Liquid First Is "Solid" in Naïve Non-Small Cell Lung Cancer Patients: Faster Turnaround Time With High Concordance to Solid Next-Generation Sequencing.

Purpose: Molecular profiling is crucial in naïve non-small cell lung cancer (NSCLC). While tissue-based analysis is challenged by turnaround time and scarcity of tissue, there is increasing demand for liquid biopsy. We aimed to analyze the use of upfront liquid biopsy as a molecular profiling approach.

Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC).

Background: fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited.

Methods: The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and fusions; fusion prevalence with and without a co-existing mutation was assessed.

Comparing Cardiac Output Measurements Using a Wearable, Wireless, Noninvasive Photoplethysmography-Based Device to Pulse Contour Cardiac Output in the General ICU: A Brief Report.

Objectives: Cardiac output (CO) measurements in the ICU are usually based on invasive techniques, which are technically complex and associated with clinical complications. This study aimed to compare CO measurements obtained from a noninvasive photoplethysmography-based device to a pulse contour cardiac output device in ICU patients.

Design: Observational, prospective, comparative clinical trial.

Patient-Reported Outcome Measures After Hospitalization During the COVID-19 Pandemic: A Survey Among COVID-19 and Non-COVID-19 Patients.

Background: Many people recovering from COVID-19 suffer from long-term sequelae. The objective of this study was to assess health-related quality of life (HRQoL) in COVID-19 patients several months after discharge.

Methods: We conducted a retrospective cross-sectional case-control study on COVID-19 and non-COVID-19 pneumonia patients admitted to Shamir Medical Center, Israel (03-07/2020).

Early Blood-based Liquid Biopsy in Patients with Treatment-naïve Metastatic Adenocarcinoma of the Lung: A Case Series.

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.

Clinical Course and Outcomes of Severe Covid-19: A National Scale Study.

Unlabelled: Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined.

Methods: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020.

Improving blood glucose level predictability using machine learning.

This study was designed to improve blood glucose level predictability and future hypoglycemic and hyperglycemic event alerts through a novel patient-specific supervised-machine-learning (SML) analysis of glucose level based on a continuous-glucose-monitoring system (CGM) that needs no human intervention, and minimises false-positive alerts. The CGM data over 7 to 50 non-consecutive days from 11 type-1 diabetic patients aged 18 to 39 with a mean HbA1C of 7.5% ± 1.

Oocyte maturation in plasma or follicular fluid obtained from lipopolysaccharide-treated cows disrupts its developmental competence.

Mastitis has deleterious effects on ovarian function and reproductive performance. We studied the association between plasma or follicular fluid (FF) obtained from endotoxin-induced mastitic cows, and oocyte developmental competence. Lactating Holstein cows were synchronized using the Ovsynch protocol.

The Clinical Impact of Comprehensive Genomic Testing of Circulating Cell-Free DNA in Advanced Lung Cancer.

Introduction: Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables noninvasive genomic analysis of NSCLC patients. Although plasma-detected genomic alterations (GAs) have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decisions.

Methods: This retrospective study of stage IIIB/IV NSCLC patients between the years 2014 and 2017 in Israel used cfDNA NGS (Guardant360; Guardant Health, Inc.

Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience.

Background: Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.

Objective: To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.

Patients And Methods: This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy.

[THE IMPACT OF MOLECULAR PROFILING USING NEXT-GENERATION SEQUENCING IN ADVANCED LUNG CANCER].

Background: In the last decade, important advances in understanding the lung cancer cellular signal pathways have led to the designing of targeted drugs that significantly prolong survival. Recent data shows that 64% of lung adenocarcinomas harbor at least one activating driver mutation, including treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS) reveals more clinically meaningful genomic alterations as compared to currently used diagnostic tests.

Quantification of specific T and B cells immunological markers in children with chronic and transient ITP.

Background: Immune thrombocytopenic purpura (ITP) is characterized by a transient (nonchronic) or permanent (chronic) decline in the number of platelets. Predicting the course of ITP, at the time of diagnosis, is of importance. Here we studied at diagnosis, clinical and immunological parameters in order to distinguish between different courses.

RET Fusion Lung Carcinoma: Response to Therapy and Clinical Features in a Case Series of 14 Patients.

Background: RET (rearranged during transfection) fusions have been reported in 1% to 2% of lung adenocarcinoma (LADC) cases. In contrast, KIF5B-RET and CCDC6-RET fusion genes have been identified in 70% to 90% and 10% to 25% of tumors, respectively. The natural history and management of RET-rearranged LADC are still being delineated.

A novel swine model of ricin-induced acute respiratory distress syndrome.

Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis.

Clinical Impact of Hybrid Capture-Based Next-Generation Sequencing on Changes in Treatment Decisions in Lung Cancer.

Introduction: Targeted therapy significantly prolongs survival in lung adenocarcinoma. Current diagnostic guidelines include only EGFR and anaplastic lymphoma receptor tyrosine kinase gene (ALK) testing. Next-generation sequencing (NGS) reveals more actionable genomic alterations than do standard diagnostic methods.

Clinical utility and treatment outcome of comprehensive genomic profiling in high grade glioma patients.

Genomic research of high grade glioma (HGG) has revealed complex biology with potential for therapeutic impact. However, the utilization of this information and impact upon patient outcome has yet to be assessed. We performed capture-based next generation sequencing (NGS) genomic analysis assay of 236/315 cancer-associated genes, with average depth of over 1000 fold, to guide treatment in HGG patients.

Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing.

Purpose: Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation.

Experimental Design: A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed.

Screening for germline mutations in breast/ovarian cancer susceptibility genes in high-risk families in Israel.

We evaluated the clinical utility of screening for mutations in 34 breast/ovarian cancer susceptibility genes in high-risk families in Israel. Participants were recruited from 12, 2012 to 6, 2015 from 8 medical centers. All participants had high breast/ovarian cancer risk based on personal and family history.

Metastatic Salivary Gland Tumors: A Single-Center Study Demonstrating the Feasibility and Potential Clinical Benefit of Molecular-Profiling-Guided Therapy.

We evaluated the use of molecular profiling (MP) for metastatic salivary gland adenoid cystic carcinoma (SACC), for which there is no standard treatment. MP (Caris Molecular Intelligence) was performed on biopsy samples from all metastatic SACC patients attending a tertiary medical center between 2010 and 2013 (n = 14). Treatment was selected according to the biomarkers identified.

Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study.

This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.

Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer.

Background: The U.S. Food and Drug Administration-approved method for detecting EML4-ALK rearrangement is fluorescence in situ hybridization (FISH); however, data supporting the use of immunohistochemistry (IHC) for that purpose are accumulating.