Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.

Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals.

Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy.

Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC.

Three-Dimensionally Printed Simulated Tracheas to Improve Cricothyrotomy Skills Among Anesthesia Providers.

Cricothyrotomy proficiency is imperative for anesthesia providers; however, opportunities to perform this skill are infrequent making skill maintenance essential. Increased accessibility of three-dimensional (3D) printing allows for production of low-cost simulation models. The models used for simulation-based teaching and deliberate practice facilitate skill development and refinement.

Phylogenetic and geographical analysis of a retrovirus during the early stages of endogenous adaptation and exogenous spread in a new host.

Most retroviral endogenization and host adaptation happened in the distant past, with the opportunity to study these processes as they occurred lost to time. An exception exists with the discovery that koala retrovirus (KoRV) has recently begun its endogenization into the koala (Phascolarctos cinereus) genome. What makes this opportunity remarkable is the fact that Northern Australian koalas appear to be undergoing endogenization with one KoRV subtype (KoRV-A), while all subtypes (KoRV-A-I) coexist exogenously, and Southern Australian koalas appear to carry all KoRV subtypes as an exogenous virus.

FLT3 Inhibition in Acute Myeloid Leukaemia - Current Knowledge and Future Prospects.

Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in 30% of acute myeloid leukaemia (AML) patients at diagnosis and confer an adverse clinical prognosis. Mutated FLT3 has emerged as a viable therapeutic target and a number of FLT3-directed tyrosine kinase inhibitors have progressed through clinical development over the last 10-15 years. The last two years have seen United States Food and Drug Administration (US FDA) approvals of the multi-kinase inhibitor midostaurin for newly-diagnosed FLT3-mutated patients, when used in combination with intensive chemotherapy, and of the more FLT3-selective agent gilteritinib, used as monotherapy, for patients with relapsed or treatment-refractory FLT3-mutated AML.

Formulating a Stable Mannitol Infusion while Maintaining Hyperosmolarity.

Mannitol infusion is commonly used in the treatment of intracranial hypertension following traumatic brain injury. It has long been known to have stability issues, specifically, mannitol recrystallises from solutions greater than 10% / in ambient conditions. This can happen at any time, whether on the pharmacy shelf or during a medical procedure.

Comparison of wound strength, histologic, and aesthetic outcomes after microsurgical versus conventional skin closure in a rat model.

The purpose of this study was to compare the healing, strength, and cosmetic outcome of linear incisions after repair with the naked eye, surgical loupes, or a surgical microscope. Two parallel incisions were made on the dorsal skin of Sprague-Dawley rats ( = 36) and the rats randomized into four groups. A single surgeon repaired the incisions using 5-0 poliglecaprone in a running subcuticular pattern using the naked eye (Group I), surgical loupes with 2.

Microcystic Adnexal Carcinoma: A Rare, Commonly Misdiagnosed Malignancy.

Microcystic adnexal carcinoma (MAC) is a rare, malignant cutaneous neoplasm that often presents as an inconspicuous, benign appearing lesion. Patients most commonly are asymptomatic and present for improved cosmesis, however perineural invasion may result in local numbness, paresthesia or pruritus. Although distant metastasis is rare, MAC has an increased propensity for local invasion, often resulting in significant morbidity as late presentation and misdiagnosis are common.

Patient Experience Factors and Health-Related Quality of Life in Hospitalized Individuals.

Purpose: To identify a relationship between patient satisfaction with the hospital experience and health-related quality of life (HRQOL), as well as determine predictors of each variable.

Participants & Setting: 50 patients with cancer in two adult oncology units in an academic health sciences center.

Methodologic Approach: A descriptive, cross-sectional design was used.

Screening for Postpartum Depression by Hospital-Based Perinatal Nurses.

Purpose: The primary purpose of this study was to evaluate acceptability by new mothers of postpartum depression (PPD) screening and education about community resources by hospital-based perinatal nurses. A secondary purpose was to determine further screening for PPD that women received by community providers in the first few weeks after birth.

Methods: The study design was descriptive.

Difluoromethylornithine Combined with a Polyamine Transport Inhibitor Is Effective against Gemcitabine Resistant Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is highly chemo-resistant and has an extremely poor patient prognosis, with a survival rate at five years of <8%. There remains an urgent need for innovative treatments. Targeting polyamine biosynthesis through inhibition of ornithine decarboxylase with difluoromethylornithine (DFMO) has had mixed clinical success due to tumor escape via an undefined transport system, which imports exogenous polyamines and sustains intracellular polyamine pools.

Parent Education is Changing: A Review of Smartphone Apps.

Purpose: The purpose was to critique existing parenting apps using established criteria and health literacy guidelines.

Study Design: Descriptive methodology was used.

Methods: The Apple App Store was searched using the terms parenting, child health, and infant health.

Description of Nurse Scientists in a Large Health Care System.

Replicating a research study that described the work of nurse scientists in children's hospitals, the purpose of the study was to describe the role, activities, and outcomes of nurse scientists employed in a national health care organization. The characteristics of nurses filling the nurse scientist role in clinical settings and outcomes associated with the role have not been extensively described. The setting of this study is ideal since the organization includes facilities of various sizes located in rural, urban, and suburban areas in 18 states.

Isolation and Structure of Cancer Cell Growth Inhibitory Tetracyclic Triterpenoids from the Zimbabwean Monadenium lugardae.

The Zimbabwean medicinal plant Monadenium lugardae was evaluated as a potential source of new anticancer constituents. Four new tetracyclic triterpene (1-4) were isolated, accompanied by four previously known triterpenes (5-8). Against a panel of human tumor cell lines, lugardstatins 1 (1) and 2 (2) had good cancer cell growth inhibitory activity.

Spontaneous pneumomediastinum: an important differential in acute chest pain.

A 38-year-old man presented with pleuritic chest pain that was present on waking and localised to the left costal margin with no radiation. He was otherwise asymptomatic and denied preceding trauma, heavy lifting, coughing or recent vomiting. Observations and examination were unremarkable; however, a chest radiograph showed a pneumomediastinum.

Autoimmune Demyelinating Polyneuropathy as a Manifestation of Chronic Graft-versus-Host Disease after Adult Cord Blood Transplantation in a Patient with Chronic Lymphocytic Leukemia.

Immune mediated demyelinating disease after allogeneic stem cell transplantation is a rare entity with unclear etiology. Acute inflammatory demyelinating polyneuropathy (AIDP) has been reported after related and adult unrelated allogeneic stem cell transplantation but no such case has been reported after unrelated cord blood transplantation. We hereby present the first case of AIDP after double umbilical cord blood transplantation (DUCBT).

Reliable genotyping of the koala (Phascolarctos cinereus) using DNA isolated from a single faecal pellet.

The koala, an Australian icon, has been added to the threatened species list. Rationale for the listing includes proposed declines in population size, threats to populations (e.g.

The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1).

Cephalostatin 1 (1), a remarkably strong cancer cell growth inhibitory trisdecacyclic, bis-steroidal pyrazine isolated from the marine tube worm Cephalodiscus gilchristi, continues to be an important target for practical total syntheses and a model for the discovery of less complex structural modifications with promising antineoplastic activity. In the present study, the cephalostatin E and F rings were greatly simplified by replacement at C-17 with an α-pyrone (in 12), typical of the steroidal bufodienolides, and by a dihydro-γ-pyrone (in 16). The synthesis of pyrazine 12 from 5α-dihydrotestosterone (nine steps, 8% overall yield) provided the first route to a bis-bufadienolide pyrazine.

Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs.

Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line.

Antineoplastic agents. 592. Highly effective cancer cell growth inhibitory structural modifications of dolastatin 10.

The dolastatin series of unique peptides, originally discovered as constituents of the sea hare Dolabella auricularia, is of increasing importance in providing biological leads, especially to new and useful anticancer drugs. Dolastatin 10 and three analogues, minor structural modifications designated auristatins, are currently in human cancer clinical trials. The present study was undertaken to explore delivery to the cancer sites by way of phosphate or quinoline modifications.

Antineoplastic agents 582. Part 1: Isolation and structure of a cyclobutane-type sesquiterpene cancer cell growth inhibitor from Coprinus cinereus (Coprinaceae).

Bioassay-guided (murine P388 lymphocytic leukemia and human cancer cell lines) separation of an ethyl acetate extract prepared from the inky cap fungus Coprinus cinereus led to the isolation of three new sesquiterpenes, 7,7a-diepicoprinastatin 1 (1), 14-hydroxy-5-desoxy-2S,3S,9R-illudosin (2), and 4,5-dehydro-5-deoxyarmillol (3), together with the known armillol (4). The structure and relative configuration of 1 was determined by single-crystal X-ray diffraction experiments. The structures of compounds 2, 3, and 4 were each deduced by a combination of HRMS and 1D and 2D NMR techniques.

Retrospective growth analysis of Atlantic salmon Salmo salar and implications for abundance trends.

Scale archives of Atlantic salmon Salmo salar from Maine, U.S.A.

Antineoplastic agents. 573. isolation and structure of papilistatin from the papilionid butterfly Byasa polyeuctes termessa.

Bioassay-guided separation of an extract of the wings from a Taiwan butterfly, Byasa polyeuctes termessa, allowed isolation of a new cancer cell growth inhibitor designated papilistatin (1a). The structure was determined by analysis of 1D and 2D NMR spectra and by HRMS. Against a panel of six human and the murine P388 leukemia cancer cell lines, papilistatin exhibited cancer cell growth inhibition with GI(50)'s of 0.

An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins.

Human cancer and other clinical trials under development employing combretastatin A-4 phosphate (1b, CA4P) should benefit from the availability of a [(11)C]-labeled derivative for positron emission tomography (PET). In order to obtain a suitable precursor for addition of a [(11)C]methyl group at the penultimate step, several new synthetic pathways to CA4P were evaluated. Geometrical isomerization (Z to E) proved to be a challenge, but it was overcome by development of a new CA4P synthesis suitable for 4-methoxy isotope labeling.

E-Combretastatin and E-resveratrol structural modifications: antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes.

As part of a broad-based SAR investigation of E-resveratrol (strong sirtuin activator and antineoplastic) and the anticancer vascular-targeting combretastatin-type stilbenes, a series of twenty-three beta-E-nitrostyrenes was synthesized in order to evaluate potential antineoplastic, antitubulin, and antimicrobial activities. The beta-E-nitrostyrenes evaluated ranged from monosubstituted phenols to trimethoxy and 3-methoxy-4,5-methylenedioxy derivatives. Two of the beta-nitrostyrenes were synthesized as water-soluble sodium phosphate derivatives (4t, 4v).