Bispectral Index monitoring of palliative sedation for home withdrawal of tracheostomy ventilation: A case report.

Background: Tracheostomy ventilation in motor neurone disease is an uncommon life-sustaining treatment. Best practice is having a plan for ventilation withdrawal, but the literature to guide practice is limited. Case reports have documented standard doses of opioids and benzodiazepines used for sedation in such cases.

DNA methylation landscapes in DIPG reveal methylome variability that can be modified pharmacologically.

Background: Diffuse intrinsic pontine glioma (DIPG) is a uniformly lethal brainstem tumor of childhood, driven by histone H3 K27M mutation and resultant epigenetic dysregulation. Epigenomic analyses of DIPG have shown global loss of repressive chromatin marks accompanied by DNA hypomethylation. However, studies providing a static view of the epigenome do not adequately capture the regulatory underpinnings of DIPG cellular heterogeneity and plasticity.

Nurses' encounters with patients having end-of-life dreams and visions in an acute care setting - A cross-sectional survey study.

Aim: This study aimed to estimate the proportion of acute care nurses witnessing end-of-life dreams and visions or having these reported by a patient or relative, and to canvass their related attitudes and beliefs.

Design: A cross-sectional survey study was conducted from February 2023 to May 2023.

Setting/participants: Participants were medical and surgical nurses from a 200-bed acute care hospital in metropolitan Australia.

FDA Approval Summary: Dabrafenib in Combination with Trametinib for BRAFV600E Mutation-Positive Low-Grade Glioma.

On March 16, 2023, the FDA approved dabrafenib in combination with trametinib (Tafinlar, Mekinist; Novartis Pharmaceuticals Corporation) for the treatment of pediatric patients with low-grade glioma (LGG) with a BRAFV600E mutation who require systemic therapy. FDA also approved oral formulations of both drugs suitable for patients who cannot swallow pills. This approval was based on the LGG cohort from study CDRB436G2201 (NCT02684058), a multicenter, open-label trial in which pediatric patients with LGG with a BRAFV600E mutation were randomly assigned 2:1 to dabrafenib plus trametinib (D+T) or carboplatin plus vincristine (C+V).

Dexmedetomidine for end of life sedation: retrospective cohort comparison study.

Objectives: Infused sedatives are often utilised to alleviate distress at the end of life. Which sedative best achieves this is unknown. This study compares breakthrough medication requirements of patients treated with the novel agent dexmedetomidine compared with patients treated with standard-care sedatives.

A Phase II Trial of Guadecitabine in Children and Adults with SDH-Deficient GIST, Pheochromocytoma, Paraganglioma, and HLRCC-Associated Renal Cell Carcinoma.

Purpose: Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinoma (HLRCC-RCC), and gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, and many targeted therapies. We evaluated guadecitabine, a dinucleotide containing the DNA methyltransferase inhibitor decitabine, in these patient populations.

Patients And Methods: Phase II study of guadecitabine (subcutaneously, 45 mg/m2/day for 5 consecutive days, planned 28-day cycle) to assess clinical activity (according to RECISTv.

Use of Telemedicine in the Diagnosis of Cervical Spondylotic Myelopathy in a US Veteran During the COVID-19 Pandemic: A Case Report.

Objective: The purpose of this case study was to describe the diagnosis of cervical spondylotic myelopathy through telemedicine during the COVID-19 pandemic.

Clinical Features: A 57-year-old male patient was evaluated at a Veterans Affairs chiropractic clinic via video telemedicine for evaluation regarding neck pain and bilateral arm paresthesia.

Intervention And Outcome: During the initial evaluation performed by video telemedicine, the doctor of chiropractic was concerned about the possibility of cervical spondylotic myelopathy.

End-of-life dreams and visions: A systematic integrative review.

Objectives: End-of-life dreams and visions (ELDVs) have been reported throughout history. We aimed to synthesize the research literature on ELDVs to determine the proportions of patients, bereaved families, healthcare professionals, and volunteers reporting ELDVs; ELDV content, timing, and interpretation; and any evidence-based approaches to ELDV-related care.

Methods: A systematic review protocol was registered with PROSPERO (CRD4021282929).

Donor T cell DNMT3a regulates alloreactivity in mouse models of hematopoietic stem cell transplantation.

DNA methyltransferase 3a (DNMT3a) is an important part of the epigenetic machinery that stabilizes patterns of activated T cell responses. We hypothesized that donor T cell DNMT3a regulates alloreactivity after allogeneic blood and marrow transplantation (allo-BMT). T cell conditional Dnmt3a KO mice were used as donors in allo-BMT models.

Vascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina.

Here, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated human naïve epiblast-like pluripotent state. Naïve diabetic vascular progenitors (N-DVP) differentiated from patient-specific naïve diabetic hiPSC (N-DhiPSC) possessed higher vascular functionality, maintained greater genomic stability, harbored decreased lineage-primed gene expression, and were more efficient in migrating to and re-vascularizing the deep neural layers of the ischemic retina than isogenic diabetic vascular progenitors (DVP). These findings suggest that reprogramming to a stable naïve human pluripotent stem cell state may effectively erase dysfunctional epigenetic donor cell memory or disease-associated aberrations in patient-specific hiPSC.

Breakthrough Medication in Unresponsive Palliative Care Patients: Indications, Practice, and Efficacy.

Context: An unresponsive patient's need and their response to breakthrough medication is determined by clinical assessment and/or observational measures. How closely these methods match the patient's experience is unknown.

Objectives: Determine the efficacy and effectiveness of breakthrough medication in unresponsive patients and the perception of patient comfort made by nurses and family.

Correlation Between Observational Scales of Sedation and Comfort and Bispectral Index Scores.

Context: When palliative care patients enter the phase of unconsciousness preceding death, it is standard practice to initiate or continue a subcutaneous infusion of an opioid plus or minus a sedative. The doses are determined somewhat empirically and adjustments are based on clinical assessment and observational measures of sedation and comfort. Following reports that these observational measures could be misleading, this study assesses their validity by comparing them with an objective measure of sedation, the Bispectral Index Score (BIS).

Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line.

Developmental reprogramming techniques have been used to generate induced pluripotent stem (iPS) cells from both normal and malignant cells. The derivation of iPS cells from cancer has the potential to provide a unique scientific tool to overcome challenges associated with the establishment of cell lines from primary patient samples and a readily expandable source of cells that may be used to model the initial disease. In the current study we developmentally reprogrammed a metastatic Ewing sarcoma (EWS) cell line to a meta-stable embryonic stem (ES)-like state sharing molecular and phenotypic features with previously established ES and iPS cell lines.

An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia.

To define the mutation spectrum in non-Down syndrome acute megakaryoblastic leukemia (non-DS-AMKL), we performed transcriptome sequencing on diagnostic blasts from 14 pediatric patients and validated our findings in a recurrency/validation cohort consisting of 34 pediatric and 28 adult AMKL samples. Our analysis identified a cryptic chromosome 16 inversion (inv(16)(p13.3q24.

The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300).

The impact of unrelieved patient suffering on palliative care nurses.

Aim: to describe the impact of unrelieved patient suffering on nurses working with palliative care patients.

Design: This was a qualitative descriptive design using semi-structured interviews.

Sample: nine experienced palliative care nurses were interviewed.