Israel Medical Association Journal

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: 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: Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency disorder, typically presenting with hypogammaglobulinemia and recurrent infections. Mechanistically, CVID is caused by abnormal B-cell maturation or function. These abnormalities lead to an impaired ability to generate a normal quantity or diversity of antibodies and an impaired response to neo-antigens. In addition to the resulted immunodeficiency, CVID can also involve immune dysregulation affecting different organ systems, with the lungs being one of the more commonly involved organs. Granulomatous lymphocytic interstitial lung disease (GLILD) is a challenging and well known CVID-related complication. It is associated with high morbidity and increased risk of mortality.

Objectives: To describe the clinical and immunological features of five CVID patients with radiologic and/or pathologic features consistent with granulomatous lymphocytic interstitial lung disease.

Methods: We conducted a review of clinical, laboratory, imaging, and pathology data, as well as B-cell and T-cell immunophenotyping of patient PBMCs, focusing on unique characteristics of CVID GLILD patients.

Results: CVID GLILD patients showed several clinical characteristics, including multiorgan involvement with cytopenias and lymphoproliferation but without significant gastrointestinal involvement. B-cell phenotyping showed abnormal B-cell maturation and development with severely impaired class switching. In addition, unique T-cell phenotype with low to near-absent naive CD4⁺ T cells was observed.

Conclusions: Lung involvement in the form of GLILD is associated with significant co-morbidity and typical B-cell and T-cell immunophenotyping. Patients should be actively screened for the possibility of GLILD, especially when regularly performed lymphocyte immunophenotyping suggests similar patterns.

Background: Noise-induced hearing loss (NIHL) is a prevalent hearing impairment, second only to age-related hearing loss. A change in the listening habits of adolescents may have contributed to the documented increase of hearing impairments in that age group.

Objectives: To examine the prevalence of NIHL among healthy young adults.

Methods: We conducted a retrospective study to examine audiograms of healthy candidates for the Israeli Air Force flight academy between 2018 and 2023. Hearing tests were performed by an expert audiologist using an audiometer.

Results: A total of 1940 audiograms were analyzed. The age range of the patients was 17–19 years. Using the British Society of Audiology classification, 174 (8.97%) audiograms and 313 frequencies were classified as impaired. The 8 kHz was the most affected frequency, accounting for 116 cases (37%).

Conclusions: Hearing impairment prevalence increased from 1% at entry into the education system to 8.45% at the end, respectively. Detecting hearing impairments early may minimize future disability and may reduce future disability and rehabilitation costs. Hearing screens for young adults due to the change in listening habits of adolescents may prove useful.

Background: Exertional heat stroke (EHS) is common among individuals engaged in high-intensity physical activity. It can lead to long-term organ damage and be a life-threatening condition when diagnosed and treated incorrectly.

Objectives: To track the changes in biomarkers among EHS patients, to suggest a standardized protocol of clinically relevant biomarkers to be followed during hospitalization

Methods: We conducted a retrospective analysis on biomarker changes in seven EHS patients (aged 18–25 years) who were hospitalized for a minimum of 84 hours. Diagnosis of heat stroke was based on extreme body temperature and neurological deficits. Biomarkers indicative of kidney function, liver function, coagulation, muscle breakdown, and systemic inflammation during their hospitalization were analyzed.

Results: The initial average rectal temperature (T_re) was 41.1°C. Patients were cooled to approximately 38.5°C before being transferred to the emergency department (ED). Within the first 24–36 hours of hospitalization, biomarker levels reach peak levels depending on EHS severity. Renal biomarkers rose to 1.5–3 times normal values, while transaminases increased 7–15 times. Creatine phosphokinase, indicating muscle injury, reached an average of 100 times its reference range. Within 24–72 hours. all biomarker levels were normalized.

Conclusions: There is often a gap between the initial temperature of an EHS patient and the temperature recorded at ED admission after cooling. Accurate assessment is context-specific and requires precise biomarker follow-up. Clinical evaluation should continue for at least 48 hours to track organ damage and guide prognosis.

Background: Age is a well-established prognostic factor in civilian trauma, where adverse outcomes increase with ages. Whether this pattern holds true in military trauma, where populations, injury mechanisms, and systems of care differ fundamentally, remains uncertain. A large-scale mobilization of Israeli Defense Forces (IDF) reservists provided an opportunity to examine this association.

Objectives: To clarify whether older service members experienced less favorable outcomes compared with younger counterparts.

Methods: This retrospective cohort study included IDF casualties recorded in the IDF Trauma Registry and the Israel National Trauma Registry between 27 October 2023 and 19 January 2025. Participants were categorized by age: 18–21 years, 22–39 years, and ≥ 40 years. Primary outcomes included 24-hour and 30-day mortality, intensive care unit admission (ICU), and hospitalization ≥ 7 days.

Results: Of 4905 casualties, 40.4% were 18–21 years of age, 54.2% were 22–39, and 5.4% were ≥ 40. Injury severity, evacuation times, pre-hospital interventions, and admission vital signs were similar across groups. Adjusted analyses showed no significant age-related differences in mortality, ICU admission, or prolonged hospitalization. Subgroup analysis of casualties with injury severity score ≥ 16 yielded comparable results.

Conclusions: In this large military trauma cohort, no significant association was found between age and mortality, ICU admission, or prolonged hospitalization. These findings were observed in a generally healthy military population receiving organized trauma care and suggest that, within this context, chronological age alone may not be an appropriate criterion for determining reserve service eligibility.

Operational forces increasingly face concurrent sleep restrictions and thermal strain, yet mission planning lacks field-relevant guidance on their combined cognitive effects and management. This critical narrative review synthesizes laboratory, field, and military-relevant evidence on how sleep loss and heat stress affect sustained attention, drowsiness, reaction time, executive control, and feedback-guided decision making. Sleep deprivation produces dose-responsive vigilance instability across total sleep deprivation and chronic partial restriction, with lapses and response-time variability providing sensitive monitoring endpoints. Heat stress produces task-dependent cognitive costs. Simple reaction time may remain relatively preserved during modest strain, whereas executive control, working memory, inhibition, and cognitive flexibility appear more vulnerable as physiological reserve narrows, particularly during dehydration, exertion, and protective equipment use.

Military multistressor studies show broad cognitive deterioration when sleep restriction co-occurs with heat, dehydration, undernutrition, and sustained workload. However, bundled designs cannot determine whether sleep and heat act additively, synergistically, or through threshold-dependent interactions. Key gaps include factorial sleep × heat trials, standardized cognitive batteries, mechanistic telemetry, and prospective modeling of moderators such as trait-like sleep-loss vulnerability, baseline sleep debt, chronotype, heat acclimation, hydration practices, protective-equipment burden, and sex. Commanders and medical planners should treat concurrent sleep restriction and thermal strain as a compounded operational risk state and apply layered controls, including protected sleep, scheduling, cooling, hydration, work-rest cycles, objective vigilance screening, task rotation, and supervisory cross-checks for high-consequence decisions.

Background: The management of symptomatic abdominal aortic aneurysms (AAA) remains a surgical challenge.

Objectives: To compare the outcomes of endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in patients with symptomatic AAA.

Methods: Patients treated for symptomatic AAA between April 2020 and April 2025 were retrospectively analyzed, comparing perioperative mortality and major adverse events between EVAR and OSR.

Results: A total of 494 AAA patients were identified, 49 (9.9%) were symptomatic (40 [81.6%] EVAR group, 9 [18.4%] OSR group). Patients undergoing OSR had a higher rate of juxtarenal involvement (OSR 6/9 [66.7%] vs. EVAR 3/40 [7.5%]; P < 0.001). Any signs of rupture were more prevalent in the EVAR group (27/40 [67.5%] vs. OSR 2/9 [22.2%]; P = 0.013). Technical success was achieved in 83.7% (n=41/49). In-hospital mortality was 22.4% (n=11/49), with no difference between groups (EVAR 9/40 [22.5%] vs. OSR 2/9 [22.2%]; P = 0.986). At logistic regression analysis, open repair was associated with a significantly higher risk of major complications (odds ratio [OR] 16.9, 95% confidence interval [95%CI] 1.79–158.3, P = 0.013), and a shock index > 0.9 remained an independent predictor of intra-hospital mortality (OR 372.5, 95%CI 1.58-87889.4, P = 0.034). During a mean follow-up of 28.8 ± 18.6 months, late mortality was 18.4% (n=7/38). Estimated survival analysis over 60 months did not demonstrate a significant difference between groups (log-rank test, P = 0.317).

Conclusions: Both EVAR and OSR yield satisfactory technical outcomes. Hemodynamic instability at presentation remains a critical predictor of mortality.

Chronic Q fever, caused by Coxiella burnetii, is a persistent infection that primarily affects individuals with underlying valvular or vascular abnormalities. The standard treatment regimen consists of prolonged dual therapy with doxycycline and hydroxychloroquine, typically administered for a minimum of 18 months [1]. This combination targets both the intracellular pathogen and the acidic vacuolar environment in which it resides. A key indicator of therapeutic response is the progressive decline in phase I IgG antibody titers, which is generally observed within the first few months of treatment [2].

However, in rare instances, antibody titers may remain persistently elevated despite prolonged therapy, raising concerns about treatment failure, resistance, or host-related factors. The following case highlights an unusual drug interaction that interfered with treatment efficacy, ultimately preventing complete clinical resolution.

Background: Gait disturbances are common in patients undergoing hemodialysis and are associated with increased fall risk, mobility decline, and adverse health outcomes. Prior research suggests that hemodialysis may impact gait parameters such as speed, stride length, and variability; however, findings are inconsistent.

Objectives: To evaluate acute changes in gait metrics before and after hemodialysis using an artificial intelligence (AI) based video gait analysis system.

Methods: We initially enrolled 38 hemodialysis patients, two were excluded due to clothing interference with video analysis (27.8% female, 72.2% male). AI-driven gait analysis was performed immediately before and after dialysis. The system extracted spatiotemporal gait and joint range of motion. Statistical analyses included the Shapiro-Wilk test for normality, Wilcoxon signed-rank tests for non-normally distributed data, and paired t-tests for normally distributed data (P < 0.05).

Results: Gait speed (0.59 m/sec pre-dialysis) remained unchanged post-dialysis (P = 0.876), as did cycle length and time. However, step length significantly decreased post-dialysis (P = 0.001), suggesting a more conservative gait pattern. Knee flexion and extension increased slightly but did not reach statistical significance.

Conclusions: Dialysis does not acutely affect overall gait speed but significantly reduces stride length. Post-dialysis fatigue or hemodynamic shifts may alter walking patterns, highlighting the need for fall prevention strategies and physical rehabilitation interventions in dialysis care. AI-based gait analysis may provide a practical tool for monitoring mobility changes in hemodialysis patients.

Background: Continuous-flow left ventricular assist devices (CF-LVADs) have yielded improved outcomes compared with pulsatile-flow devices; however, significant rates of gastrointestinal bleeding (GIB) have been observed. The HeartMate 3 left ventricular assist device (HM3-LVAD) (Abbott, Inc., Chicago, IL, USA) includes new features, such as an artificial pulse, which may decrease GIB prevalence compared to the HeartMate 2 left ventricular assist device (HM2-LVAD).

Objectives: To evaluate the incidence, predictors, and clinical outcomes of GIB in patients supported by the HM3-LVAD.

Methods: From 2016 until 2024, 180 patients with chronic heart failure underwent HM3-LVAD implantation. Records were reviewed to determine the post-implant GIB prevalence, location of the bleeding, and associated morbidity and mortality. Univariate and multivariate analyses were conducted to identify independent predictors of GIB.

Results: GIB occurred in 25 patients (14%) with a duration of support ranging from 1 to 1821 days. Sources of GIB included the small bowel and rectum in eight patients each, large bowel in one, and stomach in two. No clear source was identified in 11 patients. Recurrent GIB occurred in 16 patients (64%). There were no deaths attributable to GIB. None of the historical or demographic parameters were found to be independent predictors of GIB.

Conclusions: GIB is a frequent source of morbidity for patients on HM3-LVAD support but does not significantly impact survival. As the implantation of CF-LVADs with non-pulsatile flow gains popularity for both bridge-to-transplant and destination therapy, a better understanding of the pathophysiology of GIB in these patients will reduce the prevalence of this complication.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease leading to end-stage lung disease (ESLD). Single lung transplantation (SLT) is the primary treatment option for IPF; however, the native lung continues to influence post-transplant outcomes.

Objective: To determine whether the native lung continues to deteriorate under post-transplantation immunosuppression treatment by assessing chest computed tomography (CT) and perfusion scans.

Methods: We conducted a single-center retrospective analysis of patients who underwent SLT for IPF between 2016 and 2023. Serial chest CT scans assessed native lung changes. CT signs of fibrosis were scored for severity according to published criteria for defining pulmonary fibrosis disease progression. Lung volumes and perfusion were calculated.

Results: Among 57 patients (mean age 57 years; 33% female), 42% died during follow-up (median survival 95 months). The most common immunosuppressive regimen (54% of patients) included prednisone, calcineurin inhibitor, and mycophenolate mofetil. CT analysis demonstrated that in 41/57 (72%) patients, fibrosis signs continued to deteriorate. There was also a significant correlation decline in native lung volume and perfusion scans over time (P = 0.0003, P < 0.0001, respectively) (r = 0.82, P = 0.03).

Conclusions: Fibrotic progression in the native lung persists after SLT as demonstrated by both chest CT and nuclear perfusion scan, thus highlighting the importance of ongoing monitoring for accuracy and complications assessment, integrating it into routine surveillance, and ensuring it is consistently considered in post-transplant assessments.

Background: Neurofilament light chain (NfL) is an established biomarker for detecting axonal injury in various neurological disorders. The Quanterix Single Molecule Array (Simoa) is the current standard; however, automated immunoassays, such as the Siemens Atellica and Centaur, may serve as alternatives.

Objectives: To compare NfL measurements obtained with the Centaur system to those from the Simoa-SR-X. To assess their agreement and applicability in clinical practice, research, and animal studies.

Methods: NfL levels were measured in 27 human serum, 8 plasma, and 16 cerebrospinal fluid (CSF) samples, and 9 murine serum samples, by Centaur and Simoa systems. NfL levels in concomitantly drawn serum and plasma were compared in 8 humans. The agreement between platforms was evaluated.

Results: NfL levels measured by Centaur and Simoa systems demonstrated a strong correlation in serum (Spearman r=0.97, P < 0.0001) and plasma (Pearson R²=0.95, P < 0.0001). Centaur measurements were higher (P = 0.01) than Simoa. Most importantly, system-specific Z-scores corrected these differences. Serum and plasma levels measured by the Centaur system correlated strongly (R²=0.98, P < 0.0001) and showed similar results. CSF levels measured by the Centaur system were lower (52% bias) than those measured by Simoa, with poor correlation at concentrations within the normal range (R²=0.32, P = 0.11). Mouse serum results showed a strong correlation between systems (R²=0.86, P < 0.001) with similar values.

Conclusions: The Centaur system offers an alternative to Simoa for measuring NfL in human serum, plasma, and murine serum. System-specific age-adjusted Z-scores are essential for interpretation. CSF evaluation requires further assessment.

Pulmonary medicine, a major subspecialty of internal medicine, has advanced dramatically over the past decade and continues to grow at an impressive pace. The subspeciality is a uniquely multifaceted field, requiring thoughtful integration of the patient’s history, physical findings, laboratory data, and imaging to reach an accurate diagnosis and suggest proper treatment. This clinical depth is complemented by a rapidly expanding therapeutic arsenal for complex lung diseases. At the same time, technological progress has transformed our practice. Innovations in imaging and in both diagnostic and therapeutic bronchoscopy–central components of interventional pulmonology–have evolved so rapidly that tools used only a decade or two ago now seem outdated [1]. All these advancements offer meaningful opportunities to enhance the health outcomes of our patients. What a fascinating specialty and what an exciting time to be a pulmonologist.