AMPK-mediated regulation of endogenous cholesterol synthesis does not affect atherosclerosis in a murine Pcsk9-AAV model.

BACKGROUND AND AIMS: Dysregulated cholesterol metabolism is a hallmark of atherosclerotic cardiovascular diseases, yet our understanding of how endogenous cholesterol synthesis affects atherosclerosis is not clear. The energy sensor AMP-activated protein kinase (AMPK) phosphorylates and inhibits the rate-limiting enzyme in the mevalonate pathway HMG-CoA reductase (HMGCR). Recent work demonstrated that when AMPK-HMGCR signaling was compromised in an Apoe-/- model of hypercholesterolemia, atherosclerosis was exacerbated due to elevated hematopoietic stem and progenitor cell mobilization and myelopoiesis. We sought to validate the significance of the AMPK-HMGCR signaling axis in atherosclerosis using a non-germline hypercholesterolemia model with functional ApoE. METHODS: Male and female HMGCR S871A knock-in (KI) mice and wild-type (WT) littermate controls were made atherosclerotic by intravenous injection of a gain-of-function Pcsk9D374Y-adeno-associated virus followed by high-fat and high-cholesterol atherogenic western diet feeding for 16 weeks. RESULTS: AMPK activation suppressed endogenous cholesterol synthesis in primary bone marrow-derived macrophages from WT but not HMGCR KI mice, without changing other parameters of cholesterol regulation. Atherosclerotic plaque area was unchanged between WT and HMGCR KI mice, independent of sex. Correspondingly, there were no phenotypic differences observed in hematopoietic progenitors or differentiated immune cells in the bone marrow, blood, or spleen, and no significant changes in systemic markers of inflammation. When lethally irradiated female mice were transplanted with KI bone marrow, there was similar plaque content relative to WT. CONCLUSIONS: Given previous work, our study demonstrates the importance of preclinical atherosclerosis model comparison and brings into question the importance of AMPK-mediated control of cholesterol synthesis in atherosclerosis.

Targeting S6K/NFκB/SQSTM1/Polθ signaling to suppress radiation resistance in prostate cancer.

In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances in delivery, radiotherapy continues to negatively affect treatment outcomes and quality of life due to resistance and late toxic effects to the surrounding normal tissues such as bladder and rectum. It is essential to develop new and effective strategies to achieve better control of tumor. We found that ribosomal protein S6K (RPS6KB1) is elevated in human prostate tumors, and contributes to resistance to radiation. As a downstream effector of mTOR signaling, S6K is known to be involved in growth regulation. However, the impact of S6K signaling on radiation response has not been fully explored. Here we show that loss of S6K led to formation of smaller tumors with less metastatic ability in mice. Mechanistically we found that S6K depletion reduced NFκB and SQSTM1 (p62) reporter activity and DNA polymerase θ (POLθ) that is involved in alternate end-joining repair. We further show that the natural compound berberine interacts with S6K in a in a hitherto unreported novel mode and that pharmacological inhibition of S6K with berberine reduces Polθ and downregulates p62 transcriptional activity via NFκB. Loss of S6K or pre-treatment with berberine improved response to radiation in prostate cancer cells and prevented radiation-mediated resurgence of PSA in animals implanted with prostate cancer cells. Notably, silencing POLQ in S6K overexpressing cells enhanced response to radiation suggesting S6K sensitizes prostate cancer cells to radiation via POLQ. Additionally, inhibition of autophagy with CQ potentiated growth inhibition induced by berberine plus radiation. These observations suggest that pharmacological inhibition of S6K with berberine not only downregulates NFκB/p62 signaling to disrupt autophagic flux but also decreases Polθ. Therefore, combination treatment with radiation and berberine inhibits autophagy and alternate end-joining DNA repair, two processes associated with radioresistance leading to increased radiation sensitivity.

Relationship Between Hip Capsular Thickness and Instability After Previous Hip Arthroscopic Surgery: A Matched-Cohort Analysis.

Background: Thinner anterior hip capsules are associated with hip laxity, but there is little known about the impact of capsular thickness on the development of instability after primary hip arthroscopic surgery. Purpose: To investigate the relationship between hip capsular thickness as measured on preoperative magnetic resonance imaging (MRI) and the development of hip instability after hip arthroscopic surgery for femoroacetabular impingement. Study Design: Case-control study; Level of evidence, 3. Methods: We reviewed revision hip arthroscopic procedures performed between January 1, 2019, and May 1, 2021, at a single institution. Inclusion criteria were preoperative MRI/magnetic resonance arthrography, completion of the study traction protocol, and asymmetric distraction between the hips of ≥3 mm on examination under anesthesia. A comparison group of patients treated for femoroacetabular impingement with primary hip arthroscopic surgery who did not develop capsular instability were matched 1:1 to the patients with instability. Superolateral hip capsular thickness was measured on MRI before index surgery. Analysis was conducted using independent-samples t tests and multivariable linear regression. Results: A total of 44 patients were included, with 22 patients each in the instability and no-instability groups. The mean capsular thickness was lower in the patients with hip instability than in those without (1.9 ± 0.6 vs 3.4 ± 1.1 mm, respectively; P < .001). Decreased capsular thickness was significantly associated with hips with instability versus no-instability (ß = -1.468 [95% CI, -2.049 to -0.887]; P < .001). Conclusion: Thinner preoperative hip capsules in the region of the iliofemoral ligament were seen in patients who subsequently underwent revision arthroscopic surgery for hip instability compared to patients who underwent primary hip arthroscopic surgery without subsequent revision. Patients at a higher risk for the development of postoperative hip instability had a superolateral hip capsular thickness of <2 mm.

Myosin XV is a negative regulator of signaling filopodia during long-range lateral inhibition.

The self-organization of cells during development is essential for the formation of healthy tissues and requires the coordination of cell activities at local scales. Cytonemes, or signaling filopodia, are dynamic actin-based cellular protrusions that allow cells to engage in contact mediated signaling at a distance. While signaling filopodia have been shown to support several signaling paradigms during development, less is understood about how these protrusions are regulated. We investigated the role of the plus-end directed, unconventional MyTH4-FERM myosins in regulating signaling filopodia during sensory bristle patterning on the dorsal thorax of the fruit fly Drosophila melanogaster. We found that Myosin XV is required for regulating signaling filopodia dynamics and, as a consequence, lateral inhibition more broadly throughout the patterning epithelium. We found that Myosin XV is required for limiting the length and number of signaling filopodia generated by bristle precursor cells. Cells with additional and longer signaling filopodia due to loss of Myosin XV are not signaling competent, due to altered levels of Delta ligand and Notch receptor along their lengths. We conclude that Myosin XV acts to negatively regulate signaling filopodia, as well as promote the ability of signaling filopodia to engage in long-range Notch signaling. Since Myosin XV isoforms are present across several vertebrate and invertebrate systems, this may have significance for other long-range signaling mechanisms.

Antitumor efficacy and safety of unedited autologous CD5.CAR T cells in relapsed/refractory mature T-cell lymphomas.

ABSTRACT: Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires additional gene modifications to overcome fratricide because of shared T-cell antigens on normal and malignant T cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels in transduced T cells while retaining strong cytotoxicity against CD5+ malignant cells. In our first-in-human phase 1 study (NCT0308190), second-generation autologous CD5.CAR T cells were manufactured from patients with r/r T-cell malignancies. Here, we report safety and efficacy data from a cohort of patients with mature T-cell lymphoma (TCL). Among the 17 patients with TCL enrolled, CD5 CAR T cells were successfully manufactured for 13 out of 14 attempted lines (93%) and administered to 9 (69%) patients. The overall response rate (complete remission or partial response) was 44%, with complete responses observed in 2 patients. The most common grade 3 or higher adverse events were cytopenias. No grade 3 or higher cytokine release syndrome or neurologic events occurred. Two patients died during the immediate toxicity evaluation period due to rapidly progressive disease. These results demonstrated that CD5.CAR T cells are safe and can induce clinical responses in patients with r/r CD5-expressing TCLs without eliminating endogenous T cells or increasing infectious complications. More patients and longer follow-up are needed for validation. This trial was registered at www.clinicaltrials.gov as #NCT0308190.

Choline metabolism underpins macrophage IL-4 polarization and RELMα up-regulation in helminth infection.

Type 2 cytokines like IL-4 are hallmarks of helminth infection and activate macrophages to limit immunopathology and mediate helminth clearance. In addition to cytokines, nutrients and metabolites critically influence macrophage polarization. Choline is an essential nutrient known to support normal macrophage responses to lipopolysaccharide; however, its function in macrophages polarized by type 2 cytokines is unknown. Using murine IL-4-polarized macrophages, targeted lipidomics revealed significantly elevated levels of phosphatidylcholine, with select changes to other choline-containing lipid species. These changes were supported by the coordinated up-regulation of choline transport compared to naïve macrophages. Pharmacological inhibition of choline metabolism significantly suppressed several mitochondrial transcripts and dramatically inhibited select IL-4-responsive transcripts, most notably, Retnla. We further confirmed that blocking choline metabolism diminished IL-4-induced RELMα (encoded by Retnla) protein content and secretion and caused a dramatic reprogramming toward glycolytic metabolism. To better understand the physiological implications of these observations, naïve or mice infected with the intestinal helminth Heligmosomoides polygyrus were treated with the choline kinase α inhibitor, RSM-932A, to limit choline metabolism in vivo. Pharmacological inhibition of choline metabolism lowered RELMα expression across cell-types and tissues and led to the disappearance of peritoneal macrophages and B-1 lymphocytes and an influx of infiltrating monocytes. The impaired macrophage activation was associated with some loss in optimal immunity to H. polygyrus, with increased egg burden. Together, these data demonstrate that choline metabolism is required for macrophage RELMα induction, metabolic programming, and peritoneal immune homeostasis, which could have important implications in the context of other models of infection or cancer immunity.

Global biodiversity data suggest allopolyploid plants do not occupy larger ranges or harsher conditions compared with their progenitors.

Understanding the factors determining species' geographical and environmental range is a central question in evolution and ecology, and key for developing conservation and management practices. Shortly after the discovery of polyploidy, just over 100 years ago, it was suggested that polyploids generally have greater range sizes and occur in more extreme conditions than their diploid congeners. This suggestion is now widely accepted in the literature and is attributed to polyploids having an increased capacity for genetic diversity that increases their potential for adaptation and invasiveness. However, the data supporting this idea are mixed. Here, we compare the niche of allopolyploid plants to their progenitor species to determine whether allopolyploidization is associated with increased geographic range or extreme environmental tolerance. Our analysis includes 123 allopolyploid species that exist as only one known ploidy level, with at least one known progenitor species, and at least 50 records in the Global Biodiversity Information Facility (GBIF) database. We used GBIF occurrence data and range modeling tools to quantify the geographic and environmental distribution of these allopolyploids relative to their progenitors. We find no indication that allopolyploid plants occupy more extreme conditions or larger geographic ranges than their progenitors. Data evaluated here generally indicate no significant difference in range between allopolyploids and progenitors, and where significant differences do occur, the progenitors are more likely to exist in extreme conditions. We concluded that the evidence from these data indicate allopolyploidization does not result in larger or more extreme ranges. Thus, allopolyploidization does not have a consistent effect on species distribution, and we conclude it is more likely the content of an allopolyploid's genome rather than polyploidy per se that determines the potential for invasiveness.

Patients Have Poor Postoperative Recall of Information Provided the Day of Surgery but Report Satisfaction With and High Use of an E-mailed Postoperative Digital Media Package.

Purpose: To understand what portions of the surgical day patients remember, what parts of an e-mailed media package regarding their surgery patients are used, and how that information affects their surgical experience. Methods: Patients undergoing an outpatient arthroscopic procedure were approached in the preoperative area and asked to remember 3 words. Postoperatively, they were seen by the surgeon to discuss surgical findings and instructions. They were then e-mailed a multimedia package containing a thank you letter, postoperative instructions, annotated arthroscopy images, and a personalized video from the surgeon. Patients were called 2 to 5 days after surgery to answer survey questions and recall the 3 words they were told on the day of surgery. Results: Of the 160 patients, 100% received and accessed the e-mail. When asked if they remembered the postoperative conversation, 125 (78.1%) patients responded yes and 35 (21.9%) responded no. When asked to rate how well they remembered the postoperative conversation, 75.2% patients rated their memory very poor (48, 38.4%) or poor (46, 36.8%). Similarly, 129 (80.6%) patients were unable to remember the 3 surgeon-related words. One hundred percent of patients strongly agreed (145, 90.6%) or agreed (15, 9.4%) the e-mail package enhanced their experience. In addition, 100% of patients strongly agreed (150, 93.8%) or agreed (10, 6.2%) the surgeon video enhanced their experience. The average e-mail shares per patient was 2.5, with 158 (98.7%) of patients sharing the e-mail at least once. Conclusions: This study shows that patients had poor memory of in-person conversations on the day of surgery. However, patients were satisfied with a postoperative multimedia package provided via e-mail after surgery. Patients interacted with the e-mail primarily on their cell phones, liked the surgeon video, and shared the e-mail with others. Level of evidence: Level IV, therapeutic case series.

Clinical and Educational Training About Diversity, Equity, Inclusion, and Justice for Pediatric Residents.

Education and clinical training about diversity, equity, inclusion, and justice (DEIJ) is essential for the personal and professional development of pediatric residents in preparation for a career providing health care to diverse pediatric populations. The ability of pediatric residents to reflect on their lived experiences while gaining perspectives about their patients has the potential to positively affect the health care of patients and decrease health inequities. Clinical rotations were established for students from underrepresented populations in medicine as a pathway for matching and diversifying pediatric residency programs with the potential to help diversify the pediatric workforce. The Accreditation Council for Graduate Medical Education formulated standards about DEIJ in pediatric residency training. Curricula, internships, and mentoring programs have been created by medical institutions and professional medical organizations to provide learning experiences about DEIJ and foster a sense of belonging. This review article highlights the multifactorial approach needed to achieve the goal of diversifying the pediatric workforce through DEIJ instruction in pediatric residency training. [Pediatr Ann. 2023;52(7):e256-e260.].

Acute decompensation of patient following an outpatient CT-guided needle biopsy: A case report.

A 74-year-old female with history of type 2 diabetes, hypertension, and uterine adenocarcinoma presented for CT-guided lung biopsy that was ultimately complicated by an arterial air embolus requiring intensive care. Systemic air embolism is a very rare event but can be devastating. Prompt recognition can be difficult due to an often-vague presentation but is essential and should be considered upon rapid deterioration of a patient's status following high risk procedures. Hyperbaric oxygen therapy is preferred; however, if this is unavailable, additional treatments are predominately supportive care with 100% supplemental oxygen, rapid volume expansion, and ionotropic medications as needed.

Arthroscopic Suprapectoral Biceps Tenodesis: The Best of Both Worlds.

Biceps tendinopathy and superior labrum anterior posterior lesions are a common source of shoulder pain and disability and can be effectively treated with biceps tenodesis. There are a variety of open and arthroscopic tenodesis techniques, but no one technique has demonstrated superiority. Arthroscopic techniques often disregard the extra-articular portions of the biceps tendon as a potential source of pain. Open techniques address this concern; however, they can be associated with wound complications, increased blood loss, nerve injury, and disruptions to surgical workflow. Here, we describe an all arthroscopic tenodesis technique at the suprapectoral zone of the tendon. This method addresses extra-articular sources of pain, while limiting the potential pitfalls of open surgery.

A haem-sequestering plant peptide promotes iron uptake in symbiotic bacteria.

Symbiotic partnerships with rhizobial bacteria enable legumes to grow without nitrogen fertilizer because rhizobia convert atmospheric nitrogen gas into ammonia via nitrogenase. After Sinorhizobium meliloti penetrate the root nodules that they have elicited in Medicago truncatula, the plant produces a family of about 700 nodule cysteine-rich (NCR) peptides that guide the differentiation of endocytosed bacteria into nitrogen-fixing bacteroids. The sequences of the NCR peptides are related to the defensin class of antimicrobial peptides, but have been adapted to play symbiotic roles. Using a variety of spectroscopic, biophysical and biochemical techniques, we show here that the most extensively characterized NCR peptide, 24 amino acid NCR247, binds haem with nanomolar affinity. Bound haem molecules and their iron are initially made biologically inaccessible through the formation of hexamers (6 haem/6 NCR247) and then higher-order complexes. We present evidence that NCR247 is crucial for effective nitrogen-fixing symbiosis. We propose that by sequestering haem and its bound iron, NCR247 creates a physiological state of haem deprivation. This in turn induces an iron-starvation response in rhizobia that results in iron import, which itself is required for nitrogenase activity. Using the same methods as for L-NCR247, we show that the D-enantiomer of NCR247 can bind and sequester haem in an equivalent manner. The special abilities of NCR247 and its D-enantiomer to sequester haem suggest a broad range of potential applications related to human health.

mRNA and tRNA modification states influence ribosome speed and frame maintenance during poly(lysine) peptide synthesis.

Ribosome speed is dictated by multiple factors including substrate availability, cellular conditions, and product (peptide) formation. Translation slows during the synthesis of cationic peptide sequences, potentially influencing the expression of thousands of proteins. Available evidence suggests that ionic interactions between positively charged nascent peptides and the negatively charged ribosome exit tunnel impede translation. However, this hypothesis was difficult to test directly because of inability to decouple the contributions of amino acid charge from mRNA sequence and tRNA identity/abundance in cells. Furthermore, it is unclear if other components of the translation system central to ribosome function (e.g., RNA modification) influence the speed and accuracy of positively charged peptide synthesis. In this study, we used a fully reconstituted Escherichia coli translation system to evaluate the effects of peptide charge, mRNA sequence, and RNA modification status on the translation of lysine-rich peptides. Comparison of translation reactions on poly(lysine)-encoding mRNAs conducted with either Lys-tRNALys or Val-tRNALys reveals that that amino acid charge, while important, only partially accounts for slowed translation on these transcripts. We further find that in addition to peptide charge, mRNA sequence and both tRNA and mRNA modification status influence the rates of amino acid addition and the ribosome's ability to maintain frame (instead of entering the -2, -1, and +1 frames) during poly(lysine) peptide synthesis. Our observations lead us to expand the model for explaining how the ribosome slows during poly(lysine) peptide synthesis and suggest that posttranscriptional RNA modifications can provide cells a mechanism to precisely control ribosome movements along an mRNA.

Embolization of pulmonary artery aneurysms in a patient with Behçet's disease complicated by coil erosion into the airway.

Behçet's disease is an inflammatory vasculitis with the unique feature of pulmonary artery aneurysms. We describe a patient with Behçet's disease and pulmonary artery aneurysms who presented with massive hemoptysis treated by coil embolization. Although there was immediate resolution of hemoptysis and improvement in hemodynamic status, 2 months later the patient reported a refractory cough and feeling of foreign body in her throat. Imaging demonstrated partial coil migration into the bronchus and trachea. Although endovascular intervention is the first-line treatment for massive hemoptysis, in patients with Behçet's disease, active inflammation and chronic steroid use may increase the risk of coil erosion and migration.

Single Institution Outcome of Minimally Invasive Enterocutaneous Fistula Management Utilizing the Biodesign® Fistula Plug.

PURPOSE: To report the outcomes of the Biodesign Fistula Plug as an alternative treatment for enterocutaneous fistulae by presenting our institutional experience from 2013 to 2020. MATERIALS AND METHODS: A retrospective review of all attempted fistula closures utilizing the Biodesign Fistula Plug at a single institution from 2012 to 2020 was performed under IRB approval and in compliance with HIPAA. Patient demographics were obtained including age at the time of the procedure, etiology, location of the fistula, history of malignancy, prior chemotherapy or radiation, and history of prior surgery or other interventions. Patient follow-up was performed through 7/2020 to evaluate for fistula closure, complications, or subsequent treatments. RESULTS: There were 25 patients who underwent 35 Biodesign Fistula Plug placements. Of these, 7 procedures were successful, defined as closure of the fistula, and 28 procedures were unsuccessful, defined as persistent fistula output or requiring further intervention on the EC fistula. There were 7 major complications, SIR classification D = 3, E = 2 and F = 2. No statistically significant risk factors were found predicting fistula plug failure although there was a trend towards patients with malignancy having unsuccessful outcome (p = 0.057). The average number of procedures for patients with successful closure was 1.4 versus 4.22 for those with unsuccessful closure. The average time to plug failure was 27.8 days (range 3-163 days), and the average time to fistula closure following plug placement was 21.4 days (range 14-30). CONCLUSION: Enterocutaneous fistulae are complex and morbid with no good treatment options. These findings demonstrate the Biodesign Fistula Plug can be successful in select patients, however, should be used with great caution due to high rate of failure and complications including two patient deaths.

The impact of whole genome and transcriptome analysis (WGTA) on predictive biomarker discovery and diagnostic accuracy of advanced malignancies.

In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology. We used National Comprehensive Cancer Network (NCCN) consensus guidelines, Food and Drug Administration (FDA) approvals, and provincially reimbursed treatments to define genomic biomarkers associated with approved targeted therapeutic options (TTOs). Tumor tissue/site of origin was reassessed for most cases using genomic analysis, including a machine learning algorithm (Supervised Cancer Origin Prediction Using Expression [SCOPE]) trained on The Cancer Genome Atlas data. WGTA was performed on 652 cases, including a range of primary tumor types/tumor sites and 15 malignant tumors of uncertain histogenesis (MTUH). At the time WGTA was performed, alterations associated with an approved TTO were identified in 39 (6%) cases; 3 of these were not identified through routine pathology workup. In seven (1%) cases, the pathology workup either failed, was not performed, or gave a different result from the WGTA. Approved TTOs identified by WGTA increased to 103 (16%) when applying 2021 guidelines. The histopathologic diagnosis was reviewed in 389 cases and agreed with the diagnostic consensus after WGTA in 94% of non-MTUH cases (n = 374). The remainder included situations where the morphologic diagnosis was changed based on WGTA and clinical data (0.5%), or where the WGTA was non-contributory (5%). The 15 MTUH were all diagnosed as specific tumor types by WGTA. Tumor board reviews including WGTA agreed with almost all initial predictive molecular profile and histopathologic diagnoses. WGTA was a powerful tool to assign site/tissue of origin in MTUH. Current efforts focus on improving therapeutic predictive power and decreasing cost to enhance use of WGTA data as a routine clinical test.

Clinical care pathway for the evaluation of patients with suspected VITT after ChAdOx1 nCoV-19 vaccination.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical care pathway was developed to guide clinicians in evaluating for VITT among patients who present with thrombocytopenia or thrombosis symptoms within 4 to 28 days after adenoviral vector vaccine exposure. All patients had enzyme-linked immunosorbent assay (ELISA) testing for platelet factor 4 (PF4) antibodies, and all cases with positive PF4-ELISA or d-dimer levels ≥2.0 mg/L fibrinogen equivalent units (FEU) had further testing for platelet-activating PF4 antibodies using a modified serotonin release assay (SRA). Between 1 May and 30 June 2021, 37% of 68 patients investigated for VITT had thrombosis, but only 3 had VITT confirmed by PF4-ELISA and SRA. Platelet counts, d-dimer levels, and ELISA optical density values were significantly different between those with and without VITT. Three patients had thrombocytopenia and thrombosis with d-dimer levels >4.0 mg/L FEU but had negative PF4-ELISA and SRA results. Patients with VITT were treated successfully with IV immunoglobulin, nonheparin anticoagulants, and corticosteroids. Our pathway demonstrated that thrombosis is common among patients investigated for VITT and that PF4-ELISA testing is necessary to confirm VITT in those presenting with thrombosis and thrombocytopenia.

Factors Associated With Unplanned Acute Care Services for Patients With Newly Diagnosed Hematologic Malignancies.

PURPOSE: This study evaluated risk factors predicting unplanned 30-day acute service utilization among adults subsequent to hospitalization for a new diagnosis of leukemia, lymphoma, or myeloma. This study explored the prevalence of medical complications (aligned with OP-35 measure specifications from the Centers for Medicare & Medicaid Services [CMS] Hospital Outpatient Quality Reporting Program) and the potential impact of psychosocial factors on unplanned acute care utilization. METHODS: This study included 933 unique patients admitted to three acute care inpatient facilities within a nonprofit community-based health care system in southern California from 2012 to 2017. Integrated comprehensive data elements from electronic medical records and facility oncology registries were leveraged for univariate statistics, predictive models constructed using multivariable logistic regression, and further exploratory data mining, with predictive accuracy of the models measured with c-statistics. RESULTS: The mean age of study participants was 65 years, and 55.1% were male. Specific diagnoses were lymphoma (48.7%), leukemia (35.2%), myeloma (14.0%), and mixed types (2.1%). Approximately one fifth of patients received unplanned acute care services within 30 days postdischarge, and over half of these patients presented with one or more symptoms associated with the CMS medical complication measure. The predictive models, with c-statistics ranging from 0.7 and above for each type of hematologic malignancy, indicated good predictive qualities with the impact of psychosocial functioning on the use of acute care services (P values < .05), including lack of consult for social work during initial admission (lymphoma or myeloma), history of counseling or use of psychotropic medications (lymphoma), and past substance use (myeloma). CONCLUSION: This study provides insights into patient-related factors that may inform a proactive approach to improve health outcomes, such as enhanced care transition, monitoring, and support interventions.