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עמוד בית
Fri, 25.07.25

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March 2025
Assaf Adar MD, Aviv D Goldbart MD, Nitzan Burrack MD, Neta Geva MD, Bracha Cohen MD, Inbal Golan-Tripto MD

Background: Acute bronchiolitis, primarily caused by respiratory syncytial virus (RSV), is the leading cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity.

Objectives: To evaluate the association between C-reactive protein (CRP) serum levels on admission and disease severity in children hospitalized due to RSV bronchiolitis.

Methods: This retrospective cohort study included children (0–24 months old) who were hospitalized due to RSV bronchiolitis (2018–2022), CRP levels taken at admission.

Results: We included 1874 children (mean age of 6.7 months, 59% males); median CRP level 1.92 mg/dl. Children with elevated CRP (> 1.92 mg/dl) were significantly older (5.1 vs. 3.8 months, P < 0.001) and had higher rates of pneumonia (9.4% vs. 4.3%, P < 0.001), urinary tract infection (UTI), (2.2% vs. 0.2%, P < 0.001), acute otitis media (AOM) (1.7% vs. 0.2%, P < 0.001), admissions to the pediatric intensive care unit (PICU) (7.4% vs. 3.7%, P < 0.001), antibiotic treatment (49.8% vs. 37.2%, P < 0.001), and longer hospitalizations (3.83 vs. 3.31 days, P < 0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk 11.6, 2.25, 1.98, 1.44, respectively, P < 0.001). CRP thresholds of 3.51, 1.9, and 2.81 mg/dl for PICU admission, UTI, and pneumonia, were calculated using Youden's index with AUC 0.72, 0.62, and 0.61, respectively.

Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

Vered Nir MD, Guy Katsenelenbogen MD, Rima Karabitski MD, Vered Schichter-Konfino MD, Adi Klein MD

Background: Community-acquired pneumonia (CAP) is a prevalent bacterial infection in children. Lung ultrasound (LUS) is gaining popularity as a diagnostic tool for pneumonia, with the added potential for monitoring disease progression. However, research on the benefits of this modality for monitoring disease progression remains limited.

Objectives: To categorize the follow-up sonographic findings of lung inflammation in pediatric patients performed 10–14 days after being diagnosed with CAP.

Methods: We conducted a prospective observational study of children aged 0–18 years, diagnosed with CAP between 2020 and 2022. LUS findings at the time of diagnosis and 10–14 days later were recorded and documented.

Results: In total, 47 children were recruited, and 22 were included in the analysis. At the time of diagnosis, 20 patients (90%) had B-lines. Air bronchograms were found in all patients, and consolidation findings were observed in seven of the examined patients (32%). At the follow-up LUS 10–14 days later, B-lines were observed in six patients (27%). Air bronchograms were observed in eight patients, and consolidation findings were observed in six (27%). In 13 patients (59%), the follow-up LUS was completely normal. These patients were younger and had lower body weights. Pathological findings persisted in 41% of the patients.

Conclusions: For most patients, LUS demonstrated a resolution. Further large-scale studies are needed to validate the findings and determine the role of LUS in pediatric CAP.

Gavriel Hain MD, Micha Aviram MD, Aviva Levitas MD, Hana Krymko MD, Aviv Goldbart MD, Inbal Golan-Tripto MD

A full-term 1-month-old female was brought to our pediatric emergency department (ED) due to 3 days of increasing respiratory distress. She was born at term to healthy, consanguineous (2nd degree) Bedouin parents after a pregnancy that lacked adequate monitoring. At birth, a physical examination revealed an imperforate anus and a recto-vestibular fistula, left hydronephrosis, large patent ductus arteriosus (PDA), and an atrial septal defect (ASD). The diagnosis of VACTER association was made. Importantly, she had no respiratory difficulties, nor hemivertebra or tethered cord.

On admission to the ED, she presented with severe respiratory distress, tachypnea, dyspnea, and hypoxemia without evidence of upper airway obstruction or stridor. Due to impending respiratory failure, she was transferred to the pediatric intensive care unit and started on non-invasive respiratory support through a high-flow nasal cannula (HFNC), which partially relieved her work of breathing. The nasal swab for respiratory viruses was positive for enterovirus, and her urine culture grew Escherichia coli. She was transferred to the pediatric ward after clinical improvement on day 3. Echocardiography performed for evaluation of pulmonary hypertension estimated normal pressures but revealed a vascular ring anomaly. A computed tomography (CT) angiography performed confirmed the presence of an aberrant left pulmonary artery also referred to as a left pulmonary artery sling (LPAS) [Figure 1A].

Mai Shiber MD, Nadav Shalev MD, Maor Leibzon MD, Nechama Sharon MD

Anorexia nervosa (AN) is a common psychiatric disorder primarily affecting adolescents and young adults. It is characterized by extreme restriction of food intake, distorted body image, and weight-gain anxiety. We report a case with rapid progression and severe metabolic changes in a young restrictive-type AN patient, highlighting unique aspects of this presentation and discussing pathophysiology.

An 11-year-old girl presented with a significant 29% weight loss over 4 months, leading to a body mass index (BMI) of 11.7 (< 1st BMI percentile for her sex and age). She presented with severe bradycardia and metabolic abnormalities including hypoglycemia, hypercholesterolemia, and hypothyroidism. Following diagnosis with restrictive type AN based on the DSM-5 [1] criteria and stabilization at our department, she was transferred to a specialized unit. The hypercholesterolemia our patient presented with is more typical of binge-eating/purging subtype AN, yet it was markedly elevated in this restrictive-type case.

Maayan Mandelbaum MD, Daniella Levy-Erez MD, Shelly Soffer MD, Eyal Klang MD, Sarina Levy-Mendelovich MD

Artificial Intelligence (AI), particularly large language models (LLMs) like OpenAI's ChatGPT, has shown potential in various medical fields, including pediatrics. We evaluated the utility and integration of LLMs in pediatric medicine. We conducted a search in PubMed using specific keywords related to LLMs and pediatric care. Studies were included if they assessed LLMs in pediatric settings, were published in English, peer-reviewed, and reported measurable outcomes. Sixteen studies spanning pediatric sub-specialties such as ophthalmology, cardiology, otology, and emergency medicine were analyzed. The findings indicate that LLMs provide valuable diagnostic support and information management. However, their performance varied, with limitations in complex clinical scenarios and decision-making. Despite excelling in tasks requiring data summarization and basic information delivery, the effectiveness of the models in nuanced clinical decision-making was restricted. LLMs, including ChatGPT, show promise in enhancing pediatric medical care but exhibit inconsistent performance in complex clinical situations. This finding underscores the importance of continuous human oversight. Future integration of LLMs into clinical practice should be approached with caution to ensure they supplement, rather than supplant, expert medical judgment.

Ido Somekh MD PhD, Ilan Dalal MD, Raz Somech MD PhD

Inborn errors of immunity (IEI), formerly known as primary immunodeficiencies (PID), comprise a diverse group of genetic disorders characterized by increased susceptibility to infections, autoimmunity, autoinflammatory conditions, allergies, and malignancies. These disorders exhibit a broad spectrum of clinical manifestations, including extra-hematopoietic manifestations, which may also present later in life. IEI diagnosis has significantly advanced, in line with the common use of next-generation sequencing-based genetic platforms, such as whole-exome and whole-genome sequencing. Treatment approaches have evolved beyond infection management to include curative therapies such as hematopoietic stem cell transplantation, gene therapy, and targeted pharmacologic treatments. In this review, we explore recent advancements in the understanding, diagnosis, and treatment of IEI, emphasizing the rapid progress in this expanding field.

Shoshana Revel-Vilk MD PhD, Ari Zimran MD, Aya Abramov MD, David Strich MD

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].

February 2025
Howard Amital MD MHA, Avishay Elis MD

It is indisputable that internal medicine is the cornerstone of medical activities, including medical education, in hospital clinical activities, and clinical and basic medical research.

The medical landscape in Israel is exceptionally demanding, far exceeding the norms of the countries that are members of the Organisation for Economic Co-operation and Development (OECD). We have fewer hospital beds per capita, a greater workload for each physician, and in the future, we will face the challenge of teaching more medical students across our current clinical fields.

The Israeli Society of Internal Medicine has made it its mission to advance internal medicine across all dimensions of the healthcare system in Israel. As such, for the third consecutive year, we are honored to present an issue of the Israel Medical Association Journal (IMAJ) dedicated to research in the different fields of internal medicine that are conducted by physicians from various departments across the country.

This year, we emphasize even more strongly that research is an integral part of our clinical practice. At a time when the basic sciences phase of residency is under threat, it is crucial to underscore its importance. In this issue of IMAJ, we have chosen to publish various studies that were conducted during the basic sciences phase of the residency in internal medicine, highlighting how this training period can be optimally utilized to advance research while simultaneously progressing and maturing through clinical training.

Raymond Farah MD, Rola Khamisy-Farah MD, George Arshed MD, Rashed Khatib MD, Salman Zarka MD

Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness with broad spectrum of clinical manifestations ranging from asymptomatic cases to severe complications such as acute respiratory failure, multi-organ dysfunction, and death.

Objectives: To evaluate the platelet-lymphocyte ratio (PLR) as a marker of disease severity and mortality in COVID-19 patients. To explore the relationship between PLR and other inflammatory indicators, specifically C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR).

Methods: The cohort included 400 patients (206 males, 194 females; mean age: 64.5 ± 17.1 years [range 20–100 years]) who were hospitalized between April 2020 and December 2021. Data were collected on demographic and clinical characteristics, including ward and critical care details. CRP, NLR, and PLR values were recorded on the first and last days of hospitalization. Patients were categorized based on their hospitalization outcomes.

Results: PLR statistically increased during hospitalization, from 245 ± 160 at admission to 341 ± 747 at discharge (P < 0.001). A significant association was found between PLR and both the length of hospital stay and mortality. The mean PLR in the deceased group was 445 ± 590, compared to 304 ± 795 in the survivors, P = 0.007. This finding showed a correlation between higher PLR and increased severity and mortality.

Conclusion: PLR has been identified as a relevant marker for assessing the severity of COVID-19. Elevated PLR levels are associated with cytokine storm, length of hospital stay, and mortality. The results highlight the relationship between elevated PLR and poor outcome in COVID‐19 patients, suggesting its use in monitoring disease progression and prognosis.

Yuval Kuntzman MD, Gilad Halpert PhD, Howard Amital MD MHA

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease pathway is heavily influenced by different inflammatory cytokines. There is ample evidence of cannabidiol (CBD) immunomodulation effects.

Objectives: To investigate the effect of CBD on patients with SARS-CoV-2 and to measure the impact on inflammatory cytokines.

Methods: A double blind, placebo-controlled study to compare the clinical outcomes and selected serum cytokine levels in patients with SARS-CoV-2 that received sublingual CBD extraction. Seven patients were randomized to the treatment arm and three to the placebo group.

Results: Clinical outcomes were better in the patient group that received sublingual CBD vs. patients receiving placebo treatment. Serum cytokine mean concentration levels showed differences between the two groups but of mixed trends.

Conclusions: Patients presenting with SARS-CoV-2 and receiving CBD sublingually had better outcomes than those receiving a placebo, although these results did not reflect in selected serum cytokines. Further study is needed.

Noa Bigman-Peer MD, Genady Drozdinsky MD, Irit Heruti PhD, Eran Rotman MD MHA, Irit Ayalon-Dangur MD, Anat Dagan BSc, Noa Eliakim-Raz MD

Background: Burnout is prevalent among healthcare providers and characterized by emotional exhaustion, depersonalization, and reduced personal accomplishment. The coronavirus disease 2019 (COVID-19) pandemic exacerbated burnout due to increased workloads, emotional strain, and heightened risk. Complementary medicine (CAM) interventions like shiatsu massage and reflexology have been explored as potential to mitigate burnout, particularly pandemic-related stress.

Objectives: To assess the efficacy of CAM interventions for alleviating burnout in healthcare providers treating COVID-19 patients during 2022, when the Delta variant was prevalent.

Methods: This prospective observational study included 86 healthcare providers at Rabin Medical Center, Beilinson Campus. Workers were divided into two groups: an intervention group participating in CAM activities and a control group. Participant burnout and post-traumatic stress disorder (PTSD) symptoms were evaluated using the Maslach Burnout Inventory and General Anxiety Disorder 7 at baseline and at one day and one week post-intervention.

Results: The CAM group demonstrated significant reduction in burnout scores, primarily due to an enhanced sense of accomplishment (P = 0.023), with enduring effects observed after one week, although not reaching statistical significance (P = 0.078). There was no observed difference in PTSD scores between the groups (P = 0.28).

Conclusions: The study reveals potential benefits of CAM interventions in reducing burnout symptoms among healthcare providers during the COVID-19 pandemic. The findings underscore the importance of integrating such interventions to address the mental well-being of healthcare providers, especially in high-stress environments. Further randomized controlled trials with diverse samples and extended follow-up are recommended to validate and explore these initial findings.

Shafiq Z. Azzam MD, Itai Ghersin MD MHA, Maya Fischman MD, Adi Elias MD MPH, Zaher S. Azzam MD, Wisam H. Abboud MD

Background: Several studies have shown an association between increased red blood cell distribution width (RDW) and adverse outcomes in various acute diseases. Small studies have suggested that RDW is a useful predictor of acute pancreatitis severity.

Objectives: To determine the association between RDW at admission and early mortality in acute pancreatitis. To assess whether RDW adds to the predictive ability of the Glasgow Imrie Score.

Methods: In this observational study, we included all adult patients admitted with a primary diagnosis of acute pancreatitis between January 2008 and June 2021. Patients were divided into two groups according to RDW: normal RDW (RDW ≤ 14.5%) and elevated RDW (RDW > 14.5%).

Results: Within 30 days of admission, 29/438 patients (6.6%) with increased RDW and 20/1250 patients (1.6%) with normal RDW had died: univariate analysis (odds ratio 4.6, 95% confidence interval 2.45–7.9, P < 0.001), fully adjusted model (odds ratio 3.29, 95% confidence interval 1.75–6.26, P < 0.001). We calculated receiver operating characteristic curve (ROC) for RDW alone, Glasgow Imrie Score alone, and a combination of Glasgow Imrie Score with RDW. We assessed their ability to predict 30-day mortality. Area under the ROC curve (AUC) of RDW alone was 0.671 and Glasgow Imrie Score AUC was 0.682; Glasgow Imrie Score plus RDW had an AUC of 0.769.

Conclusions: In patients with acute pancreatitis, elevated RDW at admission was independently associated with increased 30-day mortality. The addition of RDW to a pancreatitis prognostic tool such as the Glasgow Imrie Score improves its predictive ability.

Anat Ben Ari MD, Noa Rabinowicz PhD, Haim Paran MD, Or Carmi MD, Yair Levy MD

Background: Immunoglobulin 4 (IgG4) is the least abundant immunoglobulin in the sera of healthy individuals; however, its levels can vary in different diseases such as IgG4-related disease (high) or Sjögren's syndrome (low). While previous studies have suggested the importance of IgG4 in autoimmune diseases, the clinical and biological significance of high or low levels remains unclear.

Objectives: To investigate the association between IgG4 antibody levels and systemic sclerosis (SSc), as well as the clinical features of the disease.

Methods: We measured IgG4 levels in the sera of 74 SSc patients from the years 2000 to 2019 and compared them to IgG4 levels in 80 healthy donors from the Israeli national blood bank. We performed correlation analyses between IgG4 levels and various factors, including age, sex, disease subtype, disease duration, organs involved, and medications taken by the patients.

Results: Our findings revealed significantly lower IgG4 levels in SSc patients compared to healthy participants. SSc patients receiving steroid treatment exhibited prominently lower IgG4 levels. In addition, SSc patients with Raynaud's phenomenon tended to have lower IgG4 levels compared to those without Raynaud's phenomenon.

Conclusions: Our study demonstrates that IgG4 levels are lower in SSc patients. Further research is needed to elucidate whether this observation contributes to the etiology of the disease or if it represents a common manifestation among other autoimmune diseases.

Batsheva Varda MD, Arielle D. Zur, Yuval Kuntzman MD, Yonatan Shneor Patt MD, Howard Amital MD MHA, Arnon D. Cohen MD MPH PHD, Omer Gendelman MD

Background: Giant cell arteritis (GCA) is a large vessel vasculitis predominantly affecting patients over 50 years, typically managed with glucocorticoids, with treatment varying on individual patient needs. While effective for GCA, long-term glucocorticoids use poses significant risks, including the development of osteoporosis, a metabolic bone disease common in older individuals. This overlap poses a significant clinical challenge, as the treatment for GCA inadvertently raises the risk of osteoporosis and necessitates careful balance to manage both conditions effectively.

Objectives: To investigate the occurrence of osteoporosis and other co-morbid conditions in patients with GCA treated with glucocorticoids.

Methods: A retrospective cross-sectional analysis of GCA patients examined the correlation between GCA and osteoporosis by searching the Clalit Health Service database for patients over 50 years of age from January 2002 to January 2018. In addition, we conducted a logistic regression analysis stratifying for other co-morbidities to evaluate the independent association between GCA and osteoporosis.

Results: In total, 6607 GCA patients were compared with 36,066 age- and sex-matched controls. The study revealed a higher prevalence of osteoporosis in the GCA group (43%) compared to controls (27%) (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.95–2.17). In addition, hypertension, hyperlipidemia, diabetes mellitus, and ischemic heart disease were more prevalent among GCA patients. After stratifying for cardiovascular co-morbidities, GCA remained independently associated with osteoporosis (OR 2.1, 95%CI 1.96–2.26, P < 0.001).

Conclusions: Glucocorticoid-treated GCA is independently associated with osteoporosis. Healthcare providers must consider this added aspect of GCA for the treatment and management of patients.

Alena Kirzhner MD, Hefziba Green MD, Ronit Koren MD, Haitham Abu Khadija MD, Danielle Sapojnik MS, Tal Schiller MD

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

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