Daily Anesthesiology Research Analysis
Three impactful studies shape perioperative and critical care practice. A translational study identifies suPAR as a kidney-specific vasoconstrictor linking innate immunity to perioperative AKI risk. Two large perioperative cohorts show that FIB-4 liver fibrosis scores and preoperative HbA1c (including undiagnosed diabetes) independently predict 30-day postoperative complications and mortality, supporting biomarker-driven risk stratification and screening.
Summary
Three impactful studies shape perioperative and critical care practice. A translational study identifies suPAR as a kidney-specific vasoconstrictor linking innate immunity to perioperative AKI risk. Two large perioperative cohorts show that FIB-4 liver fibrosis scores and preoperative HbA1c (including undiagnosed diabetes) independently predict 30-day postoperative complications and mortality, supporting biomarker-driven risk stratification and screening.
Research Themes
- Biomarker-based perioperative risk stratification
- Innate immune mechanisms driving perioperative AKI
- Preoperative metabolic screening and optimization
Selected Articles
1. Soluble urokinase receptor is a kidney-specific vasoconstrictor.
Integrating a matched cardiac surgery cohort with porcine perfusion and intravital mouse imaging, the authors show that suPAR acts as a kidney-specific vasoconstrictor that reduces renal blood flow and glomerular perfusion. This mechanistic link between innate immune activation and renal hemodynamics provides a plausible causal pathway for perioperative AKI risk.
Impact: First mechanistic evidence that an innate immune mediator directly causes renal vasoconstriction across species and systems, reframing AKI risk beyond tubular injury. It opens biomarker-guided risk stratification and therapeutic targeting of suPAR.
Clinical Implications: Preoperative suPAR measurement may refine AKI risk prediction in cardiac and high-risk surgery; strategies to lower suPAR or blunt its vasoconstrictive signaling could prevent AKI. Anesthesiologists should consider suPAR when evaluating renal hemodynamic vulnerability.
Key Findings
- Higher suPAR levels were inversely associated with baseline eGFR in a propensity-score–matched cardiac surgery cohort.
- Ex vivo porcine kidney perfusion with suPAR reduced renal blood flow and increased renal vascular resistance.
- Intravital multiphoton imaging showed suPAR-induced afferent arteriolar constriction and reduced glomerular perfusion.
- suPAR is characterized as a predominantly kidney-specific vasoconstrictor with implications for perioperative AKI.
Methodological Strengths
- Translational, multi-system approach integrating clinical, ex vivo, and in vivo models.
- Propensity-score–matched clinical cohort strengthens causal inference alongside mechanistic imaging.
Limitations
- Exact clinical sample size and interventional suPAR-lowering trials are not reported.
- Generalizability beyond cardiac surgery and species translation requires further validation.
Future Directions: Test suPAR-guided perioperative pathways and evaluate therapies that reduce suPAR levels or block downstream vasoconstrictive signaling to prevent AKI.
BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an innate immune system-derived risk factor for acute and chronic kidney diseases. While suPAR effects on kidney epithelial cells have been reported, its impact on renal vasculature remains unknown. METHODS: We investigated how suPAR affects renal blood flow and glomerular dynamics using a translational approach integrating clinical observations from a propensity-score-matched cardiac surgery cohort, ex vivo porcine kidney perfusion, and intravital multiphoton imaging in mice. FINDINGS: In the matched clinical cohort, we found a significant inverse correlation between suPAR levels and baseline kidney function, with mean eGFR values 14.5 mL/min/1.73 m
2. Association of Liver Fibrosis Fibrosis-4 Score with Perioperative Complications and Mortality: A Retrospective Multicenter Analysis.
In 1,325,102 anesthetized patients, higher FIB-4 categories strongly associated with 30-day mortality and with AKI, myocardial injury, and pulmonary complications, with dose-response effects and robustness to age-adjusted cutoffs. This supports integrating FIB-4 into preoperative risk assessment, even in patients without known liver disease.
Impact: Massive, multicenter analysis demonstrates that a simple, readily available fibrosis score independently stratifies perioperative risk across outcomes, enabling scalable preoperative optimization.
Clinical Implications: Calculate FIB-4 during preoperative evaluation to refine discussions about 30-day mortality and complications and prioritize optimization (e.g., metabolic control, hemodynamic vigilance) for higher-risk categories.
Key Findings
- Among 1,325,102 patients, FIB-4 1.3–2.67 was associated with cOR 1.533 for 30-day mortality; FIB-4 ≥2.67 with cOR 3.765.
- Dose–response relationship between continuous FIB-4 and mortality; associations persisted with age-adjusted cutoffs.
- Elevated FIB-4 predicted AKI (cOR 1.515), myocardial injury (cOR 1.657), and pulmonary complications (cOR 1.323).
Methodological Strengths
- Extraordinarily large, multicenter cohort with mixed-effects multivariable adjustment.
- Robustness checks including age-adjusted FIB-4 thresholds and continuous modeling.
Limitations
- Retrospective design with potential residual confounding.
- FIB-4 depends on laboratory availability and may be missing in some preoperative workflows.
Future Directions: Prospective validation and interventional studies testing FIB-4–guided optimization pathways and thresholds for perioperative management.
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and related advanced fibrosis are associated with poor hepatic and extrahepatic outcomes. However, the role of liver fibrosis in surgery-related mortality remains unclear. The authors aimed to assess the association between a widely used liver fibrosis marker, the Fibrosis-4 (FIB-4) score, and 30-day postoperative mortality and complications. METHODS: A multicenter historical cohort of patients underwent general anesthesia. Data were obtained from the Multicenter Perioperative Outcomes Group dataset. Exclusion criteria included known liver diseases other than MASLD, hepatic failure, and alcohol use disorder. Risk of liver fibrosis was calculated using the FIB-4 score and categorized using the MASLD accepted predefined ranges. Mixed-effects multivariable logistic regression models were built to assess the adjusted conditional odds ratio (cOR) for the primary outcome of mortality and secondary outcomes of acute kidney injury, myocardial injury, and postoperative pulmonary complications. RESULTS: The final cohort size for the primary outcome of mortality was 1,325,102. Compared to the low-risk FIB-4 category (1.3 or less), the inconclusive FIB-4 category (1.3 to 2.67) was associated with an adjusted cOR of 1.533-fold for mortality (99.75% CI, 1.453 to 1.616), while the elevated category (FIB-4, 2.67 or greater) was associated with an adjusted cOR of 3.765-fold (99.75% CI, 3.572 to 3.969). This association persisted with the application of age-adjusted FIB-4 cutoffs in stratification by age category. A dose-response association was also observed between FIB-4 as a continuous variable and mortality. Among secondary outcomes, elevated FIB-4 was associated with a postoperative cOR of 1.515 for acute kidney injury (99.75% CI, 1.435 to 1.598), a cOR of 1.657 for myocardial injury (99.75% CI, 1.401 to 1.960), and a cOR of 1.323 for postoperative pulmonary complications (99.75% CI, 1.280 to 1.369). CONCLUSIONS: The FIB-4 score is associated with postoperative mortality and complications in a population without clinically apparent liver disease, and evaluation may have value in preoperative patient counseling and optimization.
3. Preoperative Hemoglobin A1C, Glycemic Status, and Postoperative Outcomes in General Surgery.
Using NSQIP data from 282,131 adults, both diagnosed and undiagnosed dysglycemia were common and independently associated with increased 30-day complications and mortality. Risk rose progressively with higher HbA1c, supporting routine preoperative HbA1c screening and tailored glycemic management.
Impact: Defines the perioperative risk gradient across the HbA1c spectrum and quantifies risks in undiagnosed diabetes at scale, informing screening policies.
Clinical Implications: Implement routine preoperative HbA1c testing to uncover undiagnosed diabetes and guide perioperative glucose targets and monitoring intensity.
Key Findings
- Among 282,131 patients, 36% had diagnosed diabetes and 6.4% had diabetes-range HbA1c without diagnosis.
- Complication risk increased progressively with higher HbA1c; HbA1c >9.0% associated with OR 1.32 for any complication.
- Undiagnosed diabetes was associated with higher medical complications (OR 1.11) and mortality (OR 1.24) within 30 days.
Methodological Strengths
- Very large, multicenter clinical dataset with multivariable adjustment.
- Clear stratification by diagnosed vs undiagnosed diabetes and graded HbA1c levels.
Limitations
- Retrospective design with potential selection bias in who had HbA1c measured.
- Lack of randomized glycemic management limits causal inference on treatment effects.
Future Directions: Prospective trials to test HbA1c-guided perioperative management algorithms and thresholds for intervention.
IMPORTANCE: Dysglycemia is increasingly recognized as a major contributor to adverse surgical outcomes. However, the clinical utility of preoperative hemoglobin A1C (HbA1c) screening in general surgery remains unclear. OBJECTIVE: To determine whether elevated HbA1c is associated with increased 30-day postoperative complications, readmissions, and mortality in patients undergoing general surgery procedures. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program database from 2021 to 2023. Multivariable logistic regression was used to evaluate associations between glycemic status and complications within 30 days after surgery. The multicenter database comprised more than 700 participating institutions worldwide, predominantly in the US. Participants included adult patients (18 years or older) undergoing general surgery procedures with available HbA1c data. EXPOSURES: Glycemic status categorized by documented diabetes diagnosis and HbA1c levels, ranging from normoglycemia to very poor glycemic control. Patients without a diagnosis but HbA1c levels higher than 6.4% (to convert to proportion of total hemoglobin, multiply by 0.01) were considered to have undiagnosed diabetes. MAIN OUTCOMES AND MEASURES: Main outcomes included occurrence of any, surgical, and medical complications, as well as readmissions, reoperations, and mortality within 30 days after surgery. RESULTS: Among 282 131 patients (mean [SD] age, 60 [15] years), 36% had diagnosed diabetes, whereas 6.4% had HbA1c values in the diabetes range but no diagnosis. In those patients with diabetes, risk of any complication increased progressively from near normal (HbA1c level <6.0%; odds ratio [OR], 1.06; 95% CI, 1.00-1.11) to very poor glycemic control (HbA1c level >9.0%; OR, 1.32; 95% CI, 1.25-1.39). Undiagnosed diabetes was also associated with higher risks of medical complications (OR, 1.11; 95% CI, 1.04-1.18) and mortality (OR, 1.24; 95% CI, 1.07-1.42). CONCLUSIONS AND RELEVANCE: Dysglycemia-both diagnosed and undiagnosed-is highly prevalent among general surgery patients and independently associated with increased risks of complications, readmissions, or mortality. A significant proportion of patients had HbA1c levels in the diabetes range, despite lacking a diabetes diagnosis. These findings support routine preoperative HbA1c screening and the adoption of individualized glycemic management strategies to optimize surgical risk assessment, reduce complications, and improve perioperative outcomes.