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.

Background: Pediatric urinary tract infections (UTIs) are a significant health concern, with rising antibiotic resistance complicating treatment decisions. We investigated pathogen distribution, antibiotic susceptibility patterns, and the cost-effectiveness of treatment options among hospitalized children at a tertiary medical center in Israel.

Objectives: To assess antibiotic susceptibility patterns of UTI pathogens in hospitalized children and evaluate cost-effective alternatives to gentamicin.

Methods: A retrospective analysis of 1649 pediatric UTI cases (January 2010–May 2022) at Galilee Medical Center examined patient demographics, urine culture results, and antibiotic susceptibility. A cost-effectiveness analysis was performed using incremental cost-effectiveness ratios (ICERs), based on susceptibility rates from the study and antibiotic costs from the Israel Ministry of Health, with gentamicin as the comparator.

Results: Escherichia coli was the most common pathogen (63.7%). High susceptibility rates were observed for carbapenems and amikacin (> 99%), with lower rates for gentamicin (91.7%) and ceftriaxone (87.6%). Treatment costs ranged from US$2.54 (trimethoprim/sulfamethoxazole) to US$307.80 (ertapenem). Fosfomycin demonstrated higher susceptibility than gentamicin (94.2% vs 91.7%) and lower cost (US$3.77 vs US$8.05), dominating gentamicin in cost-effectiveness analysis. Piperacillin/tazobactam and ceftriaxone were dominated by gentamicin in terms of cost-effectiveness.

Conclusions: E. coli was the predominant pathogen in pediatric UTIs among hospitalized children. Carbapenems and amikacin showed high susceptibility but were costly. Fosfomycin demonstrated high susceptibility, favorable cost-effectiveness, and the advantage of oral administration, making it a promising option for empiric treatment. Empiric antibiotic selection should integrate susceptibility patterns, clinical context, and economic considerations.

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: 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.

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: 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: 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.

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.

Ventriculoperitoneal shunt (VPS) placement is a standard treatment for pediatric hydrocephalus. However, infection remains a significant complication, occurring in 5–27% of cases, with coagulase-negative staphylococci (CONS) and Staphylococcus aureus being the most common pathogens [1]. Current guidelines recommend empirical antibiotic treatment and surgical removal of the infected shunt [2]. While shunt removal and replacement are recommended for managing shunt infections, these procedures subject the child to the risks associated with multiple surgeries. However, recent approaches have suggested that in certain cases antibiotics alone may suffice, thus avoiding the risks of surgery [3].

We describe two children with VPS infections caused by CONS who were successfully treated with vancomycin and rifampicin alone, without the need for shunt removal.

The Lancet Commission on Medicine, Nazism and the Holocaust was published in November 2023, recognized the potential dangers for the medical profession that are echoed in this history. The tragic events on 7 October 2023 have revealed just how timely and important the Commission's publication is and have raised the question of the relevance to the Holocaust to this attack. One of the continuities from this past and which has dangerous implications for current medicine, is antisemitism. Examination of the antisemitism inherent to medical education in Nazi Germany raises the question of antisemitism in current academia. Since October 7th there has been a drastic rise in antisemitism and antisemitic actions in both the academy and in medicine. We have seen outright refusal to condemn the brutal perpetrators of the October 7th massacre and continue to observe explicit support for the perpetrators from both faculty and students. Medicine, a profession whose foundational tenet is the well being of humanity–all humanity–and that hallows moral clarity, cannot allow for antisemitic speech and actions to exist within the profession. Awareness and education on this history is crucial for the medical profession so that the tragic events of the past do not happen again.

Background: Laparoscopic right hemicolectomy is considered the gold standard surgical treatment for patients with right colon malignancies. The restoration of bowel continuity can be performed by intracorporal (ICA) or extracorporal (ECA) techniques.

Objectives: To evaluate a single-center experience in laparoscopic right colectomy, comparing patients with ICA and ECA.

Methods: This is a case-control retrospective study included all patients who underwent laparoscopic right colectomy between the years 2016–2022 at our medical center. Patients were divided according to the operative technique. The study database included demographics as well as intraoperative and postoperative parameters.

Results: Overall, 125 patients were included in the study, which included 98 patients (78.4%) from the ICA group included and 27 patients in the ECA group. Both groups were comparable in demographics and co-morbidities. No significant differences were observed between the groups in intraoperative complications, length of surgery, return to the oral diet, and length of hospital stay. The incidence of postoperative ventral hernia was significantly higher in patients from the ECA group (18.5% vs. 3.1%, P = 0.012).

Conclusions: Laparoscopic right colectomy with ICA is associated with a lower rate of postoperative ventral hernias.