Israel Medical Association Journal

Background: Asthma poses unique challenges in aviation medicine. While strict criteria typically dictate waiver approvals in military aviators with asthma, the Israeli Air Force (IAF) applies a more individualized approach. Still, evidence to guide correct management is scarce.

Objectives: To assess the characteristics and long-term outcomes of military aircrew diagnosed with asthma.

Methods: This retrospective study included active and reserve aircrew who were diagnosed with asthma during annual assessments at the Israeli Aeromedical Unit between 1998 and 2024. Baseline characteristics, treatment regimes, pulmonary function tests (PFTs), and asthma exacerbations were analyzed.

Results: Thirty-two aircrew personnel (median age 30 years at diagnosis) were included in the study, with 44% serving at high-performance platforms. Six participants (19%) were classified as Global Initiative for Asthma step 4 or 5. Over an average follow-up period of 18.5 years, seven exacerbations were documented (4.0 per 100 patient-years), with no safety incidents reported. Participants' pulmonary function remained stable. Forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FVC) declined around asthma diagnosis (median of 82% predicted and 0.73, respectively) but recovered remarkably while on treatment (median 91% predicted and 0.78, respectively). Aircrew who experienced exacerbations had no statistically significant differences in demographics, disease severity or baseline PFTs.

Conclusions: With individualized management and regular monitoring, a new diagnosis of asthma in military aircrew was not associated with a significant impact on service. Our study supports a flexible, individualized approach to aeromedical management of aircrew with asthma.

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.

Background: Prophylactic intravenous antibiotics are not routinely administered prior to direct peroral cholangiopancreatoscopy. The frequency of post-procedure bacteremia has not been well studied.

Objectives: To evaluate the risk of bacteremia following endoscopic retrograde cholangiopancreatography (ERCP) with cholangiopancreatoscopy. To assess the prevalence of other infectious complications and the effect of real-life practices regarding prophylactic antibiotic administration.

Methods: We conducted a retrospective analysis on consecutive patients (2016–2022) who underwent cholangiopancreatoscopy using the single-operator SpyGlass System (Boston Scientific Corporation, USA). Prophylactic antibiotic treatment was administered based on clinical discretion. Demographic and clinical data, including procedure indication, procedure reports, blood culture results, pre- and post-procedure antibiotic treatment, hospital length, mortality, and infectious and non-infectious complications, were collected.

Results: Our single-center cohort included 75 patients who underwent ERCP with direct cholangiopancreatoscopy. We involved 63 patients in the analysis. In 17/63 patients (27%), post-procedural blood cultures were drawn based on clinical suspicion of infection. Positive cultures were found in 4/17 (23.5%) of all cultures and 4/63 (6.3%) of the entire cohort; 2/63 (3.2%) had clinically significant bacteremia. Antibiotic prophylaxis was administered to 35 patients (55.6%), with no evidence of significant reduction in bacteremia, cholangitis, hospitalization length, or mortality rates when compared to patients who did not receive prophylactic antibiotics (P > 0.05). Post-procedural cholangitis was observed in 5/63 patients (7.9%). There were no cases of acute cholecystitis or liver abscess.

Conclusions: The prevalence of bacteremia and cholangitis following ERCP with direct cholangiopancreatoscopy was 6.3% and 7.9%, respectively. Prophylactic antibiotics did not reduce post-procedural infectious adverse events.

Presacral tumors are rare and heterogeneous neoplasms that develop in the space between the rectum and sacrum. Their low prevalence and diverse embryologic origins often complicate diagnosis and management. We present the case of a 43-year-old woman who was initially misdiagnosed with a pilonidal abscess, later identified as a benign presacral tumor.

PATIENT DESCRIPTION

A 43-year-old woman presented with a gradually enlarging mass in the pilonidal region over the course of several months. She was referred to our colorectal clinic with a presumptive diagnosis of a pilonidal abscess made by her primary care physician. The patient was otherwise healthy, with no complaints of pain, fever, chills, or unintentional weight loss.

On physical examination, a non-tender mass was palpated over the coccygeal region. Notably, there were no midline pits or visible hair [Figure 1A]. Given the atypical presentation, a magnetic resonance imaging (MRI) was performed, which revealed a well-defined, large presacral bilobular thin-walled cystic mass, posterior to the rectum, without any post contrast ring-enhancement or intramural solid nodule [Figure 1B].

Due to the low anatomical position of the mass relative to the sacrum, a Kraske approach was selected for surgical excision. Under general anesthesia, the patient was placed in the prone jackknife position. A vertical midline incision was made 7 cm cephalad to the anal verge, over the coccyx. This position exposed a well-encapsulated, large presacral tumor [Figure 1C], which was excised en-bloc along with the tip of the coccyx [Figure 1D, Figure 1E].

The specimen was sent for pathological evaluation, which revealed a retrorectal epidermal cyst. The patient's postoperative course was uneventful, and she was discharged on postoperative day one.

Informed consent was obtained from the patient.

Background: Primary achalasia is a rare disorder but a significant cause of esophageal motor dysfunction. The pathophysiology of achalasia is still unknown, although an autoimmune etiology is suspected.

Objectives: To examine the presence of autoantibodies against autonomic nervous system receptors among primary achalasia patients.

Methods: In this observational cross-sectional study, we measure the levels of serum autoantibodies targeting G protein-coupled receptors of the autonomic nervous system, including adrenergic, muscarinic, endothelin, and angiotensin receptors. The study included 40 primary achalasia patients and 40 healthy controls without known history of achalasia, autoimmune diseases, or symptoms of an esophageal motility disorder.

Results: A statistically significant low level of autoantibodies against the M2 muscarinic receptor was observed in the serum of primary achalasia patients compared with the control group (P < 0.009). When exploring the two common achalasia types, a statistically significant low level of autoantibodies against type M1, M2, and M5 muscarinic receptors was observed among type 2 achalasia patients compared to patients with type 1 achalasia.

Conclusions: The finding of reduced levels of autoantibodies targeting the M2 muscarinic receptor in the serum of primary achalasia patients provides a valuable insight into the underlying pathogenesis of the disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular events, especially following acute exacerbation (AECOPD). However, there is insufficient data to identify high-risk subjects.

Objectives: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR), a marker of inflammation, and the risk of cardiovascular events following exacerbation.

Methods: This retrospective cohort included patients with COPD who were hospitalized with AECOPD between January 2016 and December 2022. We took the reference NLR before index admission and evaluated the incidence of major adverse cardiovascular events (MACE) or cardiovascular death over the following year. Multivariate analysis and competing risk regression were used to assess hazard ratio (HR) and NLR threshold for increased cardiovascular risk.

Results: In total, 15,224 patients with AECOPD completed one 1-year follow-up session. The majority were male (54%) with a mean age of 69 ± 3 years. The risk for MACE of patients in the highest NLR quartile was higher over the first year following AECOPD; however, the magnitude of effect decreased over time. After adjustment to other confounders that may increase NLR, a value > 3.5 was found with the strongest predictive power

Conclusion: Community NLR can be used to identify patients at increased risk of cardiovascular events following AECOPD, together with other risk factors. Every effort should be made to reduce exacerbation risk, and target intervention to those patients at highest risk.

Background: Lung transplantation is an advanced medical therapy reserved for patients with end-stage lung disease. Relative to other solid organ transplants, lung transplantation in children is infrequently performed. The most common etiologies for pediatric lung transplantation worldwide are cystic fibrosis, pulmonary hypertension, and children’s interstitial lung disease.

Objectives: To describe our experience in pediatric lung transplants at Israel's largest transplant center.

Methods: We performed a retrospective review of all pediatric lung transplantations conducted in our center since 1997. We recorded demographic characteristics, indication for transplantation, clinical and laboratory parameters, post-transplant complications, and survival rates.

Results: Of 965 lung transplants, 29 (3.0%) were pediatric patients who underwent lung or heart-lung transplants for end-stage lung disease. Age at transplantation ranged from 2 to 18 years, with a median of 14.0 years (IQR 11–15). Primary etiologies for transplantation were cystic fibrosis (44%), pulmonary hypertension (17%), and children’s interstitial lung disease (10%). Survival at 1, 5, 10, and 15 years post-transplant were 90%, 65%, 55%, and 20%, respectively, which is consistent with data reported by pediatric lung transplantation registries. The primary cause of mortality post-transplant was chronic lung allograft dysfunction. Four patients (13.8%) underwent re-transplant. There was no association between survival and transplant indication, nor between survival and type of procedure (lung vs. heart-lung transplant).

Conclusions: The short- and long-term outcomes from our program are consistent with published registry data. These outcomes may reflect the benefits of a centralized pediatric lung transplant program, supported by a multidisciplinary team trained in high-capacity international centers.

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to a wide spectrum of clinical severity. The gold standard diagnosis of infection is reverse transcription polymerase chain reaction of nasopharyngeal swabs, which also provides a semiquantitative assessment of viral loads by measuring cycle threshold (CT) values.

Objective: To assess whether CT values at admission can predict mortality and oxygen needs among individuals hospitalized for coronavirus disease 2019 (COVID-19).

Methods: The retrospective study included adults hospitalized for COVID-19 between 1 August 2020 and 30 April 2021 at Barzilai University Medical Center. Patients were categorized according to initial CT values as high (≥ 25) or low (< 25) values. The primary outcome was the association between CT values during admission and overall mortality.

Results: The study group included 636 patients, with a mean age of 67.2 years, 54.4% males. Overall mortality of patients with CT values < 25 was significantly higher (odds ratio for mortality 1.78 vs. patients with CT ≥ 25, P = 0.002). Significantly more patients in the low CT group required oxygen support than in the high CT group, 50% vs. 31.9% (P < 0.001). An inverse association between CT values and mortality rates remained significant in multivariate regression analysis, such that a 1-unit decrease in CT was associated with a 6% increased mortality.

Conclusions: Lower CT values at admission were associated with increased mortality among patients hospitalized for COVID-19. CT values can be used to predict outcomes among such patients.

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: The prevalence of Group A streptococcus (GAS) carriage among adults is studied less than in children. The variability of reported carriage rates is considerably large and differs among diverse geographic areas and populations.

Objectives: To evaluate the prevalence of GAS carriage among adults in Israel.

Methods: In this prospective study, conducted in a large healthcare maintenance organization in Israel, we obtained pharyngeal cultures from adults attending the clinic without upper respiratory tract complaints or fever. Patient data included sex, age, number of children, and religious sectors.

Results: From May to December 2022, eight family physicians collected a total of 172 throat swabs (86% response rate). The median age was 37 years (range 18–65); 72.7% were females, 22.7% were ultra-Orthodox Jewish, and 69.2% had children. The prevalence of GAS carriage was 6.98%, 95% confidence interval (95%CI) 3.7%–11.9%. GAS carriers were younger (31.7 vs. 39.3 years, P = 0.046), and the majority were ultra-Orthodox Jews (58.3% vs. 20%, P = 0.006). All GAS carriers were from lower socioeconomic status. When assessing risk factors for GAS carriage using multivariate analysis, only being an ultra-Orthodox Jew was positively related to GAS carriage (adjusted odds ratio 5.6, 95%CI 1.67–18.8).

Conclusion: Being an ultra-Orthodox Jew was the single variable associated with a GAS carriage, which may be related to having many children at home and living in overcrowded areas. Primary care physicians in Israel should recognize this situation when examining patients with sore throats, mainly ultra-Orthodox Jews.

Background: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision.

Objectives: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD.

Methods: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity.

Results: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively.

Conclusions: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Common variable immunodeficiency (CVID) is a heterogeneous primary immune deficiency disorder characterized mainly by defective B lymphocyte differentiation, leading to hypogammaglobinemia and defective antibody production. It is often combined with cellular immune defects. A minority of patients present during childhood and adolescence. Infections are most often sinopulmonary but can affect any system. The noninfectious complications include progressive lung disease, autoimmunity, gastrointestinal inflammatory disease, liver disease, granulomatous disease, lymphoid hyperplasia and infiltrative disease, and the development of lymphoma and other cancers. In addition to recurrent infections and bronchiectasis, patients may develop chronic interstitial lung disease, granulomatous lung disease, lymphoma, and pulmonary hypertension.

Background: Age-related changes in multiparametric magnetic resonance imaging (mpMRI) of the prostate have been reported in the general population but not in screening cohorts.

Objectives: To evaluate age-related changes on prostatic mpMRI in a screening cohort of BRCA1/2 mutation carriers.

Methods: Asymptomatic BRCA1/2 mutation carriers underwent mpMRI as part of a screening program. All included patients were followed for 3 years with no evidence of prostate cancer. mpMRIs were retrospectively evaluated by two abdominal radiologists for peripheral zone (PZ) patterns on T2 (homogenous hyperintensity, wedge-shaped hypointensities, patchy hypointensities, or diffuse hypointensity), and transition zone (TZ) pattern on T2 (homogenous, heterogeneous, nodular). Apparent diffusion coefficient (ADC) values of PZ and TZ were measured. Statistical analysis was performed using a predefined age cutoff of 50 years old.

Results: Overall, 92 patients were included: 38 in the younger age group (40–49 years) and 54 in the older age group (50–69 years). PZ homogenous hyperintensity and wedge-shaped hypointensities were more common in the older patients, whereas diffuse hypointensity was more common in younger patients (P < 0.001 for both readers) with substantial inter-reader agreement between the readers (kappa=0.643). ADC values were lower in young patients in the PZ (P < 0.001) and TZ (P = 0.003).

Conclusions: Age-related differences in mpMRI were validated in BRCA mutation carriers. As some features overlap with prostatic carcinoma, awareness is crucial, specifically to diffuse T2 hypointensities of the PZ and lower ADC values in the PZ and TZ, which are more common in younger patients.

Background: APOE genotype strongly affects plasma lipid levels and risk for cardiovascular disease and cognitive decline. Studies of apo-e allelic and APOE genotype frequencies among several populations have revealed interesting ethnic variations that might affect cardiovascular morbidity and cognition deterioration.

Objectives: To evaluate apo-e allelic frequency among Israeli newborns based on known variances in apo-e allelic frequencies in different countries.

Methods: We examined 498 consecutive neonates born at Tel Aviv Sourasky Medical Center. Umbilical cord blood was sampled for genotyping and lipids. Birth weights were recorded. Demographics and parental risk factors for atherosclerosis were obtained from the mothers.

Results: Most parents were native-born Israelis. Other countries of origin of grandparents were Morocco, Russia, and Iraq. The prevalence of APOE genotypes in Israel is APOE 2/2: 1.4%, APOE 2/3: 8.2%, APOE 3/3: 77.7%, and APOE 4/4: 11.8%. There were no associations of APOE genotype with parental country of origin. However, there was a tendency for APOE 3/4 to be more frequent in newborns of parents of Asian and African origin. Genotype 3/3 was more frequent in newborns whose parents came from Europe and America (78%) compared to those from Asia or Africa (69%).

Conclusions: It is important to determine risk factors such as APOE genotype for evaluation of premature atherosclerosis. Determining genetic and environmental risk factors may facilitate earlier treatment and prevent heart and brain atherosclerosis. APOE genotypes did not appear to affect total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride levels in newborns.

Backgrounds: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression.

Objectives: To evaluate the association between BD and depression, adjusting for established risk factors for depression.

Methods: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex.

Results: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37–2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39–2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18–39 years of age), low and high socioeconomical status, and non-smokers.

Conclusions: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.