagnosis ≤ 17 years, permanent residency in Israel, and documentation of the presence or absence of DKA at presentation.

Results: The study population included 607 patients of whom 438 met the inclusion criteria. The mean age at diagnosis was 9.1 ± 4.5 years. DKA was present at diagnosis in 156/438 patients (35.6%). The incidence of DKA was different among the three diabetes centers (P = 0.04). The DKA group was significantly younger than the non-DKA group (8.4 ± 4.5 vs. 9.5 ± 4.4, respectively, P = 0.008). DKA was significantly associated with maternal origin (Ashkenazi Jewish origin [lower] vs. non-Ashkenazi, P = 0.04) and with paternal education level (academic [lower] vs. non-academic education, P = 0.04). Stepwise logistic regression showed that maternal Ashkenazi Jewish origin has a protective effect on DKA (odds ratio [OR] 0.4, 95% confidence interval [95%CI] 0.21–0.74, P = 0.004) and that younger age is an independent risk factor (OR 1.06, 95%CI 1.01–1.1, P = 0.02).

Conclusions: A diabetes educational program targeting high-risk population groups may reduce the prevalence of DKA nationwide.

Background: Weight loss surgery is the most effective treatment for obesity, and it reduces cardiovascular and cancer risk through poorly understood mechanisms. MicroRNAs (miRNAs) are short RNA molecules that regulate the stability and translation of many mRNAs. We hypothesized that levels of specific circulating miRNAs are altered following surgery and may contribute to lower cancer risk.

Objectives: To investigate the change of miRNA following surgery.

Methods: All patients underwent gastric “sleeve operation”. RNA was isolated from sera of 21 patients (14 men, 7 women) before and 3 months after surgery. Sera were combined into two pools, which served for cDNA library construction followed by miSeq sequencing. The levels of candidate miRNAs were validated in the individual samples by QRT-PCR.

Results: Serum miR-122 was significantly up-regulated 3 months post-bariatric surgery in sera of patients, whose endothelial function had greatly improved. In addition, serum miR-122 levels correlated positively with endothelial function as measured by FMD. The changes in miR-122 levels from pre-surgery to 3 months post-surgery also tended to correlate with the respective changes in FMD.

Conclusions: The serum miR-122/miR-451 ratio may serve as a marker for endothelial function in obese patients. miR-122 is the dominant miRNA in the liver and a known tumor suppressor. Our findings suggest a role for circulating miR-122 in the maintenance of vascular endothelial cells (VECs) and in the prevention of cancer. Further studies are required to elucidate the mechanism of its secretion into circulation and its absorption by VECs, as well as its relevant cellular targets.