Israel Medical Association Journal

Background: Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive disorder caused by loss-of-function mutations in the ADA2 gene, with a broad phenotype spanning systemic vasculitis, hematologic, immune deficiency, and autoinflammatory manifestations.

Objectives: To describe a decade of DADA2 management within a uniquely diverse population.

Methods: We conducted a single-center retrospective cohort study of genetically confirmed DADA2 patients (2014–2024). Demographics, clinical manifestations, laboratory findings, treatments, and long-term outcomes were reviewed.

Results: Seventeen pediatric patients were included from two ethnic groups: Arab Muslim (12/17, 70%) and Georgian Jewish (5/17, 29%). The median age at symptom onset was 3.5 months and at diagnosis 4 years. Phenotypes were purely vasculitic/inflammatory (5/17), purely hematologic (3/17), mixed hematologic-inflammatory (6/17), or mixed hematologic-immunodeficiency (3/17). None had isolated immune deficiency. The purely vasculitic/inflammatory phenotype was confined to Georgian Jewish patients, all homozygous for p.Gly47Arg, presenting with cutaneous and ischemic manifestations. Twelve patients received TNF-α inhibitors: 9 achieved complete response, 1 partial, and 2 none, with no subsequent strokes. Arab patients more often presented with fever, red cell aplasia, cytopenias, and immunodeficiency at younger ages. Three patients underwent hematopoietic stem cell transplantation (HSCT). Two responded favorably, one died of infection-related complications after engraftment.

Conclusions: We observed a distinct, ethnicity-driven genotype–phenotype correlation: Georgian Jewish patients with homozygous p.Gly47Arg had a pure vasculitic/inflammatory phenotype responsive to TNF-α inhibitors, whereas Arab patients harbored heterogeneous variants with hematologic/ immune deficiency phenotype potentially benefiting from HSCT. Early, genetically informed diagnosis and phenotype-driven, multidisciplinary management are essential to improve outcomes.

From the first day of medical school, most physicians are indoctrinated with the concept that open communication with our patients is how medicine should be practiced. Regardless of our specialty, this forthright approach is thought to be the ideal. Whether it is taking a solid history, revealing a diagnosis, discussing therapeutic options and adverse events, discussing disease prognosis, or even conveying distressing information, this approach is the gold standard of management. We are communicating not only with the patient, but also with significant others such as family, partners, and friends; therefore, the physician must often repeat the message to different listeners. In the environment of medicine today in Canada and in many other places, is this situation ideal, and if so what is the cost?

In the setting of shortages, whether it is manpower, access to consultation or testing, therapeutic maneuvers, or blunt cost, what are the issues to consider when properly communicating with the patient? In this focus article, I do not offer new insights, just a perspective.

Background: Bloodstream infections (BSI) are associated with high morbidity and mortality. Inappropriate empirical antimicrobial therapy leads to poor outcomes.

Objectives: To evaluate the impact of clinical pharmacist intervention on the appropriateness of antibiotic treatment in patients hospitalized with bacteremia.

Methods: A retrospective study was conducted at the Soroka Medical Center in Israel. The intervention was implemented starting in July 2018. We compared 170 patients who received pharmacist intervention (August 2018 to June 2019) to 173 control patients (January 2017 to July 2018). The primary outcome was a composite of appropriate antibiotic choice and dosage.

Results: Pharmacist intervention significantly improved appropriate antibiotic dosing (97.6% vs. 91.3%, P = 0.011) and selection based on pathogen sensitivity (100% vs. 95.4%, P = 0.007). The most significant effect was observed in patients with intermediate renal function (CrCl 30–60 ml/min). Multivariate analysis confirmed pharmacist intervention as a strong predictor of appropriate treatment (odds ratio 5.00, 95% confidence interval 1.64–15.25, P = 0.005). The intervention group had longer hospital stays (median 15 vs. 9 days, P < 0.001) and lower 7-day relapse rates (2.4% vs. 8.7%, P = 0.010).

Conclusions: Clinical pharmacist interventions significantly improved the appropriateness of antibiotic treatment in patients with bacteremia, particularly in those with intermediate renal function. Despite longer hospital stays, the intervention group had lower early relapse rates than the control group. These findings support the integration of clinical pharmacists into antimicrobial stewardship programs.

Background: Healthcare utilization in patients with psoriasis has been described from the perspective of psoriasis healthcare centers. Psoriasis healthcare utilization at the population level, including appointments with family physicians, impacts the overall financial expenditure.

Objectives: To describe the utilization of healthcare services in patients with psoriasis compared to the general non-psoriasis population.

Methods: We conducted a cross-sectional, population-based analysis of data from Clalit Health Services, the largest public health service provider in Israel, comparing the annual healthcare utilization and medication consumption of all Clalit members with psoriasis in 2023 with an age- and sex-matched group at a primary care clinic. We compared up to five non-psoriasis items.

Results: The study included 835,422 people (140,927 individuals with psoriasis and 694,671 without). Patients with psoriasis had more annual physician appointments than controls, and the meetings were longer. Patients with psoriasis took more sick leave and required more hospital admission compared to the control group. Tumor necrosis factor (TNF) inhibitors were prescribed much more often to patients with psoriasis than to the control group (3147 patients vs. 1857 in the matched control). More IL-17 blockers and IL-23 blockers were also prescribed more in the psoriasis group, although at a much lower level than the TNF inhibitors.

Conclusions: Patients with psoriasis used more healthcare services than the control group. Healthcare providers should allocate more resources to psoriasis care, both for primary care and at specialized psoriasis centers.

Background: Although the epidemiology of Creutzfeldt-Jakob disease (CJD) in Israel has been studied extensively, it is unknown whether its incidence is mainly a result of vertical transmission due to the high penetrance of the E200K mutation in patients with familial CJD (f-CJD) compared to sporadic CJD (s-CJD), or whether there are other yet undiscovered contributing factors.

Objectives: To conduct an age-period-cohort (APC) analysis of Creutzfeldt-Jakob disease in Israel.

Methods: In this APC analysis, we used a web-based statistical tool to identify whether patient age, period of birth, and cohort had any effect on incidence trends of s-CJD and f-CJD.

Results: APC analysis demonstrated no significant shifts in net drift, indicating the absence of any overall trend of changes over time. Cohort analysis revealed that individuals affected by either s-CJD or f-CJD who were mostly born in Israel in the second half of the 20th century exhibited the same risk as those born mainly in Libya at the beginning of 20th century. There were no changes in risk of s-CJD and f-CJD between 1985 and 2019.

Conclusions: The incidence rates of s-CJD and f-CJD in Israel have remained unchanged, indicating that the probability of a future increase in the incidence is negligible.

Background: Vitamin B6 is an essential cofactor in amino acid metabolism. Its deficiency is linked to neuropathy, anemia, and cardiovascular risk. Deficiency is common among hemodialysis patients due to dialytic losses and restrictive diets; however, data related to high-flux (HF) dialysis membranes and Mediterranean dietary patterns are scarce.

Objectives: To assess the prevalence and determinants of deficiency in unsupplemented Israeli hemodialysis patients.

Methods: This retrospective chart review, utilizing a cross-sectional design, was conducted in August 2024. We included 27 chronic hemodialysis patients not receiving vitamin B6 supplementation, representing the available unsupplemented cohort from a unit of approximately 150 patients. Vitamin B6 status was assessed by measuring plasma pyridoxal-5'-phosphate (PLP); deficiency < 20 ng/ml. Clinical and nutritional parameters were evaluated to identify deficiency.

Results: Vitamin B6 deficiency was noted in 63% of patients (median PLP 18 ng/ml, interquartile range 13–23). The cohort was 67% male, median age 74 years. All patients were treated with HF dialyzers. No significant correlations were found between PLP levels and nutritional indices or laboratory markers. A non-significant trend was observed between older age and lower PLP levels (r = -0.35, P = 0.098).

Conclusions: Vitamin B6 deficiency was common among Israeli hemodialysis patients treated with HF dialyzers, despite a presumed Mediterranean diet. It was not associated with nutritional status, suggesting dialysis-related losses, potentially augmented by high-flux membranes, may outweigh intake. Given the high prevalence of deficiency and low cost, routine low-dose vitamin B6 supplementation may be warranted, particularly in older patients.

Background: The Dead Sea is a hypersaline lake with unique mineral concentrations. Ingestion and aspiration of its water can lead to severe electrolyte imbalances and chemical pneumonitis.

Objectives: To evaluate imaging findings from Dead Sea near-drowning victims and to correlate these findings with clinical outcomes.

Methods: We conducted a retrospective study of patients (age > 18 years) admitted to a tertiary medical center between 2004 and 2024 following Dead Sea near-drowning. Imaging studies were categorized by a radiology expert into normal, interstitial changes, unilateral consolidation, or bilateral consolidation. Clinical outcomes, including mortality and intensive care unit (ICU) admission, were analyzed across the groups.

Results: Of the 150 patients identified, 68.7% (n=103) had normal chest X-rays. Abnormal findings included bilateral consolidation 12.7% (n=19), unilateral consolidation 9.3% (n=14), and interstitial changes 9.3% (n=14). Patients with bilateral consolidation had significantly higher peak serum magnesium (median 10.5 vs. 3.1 mg/dl in the normal group; P < 0.001) and peak calcium (median 13.1 vs. 10.3 mg/dl; P < 0.001). Bilateral consolidation was a strong predictor of severity: 26.3% in-hospital mortality rate compared to 1% in the group with normal X-rays (P < 0.001). ICU admission was required for 78.9% of patients with bilateral consolidation and 71.4% with interstitial changes (P < 0.001).

Conclusion: Radiologic findings in Dead Sea near-drownings are predictive of clinical trajectory. Bilateral alveolar consolidation is an indication of massive mineral aspiration, severe hypermagnesemia, and high mortality. Early imaging is essential for risk stratification and for determining the level of care required.

Background: Elbow range of motion (ROM) is commonly assessed during initial evaluation and follow-up. While goniometry is considered the current gold standard, previous studies have raised concerns regarding its user dependence and measurement consistency.

Objective: To evaluate whether smartphone application-based elbow ROM measurements are comparable to visual estimation and goniometry in patients following elbow trauma.

Methods: We conducted a prospective cohort study of 18 patients with elbow injuries. Demographic and medical data were collected. Maximal flexion-extension active ROM was measured by goniometry, smartphone application, and visual estimation by orthopedic surgeons. Measurements were compared to determine agreement and accuracy among different modalities.

Results: Eighteen patients with elbow injuries were included. Inter-rater reliability was good to excellent across all rater groups (intraclass correlation coefficient 0.78–0.93). Using paired t-tests with Bonferroni correction, only one attending surgeon showed a significant underestimation of extension compared to goniometry (16.9° vs. 22.5°, P < 0.05). No significant differences were found for residents, other attendings, or smartphone measurements in either extension or flexion (P > 0.05). Bland-Altman analysis revealed modest mean bias within ± 6° for all methods, although limits of agreement were wide (up to ± 20–30°). Smartphone-based measurements demonstrated significantly higher and less variable Pearson correlation coefficients with goniometry compared to surgeon visual estimations (0.91–0.95 vs. 0.81–0.93, P < 0.05).

Conclusions: Smartphone-based elbow ROM measurements were statistically comparable to goniometry and demonstrated superior correlation and accuracy relative to clinical visual assessments. These findings support the integration of smartphone tools in the clinical setting.

We present a case of a 65-year-old woman diagnosed with papillary urothelial carcinoma and treated with intravesical bacillus Calmette-Guérin (BCG) instillations. The patient developed systemic BCG infection involving the liver and bone marrow (often referred to as BCGitis), complicated by hemophagocytic lymphohistiocytosis (HLH). Although BCGitis is a known adverse event, progression to HLH is rare, particularly in immunocompetent adults. Despite early recognition and escalation of therapy, including intravenous immunoglobulin (IVIG), corticosteroids, and an IL-1 antagonist, the prognosis remained poor, which was consistent with prior reports of high mortality in tuberculosis-associated HLH syndrome (TB-HLH). The diagnosis was microbiologically supported by GeneXpert Ultra, despite negative Ziehl-Neelsen staining and culture, underscoring the importance of molecular diagnostics in suspected BCG-related complications.

Eosinophilic myocarditis (EM) is a rare form of myocardial inflammation defined by eosinophilic infiltration with associated myocyte injury. Its clinical expression is heterogeneous, ranging from subtle symptoms of heart failure to fulminant cardiogenic shock. Because these features often overlap with other types of myocarditis and systemic conditions, establishing the diagnosis can be difficult. In such cases, endomyocardial biopsy (EMB) remains the reference standard.

Amyloid transthyretin (ATTR) cardiac amyloidosis is an infiltrative cardiomyopathy marked by amyloid fibril deposition in the heart's extracellular space. It usually presents with signs of heart failure, and echocardiography often shows concentric left ventricular hypertrophy (LVH), restrictive physiology, and a distinctive pattern of apical strain sparing. In recent years, the development of non-invasive diagnostic methods, as well as the availability of disease-modifying treatments, has significantly improved diagnosis and management.

To the best of our knowledge, the coexistence of ATTR cardiac amyloidosis and EM has not been previously reported. Such overlap presents distinct diagnostic and therapeutic challenges. These conditions may have synergistic effects on the structure and function of the myocardium. We describe a case of concurrent ATTR cardiac amyloidosis and EM, highlighting the role of multimodality imaging and multidisciplinary management of these overlapping pathologies.

Immunoglobulin E-mediated cow's milk allergy (IgE-CMA) is the most common food allergy in infancy. Recent evidence suggests that early infant feeding practices, particularly the pattern of cow's milk formula (CMF) exposure during the first days and months of life, may influence the risk of developing IgE-CMA. Studies indicate that transient CMF supplementation followed by prolonged avoidance is associated with an increased risk of IgE-CMA, whereas continued regular CMF consumption after initial exposure may reduce this risk. This review summarizes the current evidence regarding IgE-CMA prevention, discusses the limitations of the available data, presents the recommendations of the Israeli Association of Allergy and Clinical Immunology, and highlights key unanswered questions requiring further research.

Israel is approaching a pivotal moment in the development of its radiotherapy infrastructure. Demand for advanced radiation technologies continues to grow as the incidence of cancer rises and survival improves, placing increasing pressure on an already stretched oncology system. National planning efforts have identified the establishment of a national proton therapy center as part of Israel’s future radiotherapy infrastructure [1]. The central question is no longer whether proton therapy should exist in Israel, but rather how it should be implemented. Specifically, will national infrastructure be designed to ensure equitable clinical access and meet future demand, or will it reflect the historically limited utilization that resulted from the need to send patients abroad for treatment?