Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations.

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes.

Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Thinking outside the shunt-sterile CSF malabsorption in pilocytic astrocytomas: case series and review of the literature.

INTRODUCTION: Ventriculoperitoneal (VP) shunt insertion is the most common cerebrospinal fluid (CSF) diversionary procedure used for the treatment of chronic hydrocephalus. Sterile CSF ascites is a rare complication of VP shunt insertion. This can arise from either an overproduction of CSF or inadequate filtration of CSF at the level of the peritoneum. By either mechanism, the development of CSF ascites requires an intact VP shunt. OBJECTIVE: The authors discuss two paediatric cases diagnosed with suprasellar pilocytic astrocytomas treated with platinum-based chemotherapy, who subsequently developed sterile CSF ascites. We review the literature with regard to CSF malabsorption and discuss it as a contributing factor to shunt malfunction. CONCLUSION: CSF malabsorption with resultant ascites is a rare complication of VP shunting with many etiologies. Two common predisposing factors included the use of platinum-based chemotherapeutic agents, as well as the specific neuropathology. Further analysis of these two entities is needed in order to elucidate their role in contributing to the development of CSF ascites in this patient cohort.

Effect of health lifestyle pattern on dietary change.

PURPOSE: To examine the effect of lifestyle on the effectiveness of a low-intensity dietary intervention. DESIGN: A secondary data analysis was performed using data from the Eating Patterns Study, a randomized controlled trial that found that self-help materials with physician advice was effective in changing dietary intake and behavior. SETTING: Primary care clinics in a large health maintenance organization. SUBJECTS: A total of 2111 patients with a routine scheduled appointment with their primary care physicians. MEASURES: Participants were grouped into one of six health lifestyle patterns based on similarities in baseline measures of alcohol intake, smoking, diet quality, and exercise. Within each lifestyle pattern, changes from baseline in usual fat and fiber intake (based on a food frequency) and a fat and fiber behavior score were compared at 3 months and 12 months for intervention vs. control participants. INTERVENTION: Self-help materials delivered by a physician with advice to change diet. RESULTS: Intervention participants in the fitness lifestyle group made the largest changes relative to controls for each dietary outcome at 3 and 12 months. For intervention participants defined by their alcohol intake or current smoking, either no changes in diet were observed compared with controls, or early changes were not sustained over time. Intervention-control comparisons within the remaining lifestyle patterns showed smaller dietary changes compared with the fitness lifestyle. This finding was similar to previously published results. CONCLUSIONS: This randomized controlled trial had limited power to detect subgroup differences; however, these results suggest that lifestyle patterns may be useful in the development of effective, targeted interventions to change behavior.

Patient-controlled analgesia compared with nurse-controlled infusion analgesia after heart surgery.

A randomized, controlled clinical trial was conducted on 66 patients undergoing elective cardiac surgery to compare patient-controlled analgesia (PCA) to nurse-controlled analgesia (NCA) with continuous morphine infusion. Hourly assessment of pain (at rest and on movement) using a visual analogue scale (VAS), of respiratory rate, and level of sedation took place for the 24 h following extubation. The incidence of nausea was also recorded. Mean pain scores were calculated, and peak pain and sedation scores, together with lowest respiratory rates, were identified. Morphine consumption was measured at 24 h. No significant differences were found between the groups' scores for pain or sedation. The PCA group had significantly lower respiratory rates (P = 0.02) and a lower incidence of nausea (P = 0.008). The PCA group also consumed significantly more morphine (P = 0.0001). The study suggests a beneficial effect from PCA after cardiac surgery in reducing nausea, compared to NCA. It confirms nurse-controlled infusion analgesia as an effective form of pain relief in an intensive care and high-dependency setting.