Israel Medical Association Journal

In conflict zones like Israel and Ukraine, scientists confront a harsh reality: a war/life balance. Amid air raids, cyberattacks, and destroyed labs, they persist with their research. Despite the loss of irreplaceable data and constant uncertainty, their resilience, strength, and adaptability shine through. Submitting papers from shelters and conducting experiments between reserve duties, they continue building knowledge even as the world crumbles around them. Their determination is a quiet act of defiance and hope.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors arising from pancreatic tissue, predominantly affecting young women and possessing low malignant potential. Extrapancreatic SPNs are exceedingly uncommon. According to data from the English literature, only 30 cases of extrapancreatic SPNs had been reported by 1990, accounting for less than 1% of all reported SPNs from 2004 to 2018. The testis, paratesticular region, and ovary are the more frequently documented sites of these tumors [1,2]. Notably, to the best of our knowledge, no cases of SPN originating in the diaphragm have been reported in the English literature to date. The prevailing theory suggests that SPNs behave similarly regardless of whether they originate in the pancreas or in extrapancreatic locations.

We present the case of a 79-year-old female with a history of lung and endometrial cancer, who was diagnosed with a liver lesion during a routine follow-up ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (¹⁸F-FDG PET/CT). During surgery, the lesion was resected from the diaphragm and was confirmed to be consistent with the pathological findings of SPN.

Becoming and Being a Physician: A Developmental Journey

Shmuel P. Reis, Adina L. Kalet, W. Wayne Weston. CRC Press, 2025, Boca Raton, London, New York

This book is essentially about the evolution of knowledge regarding the DLC from its seemingly simplistic beginnings to its current extreme complexity. The authors offer a set of lenses to understanding such complexity and discerning what comprises and what may influence the DLC.

Background: The association between new-onset atopic dermatitis (AD) and the coronavirus disease 2019 (COVID-19) pandemic was scarcely documented in the literature.

Objectives: To evaluate the incidence of AD in a large nation-wide cohort over 6 years, focusing on changes in incidence following the onset of the COVID-19 pandemic.

Methods: This retrospective cohort study included all members of the largest HMO in Israel (n=4.8 million) from 2017 to 2022. Patients with newly diagnosed AD were identified using the ICD-10 code for AD (L20). Incidence rates were calculated as the number of new diagnoses per 1000 person-years. The pre-COVID period was 1/2017 to 1/2020, and post-COVID 2/2020 to 12/2022. Age-adjusted incidence rates were calculated based on the World Health Organization's standard population.

Results: The overall crude incidence of AD across the study period was 3.38/1000 person-years (PYs). From 2017 to 2022, there was a 36.97% increase in the crude incidence and a 40.44% increase in the age-adjusted incidence, with a mean annual incidence change of +6.5% and +7.1%, respectively. Both crude and adjusted annual incidence increases were significant (P < 0.001, R² = 0.98; P < 0.001, R² = 0.99, respectively). The incidence of AD at the follow-up before the COVID-19 pandemic was 3.07/1000 PYs, and after was 3.71/1000 PYs.

Conclusions: We observed a significant and nearly consistent annual increase in AD incidence from 2017 to 2022, across various sex and age groups. Further research is needed to explore the impact of the COVID-19 pandemic on rising trends in AD incidence.

Background: Limited data exist regarding the association between marital status and outcomes among octogenarian and nonagenarian patients with heart failure (HF).

Objectives: To examine the association between marital status and outcomes of octogenarian and nonagenarian patients with HF.

Methods: We conducted a retrospective analysis of 1371 octogenarians and nonagenarians who were hospitalized with HF and enrolled in the multicenter national survey in Israel between March and April 2003. The patients were followed until December 2014. Patients were classified into married (n=562) and unmarried (n=809). The clinical characteristics of the patients by marital status categories were compared by using Student's t-test for continuous variables and the chi-square test for categorical variables. Kaplan–Meier survival analysis was used to present survival estimates according to the different marital status categories and the subsequent 4-year survival probability. Multivariate stepwise Cox proportional hazard regression modeling was used to assess the independent predictors of mortality among the study population.

Results: Married patients were more likely to be male, to smoke, and to have past myocardial infarction and previous revascularization. They tended to have higher rates of peripheral vascular disease and dyslipidemia. Survival analysis showed that 4-year mortality rates were similar between married and unmarried patients. The main consistent independent predictors of 4-year mortality were age, advanced HF (New York Heart association (NYHA) > 2), advanced renal failure, low hemoglobin, high Charlson Comorbidity Index, and low admission systolic blood pressure.

Conclusions: Among the octogenarian and nonagenarian population with HF, being unmarried does not confer an increased risk of mortality. Nevertheless, unmarried patients had a different clinical profile. Higher risk profile, co-morbidities, and advanced age impact mortality among octogenarian and nonagenarian patients.

Background: Locally advanced gastric adenocarcinomas are treated with neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy. Since 2019 the standard of care for perioperative chemotherapy has been FLOT protocol. Concerns regarding the use of FLOT in elderly patients ≥ 65 years of age emerged due to the relatively high toxicity of this protocol.

Objectives: To evaluate the toxicity profile of FLOT and clinical outcome in elderly patients.

Methods: We conducted a retrospective analysis of patients with locally advanced gastric adenocarcinomas treated with FLOT between 2017–2023 at the Sheba Medical Center. The cohort was stratified by age (≥ or < 65 years). The primary outcome was overall survival (OS). Secondary outcomes were treatment-related toxicity. Kaplan-Meier analysis and Cox proportional hazard regression model were used to analyze the effect of exposure variables on OS.

Results: The study cohort included 91 patients. The median age was 60 years (IQR 50–67); 32 patients were included in the ≥ 65 years group, and 59 patients were included in the < 65 years group. Median follow-up was 40 months (IQR 17–58). Patients ≥ 65 years old received fewer cycles of FLOT compared to those < 65 years old (4.5 vs. 7 cycles, respectively, P = 0.03). Despite the difference in treatment intensity and cumulative chemotherapy dose, there was no difference in median OS between patients ≥ 65 years old compared with those < 65 years old (P = 0.68).

Conclusions: Elderly patients with locally advanced gastric adenocarcinomas received fewer cycles of perioperative FLOT without compromising clinical outcomes.

Background: Epidemiological studies have demonstrated an association between sleep deprivation (SD) and ischemic heart disease.

Objectives: To determine the effect of SD on the endothelial function and on the inflammatory profile of young healthy men following 24 hours of work without sleep.

Methods: Fourteen healthy men (age 31.3 ± 2.4 years) participated in our prospective study. Endothelial function was evaluated by the brachial artery method, measuring flow medicated percent change (FMD%) of the brachial artery by a linear array ultrasound early in the morning. Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured in saliva by ELISA.

Results: Basic FMD% was 6.7 ± 6.8%, and following SD 1.7 ± 3.3% (P = 0.009). A 5.0 ± 6.1% decrease was measured after SD. IL-1 levels increased after SD from 36 ± 21 pg/ml to 47 ± 24 pg/ml (P = 0.004), and IL-6 levels increased from 22 ± 07 pg/ml to 36 ± 11 pg/ml (P = 0.0005). A negative correlation was found between the change (decrease) in FMD% and the change (increase) in IL-1 level (r = -0.813; P = 0.001). A negative correlation was found between the decrease in FMD% and the increase in IL-6 level (r = -0.735; P = 0.003).

Conclusions: SD led to endothelial dysfunction with increase in markers of inflammation (IL-1 and IL-6), with an inverse correlation between the change (decrease) in endothelial function and the change (increase) in IL-1 and in IL-6.

Pre-Ramadan fasting planning before the month of Ramadan represents a golden opportunity for better glucose control during the month of Ramadan among patients with type 2 diabetes mellitus (T2DM). Pre-Ramadan begins 1–2 months earlier and represents a crucial period when healthcare practitioners can provide medical instructions, risk assessment, and stratification to minimize the associated risks such as postprandial hyperglycemia and hypoglycemia during Ramadan fasting. This review focuses on two important classes of drugs that are widely used in Israel incretin-based therapy, particularly the glucagon-like peptide-1 receptor (GLP-1Rc) agonists class and the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) class. In addition, we provide data regarding specific populations such as elderly patients and Bedouins living in the Negev area who require specific recommendations for safe Ramadan fasting. Our data are based on previously published guidelines, consensus statements, and our experience.

The escalating complexity of healthcare delivery underscores the demand for digital transformation in medicine. Among impactful innovations, artificial intelligence (AI)-driven scheduling solutions are being developed and deployed [1].

Safra Children’s Hospital at Sheba Medical Center is Israel’s first medical institution to implement an AI-powered scheduling platform (Equina Scheduling: https://www.equinascheduling.com/). Equina was selected for its capacity to handle the complex, rule-based environment of a training program in a tertiary pediatric hospital. Comprising approximately 70 residents, our pediatric residency program is among the nation's largest. The program manages approximately 1500 monthly shifts, encompassing 49 distinct service shifts, 22 diverse training shifts, and more than 20 different block rotations.

Background: Direct oral anticoagulants (DOACs) have significantly transformed anticoagulant therapy, improving effectiveness, safety, and convenience in managing thromboembolic conditions. However, concerns persist regarding drug-related problems (DRPs) associated with DOACs, necessitating the establishment of multidisciplinary antithrombotic stewardship programs to optimize the selection, dosing, and monitoring of DOACs.

Objectives: To evaluate the incidence and types of DRPs associated with DOACs, the frequency of clinical pharmacist consultations, the acceptance rates of the clinical pharmacist recommendations, and physicians' adherence to appropriate DOACs prescribing practices.

Methods: A retrospective cohort study was conducted over 4 months in the internal medicine departments at Shamir Medical Center (Assaf Harofeh), Israel. The study included patients aged 18 years and older who were prescribed DOACs (apixaban, rivaroxaban, and dabigatran). Data on patient characteristics and clinical outcomes were collected from electronic medical records. A clinical pharmacist reviewed and reassessed the appropriateness of DOAC prescribing.

Results: During the study period, 415 patients receiving DOACs were identified. Among them, 28.4% had inappropriate DOAC prescriptions leading to 128 recommended interventions. The most common DRP was underdosing (29.7%) followed by unjustified antiplatelet use (26.6%). Clinical pharmacists performed 85.9% of the interventions, with a physician acceptance rate of 72.7%. Patients with inappropriate DOAC prescriptions exhibited increased trends in thromboembolic events and in-hospital mortality.

Conclusions: Despite over a decade of clinical experience with DOACs, DRPs remain a significant challenge. Implementing antithrombotic stewardship programs is critical for optimizing DOACs use, reducing DRPs, and enhancing patient safety.

Background: Modern medicine has improved survival rates in burn care. However, this progress has led to a new challenge of sepsis, which has become the leading cause of death in burn patients, accounting for over 50% of mortality. The diagnosis and treatment of sepsis in the burn care unit pose significant challenges due to the hypermetabolic state of the patient, which can mask septic signs and symptoms. This situation underscores the urgent need for improved strategies in sepsis management in burn patients.

Objectives: To assess the predictors of morbidity and mortality among severe burn patients.

Methods: Rambam Health Care Campus is the referral center for burn patients in northern Israel. We reviewed 5 years of patient records, noting information regarding sepsis, laboratory results, infections, and overall morbidity and mortality. In addition, a comparative cohort of burn patient records without sepsis was compared.

Results: Thirty patients had recorded sepsis. Total and direct bilirubin were associated with higher mortality (P < 0.05). Elevated white blood cell count and platelet count at admission were also associated with mortality (P < 0.05). The most prominent burn areas were the arms, head, and legs. The leading cause of injury was fire, followed by an explosion. Burns of total body surface area ≥ 40% was associated with sepsis.

Conclusions: Sepsis is a complex challenge when diagnosing and treating burned patients. Identifying specific traits and prognostic factors is crucial to adequately treat these patients. Research in burn care and sepsis management is essential.

We report a case of true syncope with documented vasovagal syncope which occurred at the time of an alarm due to missile attack. This case shows a severe vasovagal reaction to emotional stress and fear.

The vasovagal response (neurocardiogenic response) involves an abnormal interplay of bradycardia and paradoxical vasodilation. This intense vagal stimulation can result in syncope, which may have dramatic consequences, especially in elderly patients. Such an event was triggered during a missile alarm in an 80-year-old man. To the best of our knowledge, no similar case has been previously reported [1,2]. A sinus pause is a temporary cessation of electrical impulses from the sinus node, resulting in a brief but complete halt of heart contraction. The excessive vagal input diminishes sinus node automaticity, potentially causing pauses that vary in duration from seconds to even longer periods, depending on individual susceptibility and the length and intensity of the vagal response.

Although typically transient, sinus pauses may also result in significant symptoms like lightheadedness or syncope. In severe cases, they can compromise cerebral perfusion, necessitating immediate intervention. Recognizing the risk of sinus pause in susceptible patients is essential for preventing potential complications, particularly during procedures that may provoke a strong vasovagal reaction.

Background: In times of war, healthcare systems face the dual challenge of attending to the medical needs of injured soldiers and civilians as well as struggling to meet the everyday healthcare demands of civilians.

Objectives: To assess the correlation between exposure to war and the likelihood of spontaneous abortion (SAB) and to compare it to a similar period in previous years.

Methods: We conducted a retrospective study comparing the rate of SAB during war to the previous years.

Results: During the Iron Swords war, 381 patients out of 3245 (11.74%) were diagnosed with SAB, compared to 530 of 4080 (13%) in 2022, 536 of 3387 (13.8%) in 2021, and 516 of 3798 (13.6%) in 2020. The median gestational age at diagnosis was similar between the groups, with most cases identified during the first trimester. The study group exhibited a significantly higher prevalence of smoking (18.47% vs. 7.75% vs. 6.3% vs. 9.3%, P = 0.03), with no differences in the prevalence of chronic diseases and in the method of pregnancy termination.

Conclusions: Exposure to stress due to war during early pregnancy appears to have no significant impact on the rate of SAB.

Scleromyxedema is a rare, chronic cutaneous mucinosis characterized clinically by diffuse indurated plaques, numerous waxy papules, and potential for systemic involvement, including neurological, pulmonary, and gastrointestinal complications. It can significantly impact the clinical course and patient prognosis [1].

Histologically, scleromyxedema typically manifests in two main forms. The classic form, the most common variant, is characterized by dense mucin deposition within the dermis, an increase in fibroblasts, and thickened collagen. The granuloma annulare-like variant, accounting for approximately 23% of cases, mimics granuloma annulare and is characterized by interstitial granulomatous infiltration and, in some cases, palisaded granulomas within the dermis. This unusual variant presents a significant diagnostic challenge due to its overlap with other granulomatous conditions, potentially causing diagnostic delays [2].

The lack of standardized treatment regimens makes managing scleromyxedema complex. Intravenous immunoglobulin (IVIG) has emerged as a leading therapeutic option, demonstrating efficacy in controlling both cutaneous and systemic manifestations. Other options include systemic steroids, thalidomide, retinoids, and melphalan [3].

These cases underscore the challenges of recognizing the clinical and histologic variability of scleromyxedema, which may lead to a delay in the diagnosis. Early diagnosis is critical given the potential for systemic involvement (neurological, gastrointestinal, and muscular) and the association of scleromyxedema with monoclonal gammopathy of undetermined significance (MGUS), which might progress to multiple myeloma. Consequently, timely hematologic evaluation and ongoing surveillance are warranted.

Background: Silicone breast implants (SBIs) are associated with subjective and autoimmune related manifestations, ranging from reported symptoms such as depression and fatigue to diseases such as Sjögren's syndrome and systemic sclerosis.

Objectives: To examine whether autoantibodies directed against autonomic nervous system receptors are associated with reported symptoms of dry mouth and eyes in patients with SBIs.

Methods: ELISA assays were used to evaluate a panel of 11 autoantibodies in the sera of patients with SBIs and age-matched healthy controls.

Results: Four autoantibodies (anti-angiotensin II type 1 receptor, anti-β1 adrenergic receptor, anti-muscarinic receptors M2, and anti-muscarinic receptors MR) had significantly lower median titers in SBI recipients who reported dry mouth compared to the control group (9.9 vs. 15.7, P < 0.001; 8.8 vs. 23.3, P < 0.001; 3.2 vs. 4.7, P < 0.001; and 6 vs. 8.8, P = 0.0011, respectively). Anti-muscarinic receptor M4 had significantly lower median titers in patients with SBIs who reported dry eyes compared to the control group (5.9 vs. 8.8, P = 0.0039).

Conclusions: A dysregulation of the autonomic nervous system in SBI recipients was correlated with the presence of dry mouth and dry eyes. Our results emphasize the need to further investigate the proposed involvement of the autonomic nervous system in subjective symptoms reported by SBI recipients.