Israel Medical Association Journal

Becoming and Being a Physician: A Developmental Journey

Shmuel P. Reis, Adina L. Kalet, W. Wayne Weston. CRC Press, 2025, Boca Raton, London, New York

This book is essentially about the evolution of knowledge regarding the DLC from its seemingly simplistic beginnings to its current extreme complexity. The authors offer a set of lenses to understanding such complexity and discerning what comprises and what may influence the DLC.

Obesity is a growing global health concern, with its prevalence contributing to the rise of multiple chronic conditions, including autoimmune diseases. In this review I explore the intricate relationship between obesity and autoimmunity, focusing on how excess adiposity can affect immune responses and promote the development of autoimmune disorders. Obesity alters adipose tissue architecture, promoting chronic low-grade inflammation and triggering the release of pro-inflammatory cytokines, which contribute to immune system dysregulation. Adipose tissue is no longer seen as merely an energy store but as an active endocrine organ that interacts with the immune system. The review delves into mechanisms such as the role of adipokines, altered T cell function, and the recruitment of immune cells to inflamed adipose tissue, which together exacerbate autoimmune risk in obese individuals. Genetic and environmental factors also play a critical role in these processes, as polymorphisms and high-fat diets have been shown to influence both obesity and autoimmune susceptibility. Last, the review explores potential therapeutic strategies, such as lifestyle interventions and targeting obesity-driven inflammatory pathways, which could mitigate autoimmunity. Understanding the connection between obesity and autoimmunity offers insights into more effective interventions for patients suffering from these intertwined conditions.

Background: The coronavirus disease 2019 (COVID-19) pandemic showed the need to evaluate disease severity promptly at the time of hospital admission. 

Objectives: To establish an admission protocol, which included clinical and laboratory findings. 

Methods: We conducted a retrospective study at Wolfson Medical Center, Israel, for a period of 19 months (2020–2021). We established a protocol for patients who were admitted with COVID-19 infection. The protocol parameters included demographic data, co-morbidities, immune status, oxygen level at room air on admission, oxygen demand, lymphopenia, C-reactive protein (CRP) level, lactate dehydrogenase, D-DIMER, creatinine, aspartate transferase, alanine aminotransferase, and ferritin. Based on this protocol, we defined the severity of COVID-19 at the beginning of hospitalization and started treatment without delay. This protocol included ferritin levels as a guide to severity and outcome of patients. A database was established for all the parameters of the patients included in the study. 

Results: The study included 407 patients; 207 males (50.9%), 200 females (49.1%). The age range was 18–101 years. Hyperferritinemia (> 1000 ng/dl) was one of the strongest and most significant predictors for severe disease in these patients (P < 0.001). Lymphopenia, high levels of CRP, alanine aminotransferase, aspartate transferase, lactate dehydrogenase, and creatinine also correlated with severe disease, complications, and death. 

Conclusions: Abnormal ferritin levels were a very significant and clear indicator of the development of severe COVID-19. The addition of ferritin levels to our protocol aided in finding which patients were at increased risk for morbidity and mortality.

Children affected with Poland syndrome are born with missing or underdeveloped muscles (typically pectoralis major) on one side of the body. Breast abnormalities such as unilateral hypoplasia or agenesis of the breast and nipple may also occur. Other muscles on the affected side, including other muscles in the chest wall, shoulder, arm, and hand, may be missing or underdeveloped [1]. Ribs may be noticeable due to the loss of subcutaneous fat. Sparse or absent axillary and pectoral hairs are a common manifestation of this syndrome.

Background: School closures due to the coronavirus disease 2019 (COVID-19) outbreak affected students physically, socially, and psychologically with an increase in the number of children and adolescent presenting with anxiety, depression, and drug abuse.

Objectives: To examine the impact of COVID-19 and lockdown on the mental health of minors during the pandemic period and to characterize the type and number of referrals to a regional psychiatric outpatient clinic.

Methods: This study included 380 children evaluated in an outpatient child psychiatric clinic. They were divided into two groups: before the lockdowns (BLD) (n=248), from January 2019 to February 2020, and during the lockdowns (LD) (n=132), from March 2020 to April 2021.

Results: When comparing the LD to BLD, there was increase in suicide attempts (9.8% vs. 2.8%) and in the use of psychotherapy (81% vs. 56%). There was a decrease in the diagnoses of behavior disorders (29.5% vs. 44.8%) and ADHD (29.5% vs. 50%); as well as a decrease in stimulant usage (22.7% vs. 38%). There was a statistically non-significant increase in the number of children with depression, anxiety, and drug-use disorder.

Conclusions: Many children developed educational, social, emotional, and behavioral gaps during LD, and they lost skills to deal with everyday problems due to social isolation. It is important to follow the long-term impact of the lockdowns and social isolation.

Background: Environmental, social, and governance (ESG) is a form of international private business self-regulation that aims to contribute to society from a philanthropic, activist, or charitable nature by engaging in or supporting volunteering or ethically oriented practices. The major benefit of ESG is having the organization’s workers recruited for the goal of making the world a better place. There is a growing understanding regarding the extent of the environmental impacts of health services. Therefore, the interest in measuring and reporting the sustainability of health system performance is becoming crucial. As population aging and growth in healthcare demand are two of the main challenges of the current and mainly future health services, performance, and quality measurement as well as sustainability metrices are relevant more than ever.

Objectives: To review the ESG activities at Assuta Medical Centers (AMC) that helped the organization earn the Maala Index Platinum + grade in 2021.

Methods: We reviewed the ESG elements that were implemented at AMC.

Results: AMC entered an ESG process in November 2019 and earned Platinum and Platinum+ grades from the Maala Index in 2020 and 2021, respectively. AMC won the Workforce Diversity prize for having many employees over 60 years of age. AMC activities are detailed as a case study for other health organizations in Israel and worldwide.

Conclusions: A big leading health organization can spearhead sustainable development goals model in Israel and worldwide.

Background: No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease.

Objectives: To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC.

Methods: A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014–2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion.

Results: The 27 patients in the effusion group were generally younger, more often female, and with a higher percentage of never-smokers, compared to the 54 patients of the control group. Epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) mutation tumors were found in 48% of patients in the effusion group vs. 25% in the control group. In the multivariate analysis, the unadjusted odds ratio (OR) for the development of pericardial effusion in patients with somatic mutations was significantly higher compared to wild type tumors (OR 2.65, 95% confidence interval 1.00–7.00). However, a suspected association between pericardial effusion and mutation status was found to be confounded by age. While a high rate of recurrence was observed when pericardiocentesis was initially performed (9/17, 53%), no recurrence was documented when pericardial window procedure was performed (total of 17 patients).

Conclusions: Patients with EGFR/ALK mutations may be at higher risk for the development of pericardial effusion; therefore, attending physicians need to be aware and have a high index of clinical suspicion

Background: Benign rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes (BCECTS) is a common childhood epileptic syndrome. The syndrome resolves in adolescence, but 1–7% of patients have an atypical presentation, some of which require aggressive medical treatment. Early treatment may prevent complications and neurocognitive deterioration. Variants include Landau-Kleffner syndrome (LKS) and electrical status epilepticus during sleep (ESES).

Objectives: To determine data driven identification of risk factors and characterization of new subtypes of BCECTS based on anontology. To use data mining analysis and correlation between the identified groups and known clinical variants.

Methods: We conducted a retrospective cohort study comprised of 104 patients with a diagnosis of BCECTS and a minimum of 2 years of follow-up, between the years 2005 and 2017. The medical records were obtained from the epilepsy service unit of the pediatric neurology department at Dana–Dwek Hospital, Tel Aviv Sourasky Medical Center. We developed a BCECTS ontology and performed data preprocessing and analysis using the R Project for Statistical Computing (https://www.r-project.org/) and machine learning tools to identify risk factors and characterize subgroups.

Results: The ontology created a uniform and understandable infrastructure for research. With the ontology, a more precise characterization of clinical symptoms and EEG activity of BCECTS was possible. Risk factors for the development of severe atypical presentations were identified: electroencephalography (EEG) with spike wave (P < 0.05), EEG without evidence of left lateralization (P < 0.05), and EEG localization (centrotemporal, frontal, or frontotemporal) (P < 0.01).

Conclusions: Future use of the ontology infrastructure for expanding characterization for multicenter studies as well as future studies of the disease are needed. Identifying subgroups and adapting them to known clinical variants will enable identification of risk factors, improve prediction of disease progression, and facilitate adaptation of more accurate therapy. Early identification and frequent follow-up may have a significant impact on the prognosis of the atypical variants.

Cardiac patients of all ages were managed in the past by internists who specialized in cardiology. During the past 50 years, the medical field has witnessed great strides in the management of congenital heart disease, and thus pediatric cardiology has become a subspecialty in many countries. This review article focuses on the advances in fetal cardiac interventions (FCI) since its inception by our group in 1975. Three major modes of FCI have evolved during the past 42 years: pharmacologic, closed FCI, and open FCI. All treatments require a careful approach by the heart team and are reserved for severe fetal cardiac conditions. They call for prenatal intervention in view of the severity and progressive nature of the diseases that are associated with high fetal morbidity and mortality if left untreated. The well-established pharmacologic FCI approach includes several new and effective agents with recommendations often varying between class I and class IIa and IIb. The advances in prenatal echocardiographic imaging and color flow Doppler has given an impetus to the development of the other FCI modes; however, the need for uterine incision and fetal cardiac bypass in the open technique have limited its advance. Long-term outcomes are still unknown and definite conclusions as to the efficacy and safety of FCI need further investigation, including multicenter trials with long-term data. 

A fundamental challenge for multiple sclerosis (MS) therapy is to promote repair and remyelination beyond their limited spontaneous extent. Glatiramer acetate (GA, Copaxone®), an approved treatment for MS, has been shown to induce immunomodulation as well as neuroprotection in the inflamed central nervous system (CNS) in MS and in its model, experimental autoimmune encephalomyelitis (EAE). Using electron microscopy, immunohistochemistry, and advanced magnetic resonance imaging, we have demonstrated diminished myelin damage in GA-treated mice, in both relapsing-remitting and chronic EAE, even when treatment was applied late after the disease exacerbation, suggesting repair. Furthermore, quantitative analysis indicated significant elevation in remyelinated axons in GA-treated compared to untreated EAE mice. To further prove that GA can promote myelination, we studied its effect in the developing naïve CNS, when injected postnatally. Immunohistochemical and ultrastructural analyses revealed significant increase in the number of myelinated axons, the thickness of the myelin encircling them, and the resulting g-ratios in the spinal cords of GA-injected mice compared to their phosphate-buffered saline-injected littermates. A prominent elevation in the amount of progenitor oligodendrocytes and their proliferation, as well as in mature oligodendrocytes, implied that the effect of GA is linked to the differentiation along the oligodendroglial cascade. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates. These cumulative findings indicate that GA treatment affects myelination under inflammatory as well as non-inflammatory conditions, supporting the notion that the repair process in the CNS can be up-regulated by therapy.

Background: Skin-prick tests (SPT), food-specific immunoglobulin E level (sIgE) and clinical history have limited value individually in predicting the severity of outcome of the oral food challenge (OFC). 

Objectives: To develop a score that accounts for SPT, sIgE and clinical history to predict the risk of severe reaction to the OFC. 

Methods: A 5 year retrospective chart review was performed on 983 children who underwent OFC to egg, milk and peanut. 

Results: Using multilogistic regression, four major indicators were found to be independently associated with failed OFC: sIgE (odds ratio = 1.04, P < 0.0001) , wheal size of the SPT (OR = 1.23, P < 0.0001), a history of any prior reaction to the food (OR = 1.13, P < 0.01), and a history of a prior non-cutaneous reaction (OR = 1.99, P < 0.01)  and three were independently associated with anaphylaxis: wheal size (OR = 1.16, P < 0.001), a history of a prior non-cutaneous reaction (OR = 4.24, P < 0.01), and age (OR = 1.07, P < 0.03). A Food Challenge Score (0–4) was developed which accounted for SPT wheal, sIgE, a history of a prior non-cutaneous reaction, and age. A score of 0–1 had a negative predictive value for multisystem reaction to the OFC: 95% for milk, 91% for egg and 93% for peanut. A score of 3–4 had a positive predictive value for anaphylaxis:  62% for milk, 92% for egg and 86% for peanut.

Conclusions: Severe reaction to milk, egg and peanut OFC can be predicted using a simple score that takes into account clinical data that are commonly available prior to the challenges.