Israel Medical Association Journal

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease caused by chronic obstruction of major pulmonary arteries, which can be cured by pulmonary endarterectomy. However, many CTEPH patients are not surgical candidates. Balloon pulmonary angioplasty (BPA) is an emerging technique used to treat inoperable CTEPH.

Objectives: To describe the first Israeli experience with BPA for inoperable CTEPH.

Methods: In 2017 we established a BPA program at our institution. We reviewed the outcomes to date of BPA in our center.

Results: Forty-seven BPA procedures were performed in five patients with inoperable CTEPH (4–17 procedures/patient). Mean pulmonary artery pressure improved in all patients (median decrease 17 mmHg, range 10–26 mmHg). Pulmonary vascular resistance also improved (median decrease 11 Woods Units/m², range 8–16 Woods Units/m²). Cardiac output increased in 4 of 5 patients and decreased in one. Functional capacity improved from New York Heart Association (NYHA) III to II in four patients; one patient was NYHA II at baseline without change after BPA. Six-minute walking distance improved by a median of 97 meters. (range 21–197 meters). Hemodynamic and functional improvements were sustained at follow-up 5–11 months after the last BPA procedure. BPA enabled 2 of 3 patients treated with parenteral prostanoids to be switched to oral therapy. There were no major complications.

Conclusions: We successfully established BPA as a treatment for inoperable CTEPH in our center. BPA resulted in hemodynamic and clinical improvements that were sustained over time.

Background: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets.

Objectives: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis.

Methods: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019.

Results: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects.

Conclusions: The efficacy of MyC injection should be studied prospectively.

Background: Chronic obstructive pulmonary disease(COPD) is a common and debilitating condition, often accompanied by other co-morbidities. The Hadassah Medical Center’smulti-disciplinary approach in treating COPD patients in a one-stop shopfor COPD patients is the first of its kind in Israel. It includes pulmonary physicians, a nurse coordinator, dietitian, psychotherapist, physiotherapist, and a smoking cessation program.

Objectives: To characterize efficacy of such a program in COPD patients

Methods: Demographic and clinical data from patients referred to the Hadassah COPD center, including co-morbidities, baseline symptoms (using the CAT questioner), spirometry results, 6-minute walking distance (6MWD) test and current treatment were collected and compared to the same data after 6–12 months of treatment.

Results: Some 154 patients were evaluated; mean age 64 years; 67% male; 53% current smokers. Only 74% received chronic treatment for COPD. Average body mass index was 28, CAT score 21.3, and mean FEV1 was 1.38 liters (53% of predicted).The mean exacerbation rate during the year prior to referral was 1.72 with a 1.07 annual admission rate. Following treatment, a small increase was noted in FEV1 to 1.47 liters, 54.4% of predicted; improvement in CAT scores to 16.5 with improvement seen in 70% of patients, and a 42 meter increase in the 6MWD (from 344 to 386 meters) with some improvement of effort capacity in 77% of patients. The rate of smokers decreased to 21%, and 97% of patients received medical treatment for COPD.

Conclusions: Multidisciplinary approach is feasible and efficacious in patients with COPD.

Background: The single-breath diffusing capacity of the lungs (DLCO_SB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VA_SB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCO_SB) is the DLCO_SB divided by VA_SB. Cystic fibrosis (CF) disease comprises progressive airway obstruction with bronchiectasis and parenchyma fibrosis. Yet, the KCO_SB appears insignificant in the assessment of pulmonary function in CF.

Objectives: To challenge the precision of normal KCO_SB in CF.

Methods: The authors collected pulmonary function tests (PFT) data from 74 confirmed CF patients (mean age 26 ± 10 years) with various levels of pulmonary disease severity. Tests included spirometry, DLCO_BP, and body plethysmography (_BP). Anatomical dead space was calculated by deducting anatomical dead space from total lung capacity TLC(_BP) to establish alveolar volume (VA_BP) and to determine KCO_BP. We also included individual data of arterial pCO₂ blood-gas level.  

Results: KCO_SB values were normal or higher in most patients, regardless of patient FEV1 value (R² = 0.2204; P < 0.02). In contrast, the measurements of KCO_BP were low corresponding with low FEV1 values, and negatively correlated with the elevation of trapped air and pCO₂ levels (R² = 0.1383; P = 0.0133, P > 0.05, respectively).

Conclusions: The 10- second perfusion time of the inert gas during DLCO_SB represent the communicative alveolar volume in CF patients with advanced pulmonary disease. The findings justify the use of DLCO_SB with the deterioration of FEV1 and elevation of pCO₂ levels.

Background: Transbronchial cryobiopsy (TBC) has recently emerged for the assessment of diffuse parenchymal lung disease (DPLD) as a less invasive procedure than surgical lung biopsy. The diagnostic usefulness and safety of TBC is still controversial.

Objectives: To evaluate the safety and diagnostic yield of TBC in a peripheral community medical center.

Methods: We retrospectively reviewed the charts of all patients with DPLD who underwent TBC from January 2015 to January 2020.

Results: The study comprised 97 patients. Three samples were taken from each patient with an average diameter of 0.59 cm. The histologic diagnostic yield was 54% (52 of 97 procedures). The most frequent histopathologic diagnoses were usual interstitial pneumonia in 13 patients (13%). Bleeding was observed in 19 cases (19%) and only one patient (1%) had severe bleeding. Pneumothorax developed in seven patients (7%) and one patient (1%) suffered from Interstitial lung disease exacerbation.

Conclusions: TBC was found to be safe; however, the diagnostic yield was rather low compared to other studies, which emphasizes the need for interstitial lung disease centers with expert in this field.

Background: Lung cancer is the most common cause of cancer-related death.

Objectives: To identify changing patterns of lung cancer and its histologic subtypes among different population groups in Israel over a 25 year period.

Methods: Primary lung cancers, all types and all stages, diagnosed during 1990–2014 were recorded in the Israel National Cancer Registry database. Demographic information was retrieved from the National Population Register. Age-standardized rates for the different subgroups were calculated for each year. Joinpoint software was used to analyze trends in incidence.

Results: We identified 42,672 lung cancer cases. The most common histology was adenocarcinoma (34%), followed by squamous cell carcinoma (19%), large cell/not-otherwise-specified (19%), other histologies (15%), and small cell lung cancer (11%). The adenocarcinoma incidence rose from 25.7% to 48.2% during the examined period. Large cell/not-otherwise-specified incidence peaked around 2005–2006 and declined after. Lung cancer incidence increased significantly for the population overall and specifically in Arab females, followed by Jewish females and by Arab males. Adenocarcinoma and small cell lung cancer increased in Jewish females and in Arab males. A younger age of diagnosis was seen in Arab compared to Jewish patients.

Conclusions: Jewish females and Arab males and females living in Israel demonstrated a constant increase in lung cancer incidence, mostly in adenocarcinoma and small cell lung cancer incidence. In addition, a younger age of diagnosis in Arabs was noted. Smoking reduction interventions and screening should be implemented in those populations.

For most passengers, even those with respiratory disease, air travel is safe and comfortable. Some travelers may experience hypoxia at sea level but may not need supplemental oxygen during air travel in a hypobaric hypoxic environment. For some individuals compensatory pulmonary mechanisms may be inadequate, causing profound hypoxia. In addition, venous thromboembolism/pulmonary emboli may occur, especially during long haul flights. With adequate screening, patients at risk can be identified, therapeutic solutions can be proposed for the flight, and most can travel can continue safely with supplemental oxygen and other preventive measures.

The coronavirus disease-2019 (COVID-19) and its management in patients with epilepsy can be complex. Prescribers should consider potential effects of investigational anti-COVID-19 drugs on seizures, immunomodulation by anti-seizure medications (ASMs), changes in ASM pharmacokinetics, and the potential for drug-drug interactions (DDIs). The goal of the Board of the Israeli League Against Epilepsy (the Israeli Chapter of the International League Against Epilepsy, ILAE) was to summarize the main principles of the pharmacological treatment of COVID-19 in patients with epilepsy. This guide was based on current literature, drug labels, and drug interaction resources. We summarized the available data related to the potential implications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might apply to additional future drug combinations as novel treatments emerge. They do not replace evidence-based guidelines, should those become available. Awareness to drug characteristics that increase the risk of interactions can help adjust anti-COVID-19 and ASM treatment for patients with epilepsy

Background: As part of the effort to control the coronavirus disease-19 (COVID-19) outbreak, strict emergency measures, including prolonged national curfews, have been imposed. Even in countries where healthcare systems still functioned, patients avoided visiting emergency departments (EDs) because of fears of exposure to COVID-19.

Objective: To describe the effects of the COVID-19 outbreak on admissions of surgical patients from the ED and characteristics of urgent operations performed.

Methods: A prospective registry study comparing all patients admitted for acute surgical and trauma care between 15 March and 14 April 2020 (COVID-19) with patients admitted in the parallel time a year previously (control) was conducted.

Results: The combined cohort included 606 patients. There were 25% fewer admissions during the COVID-19 period (P < 0.0001). The COVID-19 cohort had a longer time interval from onset of symptoms (P < 0.001) and presented in a worse clinical condition as expressed by accelerated heart rate (P = 0.023), leukocyte count disturbances (P = 0.005), higher creatinine, and CRP levels (P < 0.001) compared with the control cohort. More COVID-19 patients required urgent surgery (P = 0.03) and length of ED stay was longer (P = 0.003).

Conclusions: During the COVID-19 epidemic, fewer patients presented to the ED requiring acute surgical care. Those who did, often did so in a delayed fashion and in worse clinical condition. More patients required urgent surgical interventions compared to the control period. Governments and healthcare systems should emphasize to the public not to delay seeking medical attention, even in times of crises

Background: A thorough informed consent (IC) process is required before in vitro fertilization (IVF) treatments can begin because these treatments are by and large elective and they have expectable and preventable complications, such as ovarian hyper-stimulation syndrome and multi-fetal pregnancies.

Objectives: To empirically examine whether patient knowledge and understanding of potential hazards associated with IVF treatment are better after the IC process compared to before. The authors hypothesized that patients' better understanding of potential complications would be translated and expressed as rational choices of treatment alternatives.

Methods: Responses of 48 IVF patients after IC process (study group) from two IVF units in northern Israel were compared to those of 46 patients before IVF (control group).

Only women undergoing IVF for first time who were older than 18 years of age were eligible for the study.

Results: Socio-demographic parameters were found to be quite similar between the study group and the control group. Contrary to our expectations, in the study group 12 women (25.5%) considered delivery of a single baby as their optimal result, compared to 15 (32.6%) in the control group. Furthermore, preferences shifted toward triplets: eight patients (17%) after IC considered this option as their best result, compared to only five patients (11%) before IC.

Conclusions: IC process goals are not achieved under current practices, at least as far as IVF treatment are concerned. New tools and incentives should be implemented to meet the requirements dictated by the laws regarding patient rights.

Background: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease.

Objectives: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE.

Methods: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results.

Results: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function.

Conclusions: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Background: Vitamin D is essential for skeletal health. Because peak bone mass accrual occurs during childhood and adolescence, vitamin D insufficiency during this period of life could cause adverse health outcomes.

Objectives: To explore the potential sex differences in anthropometric indicators and vitamin D status among primary school-age children.

Methods: A modified food-frequency intake questionnaire was completed by 116 pre-pubertal children (52 girls, 64 boys). Body measurements were recorded and blood was drawn to assess vitamin D status. All children were of Arab-Israeli origin and lived in villages or rural areas in the north-east area of Israel.

Results: Prevalence of obesity was higher among girls (34%) compared to boys (21.9%, P = 0.018). All the children were vitamin D insufficient, and 80% were deficient. Plasma vitamin D was significantly higher among boys (12.4 ng/ml) compared to girls (9.1 ng/ml, P < 0.01). A significant negative correlation was found between vitamin D status and weight percentile for girls (r = -0.43, P < 0.05) but not for boys. There was a trend toward a statistically significant inverse correlation between vitamin D status and body fat percent in the girls (r = -0.37, P = 0.07). Sex frameworks are important for the understanding of the determinants of health and the development of effective health promotion programs.

Conclusions: Pre-pubertal girls in Arab villages should be provided with tailor-made nutrition and physical activity programs for promoting health.

Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses