Israel Medical Association Journal

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.

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].

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.

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.

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.

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].

Myositis is described as any disease-causing inflammation in muscles. Muscle weakness is the most common symptom. Etiology includes infection, injury, medication side effects, and autoimmune conditions. The treatment varies according to the cause [1]. Statin induced necrotizing autoimmune myopathy (SINAM) is an exceptionally rare yet devastating complication of statin therapy that can occur at any time after initiation. The condition is also known as anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody (anti-HMGCR antibody) myopathy. SINAM should be considered in patients who develop proximal muscle weakness and marked elevated creatine phosphokinase (CPK) while taking statin therapy [2]. We report on a patient who presented with excessive fatigue, generalized muscle pain, and weakness without dysphagia.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by an inadequate attenuation of the cytotoxic and innate immune system resulting in uncontrolled inflammation in multiple organ systems. Predominant clinical findings include fever, cytopenia, and hepatosplenomegaly [1].

Infectious diseases are a well-documented trigger of HLH, with viral infection being the most common cause. Less commonly, HLH has also been reported in the setting of bacterial infections, with rare cases described secondary to rickettsial diseases [1]. In this report, we present a case of HLH in the setting of bacterial infection with Rickettsia typhi, murine typhus.

Diabetes mellitus (DM) is a serious and growing global health challenge. The number of people diagnosed with diabetes continues to rise, and it is projected that by 2035 more than 592 million individuals worldwide will have diabetes [1]. DM can impact the heart through various mechanisms. Vascular complications are associated with diabetes and include both epicardial coronary artery and small vessel disease. Cardiomyopathy and heart failure may also occur. Insulin resistance causes cardiomyocytes to have a reduced capacity for glucose utilization, leading to increased uptake of free fatty acids. This, in turn, results in triglyceride storage and lipotoxicity, which contribute to impaired cardiac contractility [2].

Diabetes may lead to the production of advanced glycation end (AGE) products, resulting in an accumulation of reactive oxygen species. This accumulation triggers inflammation that can cause myocyte apoptosis and mitochondrial dysfunction. AGE can also contribute to cardiac fibrosis, which increases myocardial stiffness and results in heart failure with preserved ejection fraction (HFpEF) [2].

A 38-year-old immunocompetent male with a history of Hodgkin's lymphoma in remission presented to the emergency department at Rambam Hospital with infectious mononucleosis due to an acute cytomegalovirus (CMV) infection. He was also diagnosed with portal vein thrombosis (PVT). After a thorough laboratory and radiological investigation, these two diagnoses were found to be related. No other explanation was identified except for transiently detected antiphospholipid antibodies, which were assumed to be provoked by the CMV infection. In this review, we investigated the relationship between CMV infection and a hypercoagulable state. We searched the PubMed database for case reports, clinical reviews, and meta-analyses that reviewed the relationship between CMV infection and deep vein thrombosis. The incidence of thromboembolism in patients with acute CMV infection was reported to be as high as 6.4%. In addition, anti-cardiolipin antibodies were more commonly present at the time of PVT diagnosis among CMV-positive patients compared to CMV-negative patients, although these antibodies disappeared in most cases. To the best of our knowledge, there is no evidence of added benefit from antiviral therapy in patients with CMV-associated thrombosis. CMV infection may serve as a trigger for a transient hypercoagulable state.

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.

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.

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.

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.

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.