15 results on '"Fay, Katherine T."'
Search Results
2. Chronic Alcohol Ingestion Worsens Survival and Alters Gut Epithelial Apoptosis and CD8+ T Cell Function After Pseudomonas Aeruginosa Pneumonia-Induced Sepsis
- Author
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Klingensmith, Nathan J., Fay, Katherine T., Lyons, John D., Chen, Ching-wen, Otani, Shunsuke, Liang, Zhe, Chihade, Deena B., Burd, Eileen M., Ford, Mandy L., and Coopersmith, Craig M.
- Published
- 2019
- Full Text
- View/download PDF
3. Regulators of Intestinal Epithelial Migration in Sepsis
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Meng, Mei, Klingensmith, Nathan J., Liang, Zhe, Lyons, John D., Fay, Katherine T., Chen, Ching-wen, Ford, Mandy L., and Coopersmith, Craig M.
- Published
- 2019
- Full Text
- View/download PDF
4. How We Do It: Remediation Pathways in a Surgical Simulation Curriculum for Competency Improvement.
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Lovasik, Brendan P., Fay, Katherine T., Hinman, Johanna M., Delman, Keith A., Srinivasan, Jahnavi K., and Santore, Matthew T.
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COMPUTER simulation , *CURRICULUM , *INTERNSHIP programs , *CLINICAL competence , *MEDICAL education - Abstract
Objective: Validated assessment of procedural knowledge and skills with formative remediation is a foundational part of achieving surgical competency. High-fidelity simulation programs provide a unique area to assess resident proficiency and independence, as well as to assist in identifying residents in need of further practice. While several studies have validated the use of simulation to attain proficiency of specific technical skills, few have validated remediation pathways for their trainees objectively. In this descriptive analysis, we review 2 remediation pathways within our simulation training curricula and how these are used in assessments of resident proficiency.Materials and Methods: Two methods of remediation were formulated for use in high-fidelity simulation labs. One remediation pathway was a summative process, where ultimate judgment of resident competency was assessed through intra-operative assessments of a holistic skill set. The second remediation pathway was a formative "coaching" process, where feedback is given at several intervals along the pathway towards a specific technical skills competence. All general surgery residents are enrolled in the longitudinal, simulation curricula.Results: Approximately one-third of surgical residents entered into a remediation pathway for either of the high-fidelity simulation curricula. Both residents and faculty expressed support for the summative and formative remediation pathways as constructed. Residents who entered remediation pathways believed it was a beneficial exercise, and the most common feedback was that remediation principles should be expanded to all residents. Interestingly, faculty demonstrated stronger support for the formative coaching feedback model than the summative assessment model.Conclusions: Through the complementary use of both formative and summative remediation pathways, resident competence can be enriched in a constructive, nonpunitive method for self-directed performance improvement. Both trainees and faculty express high satisfaction with programs explicitly organized to ensure that skills are rated through a standardized process. [ABSTRACT FROM AUTHOR]- Published
- 2022
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- View/download PDF
5. Optimal Management of the Hyperkinetic Gallbladder: A Comparison of Outcomes Between Operative and Nonoperative Approaches.
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Williford, Michael L., Fay, Katherine T., Simpson, Francis J., Defnet, Ann M., Schuster, David M., Sethi, Ila, Lin, Edward, Davis Jr., Steven Scott, and Davis, Steven Scott Jr
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GALLBLADDER cancer , *CHOLECYSTECTOMY , *GALLBLADDER , *VENTRICULAR ejection fraction , *INSTITUTIONAL review boards , *DRUG prescribing , *SYMPTOMS , *RESEARCH , *RESEARCH methodology , *RETROSPECTIVE studies , *MEDICAL cooperation , *EVALUATION research , *BILE duct diseases , *COMPARATIVE studies , *QUESTIONNAIRES - Abstract
Background: A hyperkinetic gallbladder is defined as a hepatobiliary iminodiacetic acid (HIDA) scan ejection fraction (EF) of >80%. This condition is poorly described, and there is no current consensus on optimal management. The intent of this study was to determine if cholecystectomy improves symptoms in patients with a hyperkinetic gallbladder when compared to those managed nonoperatively and if there were variables predictive of symptom improvement with or without cholecystectomy.Materials and Methods: This retrospective study included patients from 3 academic hospitals in the Atlanta metro area between the years 2006 and 2018. All patients with an EF >80% were included. Following voluntary exclusion patients were contacted by phone. Each patient was administered a questionnaire regarding their surgical history, medical management, and current symptom profile via Otago score. Institutional Institutional Review Board approval was obtained.Results: 4785 HIDA scans were performed, and 194 reported an EF >80% (incidence 15.7%). 96% of these scans were reported as normal by the radiologist. 68 patients were able to be contacted by phone and completed the questionnaire. 18 patients underwent cholecystectomy, and 89% reported that their symptoms attributed to gallbladder disease were no longer present. 50 patients did not undergo cholecystectomy, and alternate diagnoses, medication prescriptions, diet modification, emergency department visits, and Otago score were higher in this cohort.Discussion: Patients who undergo cholecystectomy for a diagnosis of hyperkinetic gallbladder, on average, report improvement in symptoms when compared to patients managed nonoperatively. This study supports the practice of reporting and managing hyperkinetic gallbladders as a pathologic entity. [ABSTRACT FROM AUTHOR]- Published
- 2021
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6. Chronic Alcohol Ingestion Worsens Survival and Alters Gut Epithelial Apoptosis and CD8+ T Cell Function After Pseudomonas Aeruginosa Pneumonia-Induced Sepsis.
- Author
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Klingensmith, Nathan J., Fay, Katherine T., Lyons, John D., Chen, Ching-wen, Otani, Shunsuke, Liang, Zhe, Chihade, Deena B., Burd, Eileen M., Ford, Mandy L., and Coopersmith, Craig M.
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- 2019
- Full Text
- View/download PDF
7. Increased mortality in CD43-deficient mice during sepsis.
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Fay, Katherine T., Chihade, Deena B., Chen, Ching-Wen, Klingensmith, Nathan J., Lyons, John D., Ramonell, Kimberly, Liang, Zhe, Coopersmith, Craig M., and Ford, Mandy L.
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CD43 antigen , *LABORATORY mice , *MORTALITY , *T cells , *APOPTOSIS - Abstract
CD43 is a large transmembrane protein involved in T cell activation. Previous studies of CD43-/- mice in viral models have demonstrated a role for CD43 in Th1/Th2 skewing, activation of Foxp3+ Treg, and T cell apoptosis. However, the role of CD43 during sepsis has never been tested. Thus, we interrogated the role of CD43 during sepsis using a murine cecal ligation and puncture (CLP) model, and found that CD43-/- mice demonstrated significantly worsened mortality compared to B6 mice following CLP. Phenotypic analysis of splenocytes isolated 24 h after septic insult revealed significantly increased apoptosis of central memory cells in both CD4+ and CD8+ T cell compartments in CD43-/- septic mice compared to WT septic mice. Furthermore, CD43-/-septic mice exhibited a prominent Th2 skewing following sepsis relative to WT septic mice, as evidenced by a significant decrease in the frequency of IL-2+ CXCR3+ TH1 cells as a significant increase in the frequency of IL-4+ CCR4+ TH2 cells. Finally, septic CD43-/- animals contained significantly fewer CD25+ Foxp3+ TReg cells as compared to WT septic animals. Importantly, depleting CD25+ Treg eliminated the increased mortality observed in CD43-/- mice. Taken together, these data demonstrate an important role of CD43 in modulating immune dysregulation and mortality following sepsis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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8. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.
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Ramonell, Kimberly M., Zhang, Wenxiao, Hadley, Annette, Chen, Ching-wen, Fay, Katherine T., Lyons, John D., Klingensmith, Nathan J., McConnell, Kevin W., Coopersmith, Craig M., and Ford, Mandy L.
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CHEMOKINE receptors ,SEPTICEMIA treatment ,T cells ,CD4 antigen ,MULTIPLE organ failure ,ANTI-inflammatory agents ,ANIMAL models in research - Abstract
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4
+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients. [ABSTRACT FROM AUTHOR]- Published
- 2017
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9. The intestinal microenvironment in sepsis.
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Fay, Katherine T., Ford, Mandy L., and Coopersmith, Craig M.
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SEPSIS , *GASTROINTESTINAL system physiology , *MULTIPLE organ failure , *HUMAN microbiota , *LYMPHOCYTES - Abstract
The gastrointestinal tract has long been hypothesized to function as “the motor” of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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10. Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.
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Lyons, John D., Mittal, Rohit, Fay, Katherine T., Chen, Ching-Wen, Liang, Zhe, Margoles, Lindsay M., Burd, Eileen M., Farris, Alton B., Ford, Mandy L., and Coopersmith, Craig M.
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CD4 antigen ,LUNG cancer patients ,SEPSIS ,CELL proliferation ,CANCER-related mortality ,T cells ,APOPTOSIS ,LABORATORY mice ,PATIENTS - Abstract
Background: Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered. Methods: C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival. Results: Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003). Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury. Conclusions: Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on the models used. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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11. The gut microbiome alters immunophenotype and survival from sepsis.
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Fay, Katherine T., Klingensmith, Nathan J., Ching-Wen Chen, Wenxiao Zhang, Yini Sun, Morrow, Kristen N., Zhe Liang, Burd, Eileen M., Ford, Mandy L., and Coopersmith, Craig M.
- Abstract
The microbiome is increasingly implicated in immune regulation and mortality from sepsis. Mice with identical genetic backgrounds but distinct microbiomes were obtained from different vendors and analyzed following cecal ligation and puncture (CLP). ß diversity of the microbiome measured from feces demonstrated significant differences between The Jackson Laboratory (Jax; Bar Harbor, ME, USA) and Charles River Laboratories (CR; Wilmington, MA, USA) C57/B6 mice. Jax mice had 7-d mortality of 90% following CLP, whereas CR mice had a mortality of 53%. Differences in vendor were associated with altered immunophenotype with increased splenic IFN-κ+CD4+ T cells, effector memory CD4+ T cells, and central memory CD4+ T cells and increased Peyer's patch effector memory CD4+ T cells in septic CR mice. To determine whether differences in the microbiome were responsible for these differences, Jax and CR mice were cohoused for 3 wk, after which they assumed a similar microbiota composition. Cohoused mice had improved survival following CLP compared to Jax mice and had similar survival regardless of their vendor of origin. All differences in immunophenotype between septic Jax and CR mice disappeared following cohousing. These findings suggest that the microbiome plays a crucial role in survival and the host immune response from sepsis and represents a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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12. CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.
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Paterson CW, Fay KT, Chen CW, Klingensmith NJ, Gutierrez MB, Liang Z, Coopersmith CM, and Ford ML
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- Animals, Mice, CD4-Positive T-Lymphocytes, CTLA-4 Antigen, Memory T Cells, Ethanol adverse effects, Sepsis drug therapy, Immune Checkpoint Inhibitors therapeutic use
- Abstract
Chronic alcohol use increases morbidity and mortality in the setting of sepsis. Both chronic alcohol use and sepsis are characterized by immune dysregulation, including overexpression of T cell coinhibitory molecules. We sought to characterize the role of CTLA-4 during sepsis in the setting of chronic alcohol exposure using a murine model of chronic alcohol ingestion followed by cecal ligation and puncture. Results indicated that CTLA-4 expression is increased on CD4+ T cells isolated from alcohol-drinking septic mice as compared with either alcohol-drinking sham controls or water-drinking septic mice. Moreover, checkpoint inhibition of CTLA-4 improved sepsis survival in alcohol-drinking septic mice, but not water-drinking septic mice. Interrogation of the T cell compartments in these animals following pharmacologic CTLA-4 blockade, as well as following conditional Ctla4 deletion in CD4+ T cells, revealed that CTLA-4 deficiency promoted the activation and proliferation of effector regulatory T cells and the generation of conventional effector memory CD4+ T cells. These data highlight an important role for CTLA-4 in mediating mortality during sepsis in the setting of chronic alcohol exposure and may inform future approaches to develop targeted therapies for this patient population., (Copyright © 2024 The Authors.)
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- 2024
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13. Junctional adhesion molecule-A deletion increases phagocytosis and improves survival in a murine model of sepsis.
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Klingensmith NJ, Fay KT, Swift DA, Bazzano JM, Lyons JD, Chen CW, Meng M, Ramonell KM, Liang Z, Burd EM, Parkos CA, Ford ML, and Coopersmith CM
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- Animals, Cell Adhesion Molecules genetics, Disease Models, Animal, Immunoglobulin A, Mice, Mice, Inbred C57BL, Phagocytosis, Receptors, Cell Surface genetics, Cell Adhesion Molecules metabolism, Junctional Adhesion Molecule A, Receptors, Cell Surface metabolism, Sepsis genetics
- Abstract
Expression of the tight junction-associated protein junctional adhesion molecule-A (JAM-A) is increased in sepsis, although the significance of this is unknown. Here, we show that septic JAM-A -/- mice have increased gut permeability, yet paradoxically have decreased bacteremia and systemic TNF and IL-1β expression. Survival is improved in JAM-A-/- mice. However, intestine-specific JAM-A-/- deletion does not alter mortality, suggesting that the mortality benefit conferred in mice lacking JAM-A is independent of the intestine. Septic JAM-A-/- mice have increased numbers of splenic CD44hiCD4+ T cells, decreased frequency of TNF+CD4+ cells, and elevated frequency of IL-2+CD4+ cells. Septic JAM-A-/- mice have increased numbers of B cells in mesenteric lymph nodes with elevated serum IgA and intraepithelial lymphocyte IgA production. JAM-A-/- × RAG-/- mice have improved survival compared with RAG-/- mice and identical mortality as WT mice. Gut neutrophil infiltration and neutrophil phagocytosis are increased in JAM-A-/- mice, while septic JAM-A-/- mice depleted of neutrophils lose their survival advantage. Therefore, increased bacterial clearance via neutrophils and an altered systemic inflammatory response with increased opsonizing IgA produced through the adaptive immune system results in improved survival in septic JAM-A-/- mice. JAM-A may be a therapeutic target in sepsis via immune mechanisms not related to its role in permeability.
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- 2022
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14. A longitudinal cadaver-based simulation curriculum creates sustainable increases in resident confidence and exposure to fundamental techniques: Results of a 5-year program evaluation.
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Lovasik BP, Kim SC, Wang VL, Fay KT, Santore MT, Delman KA, and Srinivasan JK
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- Anatomy education, Cadaver, Dissection, General Surgery statistics & numerical data, Humans, Internship and Residency statistics & numerical data, Longitudinal Studies, Program Evaluation, Simulation Training organization & administration, Simulation Training statistics & numerical data, Surgical Procedures, Operative education, Surveys and Questionnaires, Clinical Competence statistics & numerical data, Curriculum, General Surgery education, Internship and Residency methods, Simulation Training methods
- Abstract
Introduction: For the past five years, our surgical residency program has led a cadaver-based simulation course focused on fundamental surgical maneuvers. This study aimed to quantify the impact of this course on resident exposure to surgical skills and longitudinal impact on resident education., Methods: General surgery residents participated in an annual cadaver-based simulation curriculum. Participants completed surveys regarding improvements in knowledge and confidence; these results were stratified between course iterations (P1: 2 years, 2014-15; P2: 3 years, 2016-2018)., Results: Residents reported a sustained increase in knowledge of anatomy and technical dissection, confidence in performing operative skills independently, and exposure to operative skills that were otherwise not encountered in clinical rotations. Junior residents demonstrated an increase in gaining skills they would otherwise not achieve (87% vs. 98%, p = 0.028) and confidence to safely perform these procedures in the clinical setting (94% vs. 100%, p = 0.077)., Conclusion: This annual, longitudinal cadaver-based skills course focused on fundamental maneuvers demonstrates a sustained impact in resident and faculty surgical confidence in resident's operative skills as a component of a longitudinal simulation curriculum to enhance competency-based promotion., (Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
15. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.
- Author
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Ramonell KM, Zhang W, Hadley A, Chen CW, Fay KT, Lyons JD, Klingensmith NJ, McConnell KW, Coopersmith CM, and Ford ML
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- Animals, CD8-Positive T-Lymphocytes immunology, Female, Flow Cytometry, Immunologic Memory, Male, Mice, Mice, Inbred C57BL, Sepsis microbiology, Survival Analysis, CD4-Positive T-Lymphocytes immunology, Disease Models, Animal, Receptors, CXCR4 antagonists & inhibitors, Sepsis immunology
- Abstract
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.
- Published
- 2017
- Full Text
- View/download PDF
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