Israel Medical Association Journal

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: 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: 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.

The long-standing Iran–Israel conflict escalated sharply in April 2024, with Iran’s attack on Israeli territory (13–14 April) and Israel’s retaliation in Isfahan (19 April) [1]. As predicted, a full-scale war erupted between 13–24 June 2025 involving direct strikes on sovereign land and vital infrastructure.

Plastic and reconstructive surgery is a specialty that has an important place in the surgical field. Plastic surgeons cooperate with all surgical disciplines to solve complex multidisciplinary surgical cases. This issue of the Israel Medical Association Journal (IMAJ) covers some of the groundbreaking treatments being performed by plastic surgeons in Israel.

The articles show the wide and complex range of issues where plastic surgery is needed, including hospital-based breast reconstructions, oncologic resections, and innovative lymphedema surgery, as well as aesthetic procedures. The efforts of plastic surgeons have been especially highlighted due to the Iron Swords war, which started on 7 October 2023. Injuries included complex burns and amputations that required attention under fire. In addition, advances were achieved through cutting‑edge reconstructive microsurgical traumatic solutions. Together, these articles highlight how Israeli teams have leveraged experience in trauma, high‑volume civilian and military caseloads and innovative inspirations that have generated knowledge that may be broadly applicable to surgeons worldwide.

Burn injuries pose a significant challenge in mass casualty scenarios. They require rapid and effective intervention to optimize patient outcomes. In this case report, we present the management of three severely burned patients following the October 7th terrorist attack in Israel. Our objective is to highlight the role of NexoBrid® (MediWound Ltd, Yavne, Israel) enzymatic debridement [1] as a primary intervention and discuss the challenges encountered in a mass casualty setting.

Background: Behcet's syndrome (BS) is a multisystem syndrome that typically manifests as recurrent oral and genital ulcers, as well as other systemic manifestations. Few studies describing the characteristics of BS among Israeli patients have been published.

Objectives: To describe the characteristics of BS patients and to compare Jewish and Arab subpopulations.

Methods: We retrospectively reviewed electronic medical records and extracted demographic, clinical, laboratory, and medication data for each patient. We compared the Jewish and Arabic BS patients.

Results: The cohort included 98 patients. Males constituted 49 (50%); mean age at the time of diagnosis was 29.9 years; 71 (72.4%) were Arab and 27 (27.6%) were Jewish. Oral ulcers were evident in 93 patients (94.9%) and genital ulcers in 54 (55.1%). Involvement of the skin, joints, eyes, gastrointestinal tract, and neurologic and vascular systems were demonstrated among 42 (42.9%), 57 (58.2%), 47 (48.0%), 8 (8.2%), 10 (10.2%), and 15 (15.3%), respectively. HLA B51 was positive in 24 of 37 (64.9%). Pathergy was positive in 8 of 12 (66.7%). Colchicine was used in 82 (83.7%), azathioprine 47 (48%), methotrexate 16 (16.3%), apremilast 10 (10.2%), cyclosporine-A 8 (8.2%), adalimumab 26 (26.5%), infliximab 12 (12.2%), cyclophosphamide 1 (1.0%), tocilizumab 2 (2.0%), and anti-coagulation 6 (6.1%). The Arab and Jewish subpopulations were significantly different regarding male proportion, 40 (56.3%) vs. 9 (33.3%), P = 0.042.

Conclusions: BS is more common among Arabs in northern Israel, but no significant clinical or demographic differences were found except for a higher proportion of male patients among Arabs.

Infant botulism is a rare and potentially fatal condition caused by intestinal colonization with Clostridium botulinum. Enteric toxin causes intestinal immobility and progressive descending paralysis due to the effect on acetylcholine release at the neuromuscular junction and other cholinergic nerve terminals, particularly in the gut [1].

We present a case of infant botulism, describe the characteristics of the disease, and focus on early diagnosis.

Background: Botulinum toxin (BT) can alleviate limb dystonia, but limited insurance coverage hinders its utilization.

Objectives: To compare the therapeutic efficacy of BT injections for spasticity and dystonia of the limbs.

Methods: BT injections of hypertonic limbs were administered under ultrasound guidance between 2019 and 2024 for either limb dystonia or limb spasticity.

Results: Of 74 patients included, 57 were diagnosed with spasticity and 17 with dystonia. In total, 276 therapeutic cycles were administered. The dropout rates were 45.6% in the spasticity group and 41.2% in the dystonia group (P = 0.48). There was no significant difference in subjective motor improvement between dystonia and spasticity (P = 0.16). Dystonia patients reported significantly better pain relief (98.5 ± 4.9% vs. 72.4 ± 35.6% respectively, P < 0.001). Notably, 74.3% of dystonia treatments reported moderate or marked improvement, whereas only 54.0% of spasticity treatments did (P > 0.05), based on patient the global impression of change (PGI-C) scale. Side effects were infrequent.

Conclusions: BT injections for limb spasticity and dystonia are partially effective. Nonetheless, the dropout rate is high. While BT injections are more effective in relieving pain for dystonia compared to spasticity, disease severity gradually improves over time in treated patients with spasticity but not with dystonia.

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

Background: Wilson disease (WD) is an autosomal recessive disease characterized by a defect in hepatocellular copper transport with a wide spectrum of clinical manifestations and reported prevalence.

Objectives: To study the epidemiology and clinical manifestations of WD between two ethnic groups, Jewish and Bedouins, with different marriage patterns, in southern Israel.

Methods: We conducted a retrospective study investigating the clinical course and laboratory characteristics of children diagnosed with WD who were treated at Soroka University Medical Center.

Results: Sixteen patients were diagnosed between 2000 and 2021 (8 males, 50%), 14 were of Bedouins origin. The total cohort prevalence was 1:19,258 while the prevalence of the disease was significantly higher among Bedouins compared to Jews (1:10,828 vs.1:78,270, P-value = 0.004). The median age at diagnosis was 10.2 years, without a significant difference between the groups. The most common presenting symptom was hepatic manifestations: 81.2% had elevated transaminases, 12.5% had jaundice, 25% had neurological symptoms, one had a Kayser-Fleischer ring, and one had psychosis. The mean ceruloplasmin level was 3.0 mg/dl. During follow-up, nine patients normalized transaminases with treatment, while three required liver transplantation. There was no significant difference in the clinical presentation and disease course between the two ethnic groups.

Conclusions: Our cohort showed a high prevalence of WD compared to previous studies, especially among the Bedouin population, which has a high consanguinity rate. The prognosis of WD in our population is similar to other studies and depends mainly on treatment compliance.

It is indisputable that internal medicine is the cornerstone of medical activities, including medical education, in hospital clinical activities, and clinical and basic medical research.

The medical landscape in Israel is exceptionally demanding, far exceeding the norms of the countries that are members of the Organisation for Economic Co-operation and Development (OECD). We have fewer hospital beds per capita, a greater workload for each physician, and in the future, we will face the challenge of teaching more medical students across our current clinical fields.

The Israeli Society of Internal Medicine has made it its mission to advance internal medicine across all dimensions of the healthcare system in Israel. As such, for the third consecutive year, we are honored to present an issue of the Israel Medical Association Journal (IMAJ) dedicated to research in the different fields of internal medicine that are conducted by physicians from various departments across the country.

This year, we emphasize even more strongly that research is an integral part of our clinical practice. At a time when the basic sciences phase of residency is under threat, it is crucial to underscore its importance. In this issue of IMAJ, we have chosen to publish various studies that were conducted during the basic sciences phase of the residency in internal medicine, highlighting how this training period can be optimally utilized to advance research while simultaneously progressing and maturing through clinical training.

Background: On 7 October 2023, an armed conflict erupted between Hamas and Israel, leading to numerous combat casualties.

Objectives: To describe computed tomography (CT) findings of combat casualties at a tertiary medical center during the first 3 months of the conflict.

Methods: A retrospective observational study was conducted on patients admitted between 7 October 2023 and 7 January 2024. Adults with conflict-related trauma who underwent chest, abdomen, and pelvis (body) trauma protocol CT scans were included.

Results: Of 272 patients who underwent body trauma protocol CT, 112 combat-related adults were included, mean age of 27 years and one female. In total, 82 patients (73%) underwent additional scans of the head and neck or extremities. Fractures were observed in 53 patients (47%). Vascular injuries were present in 40 patients (35%). Limb injuries were most common, affecting 37 patients (33%), which prompted a protocol update. Lung injuries were the most common in body CT: 30 patients (27%). Head and neck injuries were seen in 21 patients (18%). Multisystem trauma was present in 24 patients (21%). A total of 83 patients (74%) underwent surgery, mostly orthopedic/soft tissue surgeries (63%); 15 (13%) underwent abdominal surgery, with bowel injuries confirmed in eight cases.

Conclusions: CT scans are an important tool in conflict trauma management. Limb injuries were the most frequent, necessitating protocol adjustments. Lung injuries were the most common body injury; 21% of patients had multisystem trauma. Most patients required surgery.

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on patient populations can be divided to direct consequences of the disease and indirect implications of changes imposed on the national healthcare systems. The impact of the later survival of chronic hemodialysis patients is still unknown.

Objectives: To examine the impact of quarantine on health outcomes of dialysis patients.

Methods: In a retrospective case-controlled study, we compared chronic hemodialysis patients from two separate timeframes: during a quarantine period and a parallel time without quarantine.

Results: The study included 344 hemodialysis patients. Baseline characteristics were compared between those enrolled in 2015 and those enrolled in 2020. Despite comparable clinical parameters, a statistically significant increase in the 6-month mortality rate was observed in 2020 (1.2% vs. 6.7%, P = 0.01), primarily attributed to sepsis. Notably, no deaths were attributed to COVID-19 in 2020. Interdialytic weight gain and dialysis quality remained similar between the two groups, with a mild trend toward excessive weight gain in 2020. Secondary outcomes after 6 months did not significantly differ, except for lower sodium values in 2015 compared to 2020.

Conclusions: Dialysis patients experienced disproportionate effects from the COVID-19 pandemic, even with continuous care and no direct virus-related fatalities. The findings showed unintended consequences of quarantine measures, highlighting adverse impact on both physical and mental health. Recognizing and addressing these consequences are imperative for minimizing their impact in future pandemics, emphasizing the importance of proactive measures in healthcare planning.