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: Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. There are conflicting reports on whether colonoscopies performed during the morning shift have higher adenoma detection rates.

Objectives: To investigate the differences in polyp detection rate (PDR) in colonoscopies between morning and afternoon shifts.

Methods: In a retrospective, multicenter study involving a large cohort, we analyzed all colonoscopies conducted between 2016 and 2023 across seven endoscopy departments. The PDR was compared between morning and afternoon shifts.

Results: We included 368,997 colonoscopies: 213,795 (57.9%) performed during the morning shift and 155,202 (42.1%) during the afternoon shift. Patients undergoing colonoscopies during the morning shift were more frequently female (53.8% vs. 51%, P < 0.001) and tended to be older compared to those in the afternoon shift (average age of 56.97 ± 12.6 vs. 55.6 ± 12.9, P < 0.001). Colonoscopies conducted during the morning shift exhibited a higher cecum intubation rate (CIR) (96.7% vs. 95.6%, P < 0.001). During the morning shift, higher rates of PDR (32.9% vs. 29.9%, P < 0.001) were observed. In the multivariate analysis, after adjusting for other variables, age, male sex, polyp follow-up, fecal occult blood test, morning shift, familial history of CRC, and rectal bleeding demonstrated statistically significant associations (P < 0.001) for PDR.

Conclusions: Colonoscopies during the morning shift yielded a higher PDR and CIR than those in the afternoon. To improve this rate, endoscopists working the afternoon shift must be provided with the right conditions.

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.

Fasting, a practice with deep historical roots, has gained scientific attention for its potential benefits on human health, particularly in autoimmune diseases. In this review, we explored the impact of fasting on immune function and autoimmunity. Autoimmune diseases, characterized by the immune system's attack on the body’s own tissues, are influenced by genetic, environmental, and dietary factors. Various forms of fasting (intermittent, water fasting, calorie restriction, ketogenic diets, and time-restricted feeding) affect metabolism, immune modulation, and inflammation reduction. These changes can promote autophagy, stem cell renewal, and immune system rebalancing by offering potential therapeutic effects for autoimmune conditions. Although more research is needed, fasting may serve as an adjunctive therapy for immune-mediated diseases by reducing symptoms and promoting remission. However, fasting must be approached with caution, particularly for individuals with specific autoimmune disorders. We reviewed the physiological changes during fasting, types of fasting regimens, and the clinical relevance in autoimmunity. Further studies are needed to validate these observations in patient populations.

Background: Solid organ transplant (SOT) recipients represent a particularly vulnerable group due to their reliance on immunosuppressive therapies. Previous studies indicated a mortality rate of 20%-30% among SOT recipients with coronavirus disease 2019 (COVID-19). With the advent of the Omicron variant in November 2021, characterized by milder symptoms and lower mortality rates in the general population, safety measures relaxed, potentially impacting vulnerable populations like SOT recipients.

Objectives: To investigate mortality and morbidity among hospitalized SOT recipients with COVID-19 infection during the Omicron wave.

Methods: A retrospective, propensity-matched cohort study conducted at the Rabin Medical Center, Israel, spanned from November 2021 to June 2023. Adult SOT recipients hospitalized with COVID-19 were compared to matched controls.

Results: Among 139 hospitalized SOT recipients and 209 controls, SOT recipients hospitalized with COVID-19 displayed higher in-hospital mortality (19% vs. 11%) and 90-day all-cause mortality (30% vs. 17%). In addition, the 90-day readmission rate was significantly higher among SOT recipients (43% vs. 31%). Multivariable analysis confirmed these trends, with SOT recipients exhibiting increased risk for mortality, readmission, invasive ventilation, and intensive care unit admission.

Conclusions: The heightened vulnerability of hospitalized SOT recipients during the Omicron wave was characterized by higher mortality and readmission rates compared to matched controls. Despite the perceived milder nature of the Omicron variant, SOT recipients remain disproportionately affected. Continued vigilance and targeted interventions are necessary for this population including vaccinations and adherence to preventive measures. Investigating this population’s outcomes through the changing COVID-19 variants is still warranted.

Background: The increasing use of micromobility solutions (MMS), including electric scooters, electric, and non-motorized bicycles, has revolutionized urban transportation. We addressed the rising incidence of injuries related to pedestrian-MMS accidents, with a specific focus on pedestrian injuries.

Objectives: To improve clinician comprehension of patient characteristics and injuries associated with pedestrian-MMS accidents and to provide insights for injury prevention, policy making, and urban planning.

Methods: We conducted a retrospective analysis, June 2017 to January 2023, of pedestrians who were admitted to the emergency department post-MMS accidents. Data included patient characteristics, type of MMS, time of the accident, and outcome variables including type of injury, hospitalization, and surgical treatment.

Results: The study cohort included 498 pedestrians (57.7% women), with a mean age of 42.3 ± 21.8 years. Nighttime accidents were 53.2% of cases. Fractures were the dominant type of injury (18.3% of the total cohort). Age, particularly those ≥ 60 years, significantly (P < 0.05) influenced fracture, hospitalization, and surgery rates (30.6%, 22.4%, and 12.6%, respectively). The odds ratio of having a fracture for pedestrians ≥ 60 years was 5.35 (P = 0.008). Interestingly, the type of MMS did not significantly affect outcomes.

Conclusions: Age emerged as a critical factor in injury severity, emphasizing the need for age-specific safety measures in urban environments. The type of MMS did not show a significant influence on outcomes, emphasizing the importance of a comprehensive regulation of all MMS types. The high rate of accidents during nighttime calls for focused interventions during this period to prevent accidents.

Minocycline is a tetracycline antibiotic prescribed to treat various infections, acne vulgaris, and rosacea. In addition to its antibiotic activity, it possesses anti-inflammatory properties, including reducing the production of proinflammatory cytokines, suppressing neutrophil chemotaxis, activating superoxide dismutase, and inhibiting phagocytosis. Among its side effects are hypersensitivity syndrome reactions, drug-induced lupus, and polyarteritis nodosa (PAN) [1].

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

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.

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.

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.

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.