Israel Medical Association Journal

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: 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: 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.

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.

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.

Background: Acute skin infections, like cellulitis or erysipelas, are common and respond well to antibiotic treatment. However, complete resolution of the inflammatory process is often slow and associated with prolonged pain and reduced mobility. Several studies have indicated that acupuncture may effectively treat inflammatory skin diseases.

Objectives: To evaluate the efficacy of acupuncture for treating cellulitis in patients hospitalized in internal medicine departments.

Methods: In this pilot randomized sham-controlled trial, patients hospitalized with cellulitis in internal medicine departments were randomized to acupuncture or sham acupuncture, in addition to standard care. The primary outcome was the degree of improvement in the cellulitis score at day 4 of hospitalization. Secondary endpoints included patient pain self-assessment and local and systemic inflammatory signs.

Results: The study comprised 29 patients; 15 treated with acupuncture, 14 by a sham procedure. At day 4, patients in the acupuncture arm had an improved cellulitis score (4.1 ± 2.8) compared with the sham-control group (7.9 ± 3.3, P = 0.003). Pain intensity based on the Visual Assessment Scale was lower in the acupuncture group 3.8 ± 2.7 vs. 6.3 ± 2.8; P = 0.023. There was no difference in the rate of leukocyte change. However, C-reactive protein significantly decreased to 27.0 ± 22.1 mg/L at day 4 following acupuncture compared to 63.9 ± 51.9 mg/L (P = 0.025).

Conclusions: In our pilot study, we found acupuncture to be efficacious as an adjunctive therapy in the treatment of leg cellulitis. A large-scale trial on the effectiveness of acupuncture for skin infections is needed.

The Dina Recanati School of Medicine at Reichman University offers a unique approach to preclinical medical education, combining strong scientific foundations with practical, clinical applications. This 4-year program includes two preclinical years focused on core medical knowledge and two clinical years of rotations. The curriculum emphasizes small-group learning, early clinical exposure, and a system-based block structure. Starting from the first week of the preclinical years, students will participate in biweekly clinical days, using simulations, virtual reality, and patient interactions to develop practical clinical skills. The community clinic mentorship offers real-world experience that complements the clinical program taught in class during the same week. Research is central, with students conducting supervised projects aimed at a medical doctor thesis publication. The teaching model ensures relevance by integrating clinical cases into all courses, guided by practicing physicians. Daily quizzes and block-style assessments replace traditional examination periods, promoting consistent learning. The innovative program balances clinical practice with scientific knowledge, preparing students for the challenges of modern medicine.

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: Hospital-at-Home (HaH) programs offer medical services in the patient's home as an alternative to hospitalization across various medical fields. Previous studies have demonstrated that HaH provides several benefits for patients and the healthcare system. Rambam Health Care Center was the pioneer hospital in introducing HaH in Israel. Since April 2021, in collaboration with Maccabi Healthcare Services, the center has been providing home hospitalization services for patients with acute internal medicine illnesses based on an innovative model.

Objectives: To describe demographic data, background diseases, indications for HaH admissions, length of stay (LOS), 1-month and 1-week readmission rates, home mortality, and 1-month mortality.

Results: The study included 262 patients (135 men, 127 women), mean age 69.7 years (range 24–98, median 73). Patients had significant co-morbidities, with a Charlson Comorbidity Index score of 6.7. Among the patients, 170 were independent, 61 were incapacitated, and the remainder had various functional limitations. Most admissions were from internal medicine departments, 39 originating from the emergency department and the rest from other acute care wards. The primary indications for HaH admission included pneumonia, urinary tract infections, and cellulitis. The average hospital LOS was 48.9 hours, while the HaH LOS was 3.43 days. Readmission rates for the same initial conditions were 10% within 1 week and 14% within 1 month. Twenty-one patients died within 1 month of discharge from HaH, including one death during the HaH period.

Conclusions: This study highlighted the feasibility of home hospitalization as a viable alternative to traditional inpatient care in internal medicine.

Rehabilitation plays a crucial role in improving clinical outcomes for cardiac patients. The accessibility of traditional cardiac rehabilitation programs is often hindered by factors such as cost and geographical distance. In recent years, wearable monitor-based remote rehabilitation has emerged as a potential solution to improve accessibility. In this systematic review, we assessed the recent literature on remote cardiac rehabilitation utilizing wearable monitors. We conducted a comprehensive literature review using the MEDLINE database, focusing on all studies published in English until June 2023. The search utilized the keywords cardiac rehabilitation and remote monitoring to identify relevant studies on clinical outcomes, wellbeing, and adherence. Filters were applied to include human subjects only. Reviews, meta-analyses, and systematic reviews were used to expand the search, but excluded from the primary selection process. A total of 14 relevant papers were included following the selection process: nine randomized controlled trials and five cohort studies. The synthesis of articles found that remote cardiac rehabilitation monitored by wearable devices is as safe and effective as conventional rehabilitation and more effective than medical observation only. In addition, it enhances the availability of cardiac rehabilitation in cases of limited accessibility. Several limitations require further research including expanding the demographic diversity of the participants and improving the ease of use of the technology. While remote cardiac rehabilitation monitored by wearable devices shows promise, further research is needed to expand the participant pool and refine the wearable monitor technology's usability.

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: The lifestyle of the Arab population in Israel has changed in the last few decades, and modernization and urbanization have impacted the prevalence of chronic diseases.

Objectives: To investigate the prevalence of chronic diseases in the Arab population compared to the Jewish population in Israel.

Methods: This retrospective study included Arab and Jewish people insured by Israel’s largest health maintenance organization. Demographic data and data regarding chronic diseases were collected. Crude prevalence and age group adjusted prevalence were calculated.

Results: In total, 863,116 Arab and 3,674,863 Jewish people were included in the analysis. We found that 18.3% of the Arab population had a diagnosis of diabetes mellitus and 28.8% had obesity compared to 17.5% and 22.5% in the Jewish population, P < 0.001, respectively. The prevalence of chronic heart failure, chronic ischemic heart disease, cerebrovascular accidents, hypertension, and myocardial infarction among Arabs was higher in all age groups compared to Jewish patients. Arab males had higher frequency rates of obesity and hemodialysis treatment compared to Jewish males. The proportion of women with diabetes mellitus, hemodialysis treatment, iron deficiency anemia, or obesity was greater among Arab females.

Conclusions: Significant differences were found in the prevalence of chronic diseases among Arab and Jewish patients in Israel. Culturally relevant interventions are crucial for disease prevention, early diagnosis, and management of chronic diseases among different ethnic groups.

Leeches belong to the class Hirudinea of the phylum Annelida. There are approximately 650 known species of leeches, some terrestrial, some marine, and most freshwater. Although some are predators, most leeches are hematophagous, and all are hermaphrodites [1].

The leeches Limnatis nilotica, Praeodella guineensis, Myxobdella africana, Dinobdella ferox, and Hirudo troctina occasionally invade human orifices such as the eyes, nasopharyngeal region, urethra, vagina, and rectum. They cause mucosal, orificial, vesical, or internal hirudiniasis depending on the location of the leech [1]. Infection usually occurs by drinking contaminated water or bathing in stagnant streams, pools, or springs. While most blood-feeding leeches feed as ectoparasites for short periods of time, those that feed on mucous membranes have been known to remain in an orifice for days or weeks. Hematuria, hemoptysis, hematemesis, epistaxis and rectal bleeding, dysphonia, cough, tickling, and dyspnea may occur [1].

We report the case of a male patient who entered freshwater pools in Israel and was infected with L. nilotica.

Takotsubo cardiomyopathy (TC) is a temporary and reversible hypokinesia of the left ventricle's apical area of the heart mediating systolic abnormality. This phenomenon resembles myocardial infarction but without coronary artery disease (CAD) [1]. The prevalence is 1.0–2.5% annually. Most of the patients with TC are postmenopausal women [2]. Over-stimulation of the sympathetic system, microvascular and myocardial tissue metabolism abnormality, and coronary artery vasospasm are linked to TC [2]. The criterion of the diagnosis consists of temporary hypokinesis or akinesis in left ventricle segments with or without apical involvement, electrocardiogram (ST-segment elevation and/or T-wave inversion), or significant elevation of serum cardiac troponins and non-existence of pheochromocytoma or myocarditis [3]. The pathognomonic finding of TC during echocardiography is apical ballooning involving the left ventricle. This unique morphology was reported to present in 75% of patients [2,3]. In 25% of patients. The morphology was reported to follow a mid-ventricular ballooning pattern due to mid-LV akinesis with no disturbance of apical and basal contraction [2,3].