Israel Medical Association Journal

Background: Patients diagnosed with coronavirus disease-19 (COVID-19) who deteriorate to respiratory failure and require mechanical ventilation may later need to be weaned from the ventilator and undergo a rehabilitation process. The rate of weaning COVID-19 patients from mechanical ventilation is unknown.

Objective: To present our experience with ventilator weaning of COVID-19 patients in a dedicated facility.

Methods: A retrospective cohort study was conducted of 18 patients hospitalized in a COVID-19 dedicated ventilator weaning unit.

Results: Eighteen patients were hospitalized in the dedicated unit between 6 April and 19 May 2020. Of these, 88% (16/18) were weaned and underwent decannulation, while two patients deteriorated and were re-admitted to the intensive care unit. The average number of days spent in our department was 12. There was no statistically significant correlation between patient characteristics and time to weaning from ventilation or with the time to decannulation.

Conclusions: Despite the high mortality of COVID-19 patients who require mechanical ventilation, most of the patients in our cohort were weaned in a relatively short period of time. Further large-scale studies are necessary to assess the cost effectiveness of dedicated COVID-19 departments for ventilator weaning.

Background: Primary spontaneous pneumothorax (PSP) tends to occur in young adults without underlying lung diseases and is usually followed by limited symptoms, while secondary spontaneous pneumothorax (SSP) is a complication of a pre-existing lung disease. Surprisingly, for such common conditions, there is a considerable inconsistency regarding management guidelines.

Objectives: To evaluate the risk factors for spontaneous pneumothoraxes and to summarize outcomes and complications based on our clinical experience.

Methods: This retrospective study group was comprised of 250 consecutive patients older than 18 years of age who were diagnosed with spontaneous pneumothorax and hospitalized at the Meir Medical Center (2004–2017). Data on demographic characteristics, indicating symptoms, chest X-rays, and chest computed tomography (CT) results were collected. Our experience and outcomes were then compared to a large multicenter study.

Results: Most of the patients were male (85%) and past or current smokers; 69% presented with PSP, while the rest were SSP. No occupational relation was noted. About 55% of the cases presented with a moderate or large pneumothorax (over 1/3 hemithorax). Most patients (56%) required chest tube drainage and 20% undergone surgery. Nearly 10% presented with a recurrent pneumothorax with the mean time to recurrence being 11 ± 20 days. Although the length of hospital stay of patients that underwent surgery was the longest (P < 0.001) for both PSP and SSP, the recurrence rate was actually reduced, suggesting some benefit for the surgical treatment option.

Conclusions: Our experience showed that the traditional approach to the PSP treatment should be further considered, as previously suggested.

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: Lung percutaneous needle biopsy (PNB) is routinely used to diagnose lung cancer. The most prevalent complications of PNB are pneumothorax and bleeding. Differences in characteristics of medical procedures between rural and urban hospitals are well known.

Objectives: To compare characteristics of patients and lesions between two hospitals and to evaluate whether lung PNB complications differ in rural vs. urban settings.

Methods: The authors examined case records of 561 patients who underwent lung biopsy at two different medical centers in Israel: Tel Aviv Sourasky Medical Center (urban) and Barzilai Medical Center (rural). To evaluate the complication rates, the authors analyzed findings from chest X-ray performed 2 hours after biopsy and computed tomography (CT) images at the site of biopsy.

Results: The study comprised 180 patients who underwent lung biopsy at Barzilai and 454 at Sourasky. The rate of pneumothorax did not differ between centers (12% at Barzilai and 19% at Sourasky, P = 0.08). Distance from pleura was positively correlated to pneumothorax occurrence in both centers; however, neither lesion size nor lesion locus was found to be a risk factor for pneumothorax. Mild bleeding at the biopsy site occurred equally at Barzilai and Sourasky (32% vs. 36%, P = 0.3, respectively). Furthermore, immediate CT post-biopsy at Barzilai showed 95% negative predictive value, showing that a CT scan performed immediately after lung biopsy cannot replace the routine follow-up chest X-ray in predicting iatrogenic pneumothorax.

Conclusions: CT-guided percutaneous lung biopsies are comparable between rural and urban hospitals regarding procedure characteristics and complication rates.

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: Our 1600-bed teaching hospital opened the first physician-led specialist pleural service in Israel in November 2016. Thoracentesis is one of the frequently performed procedures in clinic.

Objectives: To review the incidence of thoracentesis-related symptoms, complications, and risk factors in a specialist pleural clinic.

Methods: Prospective analysis was conducted of 658 ultrasound-assisted thoracenteses between November 2016 and November 2019. Data were collected on patient demographics, clinical characteristics, procedural aspects, symptoms, complications, and additional interventions required.

Results: Of the procedures, 24% were accompanied by a reported symptom of any intensity or duration. Cough and chest discomfort were noted in 56.4% and 52% of these cases, respectively. Large-volume drainage was associated with symptoms (P = 0.002). Ultrasound-estimated effusion volume before drainage predicted pain (P = 0.001) and pneumothorax (P = 0.021). Of 8 cases of pneumothorax, 6 were due to non-expandable lung. Two patients were hospitalized (0.3%), and one required a chest drain.

Conclusions: Symptoms are a common feature of thoracentesis even when performed by experienced operators in ideal settings. Complications, however, are rare when the procedure is performed with bedside ultrasound and attention is paid to patient-reported symptoms and volume drained. Specialist pleural clinics provide a good model for a standardized approach to safe performance of this common procedure.

Background: Guidelines recommend testing for multiple biomarkers in non-small cell lung cancer (NSCLC) tumors. Blood-based liquid biopsy analyzing cell-free DNA (cfDNA) could be used in addition to tumor biopsy genotyping, especially if tissue/time are limiting.

Objectives: To investigate the clinical utility of early cfDNA analysis (Guardant360^® CDx) in treatment-naïve NSCLC patients.

Methods: A prospective cohort of treatment-naïve patients with metastatic NSCLC who underwent tumor and cfDNA analysis between 12/2018 and 2/2019 were included.

Results: Ten patients were included: 6 males, median age 70.5 years (range 48–87), 8 prior smokers. Liquid biopsy was sent when cancer cells were detected in the biopsy specimen. Median time from diagnosis to receiving the report on the last biomarker from the tumor biopsy was 20 days (range 9–34); median time from blood draw to receiving the cfDNA findings was 9 days (range 7–12). The median difference between the cfDNA and the tumor analysis reports was 20 days (range 9–28). Actionable biomarkers were identified in four patients by both the biopsy analysis and the cfDNA analysis (2cases with EGFR mutations, one with ROS1 fusion, and one with EML4-ALK fusion for whom the biopsy analysis also identified an EGFR mutation not detected in the cfDNA analysis). Overall, eight patients received treatment (2 died before treatment initiation). Three patients received biomarker-based treatment (1 osimertinib, 1 alectinib, and 1 crizotinib).

Conclusions: These findings suggest that cfDNA analysis should be ordered by the pulmonologists early in the evaluation of patients with NSCLC, which might complement the tumor biopsy.

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: While the routine performance of terminal ileum (TI) intubation during colonoscopy procedures is perceived to have a low yield, its utility during colonoscopies performed for specific indications have not been well studied.

Objectives: To assess the diagnostic yield of an indication-based ileoscopy in real-life practice.

Methods: The authors reviewed endoscopic reports of patients who underwent colonoscopies over an 8-year period (2011–2018) and had routine ileoscopy during these procedures. Demographic data, indications for colonoscopy, and endoscopic findings were documented. Diagnostic yield and odds ratio for TI findings were calculated.

Results: Over 30,000 colonoscopy reports performed during the study period were reviewed. Ilesocopy was performed in 1800 patients, 216 patients had findings in the TI (ileitis or ulcers). TI findings were more prevalent in younger ages (38.3 ± 17.6 vs. 43.6 ± 20, P < 0.05). The greatest yield of ileoscopy was evident when performed for the evaluation of chronic abdominal pain and diarrhea (14.4% vs. 9.3%, odds ratio [OR] 1.62, P < 0.05). Positive fecal occult blood test (FOBT) (OR 0.1, 95% confidence interval [95%CI] 0.02–0.5, P = 0.005) and constipation (OR 0.44, 95%CI 0.2–0.9, P = 0.04) were negatively associated with TI findings.

Conclusions: Ileoscopy may have the greatest utility in evaluating suspected inflammatory bowel disease (IBD) patients, but may not add value to the evaluation of constipation and positive FOBT

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.