Israel Medical Association Journal

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: 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.

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.

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.

The Dina Recanati School of Medicine at Reichman University was founded as a testament to the Zionist vision of its founders: Prof. Uriel Reichman, Mr. Oudi Recanati, and prominent leaders from Israel’s foremost medical institutions, including Rabin Medical Center, Schneider Children’s Medical Center, Clalit Health Services, Maccabi Healthcare Services, Edmond and Lily Safra Children's Hospital, and the Sheba Medical Center. United by a shared purpose, they established the school to tackle a critical challenge in Israeli healthcare: the growing need for locally trained physicians.

Among the people who contributed to the idea were the editors of the Israel Medical Association (IMAJ), Prof. Yehuda Shoenfeld, Prof. Joshua Shemer, and Prof. Zvi Spirer who presented the idea to Prof. Reichman, 10 years ago.

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.

On 9 August 1938, prisoners from Dachau concentration camp near Munich were sent to the town of Mauthausen in Austria to begin building a new camp. The site was chosen because of the nearby granite quarry and its proximity to Linz [1,2].

Mauthausen initially served as a prison camp for common criminals, prostitutes, and other categories of incorrigible law offenders. However, on 8 May 1939, it was converted to a labor camp. Later, Mauthausen KL became a Nazi concentration camp on a hill above the market town of Mauthausen, approximately 20 kilometers from Linz. It was complemented with dozens of subcamps in the surrounding areas.

Background: On 7 October 2023, an armed conflict erupted between Hamas and Israel, leading to numerous combat casualties.

Objectives: To describe computed tomography (CT) findings of combat casualties at a tertiary medical center during the first 3 months of the conflict.

Methods: A retrospective observational study was conducted on patients admitted between 7 October 2023 and 7 January 2024. Adults with conflict-related trauma who underwent chest, abdomen, and pelvis (body) trauma protocol CT scans were included.

Results: Of 272 patients who underwent body trauma protocol CT, 112 combat-related adults were included, mean age of 27 years and one female. In total, 82 patients (73%) underwent additional scans of the head and neck or extremities. Fractures were observed in 53 patients (47%). Vascular injuries were present in 40 patients (35%). Limb injuries were most common, affecting 37 patients (33%), which prompted a protocol update. Lung injuries were the most common in body CT: 30 patients (27%). Head and neck injuries were seen in 21 patients (18%). Multisystem trauma was present in 24 patients (21%). A total of 83 patients (74%) underwent surgery, mostly orthopedic/soft tissue surgeries (63%); 15 (13%) underwent abdominal surgery, with bowel injuries confirmed in eight cases.

Conclusions: CT scans are an important tool in conflict trauma management. Limb injuries were the most frequent, necessitating protocol adjustments. Lung injuries were the most common body injury; 21% of patients had multisystem trauma. Most patients required surgery.

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: 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.