Citations

Introduction: Patients with cognitive impairments, who may be unable to engage in traditional psychotherapies, may require support through non-cognitive interventions. This review synthesizes the existing literature to assess the evidence base for these interventions and to propose future directions for research. Methods: A comprehensive literature search was conducted across seven electronic databases on October 17, 2024. Eligible studies assessed psychological, emotional, social, or spiritual outcomes. Results: Seventy-three studies were included, conducted across 18 countries. Music therapy and art therapy had the strongest empirical support, with consistent effects on distress, emotional expression, social and spiritual connectedness, and finding meaning. Other approaches, including movement therapy, spiritual interventions, and pet therapy, showed promising but preliminary results. Aromatherapy and massage therapy yielded mixed findings, while energy-based methods lacked robust evidence. Most studies had a high risk of bias, primarily due to confounding. Few interventions were conducted with patients with cognitive impairments, despite their potential relevance. Conclusion: A variety of interventions compatible with cognitive impairment show promise in palliative care settings. However, existing empirical support is constrained by bias and a lack of research in cognitively-impaired populations.

Abstract Sex differences in cancer outcome, including that of glioblastoma (GBM), are shaped by biological, hormonal, and immunological factors and impact disease progression, treatment responses, survival, and tumor microenvironment (TME) interactions. Platelets regulate the immune responses and tumor progression in many cancers, but it is not clear how they contribute to these sex-based differences by affecting the dynamics of the TME. Here, we show that GBM patients exhibit heightened platelet reactivity driven by PAR4 signaling. In murine GBM models, both pharmacological inhibition of PAR4 using BMS986120 and genetic deletion of PAR4 significantly prolong survival in females but not males. This survival advantage is estrogen dependent: it is preserved in chromosomal male-hormonal female mice within the four-core genotype model and is rescued in ovariectomized mice treated with estrogen. The survival benefit is TME specific and is mediated by platelet-driven enhancement of CD8⁺ T cell infiltration into the tumor. Inhibition of platelet PAR4 signaling increases calcium signaling through an estrogen-dependent interaction between PAR4 and estrogen receptor β (ERβ)—a receptor interaction not previously described. PAR4-activated platelets within the TME suppress CD8⁺ T cell function, and depletion of CD8⁺ T cells abolishes both the tumor-induced platelet reactivity and the survival benefit conferred by PAR4 inhibition. These findings establish platelet-mediated PAR4 signaling as a critical driver of tumor progression and identify sex-specific immune responses as key to therapeutic efficacy.

Objective: Describe changes in symptoms of velopharyngeal insufficiency (VPI)—hypernasality, audible nasal emission, and VPI-related quality of life—following LeFort I osteotomy in individuals with cleft palate +/- cleft lip. Design: Single-center, retrospective cohort study. Participants: Twenty-one patients with a history of cleft palate repaired in infancy were included in this study. Ten patients had no prior history of VPI surgery and eleven had a pharyngeal flap in place at the time of LeFort I osteotomy. The mean age at time of surgery was 17.2 years. Main Outcome Measure: Pre- and postoperative hypernasality severity, frequency of audible nasal emission, and total score on the VPI Effects on Life Outcomes youth questionnaire (VELO-Y) before and after LeFort osteotomy I. Fischer exact test was used to assess differences between groups for categorical variables and a t test was used for continuous variables. Results: Patients with no prior history of VPI management had a significant increase in hypernasality severity compared with those with a pharyngeal flap in place at the time of surgery ( P =0.004). Patients without a prior history of VPI management also had a significant increase in frequency of audible nasal emission, while patients with a pharyngeal flap had decreased audible nasal emission ( P =0.004). There was not a significant difference between groups for change in the total score on the VELO-Y ( P =0.16). Conclusions: Findings from this study may improve preoperative counseling provided to patients and caregivers on the risk of acquiring VPI after LeFort I osteotomy based on prior VPI surgical history.

Background Patients with advanced cancer experience a substantial amount of existential and emotional distress. Dignity therapy (DT) is a brief, individualized psychotherapy that aims to relieve existential distress and improve the experiences of individuals impacted by serious illness. Aim To evaluate the feasibility and acceptability of virtual DT (vDT) among patients with advanced cancer. Methods This pilot study recruited adult patients with advanced cancer and an expected prognosis >6 months. The vDT intervention consisted of 2 sessions of guided interviews focused on life review, discussion, and development of a generativity document (GD). Feasibility and acceptability were assessed quantitatively and with semi-structured interviews. Effectiveness measures (distress, dignity impact scale, quality of life [QOL]) were administered pre/post intervention. Results Thirty-one patients referred from a palliative care clinic were eligible. Twenty-one consented and 15 received a final GD. Patients who completed final assessments (N = 9) reported satisfaction with their experience and would recommend the therapy to others. Patients found the virtual component of the intervention acceptable, and the majority noted an improvement in their dignity. Qualitative analysis revealed themes of study team effectiveness, perspectives on intervention processes, benefits to self, and benefits to loved ones. Conclusion Participation in vDT intervention was feasible and acceptable for patients. Patients appreciated the connection with the interviewer, the process, and the benefit of having a document to share with loved ones. Preliminary effectiveness data suggest vDT improves sense of dignity.

Pharmacogenomics (PGx) has the potential to improve prescribing practices. In 2012, our institution developed a multidisciplinary program to implement PGx-CDS to support the clinical practice. CDS has been implemented for 45 drug-gene interactions, in 42,000 patients with PGx tests results, and in 2023, approximately 9281 CDS interventions have triggered at the time of prescribing. The program has been successful.

Intronic GGGGCC hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Despite its intronic location, this repeat avidly supports synthesis of pathogenic dipeptide repeat (DPR) proteins via repeat-associated non-AUG (RAN) translation. However, the template RNA species that undergoes RAN translation endogenously remains unclear. Using long-read based 5′ RNA ligase-mediated rapid amplification of cDNA ends (5′ Repeat-RLM-RACE), we identified C9orf72 transcripts initiating within intron 1 in a C9BAC mouse model, patient-derived iNeurons, and iNeuron-derived polysomes. These cryptic m 7 G-capped mRNAs are at least partially polyadenylated and are more abundant than transcripts derived from intron retention or circular intron lariats. In RAN translation reporter assays, intronic template transcripts–even those with short (32 nucleotide) leaders–exhibited robust expression compared to exon–intron and repeat-containing lariat reporters. To assess endogenous repeat-containing lariat RNA contributions to RAN translation, we enhanced endogenous lariat stability by knocking down the lariat debranching enzyme Dbr1. However, this modulation did not impact DPR production in patient-derived iNeurons. These findings identify cryptic, linear, m 7 G-capped intron-initiating C9orf72 mRNAs as an endogenous template for RAN translation and DPR production, with implications for disease pathogenesis and therapeutic development.

Abstract Background Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic. Methods Patients received VOS following symptom resolution after standard-of-care antibiotics. Pretreatment baseline (within 3 days following antibiotic completion) and Week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS. Results rCDI rates through Week 8 were similarly low in both frCDI and mrCDI patients (6.5% versus 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (P > .05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1. Conclusions These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.

Clonus is a disabling symptom of upper motor neuron dysfunction in patients with multiple sclerosis (MS). We report immediate termination of mechanically evoked clonus by epidural lumbosacral spinal cord stimulation (ES) in a 58-year-old man with secondary progressive MS. This observation was captured during training using video and skin surface electromyography of soleus muscle activity. ES immediately reduced mechanically evoked clonus duration and cycle count compared to trials without stimulation, as determined by a Kruskal–Wallis test ( p < 0.05, n = 2–3 trials), and reverted to baseline status when stimulation was off.