About

Philip A Efron, MD, FACS, FCCM, is a distinguished medical professional associated with UF Health. His credentials include board certifications and fellowships, indicating a high level of expertise and recognition in his field. The biography emphasizes his role within the UF Health community, which is a collaboration involving the University of Florida Health Science Center, Shands hospitals, and other healthcare entities. While specific details about his research focus, background, or key contributions are not provided in the available text, his titles and affiliations suggest a significant involvement in clinical practice, education, and possibly research within the medical and surgical domains.

Research topics

• Medicine
• Internal medicine
• Intensive care medicine
• Emergency medicine
• Biology
• Immunology
• Genetics
• Artificial Intelligence
• Machine Learning
• Computer Science
• Data Mining
• Surgery
• Medical emergency
• Bioinformatics
• Psychology
• Data science
• Gastroenterology
• Anesthesia

Selected publications

• Preterm birth skews the developmental trajectory of myeloid-derived suppressor cells in the first 48 hours of life: single-cell transcriptomics and inferred intercellular communication

  Molecular Medicine · 2026-03-27

  articleOpen access

  Prematurity is a leading cause of neonatal and childhood mortality, with infections driving early deaths. Innate immunity provides frontline defense after birth and is shaped in part by myeloid-derived suppressor cells (MDSCs). The role of MDSCs in regulation of neonatal immunity, especially in the context of prematurity, remains elusive. We sought to understand the transcriptional landscape of neonatal immune myeloid regulators, specifically differences between preterm and full-term neonates. Insight into specific cellular networks could help understand how to skew preterm MDSCs’ development towards classical immunotolerant and anti-microbial mechanisms. This cross-sectional study used single-cell RNA sequencing to characterize the neonatal MDSC transcriptional landscape, developmental trajectories, and predicted signaling networks within 48 h after birth. Peripheral blood mononuclear cells were isolated from 7 preterm neonates (< 36 weeks gestational age), 6 full-term neonates (> 37 weeks), and 6 healthy adult (21–45 years old, control). Primary exposure was premature birth and neonatal intensive care hospitalization from a single-center, academic tertiary care hospital between 2023 – 2024. Among ~ 339,000 cells, preterm neonates exhibited enrichment of polymorphonuclear MDSCs (10.6% ± 5.3%) vs full-term (2.6% ± 1.3%) and adults (0.4% ± 1.3%). Trajectory analysis identified a prematurity-associated differentiation branch characterized by inflammatory signaling, mitochondrial stress, and heightened protein-translation programs, distinct from a conserved, tolerogenic MDSC trajectory present across ages. Cell-communication modeling showed intensified outgoing and incoming signaling via ADGRE, RESISTIN, TGF-β, ANNEXIN, and ICAM networks. Antigen presentation signatures suggested preserved MHC-I output and diminished MHC-II interactions in neonates, with increased MHC-I input to preterm polymorphonuclear MDSCs. Prematurity is associated with early divergence of MDSC maturation toward an inflammatory and metabolically stressed PMN-MDSC state with altered immune communication. These findings identify cellular mechanisms that may contribute to the heightened tissue damage and infection susceptibility of preterm neonates and highlight MDSC signaling as a potential target for early-life immunomodulatory interventions.

  PublisherDOI

• Spatial single-cell multiomics reveals peripheral immune dysfunction in Parkinson’s and inflammatory bowel disease

  npj Parkinson s Disease · 2026-01-16

  articleOpen access

  Abstract Parkinson’s disease (PD) is the fastest-growing neurodegenerative disease in the world 1 . Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD 2–4 . We investigated peripheral relationships that may underlie mechanisms along the gut–blood axis that contribute to PD progression. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized and identified inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be one catalyst that primes circulating immune cells to body-first PD progression.

  PublisherOA PDFDOI

• CN-RNN: a Deep Learning Framework for Copy Number Variation Detection with Exome Sequencing Data

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-15

  articleOpen access

  Abstract Copy number variations (CNVs) are major structural genomic variants that contribute to a wide range of human diseases. Accurate detection of CNVs from whole-exome sequencing (WES) data has been a long-sought goal for clinical and population genetic studies. Despite recent progress, existing WES-based CNV callers still suffer from high false-positive rates and reduced recall for short-length variants, and current deep learning methods have not fully used complementary information in region-level genomic features. Here we present CN-RNN, a deep learning-based CNV caller for WES data. The model combines a bidirectional long short-term memory (BiLSTM) branch that captures local depth changes and contextual dependencies across neighboring exons with a parallel multi-layer perceptron (MLP) branch that encodes region-level metadata such as GC content, mappability, and exon length. CN-RNN was trained on the Autism Sequencing Consortium (ASC) parent-child trio cohort using the Mendelian rule of inheritance to ensure high-quality training sets. It was evaluated across three independent datasets, in which we showed that CN-RNN outperformed existing WES-based CNV callers and deep learning methods. CN-RNN offers a scalable, accurate tool for CNV profiling in WES-based studies and supports broader application of CNV analysis in population and clinical research. CN-RNN is available at https://github.com/FeifeiXiao-lab/CN-RNN .

  PublisherDOI

• Divergent chromatin remodeling trajectories in CD66b ⁺ MDSCs distinguishes recovery from chronic critical illness after sepsis

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-23

  articleOpen access

  ABSTRACT Sepsis remains a leading cause of morbidity and mortality worldwide, with survivors often following divergent trajectories: rapid recovery (RAP) or progression to chronic critical illness (CCI). CCI is characterized by persistent organ dysfunction, recurrent infections, and immune dysregulation. Myeloid-derived suppressor cells (MDSCs), which expand in number after sepsis, are implicated in this maladaptive state, yet their epigenetic regulation remains poorly understood. Here, we applied an Omni-ATAC protocol optimized to profile chromatin accessibility in CD66b + MDSCs from healthy participants (HPs) and sepsis patients across time points (day 4, day 14–21, and 6 months) and clinical outcomes (RAP, CCI, and Deceased). Dimensionality reduction analyses of genome-wide chromatin accessibility showed clear separation of sepsis and HP samples. Furthermore, these analyses revealed distinct trajectories post-sepsis diagnosis: RAP samples progressively regained HP-like chromatin states, whereas CCI samples remained epigenetically “locked” in aberrant states. Differential accessibility analysis identified thousands of promoter regions with altered accessibility, including immune checkpoint and inflammatory genes (e.g., ARG1, CD274, S100A8 / 9 ). Pathway analyses predicted global suppression of immune, metabolic, and chromatin remodeling programs in CCI, contrasting with restoration in RAP. These findings from patient-derived CD66b + MDSCs suggest that epigenetic chromatin remodeling underlies divergent recovery trajectories and highlight chromatin-modifying pathways as potential therapeutic targets to restore immune competence in sepsis patients with CCI.

  PublisherOA PDFDOI

• C-754-01. Burn Injury Drives Biphasic Macrophage Immune Reprogramming Through Locus-Specific Epigenetic Remodeling

  Journal of Burn Care & Research · 2026-03-01

  articleOpen access

  Abstract Introduction Severe burn injury is followed by immune dysfunction marked by early hyperinflammation and later immunosuppression. The underlying epigenetic mechanisms remain incompletely understood. We hypothesized that burn injury induces coordinated chromatin remodeling in macrophages that governs this biphasic immune phenotype. Methods Female C57BL/6 mice (n = 6) underwent 20% TBSA full-thickness scald injury or sham procedure. Splenic F4/80+ macrophages were isolated on days 2, 9, and 14 post-injury. Cytokine secretion was measured following TLR2 (peptidoglycan) or TLR4 (LPS) stimulation. Targeted transcriptomic profiling of &amp;gt;1300 immune/metabolic genes was performed by nanoString. Epigenetic remodeling of 180 immune loci was assessed using single-molecule Methyltransferase accessibility protocol for individual templates combined with flap-enabled next-generation capture (MAPit-FENGC) to simultaneously measure DNA methylation and chromatin accessibility. Results Macrophages from burn mice demonstrated a biphasic trajectory. At day 2, TLR-stimulated IL-6, MCP-1, and TNFα secretion were increased versus sham (p&amp;lt;.05). By day 14, MCP-1 and TNFα responses were suppressed, while IL-10 secretion increased (p&amp;lt;.05). Transcriptomic profiling confirmed dynamic regulation of Il10, Socs3, and cell-cycle genes, with persistent repression of Nfkb1, Traf6, and Stat3. MAPit-FENGC revealed early chromatin accessibility gains at proinflammatory loci (Cxcl15, Ccl7) and progressive repression of Stat3, Tgfb1, and Nfkb1 promoters. Nucleosome repositioning at the Il10 promoter preceded transcriptional upregulation, suggesting epigenetic priming for tolerance. Conclusions Burn injury induces temporally coordinated transcriptomic and epigenetic remodeling in macrophages, shifting from hyperinflammation to immune tolerance. Locus-specific chromatin remodeling underlies this transition, highlighting mechanistic drivers of post-burn immune paralysis. Applicability of Research to Practice These findings identify macrophage epigenetic reprogramming as a targetable mechanism of burn-induced immune dysfunction. Therapeutic interventions that recalibrate macrophage chromatin states may restore balanced immunity and reduce infection risk in burn survivors. Funding for the study Supported by NIH NIGMS.

  PublisherOA PDFDOI

• Interaction of Sepsis, Disuse, and Aging on Skeletal Muscle Function and Remodeling in Male and Female Mice

  Acta Physiologica · 2026-03-18

  articleOpen access

  ABSTRACT Background Sepsis is associated with skeletal muscle weakness and atrophy, particularly in older and immobilized patients; however, how sepsis interacts with disuse, reloading, aging, and biological sex remains poorly defined. Methods Young (5 mo) and older (20 mo) male and female C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham surgery followed by hindlimb suspension (HLS) or normal ambulation (NA) for 7 days (Experiment 1). A separate cohort underwent 3 days of reloading after HLS (REL; Experiment 2). Outcomes included survival, body mass, soleus force–frequency, myofiber cross‐sectional area (CSA), macrophage infiltration (CD68 + ), extracellular matrix (ECM), and satellite cells (Pax7 + ). Results Survival was preserved in septic young mice (&gt; 84%) but reduced in older septic mice (~51%–60% males; ~57% females). Disuse was the primary driver of body mass loss during HLS/REL, with older females exhibiting the greatest decline (day 11: −19.8% ± 6.8% Sham; −17.4% ± 6.5% CLP). Disuse reduced median fiber CSA by ~27%–46% across cohorts (e.g., young males: 1840 ± 189 to 997 ± 345 μm 2 ). In Experiment 1, CD68 + macrophages increased most with combined sepsis and disuse, whereas ECM expansion was observed only in males. Pax7 + satellite cells were markedly reduced in young males with sepsis and disuse and in older mice of both sexes with sepsis. Following REL, older septic males retained force deficits, and septic females remained significantly atrophic. Conclusion Muscle disuse amplifies sepsis‐induced myopathy in an age‐ and sex‐dependent manner, with incomplete early recovery after reloading.

  PublisherOA PDFDOI

• Macrophages Polarization as a Potential Driver and a Therapeutic Target for Sepsis-induced Cognitive Impairment in Older Adults

  Shock · 2025-09-24

  articleOpen access

  Sepsis, a dysregulated host response to infection, remains a growing global health concern, particularly in older adults. While much attention focuses on acute survival, an increasing number of sepsis survivors experience persistent neurological complications, including impairments in memory, attention, and executive function. In severe cases, these may manifest as sepsis-associated delirium or progress to long-term cognitive impairment and dementia. The mechanisms driving these outcomes are complex and incompletely understood, partly due to limited baseline cognitive data and significant variability among older adults. A central feature of sepsis-induced brain dysfunction is sustained neuroinflammation, which bridges peripheral immune activation and central nervous system injury. Mounting evidence implicates macrophages, including circulating monocytes and brain-resident microglia, as key regulators of this neuroimmune axis. Inflammatory conditions during sepsis often drive macrophage polarization toward a pro-inflammatory M1 phenotype, leading to the release of cytokines and reactive oxygen species that exacerbate blood-brain barrier disruption and neuronal injury. Conversely, impaired transition to the M2 phenotype hinders inflammation resolution and tissue repair. Critically, this interaction is bidirectional, where neuroinflammatory signals from activated microglia can influence peripheral macrophage behavior, creating a self-reinforcing inflammatory loop that may prolong central nervous system damage. This process is especially concerning in older adults who may have preexisting immune vulnerabilities and varying baseline cognitive status, which presents unique challenges for therapeutic targeting. This review highlights the central and dynamic role of macrophage polarization in sepsis-associated cognitive decline. Understanding how systemic and neuroinflammatory pathways converge through macrophage signaling may reveal new therapeutic targets to mitigate long-term neurological complications in sepsis survivors. Graphical abstract-Sepsis alters the abundance and polarization of macrophage subpopulations, contributing to both short- and long-term cognitive impairment. In the acute phase, these changes may manifest as sepsis-associated delirium (SAD), while in the long term, sustained immune dysregulation and neuroinflammation may contribute to persistent cognitive deficits, including memory loss and executive dysfunction.

  PublisherDOI

• Author Correction: A consensus immune dysregulation framework for sepsis and critical illnesses

  Nature Medicine · 2025-10-27 · 4 citations

  erratumOpen access

  Correction to: Nature Medicinehttps://doi.org/10.1038/s41591-025-03956-5, published online 30 September 2025. In the version of the article initially published, Jeremiah Hinson (Department of Emergency Medicine, The Johns Hopkins University, Baltimore, MD, USA) was inadvertently omitted from the author list and contributions and has now been added to the HTML and PDF versions of the article.

  PublisherOA PDFDOI

• Language Models for Multilabel Document Classification of Surgical Concepts in Exploratory Laparotomy Operative Notes: Algorithm Development Study

  JMIR Medical Informatics · 2025-07-09 · 4 citations

  articleOpen access

  Background: Operative notes are frequently mined for surgical concepts in clinical care, research, quality improvement, and billing, often requiring hours of manual extraction. These notes are typically analyzed at the document level to determine the presence or absence of specific procedures or findings (eg, whether a hand-sewn anastomosis was performed or contamination occurred). Extracting several binary classification labels simultaneously is a multilabel classification problem. Traditional natural language processing approaches-bag-of-words (BoW) and term frequency-inverse document frequency (tf-idf) with linear classifiers-have been used previously for this task but are now being augmented or replaced by large language models (LLMs). However, few studies have examined their utility in surgery. Objective: We developed and evaluated LLMs for the purpose of expediting data extraction from surgical notes. Methods: A total of 388 exploratory laparotomy notes from a single institution were annotated for 21 concepts related to intraoperative findings, intraoperative techniques, and closure techniques. Annotation consistency was measured using the Cohen κ statistic. Data were preprocessed to include only the description of the procedure. We compared the evolution of document classification technologies from BoW and tf-idf to encoder-only (Clinical-Longformer) and decoder-only (Llama 3) transformer models. Multilabel classification performance was evaluated with 5-fold cross-validation with F1-score and hamming loss (HL). We experimented with and without context. Errors were assessed by manual review. Code and implementation instructions may be found on GitHub. Results: The prevalence of labels ranged from 0.05 (colostomy, ileostomy, active bleed from named vessel) to 0.50 (running fascial closure). Llama 3.3 was the overall best-performing model (micro F1-score 0.88, 5-fold range: 0.88-0.89; HL 0.11, 5-fold range: 0.11-0.12). The BoW model (micro F1-score 0.68, 5-fold range: 0.64-0.71; HL 0.14, 5-fold range: 0.13-0.16) and Clinical-Longformer (micro F1-score 0.73, 5-fold range: 0.70-0.74; HL 0.11, 5-fold range: 0.10-0.12) had overall similar performance, with tf-idf models trailing (micro F1-score 0.57, 5-fold range: 0.55-0.59; HL 0.27, 5-fold range: 0.25-0.29). F1-scores varied across concepts in the Llama model, ranging from 0.30 (5-fold range: 0.23-0.39) for class III contamination to 0.92 (5-fold range: 0.98-0.84) for bowel resection. Context enhanced Llama's performance, adding an average of 0.16 improvement to the F1-scores. Error analysis demonstrated semantic nuances and edge cases within operative notes, particularly when patients had references to prior operations in their operative notes or simultaneous operations with other surgical services. Conclusions: Off-the-shelf autoregressive LLMs outperformed fined-tuned, encoder-only transformers and traditional natural language processing techniques in classifying operative notes. Multilabel classification with LLMs may streamline retrospective reviews in surgery, though further refinements are required prior to reliable use in research and quality improvement.

  PublisherDOI

• Age- and Sex- Driven Transcriptional and Metabolic Diversity in Myeloid-Derived Suppressor Cells After Mouse Sepsis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-07

  preprintOpen accessSenior authorCorresponding

  Sepsis induces profound immune dysregulation, often resulting in chronic critical illness characterized by persistent immunosuppression and poor outcomes. Myeloid-derived suppressor cells (MDSCs) are central mediators of this immunosuppressive phenotype, yet the influence of age and sex on their transcriptional and metabolic states remain poorly understood. Here, we employed single-cell RNA sequencing of splenic leukocytes from young (3-4 months) and older (18-24 months) adult male and female mice subjected to a clinically relevant murine sepsis model to define age- and sex-specific MDSC phenotypes. We identified significant differences regarding age and sex in MDSC expansion, transcriptome, canonical pathway activation, RNA velocity, mitochondrial metabolism, and predicted cell-cell communication after sepsis. Using drug2cell analysis of total leukocytes we also identified cohort-specific drug target profiles. These findings underscore the importance of age and sex in shaping sepsis-induced MDSC biology and suggest that personalized immunomodulatory strategies targeting MDSCs could improve sepsis outcomes.

  PublisherOA PDFDOI

Recent grants

• Hematopoietic Stem Cell Dysfunction in the Elderly after Severe Injury

  NIH · $1.3M · 2015–2021

• Hematopoietic Stem Cell Dysfunction in the Elderly after Severe Injury

  NIH · $300k · 2015–2020

• Molecular Biology in Burns and Trauma

  NIH · $4.8M · 1999–2029

• Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology

  NIH · $8.5M · 2021–2027

Frequent coauthors

• Lyle L. Moldawer

  Florida College

  619 shared

• Alicia M. Mohr

  University of Florida

  460 shared

• Frederick A. Moore

  University Hospitals Birmingham NHS Foundation Trust

  341 shared

• Scott C. Brakenridge

  Harborview Medical Center

  340 shared

• Tyler J. Loftus

  University of Florida

  290 shared

• Ricardo Ungaro

  University of Florida

  202 shared

• Azra Bihorac

  184 shared

• Dina C. Nacionales

  University of Florida

  147 shared