Top Ten Tips Palliative Care Clinicians Should Know About the Physical Manifestations of Psychiatric Illness and Treatment.

Addressing the psychiatric aspects of serious illness in palliative care (PC) is crucial to both care delivery and outcomes. Psychiatric comorbidities are common among patients with PC needs and can significantly impact their total burden of symptomatic distress, overall quality of life, functional independence, and healthcare utilization. Yet, these aspects of care are often deferred to mental health consultant teams in the context of busy PC services and often limited human resources. To provide comprehensive and person-centered care, PC clinicians must understand the interplay between medical conditions and psychiatric presentations within a biopsychosocial framework to respond empathically, efficiently, and effectively. This article is the first of a two-part series developed in collaboration with a group of psychiatric-palliative care specialists. This article explores ten common physical manifestations of psychiatric illness and treatment among patients facing serious illnesses. The second article will provide pragmatic tips PC clinicians should know about the psychiatric manifestations of nonpsychiatric serious illness and treatment. Combined, these two articles support a holistic approach that PC clinicians can use to prioritize and integrate both mental and emotional well-being throughout the continuum of serious illness.

Top Ten Tips Palliative Care Clinicians Should Know About the Psychiatric Manifestations of Nonpsychiatric Serious Illness and Treatments.

Mental health issues are widespread and significant among individuals with serious illness. Among patients receiving palliative care (PC), psychiatric comorbidities are common and impact patient quality of life. Despite their prevalence, PC clinicians face challenges in effectively addressing the intricate relationship between medical and psychiatric disorders due to their complex, intertwined and bidirectionally influential nature. This article, created collaboratively with a team of psychiatric-palliative care experts, is the second in a two-part series examining the bidirectional relationship between medical and psychiatric illness in PC. This article explores 10 prevalent psychiatric manifestations associated with severe illness and its treatment. Building upon the first article, which focused on 10 common physical manifestations of psychiatric illness among patients receiving PC, these two articles advocate for an integrated approach to PC that prioritizes mental and emotional wellbeing across the continuum of serious illness.

Palliative Care Psychiatry: Building Synergy Across the Spectrum.

PURPOSE OF REVIEW: Palliative care (PC) psychiatry is a growing subspecialty focusing on improving the mental health of those with serious medical conditions and their caregivers. This review elucidates the current practice and ongoing evolution of PC psychiatry. RECENT FINDINGS: PC psychiatry leverages training and clinical practices from both PC and psychiatry, addressing a wide range of needs, including enhanced psychiatric care for patients with serious medical illness, PC access for patients with medical needs in psychiatric settings, and PC-informed psychiatric approaches for individuals with treatment-refractory serious mental illness. PC psychiatry is practiced by a diverse workforce comprising hospice and palliative medicine-trained psychiatrists, psycho-oncologists, geriatric psychiatrists, other mental health professionals, and non-psychiatrist PC clinicians. As a result, PC psychiatry faces challenges in defining its operational scope. The manuscript outlines the growth, current state, and prospects of PC psychiatry. It examines its roles across various healthcare settings, including medical, integrated care, and psychiatric environments, highlighting the unique challenges and opportunities in each. PC psychiatry is a vibrant and growing subspecialty of psychiatry that must be operationalized to continue its developmental trajectory. There is a need for a distinct professional identity for PC psychiatry, strategies to navigate administrative and regulatory hurdles, and greater support for novel clinical, educational, and research initiatives.

Use of person-centered language in obesity-related publications across sports medicine journals: a systematic review of adherence to person-centered language guidelines in sports medicine.

CONTEXT: Stigmatizing language or non-person-centered language (non-PCL) has been shown to impact patients negatively, especially in the case of obesity. This has led many associations, such as the American Medical Association (AMA) and the International Committee of Medical Journal Editors (ICMJE), to enact guidelines prohibiting the use of stigmatizing language in medical research. In 2018, the AMA adopted person-centered language (PCL) guidelines, including a specific obesity amendment to which all researchers should adhere. However, little research has been conducted to determine if these guidelines are being followed. OBJECTIVES: Our primary objective was to determine if PCL guidelines specific to obesity have been properly followed in the sports medicine journals that are interacted with most frequently. METHODS: We searched within PubMed for obesity-related articles between 2019 and 2022 published in the top 10 most-interacted sports medicine journals based on Google Metrics data. A predetermined list of stigmatizing and non-PCL terms/language was searched within each article. RESULTS: A total of 198 articles were sampled, of which 58.6 % were found to be not compliant with PCL guidelines. The most common non-PCL terms were "obese" utilized in 49.5 % of articles, followed by "overweight" as the next most common stigmatizing term at 40.4 %. Stigmatizing labels such as "heavy, heavier, heaviness," "fat" as an adjective, and "morbid" appeared in articles but at a lower rate. CONCLUSIONS: Our study shows that there is a severe lack of adherence to PCL guidelines in the most-interacted sports medicine journals. Negative associations between stigmatizing language and individuals with obesity will only persist if a greater effort is not made to change this. All journals, including the most prestigious ones, should adopt and execute PCL guidelines to prevent the spread of demeaning language in the medical community.

Coronary Artery Calcification and Risk of Cardiac Complication in Geriatric Trauma Population.

BACKGROUND: Better means of identifying patients with increased cardiac complication (CC) risk is needed. Coronary artery calcification (CAC) is reported on routine chest CT scans. We assessed the correlation of CAC and CCs in the geriatric trauma population. STUDY DESIGN: A prospective, observational study of patients 55 years and older who had chest CT scan from May to September 2022 at a level 1 trauma center. Radiologists scored CAC as none, mild, moderate, or severe. None-to-mild CAC (NM-CAC) and moderate-to-severe CAC (MS-CAC) were grouped and in-hospital CCs assessed (arrhythmia, ST elevation myocardial infarction [STEMI], non-STEMI, congestive heart failure, pulmonary edema, cardiac arrest, cardiogenic shock, and cardiac mortality). Univariate and bivariate analyses were performed. RESULTS: Five hundred sixty-nine patients had a chest CT, of them 12 were excluded due to missing CAC severity. Of 557 patients, 442 (79.3%) had none-to-mild CAC and 115 (20.7%) has MS-CAC; the MS-CAC group was older (73.3 vs 67.4 years) with fewer male patients (48.7% vs 54.5%), had higher cardiac-related comorbidities, and had higher abbreviated injury scale chest injury scores. The MS-CAC group had an increased rate of CC (odds ratio [OR] 1.81, p = 0.016). Cardiac complications statistically more common in MS-CAC were congestive heart failure (OR 3.41, p = 0.003); cardiogenic shock (OR 3.3, p = 0.006); non-STEMI I or II (OR 2.8, p = 0.017); STEMI (OR 5.9, p = 0.029); and cardiac-caused mortality (OR 5.27, p = 0.036). No statistical significance between pulmonary edema (p = 0.6), new-onset arrhythmia (p = 0.74), or cardiac arrest (p = 0.193). CONCLUSIONS: CAC as reported on chest CT scans demonstrates a significant correlation with CC and should warrant additional cardiac monitoring.

Social determinants of health in patients with arthritis: a cross-sectional analysis of the 2017 Behavioral Risk Factor Surveillance System.

CONTEXT: Social determinants of health (SDOH) are economic, social, and political conditions that affect a person's overall health or the health of a group of people. Researchers have investigated the effects of SDOH on various diseases, such as asthma, obesity, and chronic stress, but few publications have been made regarding its effects on arthritis. OBJECTIVES: Our primary objective was to analyze the implications of SDOH on disease severity relating to pain levels and limitations experienced among people with diagnosed arthritis. METHODS: We performed a cross-sectional analysis of the 2017 Behavioral Risk Factor Surveillance System (BRFSS). We included individuals who reported having arthritis, were over the age of 45, and who also completed the SDOH module. Pain scores from the four-question Arthritis Burden Module were correlated to question responses pertaining to SDOH to determine their associations. RESULTS: For the analysis, our sample size was 25,682, with response rates varying slightly among the SDOH questions. Individuals diagnosed with arthritis were more likely to report functional limitations if they experienced food insecurity (χ2=234.0, p<0.001), financial instability (χ2=149.7, p<0.001), or frequent stress (χ2=297.6, p<0.001). Further, we found that individuals with arthritis experiencing any domain of SDOH reported higher mean pain scores than those not experiencing that domain, with the highest pain score difference among those reporting frequent stress (Coefficient: 1.93, CI=1.74-2.13, t=19.43, p<0.001). CONCLUSIONS: Our results show that SDOH profoundly impact pain levels and limitations experienced by patients with arthritis. Although work has already begun to help alleviate burdens associated with SDOH, more research and actions are required to create equitable health throughout the population.

Top Ten Tips Palliative Care Clinicians Should Know About Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Rapidly proliferating leukemic cells cause symptoms and increase the risk of infection. While individuals may initially benefit from supportive measures, disease-directed therapy may ultimately be required for symptom management, even at the end of life, although this may also inadvertently increase symptom burden. This unpredictable illness trajectory complicates prognostic uncertainty and the timing of hospice referral, which may prohibit access to palliative therapies and lead to recurrent hospitalizations. However, emerging evidence demonstrates that early palliative care (PC) integration with standard leukemia care results in improved quality of life, psychological outcomes, and greater participation in advance care planning. To orient PC clinicians asked to care for patients with AML, this article highlights 10 salient considerations.

Innovations for the integration of palliative care for hematologic malignancies.

Specialist palliative care provides additional support to facilitate living well with a serious illness, like cancer, even while pursuing disease-directed therapy. For patients with hematologic malignancies, integrated specialist palliative care improves symptom burden, mood, and quality of life, with benefits even extending to caregivers. Despite this, patients with hematologic malignancies continue to have significant unmet palliative care needs and typically access palliative care late in their disease trajectories, if at all. In this paper, we will define specialist palliative care and review its benefits for patients with hematologic malignancies. We will discuss the unmet palliative care needs of this patient population and the barriers to integrating palliative care and oncologic care. Finally, we will explore innovations and areas of future research to enhance and optimize palliative care integration into usual cancer care treatment for patients with hematologic malignancies. We will explore the importance of ongoing clinical trials that are examining the correct "dose" of palliative care; the use of technology and telehealth; and the use of novel treatments for this patient population. Together, we will consider innovative avenues to provide palliative care to patients with hematologic malignancies and their caregivers.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8+ T cells from 14 tumor biopsies, including 6 matched pre-post neoadjuvant treatment, revealed that responding tumors had clonally expanded putative tumor-specific exhausted CD8+ tumor-infiltrating lymphocytes (TILs) with a tissue-resident memory program, characterized by high cytotoxic potential (CTX+) and ZNF683 expression, within the baseline TME. Pathologic responses after 5 weeks of PD-1 blockade were consistent with activation of preexisting CTX+ZNF683+CD8+ TILs, paralleling loss of viable tumor and associated tumor antigens. Response was associated with high numbers of CD103+PD-1+CD8+ T cells infiltrating pretreatment lesions, whereas revival of nonexhausted persisting clones and clonal replacement were modest. By contrast, nonresponder baseline TME exhibited a relative absence of ZNF683+CTX+ TILs and subsequent accumulation of highly exhausted clones. In HNSCC, revival of preexisting ZNF683+CTX+ TILs is a major mechanism of response in the immediate postneoadjuvant setting.

Mortality and re-revision following single-stage and two-stage revision surgery for the management of infected primary hip arthroplasty in England and Wales.

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. In total, 535 primary hip arthroplasties were revised with single-stage procedure (1,525 person-years) and 1,605 with two-stage procedure (5,885 person-years). All-cause re-revision was higher following single-stage revision, especially in the first three months (HR at 3 months = 1.98 (95% confidence interval (CI) 1.14 to 3.43), p = 0.009). The risks were comparable thereafter. Re-revision for PJI was higher in the first three postoperative months for single-stage revision and waned with time (HR at 3 months = 1.81 (95% CI 1.22 to 2.68), p = 0.003; HR at 6 months = 1.25 (95% CI 0.71 to 2.21), p = 0.441; HR at 12 months = 0.94 (95% CI 0.54 to 1.63), p = 0.819). Patients initially managed with a single-stage revision received fewer revision operations (mean 1.3 (SD 0.7) vs 2.2 (SD 0.6), p < 0.001). Mortality rates were comparable between these two procedures (29/10,000 person-years vs 33/10,000). The risk of unplanned re-revision was lower following two-stage revision, but only in the early postoperative period. The lower overall number of revision procedures associated with a single-stage revision strategy and the equivalent mortality rates to two-stage revision are reassuring. With appropriate counselling, single-stage revision is a viable option for the treatment of hip PJI.

Advancing Palliative Care Integration in Hematology: Building Upon Existing Evidence.

OPINION STATEMENT: Patients with hematologic malignancies and their families are among the most distressed of all those with cancer. Despite high palliative care-related needs, the integration of palliative care in hematology is underdeveloped. The evidence is clear that the way forward includes standard-of-care PC integration into routine hematologic malignancy care to improve patient and caregiver outcomes. As the PC needs for patients with blood cancer vary significantly by disease, a disease-specific PC integration strategy is needed, allowing for serious illness care interventions to be individualized to the specific needs of each patient and situation.

Clinical and cost effectiveness of single stage compared with two stage revision for hip prosthetic joint infection (INFORM): pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To determine whether patient reported outcomes improve after single stage versus two stage revision surgery for prosthetic joint infection of the hip, and to determine the cost effectiveness of these procedures. DESIGN: Pragmatic, parallel group, open label, randomised controlled trial. SETTING: High volume tertiary referral centres or orthopaedic units in the UK (n=12) and in Sweden (n=3), recruiting from 1 March 2015 to 19 December 2018. PARTICIPANTS: 140 adults (aged ≥18 years) with a prosthetic joint infection of the hip who required revision (65 randomly assigned to single stage and 75 to two stage revision). INTERVENTIONS: A computer generated 1:1 randomisation list stratified by hospital was used to allocate participants with prosthetic joint infection of the hip to a single stage or a two stage revision procedure. MAIN OUTCOME MEASURES: The primary intention-to-treat outcome was pain, stiffness, and functional limitations 18 months after randomisation, measured by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes included surgical complications and joint infection. The economic evaluation (only assessed in UK participants) compared quality adjusted life years and costs between the randomised groups. RESULTS: The mean age of participants was 71 years (standard deviation 9) and 51 (36%) were women. WOMAC scores did not differ between groups at 18 months (mean difference 0.13 (95% confidence interval -8.20 to 8.46), P=0.98); however, the single stage procedure was better at three months (11.53 (3.89 to 19.17), P=0.003), but not from six months onwards. Intraoperative events occurred in five (8%) participants in the single stage group and 20 (27%) in the two stage group (P=0.01). At 18 months, nine (14%) participants in the single stage group and eight (11%) in the two stage group had at least one marker of possible ongoing infection (P=0.62). From the perspective of healthcare providers and personal social services, single stage revision was cost effective with an incremental net monetary benefit of £11 167 (95% confidence interval £638 to £21 696) at a £20 000 per quality adjusted life years threshold (£1.0; $1.1; €1.4). CONCLUSIONS: At 18 months, single stage revision compared with two stage revision for prosthetic joint infection of the hip showed no superiority by patient reported outcome. Single stage revision had a better outcome at three months, fewer intraoperative complications, and was cost effective. Patients prefer early restoration of function, therefore, when deciding treatment, surgeons should consider patient preferences and the cost effectiveness of single stage surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN10956306.

YAP1 maintains active chromatin state in head and neck squamous cell carcinomas that promotes tumorigenesis through cooperation with BRD4.

Analysis of The Cancer Genome Atlas and other published data of head and neck squamous cell carcinoma (HNSCC) reveals somatic alterations of the Hippo-YAP pathway in approximately 50% of HNSCC. Better strategies to target the YAP1 transcriptional complex are sought. Here, we show that FAT1, an upstream inhibitor of YAP1, is mutated either by missense or by truncating mutation in 29% of HNSCC. Comprehensive proteomic and drug-screening studies across pan-cancer models confirm that FAT1-mutant HNSCC exhibits selective and higher sensitivity to BRD4 inhibition by JQ1. Epigenomic analysis reveals an active chromatin state in FAT1-mutant HNSCC cells that is driven by the YAP/TAZ transcriptional complex through recruitment of BRD4 to deposit active histone marks, thereby maintaining an oncogenic transcriptional state. This study reveals a detailed cooperative mechanism between YAP1 and BRD4 in HNSCC and suggests a specific therapeutic opportunity for the treatment of this subset of head and neck cancer patients.

Factors Associated with Health Care Utilization at the End of Life for Patients with Acute Myeloid Leukemia.

Background: Patients (≥60 years) with acute myeloid leukemia (AML) often receive intense health care utilization at the end of life (EOL). However, factors associated with their health care use at the EOL are unknown. Methods: We conducted a secondary analysis of 168 deceased patients with AML within the United States. We assessed quality of life (QOL) (Functional-Assessment-Cancer-Therapy-Leukemia), and psychological distress (Hospital-Anxiety-and-Depression Scale [HADS]; Patient-Health-Questionnaire-9 [PHQ-9]) at diagnosis. We used multivariable logistic regression models to examine the association between patient-reported factors and the following outcomes: (1) hospitalizations in the last 7 days of life, (2) receipt of chemotherapy in the last 30 days of life, and (3) hospice utilization. Results: About 66.7% (110/165) were hospitalized in the last 7 days of life, 51.8% (71/137) received chemotherapy in the last 30 days of life, and 40.7% (70/168) utilized hospice. In multivariable models, higher education (odds ratio [OR] = 1.54, p = 0.006) and elevated baseline depression symptoms (PHQ-9: OR = 1.09, p = 0.028) were associated with higher odds of hospitalization in the last seven days of life, while higher baseline QOL (OR = 0.98, p = 0.009) was associated with lower odds of hospitalization at the EOL. Higher baseline depression symptoms were associated with receipt of chemotherapy at the EOL (HADS-Depression: OR = 1.10, p = 0.042). Higher education was associated with lower hospice utilization (OR = 0.356, p = 0.024). Conclusions: Patients with AML who are more educated, with higher baseline depression symptoms and lower QOL, were more likely to experience high health care utilization at the EOL. These populations may benefit from interventions to optimize the quality of their EOL care.

Genomic and epigenomic adaptation in SP-R210 (Myo18A) isoform-deficient macrophages.

Macrophages play an important role in maintaining tissue homeostasis, from regulating the inflammatory response to pathogens to resolving inflammation and aiding tissue repair. The surfactant protein A (SP-A) receptor SP-R210 (MYO18A) has been shown to affect basal and inflammatory macrophage states. Specifically, disruption of the longer splice isoform SP-R210L/MYO18Aα renders macrophages hyper-inflammatory, although the mechanism by which this occurs is not well understood. We asked whether disruption of the L isoform led to the hyper-inflammatory state via alteration of global genomic responses. RNA sequencing analysis of L isoform-deficient macrophages (SP-R210L(DN)) revealed basal and influenza-induced upregulation of genes associated with inflammatory pathways, such as TLR, RIG-I, NOD, and cytoplasmic DNA signaling, whereas knockout of both SP-R210 isoforms (L and S) only resulted in increased RIG-I and NOD signaling. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed increased genome-wide deposition of the pioneer transcription factor PU.1 in SP-R210L(DN) cells, with increased representation around genes relevant to inflammatory pathways. Additional ChIP-seq analysis of histone H3 methylation marks showed decreases in both repressive H3K9me3 and H3K27me3 marks with a commensurate increase in transcriptionally active (H3K4me3) histone marks in the L isoform deficient macrophages. Influenza A virus (IAV) infection, known to stimulate a wide array of anti-viral responses, caused a differential redistribution of PU.1 binding between proximal promoter and distal sites and decoupling from Toll-like receptor regulated gene promoters in SP-R210L(DN) cells. These finding suggest that the inflammatory differences seen in SP-R210L-deficient macrophages are a result of transcriptional differences that are mediated by epigenetic changes brought about by differential expression of the SP-R210 isoforms. This provides an avenue to explore how the signaling pathways downstream of the receptor and the ligands can modulate the macrophage inflammatory response.

Integrating CD4+ T cell help for therapeutic cancer vaccination in a preclinical head and neck cancer model.

Head and neck squamous cell carcinomas (HNSCC) are well suited for cancer vaccination strategies. In addition to tumor-associated antigens (TAAs) and endogenous retrovirus (ERV) encoded proteins, HNSCCs have a relatively high tumor mutational burden encoding potential neoepitopes. Peptide vaccine candidates are prioritized by predicted high-affinity to major histocompatibility complex (MHC) class I with MHC-II affinity largely not being considered. Herein, we extend previous studies to evaluate therapeutic vaccination in the mouse oral cancer (MOC) 22 model. Two distinct MOC22 derived SLPs were tested - a TSA-oriented mutant intercellular adhesion molecule 1 (mICAM1) and p15E, an ERV encoded antigen. In silico prediction revealed mICAM1 SLP bore strong MHC-I and MHC-II epitopes sharing a mutant residue with vaccination significantly increasing both antigen-specific IFN-γ producing CD4+ and CD8+ T cells. By contrast, p15E SLP had a predicted high-affinity MHC-I epitope but lacked an MHC-II epitope and vaccination induced antigen-specific CD8+ but not CD4+ T cell responses. Therapeutic mICAM1 vaccination attenuated tumor growth effectively with mICAM1-specific T cells displaying durable IFN-γ production compared with p15E SLP. Furthermore, mICAM1 SLPs carrying weakened MHC-II binding epitopes were unable to control tumor growth. These data underscore the potential value of therapeutic targeting of HNSCC epitopes and highlight the importance of studying distinct antigen classes in this setting. Moreover, they raise the possibility that, at least in part, CD4+ T cell help is critical for cancer vaccination in this preclinical HNSCC model and suggest in silico prediction approaches prioritize overlapping MHC-I and MHC-II epitopes to generate potent cancer vaccines.

Perineuronal Nets and Metal Cation Concentrations in the Microenvironments of Fast-Spiking, Parvalbumin-Expressing GABAergic Interneurons: Relevance to Neurodevelopment and Neurodevelopmental Disorders.

Because of their abilities to catalyze generation of toxic free radical species, free concentrations of the redox reactive metals iron and copper are highly regulated. Importantly, desired neurobiological effects of these redox reactive metal cations occur within very narrow ranges of their local concentrations. For example, synaptic release of free copper acts locally to modulate NMDA receptor-mediated neurotransmission. Moreover, within the developing brain, iron is critical to hippocampal maturation and the differentiation of parvalbumin-expressing neurons, whose soma and dendrites are surrounded by perineuronal nets (PNNs). The PNNs are a specialized component of brain extracellular matrix, whose polyanionic character supports the fast-spiking electrophysiological properties of these parvalbumin-expressing GABAergic interneurons. In addition to binding cations and creation of the Donnan equilibrium that support the fast-spiking properties of this subset of interneurons, the complex architecture of PNNs also binds metal cations, which may serve a protective function against oxidative damage, especially of these fast-spiking neurons. Data suggest that pathological disturbance of the population of fast-spiking, parvalbumin-expressing GABAergic inhibitory interneurons occur in at least some clinical presentations, which leads to disruption of the synchronous oscillatory output of assemblies of pyramidal neurons. Increased expression of the GluN2A NMDA receptor subunit on parvalbumin-expressing interneurons is linked to functional maturation of both these neurons and the perineuronal nets that surround them. Disruption of GluN2A expression shows increased susceptibility to oxidative stress, reflected in redox dysregulation and delayed maturation of PNNs. This may be especially relevant to neurodevelopmental disorders, including autism spectrum disorder. Conceivably, binding of metal redox reactive cations by the perineuronal net helps to maintain safe local concentrations, and also serves as a reservoir buffering against second-to-second fluctuations in their concentrations outside of a narrow physiological range.

Palliative care and coping in patients with acute myeloid leukemia: Mediation analysis of data from a randomized clinical trial.

BACKGROUND: It has been shown previously that integrated palliative care for patients with acute myeloid leukemia (AML) during intensive chemotherapy leads to improvements in quality of life (QOL) and mood. Coping has been shown to mediate palliative care interventions in advanced cancer; the mechanisms by which improvements occur among patients with AML remain unexplained. METHODS: The authors conducted a secondary analysis of data from a multisite randomized trial of integrated palliative and oncology care (IPC; n = 86) versus usual care (n = 74) for hospitalized patients with AML undergoing intensive chemotherapy. IPC patients met with palliative care at least twice weekly during their initial and subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the Brief Coping Orientation to Problems Experienced Inventory to assess QOL, mood, and coping at the baseline and at weeks 2, 4, 12, and 24. Linear regression models were used to assess the effect of IPC on coping. Causal mediation regression models were used to examine whether changes in coping mediated intervention effects on patient-reported outcomes at week 2. RESULTS: One hundred sixty eligible patients (68.1%) were enrolled. Those randomized to IPC reported improvements in approach-oriented coping (P < .01) and reductions in avoidant coping (P < .05). These changes in coping mediated the intervention effects on QOL (95% CI, 2.14-13.63), depression (95% CI, -2.05 to -0.27), and anxiety symptoms (95% CI, -1.25 to -0.04). Changes in approach-oriented and avoidant coping accounted for 78% of the total palliative care intervention effect on QOL, for 66% of the effect on depression, and for 35% of the effect on anxiety symptoms. CONCLUSIONS: Palliative care integrated during intensive chemotherapy for patients with AML facilitates coping strategy use. Improvement in coping skills accounts for a substantial proportion of the effect from a palliative care intervention on patient-reported outcomes.