The impact of a web-based prognostic calculator on prognostic confidence in outpatient palliative care.

Purpose: Clinicians are often uncertain about their prognostic estimates, which may impede prognostic communication and clinical decision-making. We assessed the impact of a web-based prognostic calculator on physicians' prognostic confidence.

Methods: In this prospective study, palliative care physicians estimated the prognosis of patients with advanced cancer in an outpatient clinic using the temporal, surprise, and probabilistic approaches for 6 m, 3 m, 2 m, 1 m, 2 w, 1 w, and 3 d.

Distress, demoralization, and fulfillment among palliative care providers during the COVID-19 pandemic.

Objectives: Prolonged distress is a risk factor for burnout among health-care providers (HCP) and may contribute to demoralization. We examined sources of distress during the COVID-19 pandemic and associations with demoralization.

Methods: This prospective cross-sectional survey of HCP was conducted among palliative care providers of an academic medical center.

Assessing risk for nonmedical opioid use among patients with cancer: Stability of the CAGE-AID questionnaire across clinical care settings.

Objectives: The Cut down, Annoyed, Guilty, and Eye opener- Adapted to Include Drugs (CAGE-AID) questionnaire (CA) is a validated screening tool used to assess risk for nonmedical opioid use (NMOU) in patients receiving opioids for cancer pain. Data on consistencies and variations in responses to the CA between different clinical settings are lacking. We evaluated the frequency and consistency in scoring of the CA among patients seen between the first inpatient consult (T1) and the first outpatient follow-up (T2) visits.

Quality of End-of-Life Care during the COVID-19 Pandemic at a Comprehensive Cancer Center.

To evaluate how the COVID-19 pandemic impacted the quality of end-of-life care for patients with advanced cancer, we compared a random sample of 250 inpatient deaths from 1 April 2019, to 31 July 2019, with 250 consecutive inpatient deaths from 1 April 2020, to 31 July 2020, at a comprehensive cancer center. Sociodemographic and clinical characteristics, the timing of palliative care referral, timing of do-not-resuscitate (DNR) orders, location of death, and pre-admission out-of-hospital DNR documentation were included. During the COVID-19 pandemic, DNR orders occurred earlier (2.

Implementation of Patient Reported Outcomes in Outpatient Palliative Care: From Paper to Computer.

Background: This quality improvement project aimed to transition completion of Edmonton Symptom Assessment System (ESAS) at our supportive care clinic from paper to electronic format.

Measures: Proportion of patients who completed electronic ESAS (eESAS).

Intervention: Starting July 2018, patients could complete eESAS 24h before check-in (eESAS-before), eESAS after check-in (eESAS-after) or on paper (pESAS).

Just-in-Time Decision Making: Preliminary Findings of a Goals of Care Rapid Response Team.

Context: The COVID-19 pandemic placed the issue of resource utilization front and center. Our comprehensive cancer center developed a Goals of Care Rapid Response Team (GOC RRT) to optimize resource utilization balanced with goal-concordant patient care.

Objectives: Primary study objective was to evaluate feasibility of the GOC RRT by describing the frequency of consultations that occurred from those requested.

Synthesis of novel glutarimide ligands for the E3 ligase substrate receptor Cereblon (CRBN): Investigation of their binding mode and antiproliferative effects against myeloma cell lines.

To expand the chemical toolkit for targeted protein degradation, we report the generation of a new series of non-thalidomide Cereblon (CRBN) ligands. Readily available 2-methylidene glutarimide was converted to a series of 2-((hetero)aryl(methyl))thio glutarimides via the thio-Michael addition reaction. The compounds thus synthesized were evaluated for their affinity to the thalidomide-binding domain of human CRBN and their binding modes studied via X-ray crystallography.

Physical and Psychosocial Symptoms of Young Adult Patients Referred to the Supportive Care Mobile Team.

Young adult (YA) aged cancer patients have unique psychosocial needs with studies indicating more symptoms and emotional distress compared to older patients. Our study aimed to compare clinical characteristics and symptom distress between YAs and older adults. We retrospectively studied 896 randomly selected patients across 3 age groups: 18-39 YAs ( = 297), 40-64 ( = 300), and 65 and older ( = 299).

Patient behaviors during virtual clinic encounters in palliative care.

Telehealth use has accelerated since the COVID-19 pandemic and provided access for palliative care patients often facing challenges with travel and limited specialist availability. Our palliative care clinic at the University of Texas MD Anderson Cancer Center has rapidly adopted telehealth which continues to grow and provide care for patients since the pandemic, becoming a routine part of our center. While we strive to maintain consistency when it comes to compassionate, sensitive verbal and non-verbal communication, we have witnessed both advantages and disadvantages to telehealth services.

Preparation and Synthetic Applications of Five-to-Seven-Membered Cyclic α-Diazo Monocarbonyl Compounds.

The reactivity of cyclic α-diazo monocarbonyl compounds differs from that of their acyclic counterparts. In this review, we summarize the current literature available on the synthesis and synthetic applications of three major classes of cyclic α-diazo monocarbonyl compounds: α-diazo ketones, α-diazo lactones and α-diazo lactams.

Replacing the phthalimide core in thalidomide with benzotriazole.

The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4A E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy.

A National Survey of Palliative Care Team Compositions.

It is unclear how well palliative care teams are staffed at US cancer centers. Our primary objective was to compare the composition of palliative care teams between National Cancer Institute (NCI)-designated cancer centers and non-NCI-designated cancer centers in 2018. We also assessed changes in team composition between 2009 and 2018.

Symptom and Illness Experience for English and Spanish-Speaking Children with Advanced Cancer: Child and Parent Perspective.

Understanding the symptom and illness experience of children with advanced cancer facilitates quality care; yet, obtaining this understanding is complicated by the child's developmental level and physical and psychological health factors that affect communication. The purpose of this study was to describe the symptom and illness experience of English- and Spanish-speaking children with advanced cancer as described by the child and parent. We conducted hermeneutic phenomenological, descriptive, and interpretive interviews with eligible children and parents.

Rh -Catalyzed De-symmetrization of Ethane-1,2-dithiol and Propane-1,3-dithiol Yields Metallo-β-lactamase Inhibitors.

Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks.

An Integrated Approach to Selecting a Prepared Medical Decision-Maker.

Background: We implemented a systematic multidisciplinary process to engage new outpatients with cancer in selecting and preparing a medical decision-maker.

Measures: Templated advance care planning notes and medical power of attorney documents were used in the electronic health record by the third office visit.

Intervention: Patients were coached to meet with social work from a "culture of yes," viewed a video about the importance of selecting a prepared medical a decision-maker in English or in Spanish, and referenced cards containing simple explanations of advance directives when responding to advance directive questions.

Novel TrxR1 Inhibitors Show Potential for Glioma Treatment by Suppressing the Invasion and Sensitizing Glioma Cells to Chemotherapy.

Currently, available glioblastoma (GBM) treatment remains ineffective, with relapse after initial response and low survival rate of GBM patients. The reasons behind limited capacities for GBM treatment are high tumor heterogeneity, invasiveness, and occurrence of drug resistance. Therefore, developing novel therapeutic strategies is of utmost importance.

Preparation and in situ use of unstable -alkyl α-diazo-γ-butyrolactams in Rh-catalyzed X-H insertion reactions.

-Alkyl α-diazo-γ-butyrolactams, previously found to be unstable and to undergo unproductive dimerization to bishydrazones, were successfully converted immediately to various X-H insertion products with alcohols, aromatic amines and thiols via an in situ Rh-catalyzed reaction. With aliphatic amines or unreactive, sterically hindered anilines, the reactions tended to yield enamine adducts.

Functionalized Pt(II) and Ir(III) NIR Emitters and Their Covalent Conjugates with Polymer-Based Nanocarriers.

Two NIR-emitting platinum [Pt(N^N^C)(phosphine)] and iridium [Ir(N^C)2(N^N)] complexes containing reactive succinimide groups were synthesized and characterized with spectroscopic methods (, 1-phenyl-3-(pyridin-2-yl)benzo[4,5]imidazo[1,2-]pyrazine, , 6-(2-benzothienyl)phenanthridine, phosphine-3-(diphenylphosphaneyl)propanoic acid -hydroxysuccinimide ether, and , 4-oxo-4-((1-(pyridin-2-yl)-1-1,2,3-triazol-4-yl)methoxy)butanoic acid -hydroxysuccinimide ether). Their photophysics were carefully studied and analyzed using time-dependent density functional theory calculations. These complexes were used to prepare luminescent micro- and nanoparticles with the "core-shell" morphology, where the core consisted of biodegradable polymers of different hydrophobicity, namely, poly(d,l-lactic acid), poly(ε-caprolactone), and poly(ω-pentadecalactone), whereas the shell was formed by covalent conjugation with poly(l-lysine) covalently labeled with the platinum and iridium emitters.

Combining carbonic anhydrase and thioredoxin reductase inhibitory motifs within a single molecule dramatically increases its cytotoxicity.

A hypothesis that simultaneous targeting cancer-related carbonic anhydrase CA IX and CA XII isoforms (whose overexpression is a cancer cell's defence mechanism against hypoxia) along with thioredoxin reductase (overexpressed in cancers as a defence against oxidative stress) may lead to synergistic antiproliferative effects was confirmed by testing combinations of the two inhibitor classes against pancreatic cancer cells (PANC-1). Combining both pharmacophoric motifs within one molecule led to a sharp increase of cytotoxicity. This preliminary observation sets the ground for a fundamentally new approach to anticancer agent design.

Further exploration of DVD-445 as a lead thioredoxin reductase (TrxR) inhibitor for cancer therapy: Optimization of potency and evaluation of anticancer potential.

A series of analogs of the earlier reported lead compound DVD-445 (thioredoxin reductase inhibitor with anticancer activity) has been synthesized via a modified Ugi reaction and investigated. Seven most potent compounds (with IC below 5.00 μM against recombinant rTrxR1 enzyme) were examined for their effect on cell growth and viability, oxidative stress induction and P-glycoprotein (P-gp) inhibition in human glioblastoma cells cell line U87 and its corresponding multidrug resistant (MDR) cell line U87-TxR.

Chronic Non-Malignant Pain in Patients with Cancer Seen at a Timely Outpatient Palliative Care Clinic.

Palliative care is seeing cancer patients earlier in the disease trajectory with a multitude of chronic issues. Chronic non-malignant pain (CNMP) in cancer patients is under-studied. In this prospective study, we examined the prevalence and management of CNMP in cancer patients seen at our supportive care clinic for consultation.

Building an Infrastructure and Standard Methodology for Actively Engaging Patients in Advance Care Planning.

Purpose: With little to no infrastructure or standardized methodology in place to actively engage patients in advance care planning (ACP), The University of Texas MD Anderson Cancer Center set out to identify needed resources, develop an intervention to improve ACP, and evaluate the intervention's effects.

Methods: With the support of executive leadership, a multidisciplinary workgroup enlisted the support of ACP champions, performed a root-cause analysis, developed a detailed ACP process flow by provider role, developed patient and family education resources, and developed faculty and staff training materials. The workgroup also implemented two Plan-Do-Study-Act intervention cycles, which identified difficulty using the ACP note function in our electronic health record (EHR) as a barrier to ACP adoption.

Novel electrophilic amides amenable by the Ugi reaction perturb thioredoxin system via thioredoxin reductase 1 (TrxR1) inhibition: Identification of DVD-445 as a new lead compound for anticancer therapy.

A series of peptidomimetic compounds incorporating an electrophilic moiety was synthesized using the Ugi reaction. These compounds (termed the Ugi Michael acceptors or UMAs) were designed to target the selenocysteine catalytic residue of thioredoxin reductase 1 (TrxR1), a promising cancer target. The compounds were assessed for their potential to inhibit TrxR1 using human neuroblastoma (SH-SY5Y) cell lysate.