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: There is a rising incidence of bladder cancer (BC) in Israel and worldwide. BC is currently the fourth most common cancer in Israeli males. There are large variations in the incidence of BC observed in different populations, both in Israel and worldwide.

Objectives: To characterize the time trends and epidemiologic profile of BC in Israel regarding various population demographics.

Methods: All cases of BC reported to the Israeli National Cancer Registry between 1996 and 2016 were included. We calculated age standardized rates for BC. Joinpoint regression analysis was used to study trends in incidence as expressed by annual percent change (APC) in incidence.

Results: Between 1996 and 2016, 28,953 cases of BC were diagnosed in Israel. BC rates in Jewish males peaked in 2006 and subsequently declined (APC = -1.69, P < 0.05). Between 1996 and 2011, in-situ BC rates increased for both Jewish (APC = 28.2, P < 0.05) and Arab males (APC = 16.76, P < 0.05). Invasive BC incidence in Jewish males declined from 2005 to 2016 (APC = -7.6, P< 0.05) as well as in Arab males from 2006 to 2011 (APC = -12.0, P < 0.05).

Conclusions: In the past two decades, in situ BC rates have risen, while invasive BC rates have decreased. BC epidemiology mirrors lung cancer trends, which is expected as smoking is a significant risk factor for both. These trends are important to identify as they can affect clinical guidelines regarding screening in high-risk populations and health care planning.

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: The correlation between epidural analgesia and successful Trial of Labor After Cesarean delivery (TOLAC) remains controversial.

Objectives: To explore this correlation considering the indication for previous cesarean section (CS).

Methods: We accessed an electronic database of an obstetrics department at a university tertiary medical center. All patients admitted for a TOLAC at term with a live singleton fetus with cephalic presentation between January 2015 and December 2021 were included. The primary outcome was the mode of delivery, based on the previous CS indication. Univariate and multivariate analyses were performed to identify the effect of epidural analgesia on TOLAC success.

Results: Overall, 1522 candidates for TOLAC were included, with previous CS due to arrest of descent in 261 cases (17.1%). Epidural analgesia was administered in 1098 deliveries (72.1%), and 282 women (18.5%) underwent a repeat CS. Women in the epidural group were younger, had higher body mass index, lower parity, and more frequent induction of labor. Prior vaginal birth after cesarean was more common in the non-epidural group. Univariate analysis showed a higher rate of epidural analgesia in repeat CS cases. However, in multivariable logistic regression, epidural analgesia was not significantly associated with the risk of repeat CS, both among women whose prior CS was for arrest of descent and among those with other indications.

Conclusions: The employment of epidural analgesia seems to have no observable influence on successful outcomes of TOLAC, regardless of the indication for the preceding CS. These findings imply that epidural anesthesia in TOLAC is safe.

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: 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.

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.