Israel Medical Association Journal

Infantile hemangioma (IH) is the most common benign vascular tumor in infancy. Recent advances, particularly in beta-blocker therapy, have significantly improved the management of IHs. Early identification and treatment of IH may help reduce morbidity and associated complications. In this review, experts in pediatric dermatology in Israel who have experience in treating IH formulated national guidelines for the diagnosis and treatment of IHs, providing evidence-based recommendations for selecting appropriate therapeutic approaches. These Israeli national guidelines provide a structured approach to the diagnosis and treatment of IH, emphasizing early referral, appropriate treatment selection, and careful monitoring. The guidelines serve as a critical resource for pediatricians and dermatologists, ensuring optimal patient outcomes while minimizing complications.

Gaucher disease (GD) is an inherited autosomal recessive genetic disorder caused by mutations in the glucocerebroside (GBA1) gene [1]. These variants result in decreased activity of the lysosomal enzyme β-glucocerebrosidase (GCase), which is essential for breaking down glucocerebroside into glucose and ceramide. Consequently, activated macrophages, known as Gaucher cells, accumulate undegraded glucocerebroside. The phagocytic role and naturally high-level GCase activity of macrophages may partly explain why these cells are particularly affected in GD. The accumulation of glucocerebroside in macrophages causes an expansion in the population of these cells, leading to symptoms like hepatosplenomegaly, thrombocytopenia, anemia, bleeding tendency, growth retardation, and bone issues. Bone marrow infiltration may result in bone infarction, episodes of bone crises, and osteonecrosis, mainly of large joints and less commonly as pathological fractures. These latter skeletal complications are the most critical irreversible consequence of untreated GD, significantly impacting the quality of life of patients, and hence should be avoided by early administration of specific therapy. The accumulation of glucocerebroside in lysosomes has been linked to a pro-inflammatory state [2]. In addition, the misfolding and retention of mutant GCase within the endoplasmic reticulum (ER) has been associated with ER stress and activation of the unfolded protein response, contributing to GD phenotypic heterogeneity, inflammation, and immune dysregulation [3].

Thyroid storm-related heart failure is a rare, life threatening complication of hyperthyroidism. In refractory cases, urgent thyroidectomy is required for definitive control of thyrotoxicosis. venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a supportive measure for cardiorespiratory failure requiring continuous anticoagulation to prevent clotting. We presented two cases of thyrotoxic cardiac failure that necessitated VA-ECMO. One of the patients was successfully treated with thyroidectomy while on VA-ECMO. To the best of our knowledge, only two such cases have previously been reported.

Coronavirus disease 2019 (COVID-19), first identified in 2019, constitutes a global major public health burden. Most of morbidity and mortality is derived by the severe inflammatory reaction (cytokine release syndrome) that ensues in later stages. Baricitinib, a selective JAK inhibitor primarily used for the treatment of rheumatoid arthritis (RA) [1], was shown to reduce mortality in COVID-19 hospitalized patients in combination with remdesivir [2].

Background: Recommendations for a head computed tomography (CT) scan in elderly patients without a loss of consciousness after a traumatic brain injury and without neurological findings on admission and who are not taking oral anticoagulant therapy, are discordant.

Objectives: To determine variables associated with intracranial hemorrhage (ICH) and the need for neurosurgery in elderly patients after low velocity head trauma

Methods: In a regional hospital, we retrospectively selected 206 consecutive patients aged ≥ 65 years with head CT scans ordered in the emergency department because of low velocity head trauma. Outcome variables were an ICH and neurological surgery. Independent variables included age, sex, disability, neurological findings, facial fractures, mental status, headache, head sutures, loss of consciousness, and anticoagulation therapy.

Results: Fourteen patients presented with ICH (6.8%, 3.8–11.1%) and three (1.5%, 0.3–4.2%) with a neurosurgical procedure. One patient with a coma (0.5, 0.0–2.7) died 2 hours after presentation. All patients who required surgery or died had neurological findings. Reducing head CT scans by 97.1% (93.8–98.9%) would not have missed any patient with possible surgical utility. Twelve of the 14 patients (85.7%) with an ICH had neurological findings, post-trauma loss of consciousness or a facial fracture were not present in 83.5% (95% confidence interval 77.7–88.3) of the cohort.

Conclusions: None of our patients with neurological findings required neurosurgery. Careful palpation of the facial bones to identify facial fractures might aid in the decision whether to perform a head CT scan.

Background: Cigarette smoking is a widespread problem around the world. In Israel, the prevalence of smoking is 23%. Smokers who are Orthodox abstain from smoking during the Sabbath, i.e., from sundown Friday to sundown Saturday, due to a religious prohibition. The prevalence of smoking among Orthodox men is 13%. However, there are no data on patterns of smoking or on the addiction profiles in this population.

Objectives: To explore the smoking patterns, motivation for smoking and nicotine addiction among Orthodox Jewish men, compared to non-Orthodox men, as well as the differences in the urge to smoke and withdrawal symptoms on Saturday versus weekdays in the Orthodox group. 

Methods: The participants completed the Fagerstrom test for nicotine dependence, questionnaires on reasons for smoking and smoking patterns, as well as two brief questionnaires on the urge to smoke and withdrawal symptoms after overnight abstinence on a weekday and after the end of the Sabbath. 

Results: Both groups were strongly addicted to nicotine and there were no differences in the reasons for smoking, withdrawal symptoms and nicotine craving after an overnight abstinence on weekdays. However, religious smokers had low levels of craving for nicotine and few withdrawal symptoms during Sabbath abstinence when compared to weekdays. 

Conclusions: Although we found no difference in the baseline characteristics with regard to nicotine addiction, smoking motivation, urge to smoke and withdrawal symptoms between religious and non-religious groups, the former are able to abstain from smoking during 25 hours of the Sabbath every week with significantly fewer withdrawal symptoms compared to week days.

 

Background: Enoxaparin is frequently used as prophylaxis for deep venous thrombosis in critically ill patients. 

Objectives: To evaluate three enoxaparin prophylactic regimens in critical care patients with and without administration of a vasopressor.

Methods: Patients admitted to intensive care units (general and post-cardiothoracic surgery) without renal failure received, once daily, a subcutaneous fixed dose of 40 mg enoxaparin, a subcutaneous dose of 0.5 mg/kg enoxaparin, or an intravenous dose of 0.5 mg/kg enoxaparin. Over 5 days anti-activated factor X levels were collected before the daily administration and 4 hours after the injection.

Results: Overall, 16 patients received the subcutaneous fixed dose, 15 received the subcutaneous weight-based dosage, and 8 received the dose intravenously. Around two-fifths (38%) of the patients received vasopressors. There was no difference between anti-activated factor X levels regarding vasopressor administration. However, in all three groups the levels were outside the recommended range of 0.1 IU/ml and 0.3 IU/ml.

Conclusions: Although not influenced by vasopressor administration, the enoxaparin regimens resulted in blood activity levels outside the recommended range.

 

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.

Background: Ulcerative colitis (UC) is a common and difficult-to-treat disease. In non-smokers the relative risk of developing UC[1] is 2.9 compared with smokers, who tend to have a later onset and a milder disease. Nicotine is the component of cigarette smoke responsible for the favorable effects in UC. Nicotine is metabolized by the enzyme CYP2A6. Subjects who are homozygotes for CYP2A6*4 gene polymorphism are poor nicotine metabolizers, while homozygotes for CYP2A6*1A polymorphism are extensive metabolizers.

Objectives: To compare the frequency of CYP2A6 and CHRNA3 polymorphisms among smokers and non-smokers with UC, and their effect on disease severity.

Methods: Data on the age at onset of disease, disease activity, and treatment were obtained from questionnaires completed by the 69 subjects in our study group. CYP2A6

*1A,*4A and CHRNA3 polymorphisms were determined by polymerase chain reaction and restriction enzyme analysis.

Results: Nine percent of the patients were current smokers, 30% were former smokers and 61% non-smokers. Among smokers and former smokers 63% were homozygotes for CYP2A6*1A and 4% were homozygotes for CYP2A6*4A, whereas among non-smokers 66% were homozygotes for CYP2A6*4A (P < 0.0001). There was no significant effect of CYP2A6 or CHRNA3 genotype on UC activity.

Conclusions: We found a very high proportion of poor nicotine metabolizers among non-smoking patients with UC and a very low proportion among current and former smokers, making it difficult to determine the effect of poor metabolizer genotype on disease activity in smokers with UC. However, it may be possible to identify UC patients who are poor metabolizers of nicotine and who may benefit from nicotine or nicotine-like pharmacological treatment.

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.
 

Non-steroidal anti-inflammatory drugs, mainly ibuprofen, are extensively used in children as analgesics and antipyretics.