Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005769
Elliott Bennett-Guerrero,Jamie L Romeiser,Samuel DeMaria,Jacob W Nadler,Timothy D Quinn,Sanjeev K Ponnappan,Ryan Wang,Marjorie S Gloff,Kathleen J Lee,Matthew A Levin,Raymond D Sroka,Samuel L Stanley,Dongliang Wang,Aaron R Sasson,
BACKGROUNDSurgical resection is a widely used treatment for cancer. Patients can be "seeded" with their own cancer cells during surgery, and it has been postulated that the immune response to these circulating cancer cells can influence recurrence risk. Some preclinical and retrospective studies have suggested that propofol-based general anesthesia may be superior to volatile halogenated ethers with respect to cell-mediated immunity, implantation of circulating tumor cells, and cancer-related outcomes, but there are limited data from large randomized clinical trials.METHODSThe General Anesthetics in Cancer Resection (GA-CARES) trial is a multicenter, pragmatic, investigator-initiated, partially blinded, randomized superiority trial. Adults at five U.S. centers undergoing surgical resection of cancers associated with poor outcomes (pancreas, esophagus, lung, stomach, bile ducts, liver, bladder, or peritoneal surface) were randomized (1:1) to receive exclusive use of either propofol or volatile agent for maintenance of general anesthesia. The intent-to-treat population included all randomized patients (n = 1,766) minus 3 patients who withdrew consent before surgery. The per-protocol population included patients completing surgery, with pathologically confirmed cancer, and receiving the assigned anesthetic drug. The primary endpoint was all-cause mortality (minimum 2-yr follow-up). Secondary endpoints included disease-free survival.RESULTSAdherence to the protocol was high, with 95.9% of patients who had surgery receiving the assigned anesthetic exclusively. In contrast to the authors' hypothesis, propofol-treated patients did not exhibit better survival (propofol 230 deaths out of 881 [26.1%] vs. volatile 202 deaths out of 882 [22.9%]; hazard ratio, 1.16; 95% CI, 0.96 to 1.41; P = 0.115 by exact stratified log rank test) in the intent-to-treat population (n = 1,763). In the per-protocol population (n = 1,411), significantly more patients randomized to propofol died through 2-yr follow-up (25.5% vs. 20%; hazard ratio, 1.31; 95% CI, 1.05 to 1.64; P = 0.017). Results were similar for disease-free survival (hazard ratio, 1.10; 95% CI, 0.9 to 1.36; P = 0.428) and were consistent across numerous subgroups.CONCLUSIONSPropofol-based anesthesia is not effective at improving cancer-related outcomes in patients undergoing resection of malignancies.
{"title":"Anesthesia Type during Cancer Surgery: Results of the GA-CARES Randomized, Multicenter Trial.","authors":"Elliott Bennett-Guerrero,Jamie L Romeiser,Samuel DeMaria,Jacob W Nadler,Timothy D Quinn,Sanjeev K Ponnappan,Ryan Wang,Marjorie S Gloff,Kathleen J Lee,Matthew A Levin,Raymond D Sroka,Samuel L Stanley,Dongliang Wang,Aaron R Sasson, ","doi":"10.1097/aln.0000000000005769","DOIUrl":"https://doi.org/10.1097/aln.0000000000005769","url":null,"abstract":"BACKGROUNDSurgical resection is a widely used treatment for cancer. Patients can be \"seeded\" with their own cancer cells during surgery, and it has been postulated that the immune response to these circulating cancer cells can influence recurrence risk. Some preclinical and retrospective studies have suggested that propofol-based general anesthesia may be superior to volatile halogenated ethers with respect to cell-mediated immunity, implantation of circulating tumor cells, and cancer-related outcomes, but there are limited data from large randomized clinical trials.METHODSThe General Anesthetics in Cancer Resection (GA-CARES) trial is a multicenter, pragmatic, investigator-initiated, partially blinded, randomized superiority trial. Adults at five U.S. centers undergoing surgical resection of cancers associated with poor outcomes (pancreas, esophagus, lung, stomach, bile ducts, liver, bladder, or peritoneal surface) were randomized (1:1) to receive exclusive use of either propofol or volatile agent for maintenance of general anesthesia. The intent-to-treat population included all randomized patients (n = 1,766) minus 3 patients who withdrew consent before surgery. The per-protocol population included patients completing surgery, with pathologically confirmed cancer, and receiving the assigned anesthetic drug. The primary endpoint was all-cause mortality (minimum 2-yr follow-up). Secondary endpoints included disease-free survival.RESULTSAdherence to the protocol was high, with 95.9% of patients who had surgery receiving the assigned anesthetic exclusively. In contrast to the authors' hypothesis, propofol-treated patients did not exhibit better survival (propofol 230 deaths out of 881 [26.1%] vs. volatile 202 deaths out of 882 [22.9%]; hazard ratio, 1.16; 95% CI, 0.96 to 1.41; P = 0.115 by exact stratified log rank test) in the intent-to-treat population (n = 1,763). In the per-protocol population (n = 1,411), significantly more patients randomized to propofol died through 2-yr follow-up (25.5% vs. 20%; hazard ratio, 1.31; 95% CI, 1.05 to 1.64; P = 0.017). Results were similar for disease-free survival (hazard ratio, 1.10; 95% CI, 0.9 to 1.36; P = 0.428) and were consistent across numerous subgroups.CONCLUSIONSPropofol-based anesthesia is not effective at improving cancer-related outcomes in patients undergoing resection of malignancies.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"33 1","pages":"51-62"},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005795
Nicole E Dundas,Tyler Law,Teva Brender,Hunter Mills,Edie Espejo,Timothy A Heintz,Arthur W Wallace,Julien Cobert
The rapid adoption of large language models (LLMs) in healthcare has created opportunities for innovation but also has raised critical concerns about scientific rigor. This article provides a toolbox for clinicians, researchers, and reviewers involved with LLM studies, highlighting the importance of methodologic transparency, reproducibility, and ethical considerations. It addresses foundational aspects of LLM functioning, including their training data, inherent biases, and black-box nature. Prompt engineering strategies are reviewed to understand and optimize model interaction, emphasizing the necessity of systematic evaluation of these methods. Key challenges around interpreting outputs are discussed, advocating for explainability and fairness. It stresses clear reporting of computational resources, environmental impacts, and the risks of rapid model iteration on study obsolescence. Given the pace at which LLMs evolve, traditional peer-review practices are often outpaced, requiring new guidelines and rigorous qualitative assessments to ensure validity, fairness, and clinical utility. Recommendations to enhance reporting and reproducibility standards are provided.
{"title":"All That Shines Is Not Gold: Maintaining Scientific Rigor When Evaluating, Interpreting, and Reviewing Studies Using Large Language Models.","authors":"Nicole E Dundas,Tyler Law,Teva Brender,Hunter Mills,Edie Espejo,Timothy A Heintz,Arthur W Wallace,Julien Cobert","doi":"10.1097/aln.0000000000005795","DOIUrl":"https://doi.org/10.1097/aln.0000000000005795","url":null,"abstract":"The rapid adoption of large language models (LLMs) in healthcare has created opportunities for innovation but also has raised critical concerns about scientific rigor. This article provides a toolbox for clinicians, researchers, and reviewers involved with LLM studies, highlighting the importance of methodologic transparency, reproducibility, and ethical considerations. It addresses foundational aspects of LLM functioning, including their training data, inherent biases, and black-box nature. Prompt engineering strategies are reviewed to understand and optimize model interaction, emphasizing the necessity of systematic evaluation of these methods. Key challenges around interpreting outputs are discussed, advocating for explainability and fairness. It stresses clear reporting of computational resources, environmental impacts, and the risks of rapid model iteration on study obsolescence. Given the pace at which LLMs evolve, traditional peer-review practices are often outpaced, requiring new guidelines and rigorous qualitative assessments to ensure validity, fairness, and clinical utility. Recommendations to enhance reporting and reproducibility standards are provided.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"26 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005814
Boris D Heifets,Lingzhong Meng
{"title":"It's Not Just the Ketamine: Perioperative Care and Postoperative Delirium.","authors":"Boris D Heifets,Lingzhong Meng","doi":"10.1097/aln.0000000000005814","DOIUrl":"https://doi.org/10.1097/aln.0000000000005814","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"6 1","pages":"7-9"},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005768
Justin Joseph Skowno
{"title":"Glimpsing Oxygenation through a Glass Darkly.","authors":"Justin Joseph Skowno","doi":"10.1097/aln.0000000000005768","DOIUrl":"https://doi.org/10.1097/aln.0000000000005768","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"523 1","pages":"10-11"},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005722
Benjamin F Gruenbaum,Alexander Zlotnik,Michael Dubilet,Shahar Negev,Vladimir Zeldetz,Kiran S Merchant,Matthew Boyko
Delirium is a serious neuropsychiatric condition marked by acute confusion and cognitive decline, commonly affecting postoperative and critically ill patients. It is especially prevalent in older adults and those requiring intensive care, including patients undergoing major surgery or receiving mechanical ventilation. For anesthesiologists, delirium is a critical and often underrecognized postoperative complication with complex perioperative contributors. Intensive care unit patients with delirium face increased mortality, cognitive impairment, and persistent symptoms beyond discharge. Despite its clinical significance, the pathophysiology of delirium remains poorly understood, with no standardized classification or targeted therapy. In light of emerging evidence connecting blood-brain barrier (BBB) permeability to the onset of delirium, we found that BBB dysfunction may represent a key mechanism underlying its pathophysiology. Through a thorough examination of predisposing and precipitating factors that impair both BBB integrity and cognitive function, we identified many points of connection between BBB dysfunction and delirium specifically. We include here a summary of our diagnostic approach with the aim of improving therapeutic strategies based on preserving BBB function to prevent or mitigate delirium.
{"title":"Role of Blood-Brain Barrier Permeability in Delirium Pathophysiology and Treatment.","authors":"Benjamin F Gruenbaum,Alexander Zlotnik,Michael Dubilet,Shahar Negev,Vladimir Zeldetz,Kiran S Merchant,Matthew Boyko","doi":"10.1097/aln.0000000000005722","DOIUrl":"https://doi.org/10.1097/aln.0000000000005722","url":null,"abstract":"Delirium is a serious neuropsychiatric condition marked by acute confusion and cognitive decline, commonly affecting postoperative and critically ill patients. It is especially prevalent in older adults and those requiring intensive care, including patients undergoing major surgery or receiving mechanical ventilation. For anesthesiologists, delirium is a critical and often underrecognized postoperative complication with complex perioperative contributors. Intensive care unit patients with delirium face increased mortality, cognitive impairment, and persistent symptoms beyond discharge. Despite its clinical significance, the pathophysiology of delirium remains poorly understood, with no standardized classification or targeted therapy. In light of emerging evidence connecting blood-brain barrier (BBB) permeability to the onset of delirium, we found that BBB dysfunction may represent a key mechanism underlying its pathophysiology. Through a thorough examination of predisposing and precipitating factors that impair both BBB integrity and cognitive function, we identified many points of connection between BBB dysfunction and delirium specifically. We include here a summary of our diagnostic approach with the aim of improving therapeutic strategies based on preserving BBB function to prevent or mitigate delirium.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"3 1","pages":"203-229"},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005812
Bryan Cozart,Alexandra K Schwartz,John J Finneran
{"title":"Choosing Nerve Blocks by Hip Fracture Subtype.","authors":"Bryan Cozart,Alexandra K Schwartz,John J Finneran","doi":"10.1097/aln.0000000000005812","DOIUrl":"https://doi.org/10.1097/aln.0000000000005812","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"29 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005774
Eduardo Nunez-Rodriguez,Juan P Cata
{"title":"Volatile General Anesthetics and Oncologic Surgery: A Safe Choice.","authors":"Eduardo Nunez-Rodriguez,Juan P Cata","doi":"10.1097/aln.0000000000005774","DOIUrl":"https://doi.org/10.1097/aln.0000000000005774","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"30 1","pages":"4-6"},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-09DOI: 10.1097/aln.0000000000005809
Zhongcong Xie
{"title":"Breathing and Consciousness under General Anesthesia: A Shared Brain Circuit?","authors":"Zhongcong Xie","doi":"10.1097/aln.0000000000005809","DOIUrl":"https://doi.org/10.1097/aln.0000000000005809","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"29 1","pages":"12-14"},"PeriodicalIF":8.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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