Israel Medical Association Journal

Background: BRCA1/BRCA2 female pathogenic sequence variant (PSV) carriers in Israel are offered semiannual cancer antigen 125 (CA125) serum level determination and transvaginal ultrasound until performing risk reducing salpingo-oophorectomy (RRSO), even with the lack of proven efficacy of these procedures in providing adequate early detection of ovarian cancer.

Objectives: To report the results of longitudinal CA125 measurements in BRCA1/BRCA2 carriers as a tool for ovarian cancer detection in a single medical center in Israel.

Methods: Asymptomatic BRCA1/BRCA2 PSV carriers attending the Meirav High Risk Clinic at Sheba Medical Center for more than 3 years were eligible. Data on specific PSV, risk reducing surgeries, and cancer diagnoses were obtained from participant records. We used chi-square and Wilcoxon-Rank tests for statistical analyses.

Results: Overall, 739 (399 BRCA1, 336 BRCA2, 4 BRCA1 + BRCA2) PSV carriers were included. Mean age at the start of follow-up was 38.96 ± 11.13 years, mean follow-up time was 7.93 ± 2.34 years, (5860.80 women/years). Most participants (490/739 [66.3%]) had stable CA125 levels (± 5 U/µl). Of participants, 61 had CA125 levels > 35 U/µl at least twice (n=42) or at least doubling of marker levels to a minimum of 20 U/µl (n=19), results that have led to further cancer defining investigations. Of these, 14 and 4 were diagnosed with breast and ovarian cancer, respectively.

Conclusions: Longitudinally stable CA125 levels were noted in most BRCA1/BRCA2 PSV carriers and elevated levels were a poor marker for ovarian cancer development.

Background: Uninterrupted antithrombotic treatment (ATT) during cardiac implantable electronic device (CIED) implantation increases bleeding and device-related infections (DRI) risk. The wide-awake-local-anesthesia-no-tourniquet (WALANT) technique, using large-volume local anesthesia and adrenaline, is successful in hand surgeries but its potential to mitigate bleeding risk in CIED implantations remains unknown.

Objectives: To investigate whether WALANT protocol for CIED implantations reduces clinically significant pocket hematoma in patients with a high bleeding risk or is a contraindication for interrupting ATT.

Methods: We conducted a prospective, double-blind, randomized controlled trial with CIED surgery patients on uninterrupted ATT. They received WALANT protocol (lidocaine 1% with adrenaline 1:100,000) or standard protocol (lidocaine 1%). Following implantation, patients were blindly monitored in the ward and pacemaker clinic. Patients were monitored for bleeding outcomes post-implantation.

Results: Forty-six consecutive patients (73.6 ± 9 years, 72% male) were enrolled. In the WALANT group (n=24) no intra-pocket pro-hemostatic agents were needed, compared to 45% in the control group (P = 0.0002). Postoperative pressure dressings were used in 12.5% vs. 68% (P = 0.0002). WALANT patients had smaller hematoma areas (median 3.7 cm² IQR [1–39] vs. 46 cm² [IQR 24–76], P = 0.0004) 1-day postoperative. ATT interruption occurred in 12.5% vs. 18% (P = 0.7). Superficial skin infection rates were 4% vs. 9% (P = 0.6). No DRI occurred. No WALANT-related side effects were observed.

Conclusions: WALANT protocol in CIED implantation with uninterrupted ATT reduced pro-hemostatic agents, pressure-dressing need, and hematoma size. Larger studies are needed to assess its impact on infection rates.

Pheochromocytoma, a rare neuroendocrine tumor, classically manifests symptoms such as hypertension, palpitations, and sweating. In this report, we present an unusual case in which muscle complaints were the primary symptoms, accompanied by elevated interleukin-6 (IL-6) levels. Our findings underscore the importance of considering pheochromocytoma in the differential diagnosis of patients presenting with unexplained muscle weakness and aches, and suggests a potential link between pheochromocytoma, myositis-like symptoms, and IL-6 elevation.

Standup paddleboard surfing (SUP) is a sports activity in which a person stands upright on a surfboard and propels the board using a single paddle. It is an emerging recreational activity that is attracting public attention and gaining popularity because it promotes fitness, strength, and improved balance. In this review, we discuss the outcomes after severe cardiac events in SUP surfers. We report on six fit individuals (five males and one female, age range 41–69 years) who experienced sudden cardiac arrest (n=3) or acute myocardial infarction occurring during SUP. Cardiopulmonary resuscitation was initiated in three patients on presentation due to ventricular fibrillation. In four patients the culprit coronary artery was the left anterior descending artery treated by percutaneous coronary intervention. All patients were discharged alive. A review of the literature showed a paucity of scientific evidence to substantiate the proposed health benefits of SUP surfing. Our cluster of acute cardiac events occurring during this activity calls for heightened public awareness to better understand the physical demand required to practice SUP. There is a need for more data regarding the cardiovascular clinical aspects of this water activity, and the risks it entails.

Background: Botulinum toxin (BT) can alleviate limb dystonia, but limited insurance coverage hinders its utilization.

Objectives: To compare the therapeutic efficacy of BT injections for spasticity and dystonia of the limbs.

Methods: BT injections of hypertonic limbs were administered under ultrasound guidance between 2019 and 2024 for either limb dystonia or limb spasticity.

Results: Of 74 patients included, 57 were diagnosed with spasticity and 17 with dystonia. In total, 276 therapeutic cycles were administered. The dropout rates were 45.6% in the spasticity group and 41.2% in the dystonia group (P = 0.48). There was no significant difference in subjective motor improvement between dystonia and spasticity (P = 0.16). Dystonia patients reported significantly better pain relief (98.5 ± 4.9% vs. 72.4 ± 35.6% respectively, P < 0.001). Notably, 74.3% of dystonia treatments reported moderate or marked improvement, whereas only 54.0% of spasticity treatments did (P > 0.05), based on patient the global impression of change (PGI-C) scale. Side effects were infrequent.

Conclusions: BT injections for limb spasticity and dystonia are partially effective. Nonetheless, the dropout rate is high. While BT injections are more effective in relieving pain for dystonia compared to spasticity, disease severity gradually improves over time in treated patients with spasticity but not with dystonia.

Background: Acute cholecystitis (ACC) is one of the most common diagnoses encountered in surgical wards. A number of treatment modalities are available, and various guidelines have been developed to help decision making. Many factors influence treatment strategies, including patient age and frailty. Due to the increasing proportion of older patients, consideration into the best treatment modalities for this population are warranted.

Objectives: To determine outcomes of elderly patients with ACC according to different treatment strategies.

Methods: A retrospective analysis of consecutive patients aged ≥ 80 years who were admitted with a diagnosis of ACC between 2015 and 2019 to a single academic center. Patients were divided into three groups according to treatment: percutaneous cholecystostomy tube placement, cholecystectomy, intravenous antibiotic treatment only.

Results: Overall, 466 patients were included in the cohort. The majority (approximately 75%) were treated with antibiotics only, 17% underwent percutaneous cholecystostomy, and 8% underwent laparoscopic cholecystectomy. One-year mortality was 28.1%. The highest mortality rate was 41.6% in the cholecystostomy group (P = 0.002). In multivariable analysis age, functional status, C-reactive protein, and albumin levels were found to be independent risk factors for 1-year mortality (hazard ratio [HR] 1.08, 0.56, 0.98, 0.4, respectively). Cholecystostomy increased risk of one-year mortality compared to cholecystectomy and antibiotics alone (HR 0.61, 0.23, respectively).

Conclusions: The use of cholecystostomy for ACC in older adults is an independent risk factor for 1-year mortality. Its use in older adults should be reserved for carefully selected cases.

Nail-patella syndrome (NPS, OMIM: #161200), also known as Fong disease, hereditary osteo-onychodysplasia (HOOD), and Turner-Kieser syndrome, is a rare pleiotropic, multisystemic condition with an estimated incidence of 1 per 50,000. It is characterized mainly by developmental defects of dorsal limb structures due to symmetrical mesodermal and ectodermal abnormalities. It manifests as a classic clinical tetrad of distal digital abnormalities and fingernail dysplasia, which are typically bilateral and symmetrical, hypoplasia or absence of the patella, presence of iliac horns, and elbow deformities. It can also affect other structures (e.g., tendons, ligaments, and muscles), and may impact ophthalmic (glaucoma, increased ocular pressure and subsequent blindness), renal (nephropathy), neurological, orthopedic, and gastrointestinal systems. NPS can lead to sensorineural hearing loss and vasomotor problems [1,2]. Clinical manifestations vary greatly in frequency and severity. The prognosis is relatively good when clinical features are mild and cause no disability. However, serious and even life-threatening complications can occur. NPS is usually clinically diagnosed based on physical examination and radiological imaging. Genetic testing and renal biopsy can also assist in diagnosis confirmation.

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.

Background: Understanding medical guidelines can be challenging for patients and their families, leading to incorrect use or dosages due to inadequate or unclear explanations. Graphic organizers are tools that can help improve comprehension of medical guidelines.

Objectives: To assess the effectiveness of using designed graphic organizers to enhance comprehension of medical guidelines.

Methods: A prospective randomized controlled study was conducted at Soroka University Medical Center between 2015 and 2017. Parents of children aged 1–7 years, admitted for asthma exacerbation requiring the use of an inhaler with a spacer or for febrile convulsion requiring rectal diazepam, were enrolled. Participants were randomly assigned to receive instructions through a graphic organizer (intervention group) or plain text (control group). An assessment form was administered to evaluate the understanding of the correct steps for using the inhaler with a spacer or administering rectal diazepam. A follow-up telephone assessment was conducted after 30–60 days to evaluate recollection.

Results: Seventy-four parents with similar demographic characteristics were enrolled (intervention group [38], control group [36]). There was no significant difference in comprehension between the two groups when using medical guidelines for the two interventions. However, there was a correlation between maternal education level and long-term recollection, with an average score of 24%, 42%, and 48% among mothers with less than 8 years, 8–12 years, and over 12 years of education, respectively (P = 0.004).

Conclusions: The use of graphic organizers did not improve parent comprehension of pediatric medical guidelines. However, long-term recollection was positively correlated with maternal education level.

Background: Wilson disease (WD) is an autosomal recessive disease characterized by a defect in hepatocellular copper transport with a wide spectrum of clinical manifestations and reported prevalence.

Objectives: To study the epidemiology and clinical manifestations of WD between two ethnic groups, Jewish and Bedouins, with different marriage patterns, in southern Israel.

Methods: We conducted a retrospective study investigating the clinical course and laboratory characteristics of children diagnosed with WD who were treated at Soroka University Medical Center.

Results: Sixteen patients were diagnosed between 2000 and 2021 (8 males, 50%), 14 were of Bedouins origin. The total cohort prevalence was 1:19,258 while the prevalence of the disease was significantly higher among Bedouins compared to Jews (1:10,828 vs.1:78,270, P-value = 0.004). The median age at diagnosis was 10.2 years, without a significant difference between the groups. The most common presenting symptom was hepatic manifestations: 81.2% had elevated transaminases, 12.5% had jaundice, 25% had neurological symptoms, one had a Kayser-Fleischer ring, and one had psychosis. The mean ceruloplasmin level was 3.0 mg/dl. During follow-up, nine patients normalized transaminases with treatment, while three required liver transplantation. There was no significant difference in the clinical presentation and disease course between the two ethnic groups.

Conclusions: Our cohort showed a high prevalence of WD compared to previous studies, especially among the Bedouin population, which has a high consanguinity rate. The prognosis of WD in our population is similar to other studies and depends mainly on treatment compliance.

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].

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.