A single bout of vigorous intensity exercise enhances the efficacy of rituximab against human chronic lymphocytic leukaemia B-cells ex vivo.

Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts induce a transient relocation of NK-cells and B-cells into peripheral blood, which could be harnessed to enhance the efficacy of rituximab in CLL by relocating both target and effector cells together with rituximab in blood. In this pilot study, n = 20 patients with treatment-naïve CLL completed a bout of cycling 15 % above anaerobic threshold for âˆ¼ 30-minutes, with blood samples collected pre-, immediately post-, and 1-hour post-exercise. Flow cytometry revealed that exercise evoked a 254 % increase in effector (CD3-CD56+CD16+) NK-cells in blood, and a 67 % increase in CD5+CD19+CD20+ CLL cells in blood (all p < 0.005). NK-cells were isolated from blood samples pre-, and immediately post-exercise and incubated with primary isolated CLL cells with or without the presence of rituximab to determine specific lysis using a calcein-release assay. Rituximab-mediated cell lysis increased by 129 % following exercise (p < 0.001). Direct NK-cell lysis of CLL cells - independent of rituximab - was unchanged following exercise (p = 0.25). We conclude that exercise improved the efficacy of rituximab-mediated ADCC against autologous CLL cells ex vivo and propose that exercise should be explored as a means of enhancing clinical responses in patients receiving anti-CD20 immunotherapy.

Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy.

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model induces CR. In conclusion, our integrative analysis provides promising targets and a rationale for immunotherapeutic combination strategies.

A DELAY OF GERMINATION 1 (DOG1)-like protein regulates spore germination in the moss Physcomitrium patens.

DELAY OF GERMINATION 1 is a key regulator of dormancy in flowering plants before seed germination. Bryophytes develop haploid spores with an analogous function to seeds. Here, we investigate whether DOG1 function during germination is conserved between bryophytes and flowering plants and analyse the underlying mechanism of DOG1 action in the moss Physcomitrium patens. Phylogenetic and in silico expression analyses were performed to identify and characterise DOG1 domain-containing genes in P. patens. Germination assays were performed to characterise a Ppdog1-like1 mutant, and replacement with AtDOG1 was carried out. Yeast two-hybrid assays were used to test the interaction of the PpDOG1-like protein with DELLA proteins from P. patens and A. thaliana. P. patens possesses nine DOG1 domain-containing genes. The DOG1-like protein PpDOG1-L1 (Pp3c3_9650) interacts with PpDELLAa and PpDELLAb and the A. thaliana DELLA protein AtRGA in yeast. Protein truncations revealed the DOG1 domain as necessary and sufficient for interaction with PpDELLA proteins. Spores of Ppdog1-l1 mutant germinate faster than wild type, but replacement with AtDOG1 reverses this effect. Our data demonstrate a role for the PpDOG1-LIKE1 protein in moss spore germination, possibly alongside PpDELLAs. This suggests a conserved DOG1 domain function in germination, albeit with differential adaptation of regulatory networks in seed and spore germination.

Factors Affecting the Rate of Colonoscopy Among African Americans Aged Over 45 Years.

African Americans continue to have a low rate of colonoscopy screening despite the U.S. Preventive Services Taskforce's (USPSTF) recommendations and its proven benefits. Colonoscopy has proven to be an effective screening and therapeutic procedure. Understanding the root cause of the problem is a crucial step toward achieving the desired colonoscopy rate among this population. This paper evaluates factors that contribute to the underutilization of colonoscopy. The paper also analyzes strategies that could be maximized to increase colonoscopy rates, minimize colorectal cancer inequalities, and promote optimal colorectal health among African Americans.

Artificial Intelligence in Healthcare: Perception and Reality.

Artificial intelligence (AI) has birthed the new "big thing" in modern medicine. It promises to bring about safer and improved care that will be beneficial to patients and become a helpful tool in the hands of a skilled physician. Despite its anticipation, however, the implementation and usage of AI are still in their elementary phases, particularly due to legal and ethical considerations that border on "data." These challenges should not be brushed aside but rather be recognized and resolved to enable acceptance by all relevant stakeholders without prejudice. Once these challenges can be overcome, AI will truly revolutionize the field of medicine with improved diagnostic accuracy, a reduction in physician burnout, and an enhanced treatment modality. It is therefore paramount that AI be embraced by physicians and integrated into medical education in order to be well-prepared for our role in the future of medicine.

Cancer screening and management in the transgender population: Review of literature and special considerations for gender affirmation surgery.

BACKGROUND: Literature focused on cancer screening and management is lacking in the transgender population. AIM: To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming (TGNC) patients. METHODS: We performed a systematic search of PubMed on January 5th, 2022, with the following terms: "TGNC", OR "transgender", OR "gender non-conforming", OR "gender nonbinary" AND "cancer screening", AND "breast cancer", AND "cervical cancer", AND "uterine cancer", AND "ovarian cancer", AND "prostate cancer", AND "testicular cancer", AND "surveillance", AND "follow-up", AND "management". 70 unique publications were used. The findings are discussed under "Screening" and "Management" categories. RESULTS: Screening: Current cancer screening recommendations default to cis-gender protocols. However, long-term gender-affirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection. The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer. Management: Prior to undergoing Gender Affirmation Surgery (GAS), discussion should address cancer screening and management in the organs remaining in situ. Cancer treatment in this population requires consideration for chemotherapy, radiation, surgery and/or reconstruction. Modification of hormone therapy is decided on a case-by-case basis. The use of prophylactic vs aesthetic techniques in surgery is still debated. CONCLUSION: When assessing transgender individuals for GAS, a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential. Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social, medical, surgical and gender affirming surgery related specifications. Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes. A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS. Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address. We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature. Further research is required to ensure more comprehensive and individualized care for this population.

Nt-acetylation-independent turnover of SQUALENE EPOXIDASE 1 by Arabidopsis DOA10-like E3 ligases.

The acetylation-dependent (Ac/)N-degron pathway degrades proteins through recognition of their acetylated N-termini (Nt) by E3 ligases called Ac/N-recognins. To date, specific Ac/N-recognins have not been defined in plants. Here we used molecular, genetic, and multiomics approaches to characterize potential roles for Arabidopsis (Arabidopsis thaliana) DEGRADATION OF ALPHA2 10 (DOA10)-like E3 ligases in the Nt-acetylation-(NTA)-dependent turnover of proteins at global- and protein-specific scales. Arabidopsis has two endoplasmic reticulum (ER)-localized DOA10-like proteins. AtDOA10A, but not the Brassicaceae-specific AtDOA10B, can compensate for loss of yeast (Saccharomyces cerevisiae) ScDOA10 function. Transcriptome and Nt-acetylome profiling of an Atdoa10a/b RNAi mutant revealed no obvious differences in the global NTA profile compared to wild type, suggesting that AtDOA10s do not regulate the bulk turnover of NTA substrates. Using protein steady-state and cycloheximide-chase degradation assays in yeast and Arabidopsis, we showed that turnover of ER-localized SQUALENE EPOXIDASE 1 (AtSQE1), a critical sterol biosynthesis enzyme, is mediated by AtDOA10s. Degradation of AtSQE1 in planta did not depend on NTA, but Nt-acetyltransferases indirectly impacted its turnover in yeast, indicating kingdom-specific differences in NTA and cellular proteostasis. Our work suggests that, in contrast to yeast and mammals, targeting of Nt-acetylated proteins is not a major function of DOA10-like E3 ligases in Arabidopsis and provides further insight into plant ERAD and the conservation of regulatory mechanisms controlling sterol biosynthesis in eukaryotes.

Improving serious illness communication: a qualitative study of clinical culture.

OBJECTIVE: Communication about patients' values, goals, and prognosis in serious illness (serious illness communication) is a cornerstone of person-centered care yet difficult to implement in practice. As part of Serious Illness Care Program implementation in five health systems, we studied the clinical culture-related factors that supported or impeded improvement in serious illness conversations. METHODS: Qualitative analysis of semi-structured interviews of clinical leaders, implementation teams, and frontline champions. RESULTS: We completed 30 interviews across palliative care, oncology, primary care, and hospital medicine. Participants identified four culture-related domains that influenced serious illness communication improvement: (1) clinical paradigms; (2) interprofessional empowerment; (3) perceived conversation impact; (4) practice norms. Changes in clinicians' beliefs, attitudes, and behaviors in these domains supported values and goals conversations, including: shifting paradigms about serious illness communication from 'end-of-life planning' to 'knowing and honoring what matters most to patients;' improvements in psychological safety that empowered advanced practice clinicians, nurses and social workers to take expanded roles; experiencing benefits of earlier values and goals conversations; shifting from avoidant norms to integration norms in which earlier serious illness discussions became part of routine processes. Culture-related inhibitors included: beliefs that conversations are about dying or withdrawing care; attitudes that serious illness communication is the physician's job; discomfort managing emotions; lack of reliable processes. CONCLUSIONS: Aspects of clinical culture, such as paradigms about serious illness communication and inter-professional empowerment, are linked to successful adoption of serious illness communication. Further research is warranted to identify effective strategies to enhance clinical culture and drive clinician practice change.

Review: Targeting EZH2 in neuroblastoma.

Neuroblastoma is one of the commonest extra-cranial pediatric tumors, and accounts for over 15% of all childhood cancer mortality. Risk stratification for children with neuroblastoma is based on age, stage, histology, and tumor cytogenetics. The majority of patients are considered to have high-risk neuroblastoma, for which the long-term survival is less than 50%. Current treatments combine surgical resection, chemotherapy, stem cell transplantation, radiotherapy, anti-GD2 based immunotherapy as well as the differentiating agent isotretinoin. Despite the intensive multimodal therapies applied, there are high relapse rates, and recurrent disease is often resistant to further therapy. Enhancer of Zeste Homolog 2 (EZH2), a catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is a histone methyltransferase that represses transcription through trimethylation of lysine residue K27 on histone H3 (H3K27me3). It is responsible for epigenetic repression of transcription, making EZH2 an essential regulator for cell differentiation. Overexpression of EZH2 has been shown to promote tumorigenesis, cancer cell proliferation and prevent tumor cells from differentiating in a number of cancers. Therefore, research has been ongoing for the past decade, developing treatments that target EZH2 in neuroblastoma. This review summarises the role of EZH2 in neuroblastoma and evaluates the latest research findings on the therapeutic potential of targeting EZH2 in the treatment of neuroblastoma.

Significant Reduction in Length of Stay in Deep Inferior Epigastric Perforator Flap Breast Reconstruction With Implementation of Multimodal ERAS Protocol.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) implementation achieves earlier recovery, reduced hospital length of stay (LOS) and improved outcomes in patients undergoing deep inferior epigastric perforator (DIEP) free flaps. We sought to review our ERAS protocols and their impact on our patients' LOS compared with the literature. METHODS: This was a retrospective review of a single surgeon's experience from 2017 to 2021 of patients undergoing DIEP free-flap breast reconstruction with LOS as the primary outcome. Complication rates and patient demographics are described as secondary outcomes. RESULTS: One hundred twenty-one patients underwent DIEP free-flap breast reconstruction. After adapting ERAS protocols, there has been a 0.98 [SD, 0.17; confidence interval [CI], -1.3 to -0.64; P < 0.001) day decrease in length of stay comparing pre-ERAS to post-ERAS implementation. Length of stay has routinely decreased from an average discharge on day 4.17 (SD, 1.1; range, 3-8 days) in 2017 to discharge on day 2.91 (SD, 1.1; range, 1-5 days) in 2021. Seventy-five percent of patients in 2021 were hospitalized for 3 or fewer days compared with 75% of patients in 2017 hospitalized for 4 or more days. One patient experienced a flap failure. Our study supports successful discharge on postoperative days 2-3 compared with postoperative days 3-4 in the current literature. CONCLUSIONS: The implementation of our ERAS protocol for DIEP free-flap breast reconstruction has resulted in a shorter LOS compared with contemporary literature. The ERAS protocols can be efficiently adopted in microsurgical DIEP breast reconstruction to achieve a shorter LOS without jeopardizing patient outcomes.

DELLA functions evolved by rewiring of associated transcriptional networks.

DELLA proteins are land-plant specific transcriptional regulators that transduce environmental information to multiple processes throughout a plant's life1-3. The molecular basis for this critical function in angiosperms has been linked to the regulation of DELLA stability by gibberellins and to the capacity of DELLA proteins to interact with hundreds of transcription factors4,5. Although bryophyte orthologues can partially fulfil functions attributed to angiosperm DELLA6,7, it is not clear whether the capacity to establish interaction networks is an ancestral property of DELLA proteins or is associated with their role in gibberellin signalling8-10. Here we show that representative DELLAs from the main plant lineages display a conserved ability to interact with multiple transcription factors. We propose that promiscuity was encoded in the ancestral DELLA protein, and that this property has been largely maintained, whereas the lineage-dependent diversification of DELLA-dependent functions mostly reflects the functional evolution of their interacting partners.

Tri-Lineage Differentiation Potential of Osteosarcoma Cell Lines and Human Bone Marrow Stromal Cells from Different Anatomical Locations.

The bone cancer osteosarcoma, found mainly in adolescents, routinely forms around the growth plate/metaphysis of long bones. Bone marrow composition changes with age, shifting from a more hematopoietic to an adipocyte-rich tissue. This conversion occurs in the metaphysis during adolescence, implicating a link between bone marrow conversion and osteosarcoma initiation. To assess this, the tri-lineage differentiation potential of human bone marrow stromal cells (HBMSCs) isolated from the femoral diaphysis/metaphysis (FD) and epiphysis (FE) was characterized and compared to two osteosarcoma cell lines, Saos-2 and MG63. Compared to FE-cells, FD-cells showed an increase in tri-lineage differentiation. Additionally, differences were found between the Saos-2 cells exhibiting higher levels of osteogenic differentiation, lower adipogenic differentiation, and a more developed chondrogenic phenotype than MG63, with the Saos-2 being more comparable to FD-derived HBMSCs. The differences found between the FD and FE derived cells are consistent with the FD region containing more hematopoietic tissue compared to the FE. This may be related to the similarities between FD-derived cells and Saos-2 cells during osteogenic and chondrogenic differentiation. These studies reveal distinct differences in the tri-lineage differentiations of 'hematopoietic' and 'adipocyte rich' bone marrow, which correlate with specific characteristics of the two osteosarcoma cell lines.

Pain Control after Reduction Mammaplasty with Combination Bupivacaine and Dexamethasone Regional Block: A Randomized Controlled Trial.

BACKGROUND: There are many approaches to pain control in reduction mammaplasty. Preoperative bupivacaine regional blocks control pain relatively inexpensively ($0.07/mL), but last only 8 hours. A liposomal bupivacaine formulation lasts 72 hours but can be costly ($17.21/mL). Orthopedic and thoracic operations have demonstrated that dexamethasone ($0.44/mL) plus bupivacaine can prolong analgesia. The authors conducted a double-blind, randomized, controlled trial to determine whether dexamethasone plus bupivacaine regional block improves postoperative pain control, reduces inpatient narcotic use, and improves patient satisfaction. METHODS: Female patients were randomized into control and experimental groups. Both groups received preoperative modified block of the pectoral nerves: bupivacaine plus saline (control group) or bupivacaine plus dexamethasone (experimental group). Postoperative pain regimens were standardized. Vital signs, pain scores, narcotic consumption, and antiemetic use were recorded throughout the hospitalization. Quality-of-life surveys were distributed at the first postoperative visit. RESULTS: Fifty-one patients completed the study: 25 control and 26 experimental group patients. The experimental group averaged lower pain scores, although there was no statistically significant difference overall or at each 4-hour interval. Postoperative narcotic use was significantly lower in the experimental group (mean, 23.2 oral morphine equivalents versus 36.6 oral morphine equivalents per patient; P = 0.026). There were no differences in 4-hour interval vital signs, antiemetic use, or length of stay. Survey results showed enhanced quality of life in the experimental group, but this was not statistically significant. CONCLUSIONS: The addition of dexamethasone to bupivacaine in the preoperative modified block of the pectoral nerves block before bilateral reduction mammaplasty resulted in significantly less narcotic consumption in the hospital. This can be a cost-effective adjunct for postoperative pain control. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

DELLA proteins regulate spore germination and reproductive development in Physcomitrium patens.

Proteins of the DELLA family integrate environmental signals to regulate growth and development throughout the plant kingdom. Plants expressing non-degradable DELLA proteins underpinned the development of high-yielding 'Green Revolution' dwarf crop varieties in the 1960s. In vascular plants, DELLAs are regulated by gibberellins, diterpenoid plant hormones. How DELLA protein function has changed during land plant evolution is not fully understood. We have examined the function and interactions of DELLA proteins in the moss Physcomitrium (Physcomitrella) patens, in the sister group of vascular plants (Bryophytes). PpDELLAs do not undergo the same regulation as flowering plant DELLAs. PpDELLAs are not degraded by diterpenes, do not interact with GID1 gibberellin receptor proteins and do not participate in responses to abiotic stress. PpDELLAs do share a function with vascular plant DELLAs during reproductive development. PpDELLAs also regulate spore germination. PpDELLAs interact with moss-specific photoreceptors although a function for PpDELLAs in light responses was not detected. PpDELLAs likely act as 'hubs' for transcriptional regulation similarly to their homologues across the plant kingdom. Taken together, these data demonstrate that PpDELLA proteins share some biological functions with DELLAs in flowering plants, but other DELLA functions and regulation evolved independently in both plant lineages.

Inpatient trial of a tablet app for communicating brain injury rehabilitation goals.

PURPOSE: We examine the use of a custom iPad application, the Rehab Portal, to provide clients in an inpatient brain injury rehabilitation service with access to short videos where clinicians-or the clients themselves-discuss their current rehabilitation goals. MATERIALS AND METHODS: We developed an initial version of the Rehab Portal app based on our previous co-design with service users, their families, and clinicians. This was examined in a field trial with a series of six clients over the course of their stays in inpatient rehabilitation, collecting quantitative data on clinician and client engagement with the Rehab Portal, alongside a thematic analysis of qualitative interviews with clients and clinicians at the point of discharge. RESULTS: Engagement with the platform was high for two clients while it was limited with four more. In our thematic analysis we discuss how introduction of the Rehab Portal disrupted practice, changing how things are done, causing deviation from usual routines, adding burden, and threatening professional integrity. At the same time, where it worked well it led to a repositioning of goal planning away from being clinician directed and towards an ongoing, dynamic collaboration between clinicians, clients and their families. Finally, in some cases we identified a reverting to the status quo, with client demotivation having an unexpected impact on clinician behaviour leading to the process being abandoned. CONCLUSIONS: The current findings do not provide wholesale support for this approach, yet we continue to feel that approaches that support clinician-client communication using asynchronous video may offer considerable future value and are worthy of further investigation.IMPLICATIONS FOR REHABILITATIONThe use of a novel technique to communicate rehabilitation goals via video disrupted practice, changed how things are done, caused deviation from usual routines, added burden, and threatened professional integrity for clinicians.Where it worked well it led to a repositioning of goal planning away from being clinician-directed and towards an ongoing, dynamic collaboration between clinicians, clients and their families.Approaches that support clinician-client communication using asynchronous video may offer considerable future value and are worthy of further investigation.

Prenatal phenotype of 47, XXY (Klinefelter syndrome).

OBJECTIVE: There is a paucity of knowledge regarding the prenatal presentation of Klinefelter syndrome, or 47, XXY. Accurate prenatal counseling is critical and in utero diagnosis is currently limited by a poor understanding of the prenatal phenotype of this condition. METHODS: This is a case series of fetuses with cytogenetically confirmed 47, XXY in the prenatal period or up to age 5 years, with prenatal records available for review from four academic institutions between 2006 and 2019. Ultrasound reports were reviewed in detail to assess for increased nuchal translucency and structural abnormalities. Additionally, we reviewed results of cell-free DNA and serum analyte testing when performed to inform our understanding of the detection of fetal 47, XXY through standard genetic screening tests. RESULTS: Forty-one cases with confirmed cytogenetic diagnosis of 47, XXY and prenatal records available for review were identified: 37 had a prenatal diagnosis and 4 had a postnatal diagnosis. Nuchal translucency was increased ≥3.0 mm in 23.1% (6/26) of cases with a documented measurement. In 29.2% (7/24) of cases with a second trimester anatomical ultrasound available for review, a fetal abnormality was identified (3 brain anomalies, 1 cardiac abnormality, 1 echogenic bowel, and 2 limb abnormalities). Among those who had cell-free DNA and serum analytes performed, 92.6% (25/27) and 36.3% (4/11) had an abnormal result respectively. CONCLUSION: This case series expands our knowledge of the prenatal presentation of 47, XXY by identifying first and second trimester fetal sonographic abnormalities. Prenatal identification of this condition enables accurate counseling, focused prenatal management, and early postnatal interventions to ameliorate some of the known complications.

National advisory panels for childhood cancer in the United Kingdom: An evaluation of current practice and a best practice statement for the future.

BACKGROUND: National advisory panels (NAPs) have been established for the care of children and young people (CYP) with cancer in the United Kingdom since 2011, with an increase in panel number in recent years. Their practice has not previously been reviewed; therefore, we sought to evaluate the role, practice and impact of six selected NAPs offering expertise in ependymoma, histiocytosis, leukaemia, neuroblastoma, renal tumours and sarcoma. PROCEDURE: This service evaluation used mixed methodology, including review of NAP documentation, semi-structured interviews with the NAP chairs and an analysis of the cases referred for discussion. RESULTS: Total 1110 referrals were analysed. Results demonstrated the significant scope and amount of work undertaken by the NAPs, largely testament to the commitment of the panel members. Specific roles fulfilled have been highlighted, and NAP recommendations have been shown to influence clinical decision-making and be implemented in the majority of cases. Despite widespread good practice, areas to address have been identified; these include clarity regarding NAP membership, consistency in recommendations, the consideration of holistic information to promote personalised management and the exploration of wider multidisciplinary team roles. CONCLUSIONS: In the context of increasing demand and the escalating number of NAPs, it is timely to consider how service improvement can be facilitated. Best practice guidelines have been formulated as a product of this study, to promote a sustainable and effective model for NAPs. Review and benchmarking national panel performance against these guidelines will drive high standards of care going forward and they should be embedded as standard practice.

Goals of Care Conversations Documented By an Embedded Emergency Department-Palliative Care Team During COVID.

Background: There has been growing interest around integrating palliative care (PC) into emergency department (ED) practice but concern about feasibility and impact. In 2020, as the COVID pandemic was escalating, our hospital's ED and PC leadership created a new service of PC clinicians embedded in the ED. Objectives: To describe the clinical work of the embedded ED-PC team, in particular what was discussed during goals of care conversations. Design: Prospective patient identification followed by retrospective electronic health record chart extraction and analysis. Settings/Subjects: Adult ED patients in an academic medical center in the United States. Measurements/Results: The embedded ED-PC team saw 159 patients, whose mean age was 77.5. Nearly all patients were admitted, 48.0% had confirmed or presumed COVID, and overall mortality was 29.1%. Of the patients seen, 58.5% had a serious illness conversation documented as part of the consult. The most common topics addressed were patient (or family) illness understanding (96%), what was most important (92%), and a clinical recommendation (91%). Clinicians provided a prognostic estimate in 57/93 (61.3%) of documented discussions. In the majority of cases where prognosis was discussed, it was described as poor. Conclusion: Specialist PC clinicians embedded in the ED can engage in high-quality goals of care conversations that have the potential to align patients' hospital trajectory with their preferences.