Israel Medical Association Journal

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: Despite a significant advance in prevention and treatment of heart failure (HF), patients still struggle with decreased quality of life, high mortality, and recurrent hospitalizations. Several inflammatory cytokines have been widely investigated in the pathogenesis of HF.

Objectives: To investigate the prognostic value of fibrinogen on clinical outcomes of patients admitted with acute HF.

Methods: This retrospective study was based on data of patients hospitalized with acute HF. Demographics, laboratory, and clinical outcomes including length of stay and readmissions were obtained. We compared outcomes of patients with normal (< 430 mg/dl) and high (> 430 mg/dl) fibrinogen levels.

Results: We included 149 patients (mean age 67.6 ± 12.3 years, 73.8% male). In our cohort, 24 (16.1%) had normal fibrinogen (< 430 mg/dl) and 125 (83.9%) had high fibrinogen levels (> 430 mg/dl). Among patients with readmissions for HF, fibrinogen levels were higher (622 ± 136 vs. 470 ± 68, P < 0.001) and were associated with longer hospital stay. Fibrinogen remains an independent risk factor after adjusting to age, diabetes status, and left ventricular ejection fraction.

Conclusions: High fibrinogen levels may predict readmissions in patients with HF.

Background: Significant mitral regurgitation (MR) is associated with less spontaneous echo contrast but its effect on the occurrence of ischemic stroke in patients with atrial fibrillation (AF) is unknown.

Objectives: To examine the association of MR grade and the risk of ischemic stroke (IS) in AF patients with heart failure (HF).

Methods: We investigated 2748 patients with known AF who were hospitalized due to acute decompensated HF. All patients underwent echocardiography during hospitalization. Patients were divided into groups based on the degree of MR (high-grade MR [3–4] vs. no/low-grade MR [0–2]). The primary endpoint was IS during long term follow-up.

Results: Mean age was 79 ± 11 years, 48% were women. After 2 years of follow-up, the cumulative incidence of IS among patients with high-grade MR was significantly lower compared to patients with no/low-grade MR (6% vs. 12%, respectively; P-value = 0.0064). Multivariate Fine and Gray analysis, adjusting for CHA₂DS₂-VASc, and accounting for the competing risk of death and valve intervention, showed the presence of high-grade MR was associated with a significant 50% (P = 0.013) reduction in the risk of IS compared with no/low-grade MR. When added to the CHA₂DS₂-VASc score, MR grade allowed more accurate prediction of IS with an overall improvement of 12% (95% confidence interval 5–17%) using net reclassification index analysis.

Conclusions: Our findings suggest an inverse correlation between MR grade and the risk of stroke among AF patients with HF. These findings may be used for improved risk assessment in this population.

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.

Background: Rising rates of antibiotic resistance pose a major challenge in the treatment of Helicobacter pylori (H. pylori) infection. Current treatment guidelines emphasize the importance of acquiring local resistance data to select an effective empirical regimen.

Objectives: To analyze trends in H. pylori antibiotic resistance over two decades in Israel.

Methods: Data from Clalit Health Services for H. pylori isolates cultured from gastric biopsies between January 2007 and December 2023 were included. Susceptibility to clarithromycin, amoxicillin, metronidazole, tetracycline, and levofloxacin was determined using E-tests. Demographic and clinical variables were retrieved to identify predictors of resistance.

Results: We identified 2521 H. pylori isolates (71.6% females, mean age 44.4 ± 15.8 years). Most individuals were residents of central Israel (84.6%) and of Jewish ethnicity (87.8%). Antibiotic resistance was observed in 71.6% of isolates for clarithromycin, 64.3% for metronidazole, and 19.4% for levofloxacin. Resistance to tetracycline and amoxicillin was minimal (0.2% and 1.2%, respectively). Dual clarithromycin-metronidazole resistance occurred in 50.4%, and triple resistance (clarithromycin-metronidazole-levofloxacin) was found in 12.0%. Between 2007 and 2012, clarithromycin resistance increased 5.3% annually, then tapered (odds ratio [OR] 1.05, 95% confidence interval [95%CI] 3.84–6.85, P < 0.001). Age and prior antibiotic use were predictors of resistance for all antibiotics, with the greatest effect observed for drugs in the same class. Female sex was associated with higher resistance to levofloxacin (OR 1.62, 95%CI, 1.28–2.05, P < 0.001).

Conclusions: Antibiotic resistance to H. pylori is high in our geographical region. Nevertheless, resistance rates have remained steady over recent years.

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.

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: Ramadan, one of the core tenets of Islam, requires a rigorous fasting regimen from dawn until sunset, during which practitioners abstain from all forms of food and drink. This substantial alteration in daily habits raises pertinent questions regarding its potential implications for cardiovascular health.

Objectives: To analyze the incidence of myocardial infarction (MI) throughout the Ramadan fasting period.

Methods: We retrospectively compared the incidence of MI occurring during Ramadan with that observed during the corresponding non-Ramadan months from 2010 to 2021 using medical records of Muslim patients admitted to the Galilee Medical Center. Ramadan's timing varies from year to year. We used a 3-year comparative framework to ensure seasonal alignment.

Results: During the study period and within a well-defined geographic region, we found that among Muslims, there were 405 MIs: 201 during Ramadan and 204 during non-Ramadan periods, P = 0.282.

Conclusions: The incidence of MI during Ramadan remained stable, indicating that the fasting practice does not significantly heighten the risk of MI.

Background: Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins, is an emerging residual risk factor for atherosclerotic cardiovascular disease. Data on the prognostic significance after an ischemic stroke are limited.

Objectives: To investigate the association between RC and risk for cardiac events following hospitalization for an ischemic stroke.

Methods: Data were collected for 5697 patients (39.5% women) affiliated with Clalit Health Services and hospitalized with an acute ischemic stroke. Adjusted Cox-regression models were used to estimate the association between RC percentiles, calculated using a routine post-discharge lipid profile, and risk for future myocardial infarction (MI) or coronary revascularization.

Results: Mean age was 69 ± 10 years; 78% were treated by lipid-lowering therapies. During median follow-up of 22 months, a MI or coronary revascularization event occurred in 243 patients. After multivariable adjustment including lipid-lowering therapies and non-HDL-C, RC was associated with higher MI or revascularization risk: hazard ratio (95% confidence interval): 1.42 (1.10–1.85), 1.50 (1.11–2.02), 1.62 (1.09–2.40), and 1.93 (1.22–3.06), in those with RC percentiles ≥ 50th (23.3 mg/dl), ≥ 75th (31.8 mg/dl), ≥ 90th (42.1 mg/dl), and ≥ 95th (49.1 mg/dl), compared to < 50th percentile. When RC and non-HDL-C levels were discordant, the level of RC better reflected higher risk for adverse cardiac events.

Conclusions: Elevated RC following acute ischemic stroke is a risk factor for MI or coronary revascularization, independent of lipid-lowering therapies and non-HDL-C and may serve as a residual cardiovascular risk marker and potential treatment target in patients with ischemic stroke.

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: 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.

Background: Hypofractionation regimens shorten the overall duration of treatment, thereby reducing the risk of accelerated tumor cell repopulation following the initiation of radiotherapy. These regimens have been shown to improve overall survival and locoregional control in patients with laryngeal cancer. The toxic effects from radiotherapy for laryngeal squamous cell carcinoma (SCC) include dysphagia, mucositis, laryngeal edema, weight loss, and pain.

Objectives: To evaluate early toxicity and opioid usage associated with hypofractionation treatment of the larynx compared to standard fractionated radiotherapy.

Methods: We retrospectively analyzed 127 laryngeal SCC patients who underwent radiotherapy. Among these, 50% with early glottic cancer received hypofractionation (2.25 Gy per fraction, totaling 63 Gy) directed at the larynx, while 50% with advanced-stage disease underwent standard fractionation (2 Gy per fraction, totaling 70 Gy) targeting both the larynx and bilateral neck, with or without concurrent chemotherapy.

Results: Patients in the hypofractionation group required significantly higher dosages of opioids due to increased pain and swallowing discomfort (P < 0.05). Those in the hypofractionation group who received dexamethasone boluses experienced significantly less weight loss compared to hypofractionation patients who did not receive steroids, with some even experiencing weight gain (P < 0.005). Patients with advanced-stage cancer treated with chemoradiotherapy exhibited greater toxicity than those receiving radiotherapy alone.

Conclusions: Patients undergoing hypofractionation treatment generally require significantly higher doses of opioids than those treated with standard fractionation. Treatment protocols for patients receiving hypofractionation should include effective pain management strategies and, where feasible, the use of corticosteroids.