Israel Medical Association Journal

This focus article is a theoretical reflection on the ethics of allocating respirators to patients in circumstances of shortage, especially during the coronavirus disease-2019 (COVID-19) outbreak in Israel. In this article, respirators are placeholders for similar life-saving modalities in short supply, such as extracorporeal membrane oxygenation machines and intensive care unit beds.

In the article, I propose a system of triage for circumstances of scarcity of respirators. The system separates the hopeless from the curable, granting every treatable person a real chance of cure. The scarcity situation eliminates excesses of medicine, and then allocates respirators by a single scale, combining an evidence-based scoring system with risk-proportionate lottery.

The triage proposed embodies continuity and consistency with the healthcare practices in ordinary times. Yet, I suggest two regulatory modifications: one in relation to expediting review of novel and makeshift solutions and the second in relation to mandatory retrospective research on all relevant medical data and standard (as opposed to experimental) interventions that are influenced by the triage

Background: Consent rates for organ donation remain one of the most important factors determining the number of organs available for transplantation. Trauma casualties constitute a substantial part of the deceased organ donor pool and have unique characteristics that distinguish them from the general donor population. However, this group has not been extensively studied.

Objectives: To identify donor factors associated with positive familial consent for solid organ donation among trauma casualties.

Methods: This retrospective study included all trauma casualties who were admitted to the Rabin Medical Center, Beilinson hospital, during the period from January 2008 to December 2017, who were potential organ donors. Data collected included demographic features, the nature of the injury, surgical interventions, and which organs were donated. Data was collected from the Rabin Medical Center Trauma Registry.

Results: During the study period 24,504 trauma patients were admitted and 556 died over their hospital course. Of these 76 were potential donors, of whom 32 became actual donors and donated their organs. Two factors showed a statistically significant correlation to donation, namely female gender (P = 0.018) and Jewish religion of the deceased (P = 0.032).

Conclusions: Only a small group of in hospital trauma deaths were potential solid organ donors (13.7%) and less than half of these became actual donors. Consent rates were higher when the deceased was female or Jewish

Background: Management of acquired laryngotracheal stenosis (LTS) is challenging and often requires recurrent procedures.

Objectives: To compare the efficacy and safety of balloon dilatation (BD) versus rigid dilatation (RD) in the treatment of LTS.

Methods: A retrospective study of patients undergoing endoscopic intervention for LTS was performed.

Results: The study included 69 balloon (BD) and 48 rigid dilations (RD). Most cases were grade 3 Cotton-Meyer stenosis. Mean time interval to recurrence after BD and RD were 27.9 and 19.6 weeks, respectively. Remission of over 8 weeks was achieved in 71% of BD compared to 31.2% of RD (P < 0.05). In the BD group, dilatation of subglottic stenosis showed higher rates of remission of over 8 weeks compared to upper and mid-tracheal stenosis (92% vs. 62% and 20%, respectively, P < 0.05). Complications were encountered in 4.2% of RD and 2.9% of BD.

Conclusions: BD and RD are effective and safe procedures. Overall, BD achieved slightly better long-term results compared to RD

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection in immunocompromised patients. Clusters of PJP, especially among organ transplant recipients in clinic settings were described. Data regarding nosocomial PJP infection among inpatients are limited.

Objectives: To assess the magnitude and characteristics of inpatient healthcare-associated PJP infection (HCA-PJP) in HIV-negative patients.

Methods: A retrospective chart review of hospitalized PJP patients was performed to identify HCA-PJP. The study was performed at six medical centers in Israel from 2006 to 2016. HCA-PJP was defined as cases of hospital-onset or those with documented contact with a PJP patient. We reviewed and cross-matched temporal and spatial co-locations of patients. Clinical laboratory characteristics and outcomes were compared.

Results: Seventy-six cases of PJP were identified. Median age was 63.7 years; 64% men; 44% hematological malignancies; 18% inflammatory diseases; and 61% steroid usage. Thirty-two patients (42%) were defined as HCA-PJP: 18/32 (23.6%) were hospitalized at onset and 14/32 (18.4%) had a previous encounter with a PJP patient. Time from onset of symptoms to diagnosis was shorter in HCA-PJP vs. community-PJP (3.25 vs. 11.23 days, P = 0.009). In multivariate analysis, dyspnea at presentation (odds ratio [OR] 16.79, 95% confidence interval [95%CI] 1.78–157.95) and a tendency toward higher rate of ventilator support (72% vs. 52%, P = 0.07, OR 5.18, 95%CI 0.7–30.3) were independently associated with HCA-PJP, implying abrupt disease progression in HCA-PJP.

Conclusion: HCA-PJP was common. A high level of suspicion for PJP among selected patients with nosocomial respiratory infection is warranted. Isolation of PJP patients should be considered

Coronavirus disease-2019 (COVID‐19) is recognized as a respiratory illness, which includes pulmonary consolidations, hypoxemic states, and hypercoagulopathic tendencies with a broad clinical severity. Recently, more reports have described post-infection manifestations. These include multi-system inflammatory syndrome in children (MIS-C) with more than 400 cases published since the start of the coronavirus disease pandemic. In October 2020, the U.S. Centers for Disease Control and Prevention (CDC) published 27 cases [1] describing the new multi-system inflammatory syndrome in adults (MIS-A). Nine of the cases were reported directly to the CDC, 7 from published case reports and another 11 patients found in three distinct case series

Background: The coronavirus disease-2019 (COVID-19) social-distancing strategy, including 7 weeks of strict lockdown, enabled an extraordinary test of stay-at-home regulations, which forced a sedentary lifestyle on all children and adolescents.

Objectives: To assess the lockdown effect on pediatric weight.

Methods: A retrospective-prospective cohort study at our hospital’s pediatric outpatient clinics following the COVID-19 lockdown. Patients aged 0–18 years visiting the clinic were weighed and previous weight and other clinical data were collected from the medical charts. Weight-percentile-for-age standardization was calculated according to the U.S. Centers for Disease Control and Prevention and the World Health Organization growth tables. Pre- and post-lockdown weight-percentiles-for-age were compared using paired t-test. Multivariate analysis was conducted using linear regression model.

Results: The study was comprised of 229 patients; 117/229 (51.1%) were boys, 60/229 (26.2%) aged under 6 years. Total mean weight-percentile was significantly higher following the lockdown (40.44 vs. 38.82, respectively, P = 0.029). Boys had a significant post-lockdown weight-percentile rise (37.66 vs. 34.42, P = 0.014), whereas girls had higher baseline pre-quarantine weight-percentile of 43.42, which did not change. Patients younger than 6 years had a significant increase in weight-percentiles (39.18 vs. 33.58, P = 0.021). In multivariate analysis these correlations were preserved.

Conclusions: A general weight gain among children was noted, especially in boys during the lockdown, with substantial effect under the age of 6 years. This collateral side-effect should be considered in further quarantine regulations

Background: During the coronavirus disease-2019 (COVID-19) pandemic outbreak our blood bank developed protocols to guarantee accurate blood components to COVID-19 patients.

Objectives: To provide convalescent whole blood donor screening strategies for patients recovering from COVID-19.

Methods: We recruited COVID-19 recovering patients who met our defined inclusion criteria for whole blood donation. All blood units were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA by real time reverse transcription polymerase chain reaction (RT-PCR) and SARS-COV-2 immunoglobulin G (IgG) antibodies against the S1 domain.

Results: We screened 180 blood units from patients recovering from COVID-19. All results were negative for SARS-CoV-2 RNA and 87.2% were positive for SARS-COV-2 IgG antibodies in the plasma.

Conclusions: Blood component units from recovering COVID-19 patients are safe. Plasma units with positive IgG antibodies could serve as an efficient passive immunization for COVID-19 patients. Moreover, in the face of increased transfusion demand for treatment of anemia and coagulation dysfunction in critical ill COVID-19 patients, red blood cells units and random platelets units from convalescent donors can be safely transfused.

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: 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: 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: Fetal ventriculomegaly is one of the more common fetal anomalies detected during prenatal screening.

Objectives: To assess the rate of genetic aberrations as the cause for ventriculomegaly in these fetuses.

Methods: A historic cohort study was conducted on 164 fetuses with sonographic diagnosis of ventriculomegaly. All cases were analyzed for karyotype and 41 cases were further analyzed by chromosomal microarray (CMA). The study group was subdivided by laterality, severity, and whether the ventriculomegaly was an isolated finding or not. Subgroups were compared and the study group was compared to a control group of 209 fetuses.

Results: Karyotype aberrations were more common among fetuses with ventriculomegaly (6.6%) compared to controls (0%, P < 0.001). CMA aberrations were more common in the non-isolated ventriculomegaly cases (24.1%) compared to controls (6.2%, P = 0.031). The rate of genetic aberrations was not associated with the degree of dilatation or laterality.

Conclusions: It is equivocal whether CMA testing should be conducted on every amniotic fluid sample taken from fetuses with isolated ventriculomegaly. However, if more anomalies are detected during an anatomical survey, CMA analysis should be conducted to decrease oversights of genetic diagnoses.

Background: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment