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.

Background: Cesarean deliveries (CD) are commonly performed using neuraxial anesthesia. The use of neuraxial morphine has proven beneficial in terms of postoperative pain management; however, its effect on postoperative urine retention remains unclear.

Objectives: To determine whether morphine injection into the neuraxis during CD influences postoperative urinary retention rate.

Methods: We conducted a retrospective case-control observational study of patients undergoing CD. We compared patients using morphine injected into the intrathecal or epidural spaces (November 2020 to October 2021) to a historical cohort of patients undergoing CD without morphine (November 2019 to October 2020). The primary outcome was the rate of postoperative overt urinary retention necessitating bladder catheterization.

Results: The study group comprised 283 patients, and 313 patients in the control group were eligible for analysis. No differences were found with respect to the baseline demographic and indication for CD. The number of postpartum urinary bladder catheterizations due to urine retention was higher in the study group (5% vs. 1%, P-value = 0.003). No cases of 30-day readmission were recorded. Moreover, patients treated with neuraxial morphine required fewer repeat doses of postoperative anesthesia (oral analgesia 7.4 vs. 10.1, intravenous analgesia 0.29 vs. 0.31, oral opioids 0.06 vs. 3.70, intravenous opioids 0.01 vs. 0.45, P-value < 0.001 for all)

Conclusions: While neuraxial morphine used during CD appears to be safe and effective, the risk of postoperative urinary retention seems to be increased due to its use. Cases of overt urinary retention treated by bladder catheterization does not lead to short-term complications.

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.

Background: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD.

Objectives: To examine the correlation between CHD and brain injury using fetal brain MRI.

Methods: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations.

Results: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group.

Conclusions: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

Background: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.

Objectives: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs. 

Methods: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment. 

Results: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.

Conclusions: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported. 

 

Background: Sonographic assessment of the fetal kidneys is an integral part of the prenatal anatomical survey.

Objectives: To evaluate the fetal renal to abdominal (RTA) ratio throughout pregnancy and to investigate whether this ratio can be a potential diagnostic landmark for congenital anomalies of the kidney and urinary tract (CAKUT).

Methods: Measurements of the anterior-posterior diameters of the fetal kidney and fetal abdomen (APAD) were obtained prospectively. The RTA was calculated as the ratio between them in in two groups: normal population vs. CAKUT cases. RTA in CAKUT cases was compared to RTA in a normal population.

Results: The study group was comprised of 210 women. The mean gestational age for the fetuses was 31 ± 5.6 weeks (range 14–40 weeks). Fetal RTA ratio was found to be 0.28 ± 0.03 throughout pregnancy from early second trimester to term, with high reproducibility of measurements. During the study period the RTA was evaluated in nine cases referred for suspected CAKUT. All cases demonstrated a different ratio according to the renal anomaly. High ratio was observed in one case of overgrowth syndrome (Beckwith Wiedenmann syndrome; 0.47), three cases of infantile polycystic kidney (0.45–0.47), and three cases of a solitary kidney (0.31–0.35), while cases of dysplastic kidneys revealed a low ratio (0.14–0.18).

Conclusions: Prenatal RTA ratio is constant throughout gestation. An abnormal ratio should lead to meticulous renal investigation to rule out kidney disease.

Background: It is a challenge to diagnosis Clostridium difficile colitis.

Objectives: To determine, among patients who developed nosocomial diarrhea, whether serum procalcitonin (PCT) can distinguish between C. difficile toxin (CDT)-positive and CDT-negative patients.

Methods: This prospective study included 50 adults (>18 years) who developed diarrhea during hospitalization, 25 with a positive fecal test for CDT (study group) and 25 CDT negative (control group).

Results: Baseline demographic and underlying illnesses were similar in both groups. Duration of diarrhea was 6 ± 4 days and 3 ± 1 in the study and control groups, respectively (P = 0.001). Mean blood count was 20 ± 15 and 9.9 ± 4, respectively (P = 0.04). CRP level was higher in the study than in the control group (10.9 ± 7.4 and 6.6 ± 4.8, P = 0.028). PCT level was higher in the study group (4.4 ± 4.9) than the control group (0.3 ± 0.5, P = 0.102). A PCT level > 2 ng/ml was found in 7/25 patients (28%) and 1/25 (4%), respectively [odds ratio 9.33, 95% confidence interval (0.98 to 220), P = 0.049]. Multivariate analysis showed that only duration of diarrhea and left shift of peripheral leucocytes were significant indicators of CDT (P = 0.014 and P = 0.019, respectively). The mortality rate was 12/25 (48%) vs. 5/25 (20%), respectively (P = 0.04).

Conclusions: We found a non-significant tendency to higher PCT levels in patients with CDT-positive vs. CDT-negative nosocomial diarrhea. However, a PCT level > 2 ng/ml may help distinguish between these patients.

Background: In recent years, the role of intrapartum sonography has expanded in childbirth management, in subjective clinical situations such as arrested deliveries, or prior to instrumental deliveries.

Objectives: To assess the current use of intrapartum ultrasound by obstetricians in Israel.

Methods: An anonymous questionnaire was completed by 79 obstetricians in second- and third level- hospitals in Israel. The results were analyzed according to main subspecialty (sonography, delivery), experience and gender.

Results: A questionnaire was completed by 56 senior obstetricians and 23 interns with an average experience of 14.3 and 2.4 years, respectively. All obstetricians performed ultrasound examinations in the delivery room for basic indications such as fetal presentation during twin delivery and to rule out placenta previa. Sonographers consistently reported advanced indications as compared to senior members of delivery teams and interns in the assessment of prolonged first (52% vs. 14% vs. 14%) and second stage of labor (88% vs. 52% vs. 62%) and in assessment of fetal head station (60% vs. 30% vs. 22%), head progression during descent (48% vs. 23% vs. 11%), diagnosis of head position (88% vs. 68% vs. 60%), spine direction (92% vs. 59% vs. 53%) and asynclytism (41% vs. 20% vs. 29%).

Conclusions: Ultrasound is currently used by all physicians in the delivery room for basic indications. However, obstetric teams report a low use of advanced intrapartum ultrasound and prefer to rely on their clinical experience. Advanced intrapartum sonographic imaging should be an integral part of obstetric qualifications. A steep learning curve, along with high reproducibility, suggests that ultrasound devices will become a common tool in labor and delivery management.

Objectives: To determine the properties of HAM as an antigenic substrate for the detection of autoantibodies in pemphigus vulgaris and bullous pemphigoid.

Methods: Immunomapping and tandem liquid chromatography mass spectrometry were used to delineate the antigenic structure of HAM in 25 pemphigus patients, 41 pemphigoid patients, and 36 controls. Immunoblotting and indirect immunofluorescence were used to study the diagnostic utility of HAM, and the results were compared to those of indirect immunofluorescence on monkey esophagus, immunoblotting using normal human skin, and enzyme-linked immunosorbent assay (ELISA).

Results: Immunomapping demonstrated the presence of all the antigens known to be targeted in autoimmune bullous skin diseases, in both normal human skin and HAM, except for the absence of BP230, and low threshold levels of Dsg1, Dsg3 and Dsc3 in HAM. HAM indirect immunofluorescence demonstrated anti-basement membrane zone antibodies in 48.7% of the pemphigoid patients, and anti-intercellular space antibodies in 72.0% of the pemphigus patients. HAM immunoblotting did not demonstrate anti-BP230 antibodies, but detected anti-BP180 antibodies in 53.6% of the pemphigoid patients. It did not demonstrate anti-Dsg1 and/or anti-Dsg3 antibodies in any of the pemphigus patients. These results were inferior to those of ELISA and monkey esophagus indirect immunofluorescence.

Conclusions: Compared to other studied methods, HAM does not offer advantages in detecting autoantibodies in bullous pemphigoid and pemphigus vulgaris. 

Background: Coronary slow flow phenomenon (CSFP) is a functional and structural disease that is diagnosed by coronary angiogram.    



Objectives: To evaluate the possible association between CSFP and small artery elasticity in an effort to understand the pathogenesis of CSFP.

Methods: The study population comprised 12 patients with normal coronary arteries and CSFP and 12 with normal coronary arteries without CSFP. We measured conjugated diene formation at 234 nm during low density lipoprotein (LDL) oxidation, as well as platelet aggregation. We estimated, non-invasively, arterial elasticity parameters. Mann-Whitney non-parametric test was used to compare differences between the groups. Data are presented as mean ± standard deviation.

Results: Waist circumference was 99.2 ± 8.8 cm and 114.9 ± 10.5 cm in the normal flow and CSFP groups, respectively (P = 0.003). Four patients in the CSFP group and 1 in the normal flow group had type 2 diabetes. Area under the curve in the oral glucose tolerance test was 22% higher in the CSFP than in the normal group (P = 0.04). There was no difference in systolic and diastolic blood pressure, plasma concentrations of total cholesterol, triglycerides, high density lipoprotein, LDL and platelet aggregation parameters between the groups. Lag time required until initiation of LDL oxidation in the presence of CuSO₄ was 17% longer (P = 0.02) and homocysteine fasting plasma concentration was 81% lower (P = 0.05) in the normal flow group. Large artery elasticity was the same in both groups. Small artery elasticity was 5 ± 1.5 ml/mmHgx100 in normal flow subjects and 6.1 ± 1.9 ml/mmHgx100 in the CSFP patients (P = 0.02).

Conclusions: Patients with CSFP had more metabolic derangements. Arterial stiffness was not increased in CSFP.

 Background: Burn injuries are extremely common and may impose a serious load on public health around the world.

 Objectives: To compare mortality rates and length of hospitalization according to the identified risk factors, extent of burn, gender and age.

Methods: In this retrospective study, data from 558 archive files of hospitalization due to burns as the diagnosis in patients of all ages, between the years 2001 and 2002, were analyzed to identify the risk factors for mortality and length of hospitalization.

Results: Males comprised 62.4% of the hospitalized burn patients. The mortality rate was 3.2% (n=18) and among them 55.6% were women. Fifty percent of the fatality cases were over 48 years old, with statistically significant correlation of mortality rate and age. Most of the fatality cases (66.7%) had burns with total burn surface area (TBSA) larger than 40%. The multiple logistic regression model showed that leukocyte count on admission, TBSA, and age are the most important predictors of mortality. Smoke inhalation was not found to be an independent risk factor.

Conclusions: Using a statistical model for estimating the mortality rate, this study found that white blood cell count at admission, TBSA, and age were the most significant predictors of mortality.