Israel Medical Association Journal

Crohn's disease patients undergoing anti-tumor necrosis factor (anti-TNF) therapy such as infliximab face potential risks from opportunistic infections. We introduce the unique case of a 66-year-old male Crohn's patient, previously in remission, presenting with gastrointestinal symptoms following a trip to the Czechia. Despite concerns of reactivated tuberculosis due to infliximab, his biopsies showed the presence of Mycobacterium simiae (M. simiae). Despite this, anti-TNF therapy was continued and resulted in clinical improvement. This is a case report of M. simiae in intestinal biopsies of an immunocompromised Crohn's patient is a clinical challenge. The findings suggest the benign colonization of M. simiae potentially influences future treatment considerations in similar clinical scenarios.

Background: Enterovirus meningitis (EM) is a common central nervous system (CNS) infection with a seasonal peak in summer and fall.

Objective: To describe the epidemiologic and clinical patterns of EM in children before (2017–2019 years) and during the coronavirus disease 2019 (COVID-19) pandemic (2020–2022).

Methods: This retrospective study included children (age 0–16 years) hospitalized in a pediatric department in Israel diagnosed with EM: January 2017–December 2019 and January 2020–December 2022. The seasonal peak for each period was defined as the maximal incidence in particular months. EM was diagnosed by reverse transcription polymerase chain reaction of cerebrospinal fluid (CSF) for enteroviruses.

Results: During the study period, EM was diagnosed in 134 cases (median age 5 months [1–51], 76 [57%] males); 72 during 2017–2019 and 62 during 2020–2022. The most common presentation was fever. C-reactive protein (CRP) was elevated in 57 cases (43%). CSF profile showed pleocytosis in 130 cases (97%) and elevated protein in 80 (60%). In the 2020–2022 group, fewer patients were febrile, CRP was higher, and CSF profile showed a higher glucose level compared to the 2017–2019 group. Seasonal peaks in 2017–2019 occurred June–August, and in 2020–2022 February–April.

Conclusions: The COVID-19 pandemic altered the clinical characteristics of EM and its seasonal peak. Clinicians should be aware of changes in epidemiological patterns of EM to make appropriate diagnoses in viral infection in order to avoid unnecessary antibiotic treatment.

Postmortem sperm retrieval allows for the procreation of biological children using the sperm of a deceased male; however, the data on how to optimize this procedure and its potential long-term effect are limited. We searched medical databases (PUBMED and Cochrane) and performed a systematic review of articles published from the databases' inception until December 2023. Case reports, case studies, and reviews reporting on and investigating the methodology and outcome of postmortem sperm retrieval were included. The primary search yielded 98 publications. After assessing eligibility and evaluating with a quality assessment tool, 17 articles remained, including 11 single case reports and 6 case series. Overall, 103 clinical cases of posthumous sperm retrieval were identified, and eight deliveries were reported. Most publications lacked information regarding the conditions to which the bodies were exposed before postmortem sperm retrieval. Moreover, sperm viability assessment was not performed routinely, and there was no examination of the potential genetic and epigenetic damage that may have occurred. Currently, there is a lack of standardization for postmortem sperm retrieval procedures. The lack of specific information regarding the potential hypoxic damage to the viable sperm cells may limit the safety of using these cells for procreation. These gaps in our current knowledge are relevant and should be expressed in the informed consent given to the potential users.

Background: Chest radiograph is a standard procedure for diagnosis of pneumonia; however, interpretation shows considerable variability among observers.

Objectives: To assess the extent of agreement between pediatric residents and board-certified radiologists in interpretation of chest radiography for detection of pneumonia. To evaluate the impact of resident experience, patient age, and signs of infection on this phenomenon.

Methods: The cohort included 935 patients with suspected pneumonia admitted to the pediatric emergency department at a non-tertiary medical center in Israel 2019–2021. All patients had chest radiographs interpreted by a resident and a radiologist. Interobserver agreement was assessed using Κ and prevalence-adjusted bias-adjusted κ (PABAK) with 95% confidence intervals (95%CI). Results were stratified by resident experience (junior or senior), patient age (≤ 3 vs. > 3 years), white blood cells (≤ 15,000 vs. > 15,000 cells/ml), C-reactive protein (≤ 5 vs. > 5.0 mg/dl), and temperature (< 38.0°C vs. ≥ 38.0°C).

Results: Moderate agreement between pediatric residents and radiologists was demonstrated for diagnosis of pneumonia (κ= 0.45). After adjustment for disease prevalence, the extent of agreement increased to near-substantial (PABAK= 0.59, 95% confidence interval 0.54–0.64). The extent of agreement was higher for children over 3 years of age and in patients without clinical or biochemical features of pneumonia, especially when diagnosis of pneumonia was ruled out.

Conclusions: A second reading of chest radiographs by an experienced radiologist should be considered, particularly for patients younger than 3 years of age and in those with signs of infection and an initial diagnosis of pneumonia.

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.

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].

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.

Background: Cardiovascular disease (CVD) events are rare in premenopausal women. Nevertheless, women with depression have a higher prevalence of CVD. Patients with depression present with endothelial dysfunction and impaired ability to regenerate endothelial progenitor cells (EPCs).

Objectives: To understand the association between depression and CVD, especially in young women.

Methods: We collected peripheral blood samples from 30 premenopausal women diagnosed with major depression and 28 aged-matched healthy women. From these blood samples, we extracted RNA and conducted RNA sequencing to obtain comprehensive gene expression profiles. Gene expression analysis was performed to identify differences between the two groups.

Results: We detected 6540 differentially expressed genes between the two groups, of which 5577 were downregulated and 963 up regulated. Of these genes, we detected a significant decrease of CD144 (VE-Cadherin) (P = 0.0001), CD146 (MCAM) (P = 0.0001) and CD133 (PROM1) (P = 0.00009), all known to enhance EPCs and regeneration of damaged blood vessels. A significant increase was found in the expression of CD31 (PECAM1) (P = 0.0003) and CD45 (PTPRC) (P = 0.00001), both known to promote atherogenesis and thrombogenesis with platelet and T lymphocyte activation.

Conclusions: Young premenopausal women with depression had an impaired ability to grow colony forming units of endothelial progenitor cells (CFU-EPCs). Young women with depression are more vulnerable genetically to develop CVD because of the downregulated genes of the stem cells endothelial vascular regeneration and upregulation of genes coding for platelet and T lymphocyte activation, thus accelerating the atherosclerotic and atherothrombotic pathway.

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.

Among the advancements in echocardiography, the introduction of two-dimensional strain marked a pivotal moment in the quantitative evaluation of cardiac function. In fact, Global longitudinal strain (GLS) has emerged as a key focus due to its robust validation and evidence base. GLS provides a comprehensive assessment of left ventricular function, which offers greater sensitivity in detecting subtle changes compared to traditional metrics such as ejection fraction. In this position paper, we elucidate the rationale behind routine global longitudinal strain calculation, offering practical recommendations and insights for its implementation in clinical echocardiography. By bridging technical nuances with clinical relevance, the calculation of longitudinal strain aims to optimize patient care and enhance the diagnostic precision of echocardiographic examinations.

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.

Background: Management of patients with reported iodinated contrast media (ICM) allergy is not supported by sufficient data. It is assumed that these patients are at risk for severe reactions, and that premedication provides protection.

Objective: To examine current practice and prognosis in hospitalized patients with ICM allergy.

Methods: In this retrospective study, we analyzed data of 17,356 patients who were hospitalized between 2018 and 2022 and referred for imaging. No-allergy and allergy groups were matched by age, sex, co-morbidities, and indications for imaging. Statistical analysis compared demographic, clinical, and imaging-related parameters.

Results: Our study included records of 501 patients with ICM allergy and 16,855 with no allergy. Patients with allergy were older (70.92 ± 16.25 vs. 59.02 ± 23.74 years, P < 0.001), female preponderance (male proportion 42.5% vs. 54%, P < 0.001), and those with increased cardiovascular and metabolic co-morbidities. The rate of ICM injection was similar among patients with ICM allergy (34%) and no allergy (36%). Most patients with ICM allergy did not receive premedication. Allergic patients demonstrated increased mortality (25.9% vs. 16.5%, P < 0.001); however, this result was not associated with the diagnosis of allergy, anaphylactic reactions, or premedication.

Conclusions: ICM allergy is mostly reported in patients with advanced age and multiple co-morbidities. Mortality was not increased when compared to matched non-allergic individuals. Among patients with reported allergy who were injected with ICM, anaphylaxis was not a cause of death, although fewer than half received premedication. Prospective trials are warranted to revise the clinical approach to ICM allergy.

Background: Little is known about audiovestibular function in psoriasis, a chronic systemic inflammatory disease that affects 2% of the world’s population.

Objective: To investigate audiovestibular function in patients with psoriasis.

Methods: In this prospective case-control trial, we enrolled 33 patients with psoriasis and 30 healthy controls. Audiologic testing included audiometry, tympanometry, and otoacoustic emissions recording. The vestibular investigation consisted of a dizziness handicap inventory questionnaire, a complete clinical vestibular examination, and video head impulse testing.

Results: The psoriasis group showed significantly higher average hearing thresholds in both ears at all frequencies. Otoacoustic measurements differed significantly at 3000 Hz in the right (P = 0.026) and left ear (P = 0.034). The average dizziness handicap score was considerably higher in the psoriasis group, with a mean difference of 7.70 (P = 0.025). The number of patients with abnormal right anterior semicircular canal gain values was significantly higher in the psoriasis group (P = 0.047). Saccade analysis in the psoriasis group showed significantly higher number of patients with covert corrective saccades of the left posterior canal (P = 0.037) and significantly higher number of patients with abnormal interaural difference of corrective saccades in the plane of the right anterior-left posterior canals (P = 0.035).

Conclusions: The study demonstrates an association between psoriasis and audiovestibular impairment, which can affect quality of life. These results suggest that patients with psoriasis may be evaluated with audiometry for possible hearing loss. Vestibular testing may be pursued as clinically indicated.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive, soft-tissue sarcoma. The treatment is surgical and includes wide local excision (WLE) or Mohs micrographic Surgery (MMS). There is no consensus regarding the preferred type of surgery.

Objectives: To compare the outcomes of the two types of surgery (WLE and MMS).

Methods: This retrospective cohort study was based on the medical records of 59 patients with DFSP treated at Sheba Medical Center (using the WLE method) or Assuta Medical Center (using the MMS method) between 1995 and 2018. The data included demographics, clinical presentations, imaging, types of wound closures, pathological margin status, surgical defect sizes, recurrences, and follow-up.

Results: Of the 59 included patients, 18 (30.5%) underwent WLE and 41 (69.5%) underwent MMS. The mean age at diagnosis was 40.1 ± 14.4 years. The male-to-female ratio was 1.5:1. The main tumor location was the trunk (50% for WLE and 41.5% for MMS). The main type of closure for both procedures was primary closure. In 72.2% of WLE and 78.8% of MMS cases, the margins were free. The difference between the final surgical defect and the original tumor size was statistically significantly smaller in patients who underwent MMS. The median duration of follow-up was 6.6 years. There was no significant difference in the rate of recurrence.

Conclusions: MMS enables better tissue preservation and results in a minor surgical defect compared to WLE, with no difference in tumor recurrence between the two methods.