Israel Medical Association Journal

In recent years, we have been experiencing a technological revolution, which signifies an ethical and societal transformation. Artificial intelligence (AI) based technologies have gradually permeated all aspects of life and solidified their position. Within this context, the emergence of these technologies offers new opportunities in the medical field, including palliative care, which is aimed at alleviating suffering and improving the quality of life for terminally ill patients and their families. In Israel, the Dying Patient Act of 2005 (the law), which promotes values such as the sanctity of life and individual autonomy, allows terminally ill patients to determine their preferred treatment, and withhold life-saving treatment under certain circumstances. The law represents a significant step toward improving care for terminally ill patients, reducing pain and suffering, and respecting the patient's wishes and worldviews in their final days. However, the practical implementation of the law has encountered numerous challenges, ranging from lack of familiarity among doctors and healthcare professionals and the requirement to determining life expectancy to fulfilling the law's purpose. These challenges are associated with ethical, cultural, and religious perspectives. In this article, we describe how AI-based technologies hold immense potential in applying the law and providing palliative care based on their predictive capabilities, prognostic accuracy, and optimization of treatment as well as communication between patients and healthcare providers. However, as an innovative, developing, and complex technology, it is crucial not to overlook the ethical, societal, and legal challenges inherent in implementing and using AI-based technologies in the context of palliative care.

Background: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients.

Objective: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients.

Methods: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects.

Results: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

Background: The management of complicated appendicitis is inconclusive. Guidelines have not been established for the use of personalized antibiotic treatment.

Objectives: To investigate specific risk factors to consider during the initial first-choice antibiotic therapy in children with complicated appendicitis.

Methods: This study included all pediatric patients younger than 18 years of age who underwent a laparoscopic appendectomy during 2012–2022 at a single tertiary medical center.

Results: In total, 300 pediatric patients underwent laparoscopic appendectomy due to complicated appendicitis. The patients were treated with ceftriaxone + metronidazole (CM). For 57 (19%) patients, the empirical treatment was changed to tazobactam/piperacillin (TP) due to resistant bacteria or clinical deterioration. The presence of generalized peritonitis during surgery and C-reactive protein (CRP) levels above 20 mg/L at admission were identified as risk factors for changing the antibiotic regimen from CM to TP.

Conclusions: Generalized peritonitis and CRP > 20 gr/L were highly correlated with changing the antibiotic regimen to TP. For such patients, initial treatment with TP may result in clinical improvement and shorter hospitalization. 

Background: Presentation of intoxicated patients to hospitals is frequent, varied, and increasing. Medical toxicology expertise could lead to important changes in diagnosis and treatment, especially in patients presenting with altered mental status.

Objectives: To describe and analyze clinical scenarios during a 1-year period after the establishment of a medical toxicology consultation service (MTCS).

Methods: Cases of 10 patients with altered mental status at presentation were evaluated. Medical toxicology consultation suggested major and significant changes in diagnosis and management.

Results: Of 973 toxicology consultations performed during the study period, bedside consultation was provided for 413 (42%) patients. Of these 413, 88 (21%) presented with some level of altered mental status. We described 10 patients in whom medical toxicology consultation brought about major and significant changes in diagnosis and management.

Conclusions: Benefits may be derived from medical toxicology consultations, especially in patients with altered mental status. Medical toxicology specialists are well positioned to provide high value and expedited patient care.

The ancient, Biblical, holy Ten Commandments were presented to humanity to serve as guidelines for relationships between individuals and the deity they worship as well as a benchmark for living in civilized communities, irrespective of religious affiliation. The commandments are also embedded in medical education taught to medical students and other health professions throughout the world. Thus, the Ten Commandments are embedded in the medical communications curriculum at Adelson School of Medicine, Ariel University, Ariel, Israel. Unfortunately, most of these commandments were desecrated during the violent, hostile, merciless, and ruthless attack inflicted by the Hamas terror organization on villages, rural communities, and cities in southern Israel on 7 October 2023. We define the Ten Commandments in terms of medical education and describe their desecration by Hamas terrorists before and during the Iron Swords war.

Background: Cases of second trimester pregnancy loss can be treated either pharmacologically or by surgical evacuation. Misoprostol, an E1-prostaglandin analog, is used to facilitate the evacuation of the uterus.

Objectives: To determine the risk factors associated with patients who were treated with five or more repeated doses of misoprostol.

Methods: We conducted a retrospective study of patients treated with vaginal misoprostol at our institution between December 2016 and October 2021 for second trimester pregnancy loss.

Results: In total, 114 patients were eligible for analysis; 83 were treated with < 5 doses and 31 with ≥ 5. We recorded each case in which repeated doses were administered, irrespective of predetermined conditions such as gravidity, parity, maternal age, or gestational age. Moreover, cases of five or more misoprostol dosing were not associated with an increased complications rate, except for the increased duration of hospitalization (3.1 vs. 2.2 days, P-value < 0.01).

Conclusions: Repeated dosing could not be predicted before treatment among those treated with vaginally administered misoprostol for second trimester pregnancy loss. However, low complication rates of repeated dosing may reassure both physicians and patients regarding safety, efficacy, and future fertility.

Background: Sperm banks initially focused on providing sperm donation (SD) to heterosexual couples grappling with severe male infertility. Notable advancements in fertility treatments and sociological trends have broadened the scope of SD toward single women and same sex female couples.

Objectives: To evaluate SD recipient characteristics over the last three decades in Israel according to demographic parameters.

Methods: This retrospective cohort study included 5489 women who received SD between January 1992 and December 2021 from a tertiary referral center. We divided the overall period into six groups of five years each. A comparison of demographic characteristics of women who received SD in different periods was performed according to age at the beginning of the treatment, marital status (single women and same sex female couples, heterosexual couples), and ethnic origin.

Results: The average age of women who received SD was 37.02 ± 5.36 years. The average patient age rose from 35.08 years in 1992–1997 to 37.43 years in 2017–2021 (P-value < 0.01). The use of SD was more common among single women and same sex female couples compared to heterosexual couples in later years. Regarding single and same sex female couple, the percentage of SD recipients increased radically from 33% to 88.1% (P-value < 0.01).

Conclusions: Modern sperm banks treat older patients in non-heterosexual relationships. These trends encompass not only medical implications (e.g., in vitro fertilization vs. intrauterine insemination) but also delve into the personal and sociological impact experienced by both patients and offspring.

Higher potency bisphosphonates, typically intravenous formulations, are given at lower doses for postmenopausal women. The treatment has improved compliance compared to daily oral therapy. Since bisphosphonates are exclusively excreted via the kidneys, intravenous formulation has been associated with deterioration of renal function, specifically in the setting of preexisting renal disease or concomitant use of nephrotoxic agents [1].

Background: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel.

Objectives: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence.

Methods: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events.

Results: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time.

Conclusions: Clinician training regarding discharge of VTE patients from the ED should continue.

Background: The continuity equation (CE) used for evaluating aortic stenosis (AS) is based on values obtained from transthoracic echocardiography (TTE) with the assumption that the left ventricular outflow tract (LVOT) has a circular shape. Transesophageal echocardiography (TEE) may be used for accurate measurement of the LVOT cross-sectional area (CSA). Previous studies have focused on fusion from TEE for LVOT-CSA measurement and TTE for velocity time integrals (VTI) calculations.

Objectives: To assess aortic valve area (AVA) using parameters obtained exclusively from TEE as an alternative approach.

Methods: Thirty patients with equivocal AS based on TTE were evaluated using TEE for further assessment.

Results: The mean pressure gradient across the aortic valve (AV) was 38 ± 5.9 and 37.9 ± 7.6 mmHg in TTE and TEE, respectively, P = 0.42. LVOT-CSA was larger in TEE (3.6 ± 0.3 vs. 3.4 ± 0.3 cm², P = 0.049). VTI over the AVA was similar (98.54 ± 22.8 and 99.52 ± 24.52 cm in TTE and TEE, respectively, P = 0.608), while VTI across the LVOT was higher when measured by TTE (24.06 ± 5.8 vs. 22.03 ± 4.3 cm, P < 0.009). Using the CE, AVA was 0.82 ± 0.3 vs. 0.83 ± 0.17 cm² in TEE vs. TTE, respectively, P = 0.608. Definitive grading was achieved in all patients (26 patients defined with severe AS and 4 with moderate).

Conclusions: In equivocal cases of AS, full assessment using TEE may be a reliable modality for decision making.

In the acute settings of generalized myasthenia gravis (MG) treatment options include plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and pyridostigmines. A thymoma is associated with the disease in up to 20% of cases [1,2].

In cases where a thymoma is detected, surgical treatment to remove the tumor is recommended in certain age groups. At present, there are no clear guidelines regarding the optimal time to perform thymectomy after diagnosis of acute crisis or from the last treatment to thymectomy. Treatment is at the clinician's discretion.

Cognitive impairment due to different types of anemia is well-known. We reviewed the links between different types of anemia and the mechanism of cognition impairment as well as the direct involvement of micronutrients such as iron, vitamin B12, folic acid, and copper on cognitive function. Anemia can lead to cognitive impairment, yet the current health policy usually requires patient involvement in the treatment decision-making. Therefore, can an anemic patient be a partner to shared decision-making concerning the recommended treatment?

Background: In 2019, 1 mg subcutaneous semaglutide was registered for the treatment of diabetes in Israel. Recognition of its effect on weight has led to its use as a treatment for obesity.

Objectives: To explore physicians’ pre-therapy considerations, therapy practices, and attitudes regarding subcutaneous semaglutide for weight loss.

Methods: A 22-item questionnaire was disseminated to physicians who prescribed semaglutide 1-mg for weight loss using an authorized off-label path.

Results: In total, 127 physicians completed the questionnaire. As for pretreatment requirements, in the absence of diabetes, 30% requested a minimal body mass index of 30 kg/m². Additional requirements were documented lifestyle-change effort (67%) and prior weight loss medication use (13%). Half of the physicians regarded calorie restriction, and 23% considered physical activity as necessary for weight loss while on therapy. As for dose, most physicians (78%) started with a 0.25-mg weekly injection, 57% doubled the dose monthly, and all others recommended doubling when side effects subsided. Regarding weight loss goal, 43% of the physicians set a personal goal with each patient while 26% limited the goal to 10% of initial weight. Fewer than 50% of physicians discussed treatment duration with their patients, and 52% of patients discontinued therapy in the first 3 months. The main reasons for discontinuation were price, lack of effect, and fear of long-term side effects.

Conclusions: The diverse approaches regarding off-label use of semaglutide for weight reduction highlight the necessity to guide physicians and standardize treatment regimen.

Background: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision.

Objectives: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD.

Methods: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity.

Results: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively.

Conclusions: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Background: The French AmbUlatory Cesarean Section (FAUCS) technique was introduced to the Galilee Medical Center in September 2021. FAUCS was performed electively for interested women who meet the criteria.

Objectives: To evaluate the learning curve of senior surgeons performing FAUCS, the procedure short-term outcomes, and complications.

Methods: This retrospective study included 50 consecutive women who underwent FAUCS from September 2021 until March 2022 at our facility. Preoperative, intraoperative, postoperative, and demographic data were retrieved from patient electronic charts.

Results: The mean duration of surgery was 53.26 ± 11.62 minutes. This time decreased as the surgical team's experience increased: from a mean 58.26 ± 12.25 minutes for the first 15 procedures to a mean 51.17 ± 9.73 minutes for subsequent procedures. The mean visual analogue scale score for 24 hours was 1.08 ± 0.84 (on a 10-point scale). The rate of neonatal cord pH < 7.2 was 6%, and there were 11.3% cases of vacuum assisted fetal extraction. In total, 44% of the women were able to mobilize and urinate spontaneously by 4–6 hours. Complications included bladder injury (n=1), endometritis (n=1), and incisional hematoma (n=1). Overall, the maternal satisfaction rate was high; 94% of the women would recommend FAUCS to others.

Conclusions: FAUCS is a feasible procedure with a high satisfaction rate. Following the first 15 procedures performed by one surgical team, the operative time decreased considerably. Further randomized controlled studies are needed to compare this procedure to regular cesarean section and evaluate neonatal outcomes.