Israel Medical Association Journal

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends a ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) of less than 70% (FEV1/FVC < 0.7) after bronchodilators as the criteria for obstruction. However, because the FEV1/FVC ratio decreases with age, using a fixed ratio may lead to overdiagnosis of obstruction in the geriatric population. Using the lower limit of normal (LLN) as threshold for obstruction has been suggested.

Objectives: To determine the rate of overdiagnosis using the GOLD criteria compared to LLN in patients aged 60 and older. To find a better threshold with a minimal rate of over- and underdiagnosis.

Methods: The study population included adults aged 60 years and older who performed pulmonary function test (PFT) at Shaare Zedek Medical Center between 2014 and 2019 with results of FEV1/FVC < 0.7.

Results: We included 430 patients aged 60 years and older, 273 males (63.5%) and 157 females (36.5%). Mean age was 72 ± 8 years. Overdiagnosis was found in 35.6% of patients (95% confidence interval 31.1–40.3%) by using the GOLD criteria compared to the LLN. Overdiagnosis was reduced to 6.4% with the 0.65 threshold. The ideal point of the FEV1/FVC ratio where overdiagnosis and underdiagnosis were at their lowest rates was 0.638.

Conclusions: Use of the GOLD criteria for airflow obstruction may be associated with an overdiagnosis of more than 35% in patients older than 60 years. Lowering the FEV1/FVC ratio to < 0.65 might be more accurate in this population.

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: Interpretation of blood gases is essential for the correct practice of medicine. Normal ranges for arterial blood gases (ABG) have not been extensively studied in the older population. Also, venous blood gases and venous-arterial pCO₂ gradient have not been studied in this population, even though they signify the majority of hospitalized patients.

Objectives: To determine the normal range for ABG and the bias limits of agreement for arterial-venous difference in the elderly population.

Methods: We recruited 130 elderly patients (> 70 years) and obtained blood gas measurements from venous and arterial blood. Patients were divided into four categories: healthy patients, patients with stable chronic pulmonary disease, hospitalized patients with acute respiratory illness, and hospitalized patients without respiratory disease. Samples were analyzed in a point of care analyzer.

Results: Mean PaCO₂ was 36.9 ± 4.2 mmHg for the healthy control group, 37.0 ± 4.8 mmHg in the stable chronic respiratory group, 37.0 ± 5.0 mmHg in the non-respiratory hospitalization group, and 42.3 ± 11.4 mmHg for the respiratory hospitalization group, Kruskall-Wallis, P <0.0025. Mean bias between venous and arterial CO₂ was +10.0 mmHg with 95% limits of agreement between 2.7 mmHg and -22.8 mmHg.

Conclusions: In elderly patients, the range of PaCO₂ measurements was similar to the accepted normal range in clinical practice. Venous-arterial PCO₂ gradient had high bias and wide limits of agreement, similar to previously published studies.

Background: Lung transplantation (LT) is a viable option for end-stage chronic obstructive pulmonary disease (COPD) patients when conventional treatments fail. However, sex disparities in mortality outcomes among COPD patients awaiting LT remain understudied. LT waiting lists are generally shorter in Western countries compared to Israel.

Objectives: To evaluate sex-specific differences in mortality and co-morbidities among COPD patients awaiting lung transplantation, to identify key risk factors influencing survival.

Methods: We assessed associations between sex, co-morbidities, exacerbations, and mortality using Cox regression models, adjusting for confounders. Survival curves for lung transplant candidates were stratified by sex using Fine and Gray models.

Results: We identified 385 COPD patients listed for LT at Rabin Medical Center. Females exhibited higher rates of asthma (P = 0.008), anxiety (P = 0.005), and depression (P = 0.002); males were more frequently diagnosed with ischemic heart disease (26.5% vs. 10.83%, P = 0.001) and had a higher lung transplant rate (24.9% vs. 15%, P = 0.029). Multivariate analysis revealed that female sex (hazard ratio [HR] 1.55, 95% confidence interval [95%CI] 1.06–2.29, P = 0.025), older age (HR 1.02, 95%CI 1.002–1.054, P = 0.035), ischemic heart disease (HR 1.69, 95%CI 1.12–2.48, P = 0.011), and depression (HR 1.81, 95%CI 1.15–2.83, P < 0.01) were significantly associated with increased mortality. Females showed higher 1-year mortality rates than males (40.3% vs. 29.8%, P < 0.001).

Conclusions: Female sex is a significant risk factor for increased mortality among COPD patients awaiting LT, likely due to a higher burden of co-morbidities.

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: Lung cancer is a major cause of death worldwide. Accurate diagnosis and staging are essential for effective treatment. Mediastinal lymph node involvement determines the disease stage and influences treatment decisions, especially with new biological and immunotherapy options. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the main minimally invasive procedure for evaluating mediastinal and hilar adenopathy. It offers high sensitivity, specificity, and fewer complications than mediastinoscopy or video-assisted thoracic surgery. It also retrieves crucial molecular markers for guiding therapeutic decisions in non-small cell lung cancer.

Objectives: To evaluate the diagnostic yield of EBUS-TBNA in patients with mediastinal lymphadenopathy.

Methods: This retrospective study included patients who underwent bronchoscopy with EBUS and had lymph node malignancy between 2018 and 2023. Crossmatching was conducted by pathology and genomic study results. No informed consent was required as the study was based on the hospital database.

Results Next generation sequencing was performed on 57 specimens (83%) collected via EBUS from patients with primary non-small cell lung cancer. However, 12 of the specimens (17%) were insufficient for pathological analysis. Among these, 7 (58%) were from adenocarcinomas and 5 (42%) were from squamous cell carcinoma patients.

Conclusions: The utilization of EBUS-TBNA is an effective tool for obtaining genetically profiled diagnoses by minimally invasive means. As more genetic mutations are discovered, we expect that multigene mutation analysis will gain importance in tailoring individualized treatment plans.

Background: Sarcoidosis is a multi-organ granulomatous inflammatory disease of unknown etiology, exhibiting significant regional and ethnic variability in disease extent and clinical features.

Objectives: To investigate the clinical characteristics of sarcoidosis among Jewish and Arab populations in Israel and to compare these findings with global data.

Methods: We conducted a retrospective review on sarcoidosis patients at Rambam Health Care Campus during 2015–2023. Patients were categorized by ethnicity. Their demographic and clinical data were collected and analysed using appropriate statistical methods.

Results: The study included 284 patients (149 Jewish, 135 Arab). Jewish patients had a higher mean age at diagnosis. Diagnosis was biopsy-proven in 82% of cases, with endobronchial ultrasound being the most common diagnostic procedure. Lung involvement was present in 88% of patients, with no significant difference between Jewish and Arab populations. No significant differences were found in pulmonary function tests, blood tests, or Scadding stage distribution between the ethnic groups. When comparing the Jewish and Arab populations to the global data, lung involvement was significantly less frequent in the Jewish population. The Israeli population, both Jewish and Arab populations, had a significantly higher rate of joint manifestations whereas eye and skin manifestations appeared to be significantly lower in the Israeli population compared to global data.

Conclusion: This study highlights the diverse clinical presentations of sarcoidosis among Israeli populations compared to world data, with notable differences between Jewish and Arab patients, and within subgroups of these populations.

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.

Background: The incidence of non-tuberculous mycobacterium (NTM) infections has been rising in patients with chronic lung diseases. These infections cause significant morbidity, mortality, and elevated healthcare costs due to challenges in recognition, delayed diagnosis, and treatment. While NTM infections in natural stone silicosis are documented, the incidence in artificial stone silicosis remains unexplored despite increasing exposure to silica dust.

Objectives: To describe the clinical, radiological, and pathological features of NTM infections in patients with artificial stone silicosis and emphasize the importance of early diagnosis.

Methods: We reviewed the database of a tertiary medical center in Israel from 2010 to 2024 and identified patients with occupational artificial stone silicosis diagnosed with NTM infection.

Results: We found eight patients with occupational artificial stone silicosis, all male, aged 42–74 years. Key symptoms included dyspnea, cough, weight loss, and fever. Computed tomography revealed mediastinal lymphadenopathy, progressive massive fibrosis, calcifications, pulmonary cavitations, pleural thickening, traction bronchiectasis, pulmonary nodules, and honeycombing. Biopsies showed silicotic nodules, birefringent crystals, pulmonary alveolar silico-proteinosis, fibrosis, and honeycombing. Four patients received NTM-targeted antibiotics, and six underwent lung transplantation. Four patients died.

Conclusions: Artificial stone silicosis may be associated with NTM infections. Early diagnosis requires a high degree of clinical suspicion. New or worsening respiratory or systemic symptoms in patients with silicosis should prompt further microbiological evaluation, including sputum culture or bronchoalveolar lavage. Further studies are needed to assess the incidence of NTM infections in this population.

Cerebral arterial air embolism (CAAE) is a rare, but often fatal, complication of interventional bronchoscopy. Despite its rarity, a high index of suspicion can facilitate early diagnosis and prompt treatment. Standard of care treatment for CAAE is hyperbaric oxygen therapy, despite limited definitive data supporting its efficacy, given the conceptual potential for reversibility of neurological impairment. We describe five cases from our institution, and review the clinical presentation, pathophysiology, diagnosis, and management of suspected CAAE. Based on published case reports involving transbronchial lung biopsies (TBLB), standard of care treatment for CAAE secondary to TBLB is hyperbaric oxygen therapy, although its efficacy in this context has not been unambiguously validated in clinical practice.

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.