SurgeryPub Date : 2026-09-28DOI: 10.1016/j.surg.2026.110720
Shalmali Dharmadhikari, Robert J Beal, Brayden Martinez, Paul J Matheson, Cara Gable, Madison Sowers, Zhoudao Zhuang, Yan Li, Susan Galandiuk
{"title":"Amplification of interferon-γ-driven proinflammatory macrophage responses by granulocyte-macrophage colony-stimulating factor: Implications for colorectal cancer immunotherapy.","authors":"Shalmali Dharmadhikari, Robert J Beal, Brayden Martinez, Paul J Matheson, Cara Gable, Madison Sowers, Zhoudao Zhuang, Yan Li, Susan Galandiuk","doi":"10.1016/j.surg.2026.110720","DOIUrl":"https://doi.org/10.1016/j.surg.2026.110720","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages in colorectal cancer predominantly exhibit an immunosuppressive M2 phenotype that contributes to tumor progression and resistance to immune checkpoint inhibition. Repolarizing M2 macrophages toward a proinflammatory M1 phenotype represents a promising immunotherapeutic strategy. While interferon-γ promotes M1 macrophage activation, the effect of combining interferon-γ with granulocyte-macrophage colony-stimulating factor remains underexplored.</p><p><strong>Methods: </strong>THP-1-derived M2-like macrophages were treated with interferon-γ (0-500 ng/mL) and granulocyte-macrophage colony-stimulating factor (0-1,000 ng/mL) in a dose-matrix experiment (n = 4). M1 and M2 markers and programmed cell death-ligand 1 were quantified by quantitative real-time polymerase chain reaction at 24 hours. Secreted interleukin-6, tumor necrosis factor-α, and interleukin-10 were measured by enzyme-linked immunosorbent assay. HT-29 colorectal cancer cells were treated with macrophage-conditioned media and assessed for E-cadherin, N-cadherin, vimentin, and Ki-67. Statistical analyses included t tests and analysis of variance.</p><p><strong>Results: </strong>Interferon-γ strongly induced M1 gene expression, whereas granulocyte-macrophage colony-stimulating factor alone demonstrated modest effects. Combined interferon-γ (50 ng/mL) and granulocyte-macrophage colony-stimulating factor (500 ng/mL) amplified interleukin-6, C-X-C motif chemokine ligand 10, and tumor necrosis factor-α gene expression 5.4-fold, 2.9-fold, and 3.1-fold, respectively, beyond interferon-γ alone. Two-way analysis of variance showed no significant interaction, suggesting additive rather than synergistic enhancement. Combination treatment increased the secretion of interleukin-6 and tumor necrosis factor-α and reduced interleukin-10. Conditioned media from combination-treated macrophages increased E-cadherin and reduced N-cadherin, vimentin, and Ki-67 in HT-29 cells.</p><p><strong>Conclusion: </strong>Granulocyte-macrophage colony-stimulating factor augments interferon-γ-driven proinflammatory macrophage responses with protein-level changes and functional effects on colorectal cancer cells. The resulting macrophage secretome was associated with a less mesenchymal, less proliferative colorectal cancer-cell phenotype. Concurrent programmed cell death-ligand 1 upregulation provides a preclinical rationale for evaluating cytokine-mediated macrophage reprogramming in combination with programmed cell death protein 1/programmed cell death-ligand 1 checkpoint blockade in colorectal cancer.</p>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":" ","pages":"110720"},"PeriodicalIF":3.2,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SurgeryPub Date : 2026-09-28DOI: 10.1016/j.surg.2026.110721
Mason Friesch, Rachel Ferguson, Irena Helenowski, Laura Wool, Monica Edwards, Kevin Brown, Tyler Cohn
{"title":"Same-day discharge sleeve gastrectomy: Is inpatient care worth it?","authors":"Mason Friesch, Rachel Ferguson, Irena Helenowski, Laura Wool, Monica Edwards, Kevin Brown, Tyler Cohn","doi":"10.1016/j.surg.2026.110721","DOIUrl":"https://doi.org/10.1016/j.surg.2026.110721","url":null,"abstract":"<p><strong>Background: </strong>Same-day discharge after sleeve gastrectomy for obesity has been shown to be safe; however, the cost effectiveness of this approach is unclear. We compared 90-day charges associated with same-day discharge versus overnight stay sleeve gastrectomy.</p><p><strong>Methods: </strong>We queried the Health Care Utilization Project State Inpatient, Ambulatory Surgery, and Emergency Department databases for Florida, Georgia, Maryland, and Wisconsin. Adults undergoing sleeve gastrectomy from 2017 to 2018 were identified. Total health care charges were aggregated over 90 days. Multivariable linear and logistic regression identified factors associated with charges and readmission. Overnight stay sleeve gastrectomy patients were 4:1 propensity matched to same-day discharge sleeve gastrectomy patients.</p><p><strong>Results: </strong>Thirty-eight thousand four hundred forty-six patients met inclusion criteria: 2,105 (5.5%) same-day discharge and 36,341 (94.5%) overnight stay sleeve gastrectomies were identified. Same-day discharge was associated with decreased 90-day charges (charge ratio, 0.76; 95% confidence interval, 0.73-0.78; P < .001) and readmission (odds ratio, 0.77; 95% confidence interval, 0.60-0.98; P = .035) compared with overnight stay sleeve gastrectomy. Patients with higher comorbidity burdens had increased charges (charge ratio, 1.73; 95% confidence interval, 1.68-1.78; P < .001) and readmission rates (odds ratio, 1.91; 95% confidence interval, 1.72-2.13; P < .001). After matching, cohorts had similar rates of readmission (4.2% vs 5.2%, P = .051), emergency department visits (14% vs 14%, P > .99), postoperative visits (21% vs 22%, P = .73), and postoperative endoscopy rates (2.1% vs 2.1%, P = .99). Index charges ($47,685 ± 1,029 vs $59,648 ± 704; P < .001) and total 90-day charges ($53,132 ± 1,436 vs $66,886 ± 948; P < .001) were lower for same-day discharge.</p><p><strong>Conclusion: </strong>In appropriately selected patients, same-day discharge after sleeve gastrectomy is associated with lower 90-day health care charges and comparable clinical outcomes as overnight stay sleeve gastrectomy.</p>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":" ","pages":"110721"},"PeriodicalIF":3.2,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SurgeryPub Date : 2026-09-23DOI: 10.1016/j.surg.2026.110677
Lorenzo Hiraldo, Tyler Zander, Rachel L Wolansky, Joseph Sujka, Bruce Hall, Marshall S Baker, Paul C Kuo
{"title":"Graduate medical education funding and hospital quality: A longitudinal analysis of 881 teaching hospitals.","authors":"Lorenzo Hiraldo, Tyler Zander, Rachel L Wolansky, Joseph Sujka, Bruce Hall, Marshall S Baker, Paul C Kuo","doi":"10.1016/j.surg.2026.110677","DOIUrl":"https://doi.org/10.1016/j.surg.2026.110677","url":null,"abstract":"<p><strong>Background: </strong>Graduate medical education funding ($21 billion, fiscal year 2023) consists of direct graduate medical education and indirect medical education payments for resident training and infrastructure costs. Whether this funding impacts hospital quality remains unclear. We hypothesized that increased indirect medical education and direct graduate medical education funding per resident would be associated with improved hospital quality.</p><p><strong>Methods: </strong>We analyzed 881 teaching hospitals from 2018 to 2023 using Centers for Medicare and Medicaid Services Hospital Compare and Graham Center databases.</p><p><strong>Outcomes: </strong>Centers for Medicare and Medicaid Services 5-star rating, safety, mortality, health care-associated infections, and Medicare spending per beneficiary. Primary predictors include indirect medical education and direct graduate medical education dollars per resident, analyzed continuously. Multivariable regression adjusted for hospital size, resident volume, region, ownership, emergency services, structural confounders (case-mix index, Medicare discharge volume, and safety-net structure), and year. Hospital fixed-effects models were estimated.</p><p><strong>Results: </strong>Analysis included 4,418 hospital-years. Median total graduate medical education funding was $12.5 million per hospital-year in real 2023 dollars, with median total funding of $188,139 per resident. Adjusted for hospital characteristics, higher indirect medical education per resident was associated with better star rating, mortality, safety, and health care-associated infection performance (all P ≤ .03). After adding structural confounders, no independent association with indirect medical education per resident persisted, and none persisted within hospitals over time. Medicare discharge volume attenuated the star-rating association to null and reduced the remaining associations by 53%-75%. Documented resident wage costs did not increase while receipts approximately doubled.</p><p><strong>Conclusion: </strong>Higher graduate medical education funding per resident was not independently associated with better hospital quality. Available data cannot determine how these funds are used; therefore, transparent reporting is required to evaluate this investment.</p>","PeriodicalId":22152,"journal":{"name":"Surgery","volume":" ","pages":"110677"},"PeriodicalIF":3.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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