Tigliane Diterpenoids.

The distribution, chemistry, and molecular bioactivity of tiglianes are reviewed from the very beginning of the studies on these diterpenoids, summarizing their clinical and toxicological literature mostly in its more recent and controversial aspects, and critically analyzing various proposals for their biosynthesis.

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core.

To investigate the role of the secondary 5-hydroxy group in the activity of the anticancer drug tigilanol tiglate () (Stelfonta), oxidation of this epoxytigliane diterpenoid from the Australian rainforest plant was attempted. Eventually, 5-dehydrotigilanol tiglate () proved too unstable to be characterized in terms of biological activity and, therefore, was not a suitable tool compound for bioactivity studies. On the other hand, a series of remarkable skeletal rearrangements associated with the presence of a 5-keto group were discovered during its synthesis, including a dismutative ring expansion of ring A and a mechanistically unprecedented dyotropic substituent swap around the C-4/C-10 bond.

Cryptic Epoxytiglianes from the Kernels of the Blushwood Tree ().

The kernels of the Australian blushwood tree () are the source of the veterinary anticancer drug tigilanol tiglate (, Stelfonta) and contain a concentration of phorboids significantly higher than croton oil, the only abundant source of these compounds previously known. The oily matrix of the blushwood kernels is composed of free fatty acids and not by glycerides as found in croton oil. By active partitioning, it was therefore possible to recover and characterize for the first time a cryptic tigliane fraction, that is, the diterpenoid fraction that, because of its lipophilicity, could not be obtained by solvent partition of crude extracts.

A modified emergency severity index level is associated with outcomes in cancer patients with COVID-19.

Objective: To evaluate a modified emergency severity index (mESI)-based triage of cancer patients with coronavirus disease 2019 (COVID-19) in the emergency department (ED) and determine the associations between mESI level and ED disposition, hospital length of stay, and overall survival.

Methods: Medical records were retrospectively reviewed for all patients who presented to our institution's ED between March 22, 2020, and March 12, 2021, and tested positive for SARS-CoV-2.

Results: A total of 306 cancer patients tested positive for SARS-CoV-2, with 45% of patients triaged to level 2 (emergent) and 55% to level 3 (urgent).

Continuous and discontinuous radiofrequency energy delivery on the atrial free wall: Lesion transmurality, width, and biophysical characteristics.

Background: Although lesion transmurality is required for durable pulmonary vein isolation, excess ablation is associated with increased risk of complications.

Objective: We sought to understand the impact of interrupted radiofrequency (RF) delivery conditions on lesion characteristics in the atrial free wall.

Methods: Thirty-three (11 left atrial, 22 right atrial) RF ablation lesions were created in the atria of 6 swine using power control mode (25 W, target contact force 15 g) with 1 of 3 conditions: 15 seconds ablation (n = 8), 30 seconds ablation (n = 14), or 2 15-second ablations at the same site separated by a 2-minute interruption (15 seconds × 2) (n = 11).

Advanced non-small cell lung cancer: Rapid evaluation of EGFR status on fine-needle cytology samples using Idylla.

Advanced non-small cell lung cancer (NSCLC) needs to be managed rapidly; therefore, a rapid assessment of the epidermal growth factor receptor (EGFR) status is mandatory. Computed Tomography (CT)-guided or Ultrasound (US)-guided Fine-Needle Aspiration Cytology (FNAC) allows a rapid diagnosis of both primary and metastatic tumor through rapid on-site evaluation (ROSE) and the proper management of diagnostic material. Idylla (Biocartis, Mechelen, Belgium) is an automated RT-PCR system which evaluates the mutational status of specific genes in less than two hours.

Cardiotoxicity associated with immune checkpoint inhibitors and CAR T-cell therapy.

Introduction: The expanding use of immunotherapy and the growing population of patients with cancer has led to an increase in the reporting of immune related adverse events (irAEs). The emergency clinician should be aware of these emerging toxicities, some of which can be fatal. In this review we discuss the cardiotoxic side effects of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR T-cell) therapy.

Antibacterial Activity of a Fractionated Oil Against Pharyngeal and Ear Pathogens, Alone or in Combination With Antibiotics.

Previous studies have clearly demonstrated that the addition of lentisk oil (LO) to streptococcal cultures makes it possible to differentiate spp. into three categories with and sensitive, , , and partially sensitive, and insensitive to the product. We have investigated here whether the winterization of LO, an easy and cheap procedure that removes some of the fatty substances contained within, resulted in a better antimicrobial effect on human pathogens affecting the pharyngeal mucosa and middle ear such as .

High-Resolution Measurement of Local Activation Time Differences From Bipolar Electrogram Amplitude.

Localized changes in myocardial conduction velocity (CV) are pro-arrhythmic, but high-resolution mapping of local CV is not yet possible during clinical electrophysiology procedures. This is in part because measurement of local CV at small spatial scales (1 mm) requires accurate annotation of local activation time (LAT) differences with very high temporal resolution (≤1 ms), beyond that of standard clinical methods. We sought to develop a method for high-resolution measurement of LAT differences and validate against existing techniques.

Immune checkpoint inhibitor-associated myasthenia gravis, myositis, and myocarditis overlap syndrome.

Introduction: Case reports of immune checkpoint inhibitor (ICI) overlap syndrome of myasthenia gravis, myositis and myocarditis, are increasing in the published literature. This is a potentially fatal adverse event of ICIs and emergency physicians need to be familiar with this triad when patients present to the emergency department (ED).

Methods: We performed a retrospective chart review of the electronic medical record between September 1, 2016 to March 9, 2020.

Diagnosis and management of immune-related adverse effects of immune checkpoint therapy in the emergency department.

Rapid advances in cancer immunotherapy using immune checkpoint inhibitors have led to significantly improved survival. Rapid identification of the toxicity syndromes associated with these therapeutic agents is very important for emergency physicians because the population of patients diagnosed with cancer is increasing and cancer therapies including immune checkpoint inhibitors have become the first-line treatment for more and more types of cancer. The emergency medicine literature lags behind rapid advances in oncology, and oncology guidelines for rapid recognition and management of these emerging toxicity syndromes are not familiar to emergency physicians.

The allylic oxidation of tigliane esters.

As part of a study on the structure-activity relationships of the anticancer agent tigilanol tiglate (EBC-46, 2), the allylic oxidation of phorbol triacetate (1c) and of the acetonide of its 3αH-dihydroderivative (5) was investigated. The aim was to introduce an oxygen function at C-5 en route to point-like analogues of 2, but functionalization of C-10 was instead observed. This was followed by oxidative fragmentation of ring B to the 9,10-secotigliane derivative 6 and oxidation of the endocyclic Δ double bond to the C-6/C-10 oxygen bridged 7-oxotigliane 7.

Characteristics of cancer patients with COVID-19 in a cancer hospital.

Background: Cancer patients are vulnerable to the coronavirus disease (COVID-19) given their compromised immune system. The purpose of this study was to describe the presenting symptoms, inpatient stay trajectory, and survival outcomes, for cancer patients infected with COVID-19; who presented to the emergency department (ED) of a single center during the early months of the pandemic.

Methods: We reviewed the electronic medical records of all cancer patients diagnosed with COVID-19 at our institution for demographic information, clinical presentation, laboratory findings, treatment intervention and outcomes.

Impact of interruptions in radiofrequency energy delivery on lesion characteristics.

Background: During catheter ablation, delivery of radiofrequency (RF) energy to a target site is sometimes interrupted by catheter instability and clinical factors. The impact of interruption of RF delivery on lesion characteristics has not been characterized.

Objective: The purpose of this study was to determine the impact of interruption of RF application on lesion size.

Mechanism and magnitude of bipolar electrogram directional sensitivity: Characterizing underlying determinants of bipolar amplitude.

Background: The amplitude of bipolar electrograms (EGMs) is directionally sensitive, decreasing when measured from electrode pairs oriented oblique to a propagating wavefront.

Objective: The purpose of this study was to use a computational model and clinical data to establish the mechanism and magnitude of directional sensitivity.

Methods: Simulated EGMs were created using a computational model with electrode pairs rotated relative to a passing wavefront.

Muscle Thickness and Curvature Influence Atrial Conduction Velocities.

Electroanatomical mapping is currently used to provide clinicians with information about the electrophysiological state of the heart and to guide interventions like ablation. These maps can be used to identify ectopic triggers of an arrhythmia such as atrial fibrillation (AF) or changes in the conduction velocity (CV) that have been associated with poor cell to cell coupling or fibrosis. Unfortunately, many factors are known to affect CV, including membrane excitability, pacing rate, wavefront curvature, and bath loading, making interpretation challenging.

An Artemisia-derived natural product-based fluorescent probe for the bitter taste receptor hTAS2R38.

The discovery of taste receptors hTAS2Rs expression in extra oral tissue, especially in the gastrointestinal tract and in the respiratory system, has endowed bitter receptors of functionalities that exceed the simple perception of taste and flavour. In particular, stimulation of hTAS2Rs by bitter agents in the airway smooth muscle triggers bronchodilation of possible pharmacological relevance. To study the receptor localization in pulmonary smooth muscle cells and to investigate their biological response to hTAS2R38 activation, we have developed a fluorescent probe for hTAS2R38 starting from the sesquiterpene lactone costunolide, available in multigram amounts from Artemisia umbelliformis Lam.

Fixed volume particle trace emission for the analysis of left atrial blood flow using 4D Flow MRI.

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors.

Sepsis and Acute Myeloid Leukemia: A Population-Level Study of Comparative Outcomes of Patients Discharged From Texas Hospitals.

Background: In the United States, approximately 750,000 cases of sepsis occur annually, and 28% to 50% of affected people die. Treatment is costly, often involving admission to the intensive care unit and prolonged hospitalization. We evaluated outcomes of patients with acute myeloid leukemia (AML) and sepsis in Texas.

An improved preparation of phorbol from croton oil.

Croton oil is the only commercial source of the diterpenoid phorbol (), the starting material for the semi-synthesis of various diesters extensively used in biomedical research to investigate cell function and to evaluate in vivo anti-inflammatory activity. While efficient chemoselective esterification protocols have been developed for phorbol, its isolation from croton oil is technically complicated, and involves extensive manipulation of very toxic materials like the oil or its native diterpenoid fraction. The preparation of a crude non-irritant phorboid mixture from croton oil was telescoped to only five operational steps, and phorbol could then be purified by gravity column chromatography and crystallization.