Israel Medical Association Journal

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: 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.

Leeches belong to the class Hirudinea of the phylum Annelida. There are approximately 650 known species of leeches, some terrestrial, some marine, and most freshwater. Although some are predators, most leeches are hematophagous, and all are hermaphrodites [1].

The leeches Limnatis nilotica, Praeodella guineensis, Myxobdella africana, Dinobdella ferox, and Hirudo troctina occasionally invade human orifices such as the eyes, nasopharyngeal region, urethra, vagina, and rectum. They cause mucosal, orificial, vesical, or internal hirudiniasis depending on the location of the leech [1]. Infection usually occurs by drinking contaminated water or bathing in stagnant streams, pools, or springs. While most blood-feeding leeches feed as ectoparasites for short periods of time, those that feed on mucous membranes have been known to remain in an orifice for days or weeks. Hematuria, hemoptysis, hematemesis, epistaxis and rectal bleeding, dysphonia, cough, tickling, and dyspnea may occur [1].

We report the case of a male patient who entered freshwater pools in Israel and was infected with L. nilotica.

Background: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications.

Objectives: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM.

Methods: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared.

Results: The cohort included 89 women: 49 with HbA1c 6–8%, 29 with HbA1c 8–10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes.

Conclusions: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis and usually constitutes a diagnostic challenge. There are many causes for recurrent and chronic pancreatitis, with the main etiology being alcohol and choledocholithiasis [1]. However, the association between pancreatic divisum (PD), a common congenital anomaly of the pancreas that is rarely symptomatic, and complications of pancreatitis is still not firmly established [2]. Furthermore, the optimal management of PPF is still uncertain due to its rarity [3]. We describe a rare case of a 45-year-old woman with recurrent pancreatitis that presented with a PPF on the background of PD, successfully managed with conservative treatment. The purpose of this report is to highlight the rare association between PPF and PD together with the excellent response to conservative therapy.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

Background: Despite its wide use, evidence is inconclusive regarding the effect of percutaneous endoscopic gastrostomy (PEG) in patients with chronic diseases and dementia among hospitalized patients with malnutrition.

Objectives: To examine the effect of PEG insertion on prognosis after the procedure.

Methods: This retrospective analysis of medical records included all adult patients who underwent PEG insertion between 1 January 2009 and 31 December 2013 during their hospitalization. For each PEG patient, two controls similar in age, sex, referring department, and underlying condition were randomly selected from the entire dataset of patients admitted. The effect of PEG on mortality and repeated admissions was examined.

Results: The study comprised 154 patients, 49 referred for PEG insertion and 105 controls (mean age 74.8 ± 19.8 years; 72.7% females; 78.6% admitted to internal medicine units). Compared to controls, the PEG group had a higher 2-year mortality rate (59.2% vs. 17.1%, P < 0.001) but the 2-year readmission rate did not differ significantly (44.9% vs. 56.2% respectively, P = 0.191). Regression analysis showed PEG was  associated with increased risk of the composite endpoint of death or readmission (hazard ratio 1.514, 95% confidence interval 1.016–2.255, P = 0.041). No specific characteristic of admission was associated with increased likelihood of death or readmission. Among readmitted patients, reasons for admission and baseline laboratory data, including albumin and cholesterol, did not differ between the PEG patients and controls.

Conclusions: In-hospital PEG insertion was associated with increased mortality at 2 years but had no effect on readmissions.

Background: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients.

Objectives: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications.

Methods: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel.

Results: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15–53, range 3–60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12–80). The median time from HSCT to LTx was 96 months (IQR 63–120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications.

Conclusions: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Background: The coronavirus disease-2019 (COVID-19) outbreak had an effect on healthcare.

Objectives: To evaluate the presentation and management of patients with acute appendicitis.

Methods: A retrospective study was conducted of all patients presenting with acute appendicitis to the emergency department of a large tertiary center during March and April 2020. Clinical features, diagnostic workup, and management were compared.

Results: Seventy-four patients presented with acute appendicitis during the pandemic compared to 60 patients during the same time the year before. There were no significant differences in patient demographics: age (P = 0.65), gender (P = 0.73), smoking status (P = 0.48). During COVID-19 patients were more likely to complain of right lower quadrant pain (100% vs. 78.3%, P < 0.01). Rates of surgical treatment was similar (83.8% vs. 81.7%, P = 1); mean operative time was longer during COVID-19 (63 ± 23 vs. 52 ± 26 minutes, P = 0.03). There were no significant differences in intra-operative findings including the presence of appendiceal perforation (16.3% vs. 14.5%, P = 0.8), abscess (6.1% vs. 9.7%, P = 0.73), or involvement of cecum or terminal ileum (14.28% vs. 19.63%, P = 1). Postoperative treatment with antibiotics was more prevalent during COVID-19 (37.1% vs. 18%, P = 0.04). Length of stay (1.82 ± 2.04 vs. 2.74 ± 4.68, P = 0.2) and readmission rates (6% vs. 11.3%, P =0.51) were similar.

Conclusion: The COVID-19 pandemic did not significantly affect the presentation, clinical course, management, and outcomes of patients presenting with acute appendicitis.

Background: The novel coronavirus disease (COVID-19) pandemic changed medical environments worldwide.

Objectives: To evaluate the impact of the COVID-19 pandemic on trauma-related visits to the emergency department (ED).

Methods: A single tertiary center retrospective study was conducted that compared ED attendance of patients with injury-related morbidity between March 2020 (COVID-19 outbreak) and pre-COVID-19 periods: February 2020 and the same 2 months in 2018 and 2019.

Results: Overall, 6513 patients were included in the study. During the COVID-19 outbreak, the daily number of patients visiting the ED for acute trauma declined by 40% compared to the average in previous months (P < 0.01). A strong negative correlation was found between the number of trauma-related ED visits and the log number of confirmed cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Israel (Pearson's r = -0.63, P < 0.01). In the COVID-19 period there was a significant change in the proportion of elderly patients (7% increase, P = 0.002), admissions ratio (12% increase, P < 0.001), and patients brought by emergency medical services (10% increase, P < 0.001). The number of motor vehicle accident related injury declined by 45% (P < 0.01).

Conclusions: A significant reduction in the number of trauma patients presenting to the ED occurred during the COVID-19 pandemic, yet trauma-related admissions were on the rise

Background: Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50%

Objectives: To evaluate which IPF patients have better prognosis following LTx.

Methods: A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.

Results: Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.

Conclusions: IPF patients with higher mean PHT, older age (> 65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.