Israel Medical Association Journal

Background: Hypertensive disorders during pregnancy can lead to significant adverse outcomes. Currently, no established and effective tests have a high predictive value for preeclampsia toxemia (PET) severity and its associated adverse outcomes.

Objectives: To investigate the correlation between the aspartate aminotransferase-to-platelet ratio index (APRI) and the risk of obstetrical and neonatal adverse outcomes in women with PET.

Methods: We conducted a population-based cohort study at a tertiary medical center, which included all women who delivered between the years 2020 and 2022 and were diagnosed with PET. Women with incomplete records, multiple gestations, and fetal malformations were excluded. The median APRI of the cohort was the cut-off point to compare the risk of obstetrical and neonatal complications between low and high APRI scores. A multivariable logistic regression was used to adjust for confounders.

Results: The study included 513 women with PET who met the inclusion criteria. The median APRI score was used as a cut-off value, resulting in 255 women with an APRI score < 0.26 and 258 with a score > 0.26. A higher APRI score was significantly correlated with a small for gestational age (SGA) newborn and preterm delivery before 34 weeks after controlling for parity, previous cesarean delivery (CD), and maternal age (adjusted odds ratio 1.60, 95% confidence interval 1.01–2.55; P = 0.047, adjusted hazard ration 1.75, 95% confidence interval 1.12–3.09, P = 0.047).

Conclusions: In patients with PET, an APRI score > 0.26 was associated with an increased risk for SGA and preterm deliveries.

Background: Fetal macrosomia is a risk factor for operative vaginal delivery (VD), shoulder dystocia, obstructed labor, and cesarean section (CS). Induction of labor (IOL) may decrease these risks but also leads to longer labor, increasing the risk of CS. No data exist regarding the optimal method of IOL in macrosomic fetuses, and most studies are limited to the efficacy of medical induction.

Objective: To compare medical and mechanical IOL in macrocosmic fetuses.

Methods: This retrospective case-control study included pregnant women who underwent IOL and delivered macrosomic neonates at a tertiary center between 2010 and 2020.

Women with non-cephalic presentation, prior CS, and multiple pregnancies were excluded. The primary outcome was the mode of delivery. Secondary outcomes included neonatal and maternal complications.

Results: A total of 247 women were included in the study, 188 underwent cervical ripening with prostaglandin E2 (PGE2) regimens and 59 with a double-balloon catheter. Higher rates of prior deliveries over 4000 grams and Oxytocin use during delivery were found in the mechanical induction group. No other clinically significant differences in demographic or clinical characteristics were identified. There were no statistically significant differences in the rates of VD or CS between the groups. The indications for CS were similar. Maternal and neonatal secondary outcomes were comparable.

Conclusion: PGE2 vaginal regimens and double catheter balloons are safe and effective methods for cervical ripening during IOL in term pregnancies with macrosomic neonates. The choice of cervical ripening method did not impact the mode of delivery or maternal and neonatal outcomes.

Background: Out-of-hospital cardiac arrest (OHCA) poses a considerable health burden and offers poor prognosis. Information about OHCA in Israel is scarce.

Objectives: To present a pilot registry of prehospital and in-hospital characteristics of patients with OHCA.

Methods: A descriptive study was conducted of consecutive adult patients with OHCA treated in the field by Magen David Adom (MDA) paramedics and treated at the Sheba Medical Center.

Results: The study included 99 patients with OHCA who were brought by MDA to the Sheba Medical Center. The median age was 79 years (IQR 67–89(, 61% were male. In total, 69% of the events occurred at home, 16% at nursing facilities, 10% on streets, and 2% in public buildings. Most events (80%) were witnessed. Bystander-basic life support (BLS) was administered to 28%, 45% received BLS from an emergency medical service first responder. Automated external defibrillation was used in 40% of cases. In our cohort, 51 patients (51%) survived initial treatment in the emergency department (ED) and were hospitalized. Electrocardiography at arrival demonstrated ST-elevation in 22% of cases. Coronary angiography was performed in 19% (n=19) of patients, and 12% (n=12) underwent percutaneous intervention. Eventually, 26 patients (26%) survived to discharge with a Cerebral performance categories were as follows: 13% (n=13) with good cerebral performance, 10% (n=10) with moderate disability, and 3% (n=3) with severe disability or unconscious.

Conclusions: Among those admitted after surviving ED resuscitation, half survived to discharge. Most of those who survived hospitalization and were discharged with good neurological performance were young males.

Gross hematuria is uncommon in the neonatal period, with an estimated incidence of 0.21 per 1000 admissions in infants younger than one month. Although renal vein thrombosis is the most common cause, various etiologies, including congenital anomalies, must be considered. Anterior urethral valve (AUV) is a rare congenital anomaly that can cause severe obstruction and significantly impact the proximal urinary system [1].

Anatomically, AUV can cause obstruction of varying severity depending on the size and configuration of the valve [2]. The pathophysiology of AUV involves abnormal development of the urethral folds in the anterior urethra, typically at the penoscrotal junction, bulbar urethra, or penile urethra. These valves form cusp-like structures that allow antegrade flow of urine but obstruct during voiding, leading to progressive dilatation of the proximal urethra and upstream urinary tract [3].

Recent data from a matched cohort study at a high-risk pediatric center found that AUV patients demonstrate significantly lower creatinine levels at initial presentation and potentially better renal outcomes compared to posterior urethral valve (PUV) patients [4]. Prenatal diagnosis of anterior urethral anomalies is feasible as early as the second trimester, with characteristic findings including anterior urethral dilation and a keyhole sign on prenatal ultrasound [5]. Unlike PUV, which are more commonly reported, AUV presenting with gross hematuria in the neonatal period is exceptionally rare, making this case particularly noteworthy for clinicians.

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: Increased utilization of imaging modalities has led to a significant rise in the detection of incidental thyroid nodules (ITN). Discrepancies in the prevalence of thyroid nodules with malignant potential exist worldwide.

Objectives: To analyze demographic and clinical data among patients with thyroid nodules in our geographic region.

Methods: The medical records of patients diagnosed with symptomatic or incidental thyroid nodules at the Galilee Medical Center between 2018 and 2023 were reviewed. Demographic and clinical data were collected and analyzed.

Results: The study population included 402 patients with thyroid nodules, 292 females. Symptomatic patients were younger (mean age 55.9 vs. 60.8 years) and had larger nodules (mean size 2.5 vs. 2.1 cm) compared to incidentally diagnosed patients (P < 0.001, P < 0.001, respectively). Male patients demonstrated a higher rate of malignancy for both symptomatic and incidental nodules compared to females (P < 0.05). Pathological examination revealed that malignant nodules were smaller (mean size 2.10 cm vs. 2.87 cm) and detected at a younger age (mean age 48.56 years vs. 56.5 years), compared to benign nodules (P < 0.05, P < 0.01, respectively).

Conclusions: We found a higher prevalence of both symptomatic and ITN among females. However, malignant thyroid nodules were more frequently observed in males. Notably, malignant nodules tended to be smaller and were more commonly diagnosed in younger individuals compared to benign nodules. These findings highlight significant sex and age disparities in the occurrence and characteristics of thyroid nodules, emphasizing the need for tailored diagnostic and management strategies.

Background: The benefits of corticosteroid administration for suspected premature birth (PTB) are widely accepted. Although a single course of antenatal corticosteroids is generally considered to be safe, there are concerns regarding the safety and benefit of multiple courses. Nevertheless, many women who present with symptoms of PTB do not deliver early.

Objectives: To assess how often we used corticosteroid appropriately in our clinical practice in women who presented with risk of PTB.

Methods: Clinical data were retrospectively collected on patients who were admitted to our clinic between September 2014 and August 2015 due to risk of PTB and who were treated with prenatal corticosteroids.

Results: We identified 305 patients at risk of PTB who were treated with corticosteroids; 42.3% delivered < week 34, 22.5% delivered between weeks 34 and 37, and 35.1% delivered > 37 weeks. In women who delivered after week 37, the more time that elapsed between corticosteroids administration and delivery, the lower the pH and the APGAR scores were. Only 26% of patients delivered 2–14 days after the last steroids course of treatment.

Conclusions: The rate of term deliveries at our center after receiving antenatal corticosteroids due to prior symptoms of preterm labor was 35.1%. The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at < 37 weeks of gestation was not optimal but acceptable.

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: The management of chronic hepatitis C virus (HCV) infection in patients with concurrent severe mental illness and substance use disorder poses significant challenges to treatment initiation, adherence, and completion. Multiple barriers impede successful treatment outcomes in this population, including cognitive impairments associated with mental illness, ongoing psychoactive substance use, and inadequate social and environmental support systems.

Objectives: To implement a treatment program for HCV-infected patients during their psychiatric hospitalization. To establish a multidisciplinary task force comprising a hepatologist, psychiatric ward team (psychiatrists, nurses, social workers), and a project administrator.

Methods: We conducted a retrospective cohort study of patients hospitalized with dual diagnosis (DD) of severe mental illness and substance use disorder who tested positive for HCV antibodies. Patients underwent clinical evaluations and received treatment with direct antiviral agents during hospitalization under the supervision of the joint team. Demographic and clinical characteristics were analyzed.

Results: Between January 2018 and June 2023, 694 DD patients were hospitalized, of whom 119 tested positive for HCV antibodies (prevalence 17.1%). Twenty-seven patients (23%) completed treatment; 17 (63%) achieved confirmed sustained virologic response. Treatment discontinuation occurred primarily post-discharge from the mental health facility. Significant efforts were made to engage community caregivers to maintain continuity of care.

Conclusions: Our findings demonstrate that treating HCV in patients with concurrent severe mental illness and substance use disorder requires collaborative efforts across medical disciplines. This integrated approach during psychiatric hospitalization provides a unique opportunity for initiating and monitoring HCV treatment in this complex patient population.

Background: Cesarean section (CS) comprised almost one-third of all births. One of the complications after CS is intra-abdominal and pelvic adhesions formation.

Objectives: To investigate whether a previous CS poses an additional perioperative or postoperative risk for complications when performing a total laparoscopic hysterectomy (TLH).

Methods: We conducted a retrospective cohort study of women who had undergone a TLH between 2014 and 2020. Perioperative and postoperative complications were assessed according to the Clavien-Dindo classification system. Descriptive statistics were used to analyze the results.

Results: In total, 190 women underwent TLH during the study period, 50 (26.5%) had a previous CS (study group) and 140 (73.5%) had no history of CS. The complication rates using the Clavien-Dindo classification system were similar in both groups; however, the major complications rate was not significantly higher in the study group (CS 6% vs. no CS 1.4%, P = 0.08). Urethral injury was the most common major complication (2, 4% vs. 1, 0.7%). The duration of surgery (125 min vs. 112 min, P = 0.02), estimated blood loss (174 ml vs. 115 ml, P = 0.02), and additional postoperative endoscopic interventions (4% vs. 0%, P = 0.01) and were significantly greater in patients with a previous CS.

Conclusions: Although the need for postoperative endoscopic interventions, surgery duration, and estimated blood loss were significantly higher in patients with a previous CS, TLH remains a safe and recommended procedure for these patients. Major complications are rare and do not occur more frequently following a previous CS.

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.

Methotrexate, a folate analog antimetabolite, is one of the oldest cytotoxic drugs still in use. It is active against a variety of malignancies including bladder and breast cancer, head and neck tumors, gestational choriocarcinoma, osteogenic sarcoma, lymphomas, and leukemias.

Methotrexate is given mostly intravenously (IV), usually at standard doses (milligrams). It can also be delivered in much higher doses (grams), which is known as high-dose methotrexate (HDMTX). The intrathecal (IT) route is used particularly in children with acute lymphoblastic leukemia (ALL) and in adults with meningeal carcinomatosis. The drug may be administered orally as well, mainly in non-oncological conditions such as rheumatoid arthritis and other autoimmune diseases.