Amanda Christine Filiberto

All Publications

• Atypical presentation of symptomatic type III popliteal artery entrapment syndrome with resultant popliteal artery pseudoaneurysm formation JOURNAL OF VASCULAR SURGERY CASES INNOVATIONS AND TECHNIQUES Grimm, J., Gupta, T., Filiberto, A., Rowse, J. 2026; 12 (2): 102090

  Abstract

  Popliteal artery entrapment syndrome can cause lower extremity claudication, paresthesia, and pain. This case describes a 68-year-old man presenting with a large popliteal artery pseudoaneurysm secondary to type III popliteal artery entrapment syndrome, resulting in pain, reduced knee flexion, and lower leg paresthesia. He underwent open surgical debulking of the pseudoaneurysm sac and popliteal artery repair via a reversed great saphenous vein interposition bypass. Postoperatively, he had triphasic pedal arterial signals with improvement of his pain, paresthesia, and ambulation. This case represents a rare presentation of an uncommon condition, highlighting the importance of surgical intervention once the condition is diagnosed correctly.

  View details for DOI 10.1016/j.jvscit.2025.102090

  View details for Web of Science ID 001668433800001

  View details for PubMedID 41583725

  View details for PubMedCentralID PMC12828498

• Resource use for cholecystectomy with versus without cholangiography: A multicenter, propensity-matched analysis SURGERY Filiberto, A. C., Nyren, M. Q., Underwood, P. W., Balch, J. A., Abbott, K. L., Efron, P. A., Sarosi Jr, G. A., Bihorac, A., Upchurch Jr, G. R., Loftus, T. J. 2023; 174 (2): 152-158

  Abstract

  Intraoperative cholangiography may allow for earlier identification of common bile duct injury and choledocholithiasis. The role of intraoperative cholangiography in decreasing resource use related to biliary pathology remains unclear. This study tests the null hypothesis that there is no difference in resource use for patients undergoing laparoscopic cholecystectomy with versus without intraoperative cholangiography.This retrospective, longitudinal cohort study included 3,151 patients who underwent laparoscopic cholecystectomy at 3 university hospitals. To minimize differences in baseline characteristics while maintaining adequate statistical power, propensity scores were used to match 830 patients who underwent intraoperative cholangiography at surgeon discretion and 795 patients who underwent cholecystectomy without intraoperative cholangiography. Primary outcomes were the incidence of postoperative endoscopic retrograde cholangiography, the interval between surgery and endoscopic retrograde cholangiography, and total direct costs.In the propensity-matched analysis, the intraoperative cholangiography and no intraoperative cholangiography cohorts had similar age, comorbidities, American Society of Anesthesiologists Sequential Organ Failure Assessment scores, and total/direct bilirubin ratios. The intraoperative cholangiography cohort had a lower postoperative endoscopic retrograde cholangiography (2.4% vs 4.3%; P = .04), a shorter interval between cholecystectomy and endoscopic retrograde cholangiography (2.5 [1.0-17.8] vs 4.5 [2.0-9.5] days; P = .04), and shorter length of stay (0.3 [0.2-1.5] vs 1.4 [0.3-3.2] days; P < .001). Patients undergoing intraoperative cholangiography had lower total direct costs ($4.0K [3.6K-5.4K] vs $8.1K [4.9K-13.0K]; P < .001). There were no differences in 30-day or 1-year mortality among the cohorts.Compared with laparoscopic cholecystectomy without intraoperative cholangiography, cholecystectomy with intraoperative cholangiography was associated with decreased resource use, which was primarily attributable to decreased incidence and the earlier timing of postoperative endoscopic retrograde cholangiography.

  View details for DOI 10.1016/j.surg.2023.04.027

  View details for Web of Science ID 001050837700001

  View details for PubMedID 37188579

  View details for PubMedCentralID PMC12288731

• Methods and evaluation metrics for reducing material waste in the operating room: a scoping review SURGERY Balch, J. A., Krebs, J. R., Filiberto, A. C., Montgomery, W. G., Berkow, L. C., Upchurch Jr, G. R., Loftus, T. J. 2023; 174 (2): 252-258

  Abstract

  Operating rooms contribute up to 70% of total hospital waste. Although multiple studies have demonstrated reduced waste through targeted interventions, few examine processes. This scoping review highlights methods of study design, outcome assessment, and sustainability practices of operating room waste reduction strategies employed by surgeons.Embase, PubMed, and Web of Science were screened for operating room-specific waste-reduction interventions. Waste was defined as hazardous and non-hazardous disposable material and energy consumption. Study-specific elements were tabulated by study design, evaluation metrics, strengths, limitations, and barriers to implementation in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.A total of 38 articles were analyzed. Among them, 74% of studies had pre- versus postintervention designs, and 21% used quality improvement instruments. No studies used an implementation framework. The vast majority (92%) of studies measured cost as an outcome, whereas others included disposable waste by weight, hospital energy consumption, and stakeholder perspectives. The most common intervention was instrument tray optimization. Common barriers to implementation included lack of stakeholder buy-in, knowledge gaps, data capture, additional staff time, need for hospital or federal policies, and funding. Intervention sustainability was discussed in few studies (23%) and included regular waste audits, hospital policy change, and educational initiatives. Common methodologic limitations included limited outcome evaluation, narrow scope of intervention, and inability to capture indirect costs.Appraisal of quality improvement and implementation methods are critical for developing sustainable interventions for reducing operating room waste. Universal evaluation metrics and methodologies may aid in both quantifying the impact of waste reduction initiatives and understanding their implementation in clinical practice.

  View details for DOI 10.1016/j.surg.2023.04.051

  View details for Web of Science ID 001050796300001

  View details for PubMedID 37277308

  View details for PubMedCentralID PMC12290801

• Bilateral renal artery stenosis impacts postoperative complications after major vascular surgery SURGERY OPEN SCIENCE Filiberto, A. C., Miao, S., Ren, Y., Ozrazgat-Baslanti, T., Hensley, S. E., Jacobs, C. R., Weaver, M., Upchurch Jr, G. R., Bihorac, A., Cooper, M. 2023; 14: 17-21

  Abstract

  Incidental atherosclerotic renal artery stenosis (RAS) is common in patients undergoing vascular surgery and has been shown to be associated with postoperative AKI among patients undergoing major non-vascular surgeries. We hypothesized that patients with RAS undergoing major vascular procedures would have a higher incidence of AKI and postoperative complications than those without RAS.A single-center retrospective cohort study of 200 patients who underwent elective open aortic or visceral bypass surgery (100 with postoperative AKI; 100 without AKI) were identified. RAS was then evaluated by review of pre-surgery CTAs with readers blinded to AKI status. RAS was defined as ≥50 % stenosis. Univariate and multivariable logistic regression was used to assess association of unilateral and bilateral RAS with postoperative outcomes.17.4 % (n = 28) of patients had unilateral RAS while 6.2 % (n = 10) of patients had bilateral RAS. Patients with bilateral RAS had similar preadmission creatinine and GFR as compared to unilateral RAS or no RAS. 100 % (n = 10) of patients with bilateral RAS had postoperative AKI compared with 45 % (n = 68) of patients with unilateral or no RAS (p < 0.05). In adjusted logistic regression models, bilateral RAS predicted severe AKI (OR 5.82; CI 1.33, 25.53; p = 0.02), in-hospital mortality (OR 5.71; CI 1.03, 31.53; p = 0.05), 30-day mortality (OR 10.56; CI 2.03, 54.05; p = 0.005) and 90-day mortality (OR 6.88; CI 1.40, 33.87; p = 0.02).Bilateral RAS is associated with increased incidence of AKI as well as in-hospital, 30-day, and 90-day mortality suggesting it is a marker of poor outcomes and should be considered in preoperative risk stratification.

  View details for DOI 10.1016/j.sopen.2023.06.001

  View details for Web of Science ID 001069624400001

  View details for PubMedID 37409074

  View details for PubMedCentralID PMC10319299

• National Surgical Quality Improvement Project and acute kidney injury: Getting with the times SURGERY Filiberto, A. C., Cooper, M. 2023; 174 (1): 10

  View details for DOI 10.1016/j.surg.2022.12.027

  View details for Web of Science ID 001031439700001

  View details for PubMedID 36759211

• A simulation curriculum for laparoscopic common bile duct exploration, balloon sphincterotomy, and endobiliary stenting: Associations with resident performance and autonomy in the operating room SURGERY Nyren, M. Q., Filiberto, A. C., Underwood, P. W., Abbott, K. L., Balch, J. A., Efron, P. A., George, B. C., Shickel, B., Upchurch Jr, G. R., Sarosi Jr, G. A., Loftus, T. J. 2023; 173 (4): 950-956

  Abstract

  Laparoscopic common bile duct exploration is safe and effective for managing choledocholithiasis, but laparoscopic common bile duct exploration is rarely performed, which threatens surgical trainee proficiency. This study tests the hypothesis that prior operative or simulation experience with laparoscopic common bile duct exploration is associated with greater resident operative performance and autonomy without adversely affecting patient outcomes.This longitudinal cohort study included 33 consecutive patients undergoing laparoscopic common bile duct exploration in cases involving postgraduate years 3, 4, and 5 general surgery residents at a single institution during the implementation of a laparoscopic common bile duct exploration simulation curriculum. For each of the 33 cases, resident performance and autonomy were rated by residents and attendings, the resident's prior operative and simulation experience were recorded, and patient outcomes were ascertained from electronic health records for comparison among 3 cohorts: prior operative experience, prior simulation experience, and no prior experience.Operative approach was similar among cohorts. Overall morbidity was 6.1% and similar across cohorts. The operative performance scores were higher in prior experience cohorts according to both residents (3.0 [2.8-3.0] vs 2.0 [2.0-3.0]; P = .01) and attendings (3.0 [3.0-4.0]; P < .001). The autonomy scores were higher in prior experience cohorts according to both residents (2.0 [2.0-3.0] vs 2.0 [2.0-2.0]; P = .005) and attendings (2.5 [2.0-3.0] vs 2.0 [1.0-2.0]; P = .001). Prior simulation and prior operative experience had similar associations with performance and autonomy.Simulation experience with laparoscopic common bile duct exploration was associated with greater resident operative performance and autonomy, with effects that mimic prior operative experience. This illustrates the potential for simulation-based training to improve resident operative performance and autonomy for laparoscopic common bile duct exploration.

  View details for DOI 10.1016/j.surg.2022.11.007

  View details for Web of Science ID 000951516600001

  View details for PubMedID 36517292

  View details for PubMedCentralID PMC12290925

• Surgical resident experience with common bile duct exploration and assessment of performance and autonomy with formative feedback WORLD JOURNAL OF EMERGENCY SURGERY Nyren, M. Q. Q., Filiberto, A. C. C., Underwood, P. W. W., Abbott, K. L. L., Balch, J. A. A., Mas, F., Cobianchi, L., Efron, P. A. A., George, B. C. C., Shickel, B., Upchurch Jr, G. R. R., Sarosi Jr, G. A. A., Loftus, T. J. J. 2023; 18 (1): 13

  Abstract

  Common bile duct exploration (CBDE) is safe and effective for managing choledocholithiasis, but most US general surgeons have limited experience with CBDE and are uncomfortable performing this procedure in practice. Surgical trainee exposure to CBDE is limited, and their learning curve for achieving autonomous, practice-ready performance has not been previously described. This study tests the hypothesis that receipt of one or more prior CBDE operative performance assessments, combined with formative feedback, is associated with greater resident operative performance and autonomy.Resident and attending assessments of resident operative performance and autonomy were obtained for 189 laparoscopic or open CBDEs performed at 28 institutions. Performance and autonomy were graded along validated ordinal scales. Cases in which the resident had one or more prior CBDE case evaluations (n = 48) were compared with cases in which the resident had no prior evaluations (n = 141).Compared with cases in which the resident had no prior CBDE case evaluations, cases with a prior evaluation had greater proportions of practice-ready or exceptional performance ratings according to both residents (27% vs. 11%, p = .009) and attendings (58% vs. 19%, p < .001) and had greater proportions of passive help or supervision only autonomy ratings according to both residents (17% vs. 4%, p = .009) and attendings (69% vs. 32%, p < .01).Residents with at least one prior CBDE evaluation and formative feedback demonstrated better operative performance and received greater autonomy than residents without prior evaluations, underscoring the propensity of feedback to help residents achieve autonomous, practice-ready performance for rare operations.

  View details for DOI 10.1186/s13017-023-00480-0

  View details for Web of Science ID 000925096000002

  View details for PubMedID 36747289

  View details for PubMedCentralID PMC9901129

• Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms JVS-VASCULAR SCIENCE Filiberto, A. C., Leroy, V., Ladd, Z., Su, G., Elder, C. T., Pruitt, E. Y., Lu, G., Hartman, J., Zarrinpar, A., Garrett, T. J., Sharma, A. K., Upchurch Jr, G. R. 2023; 4: 100107

  Abstract

  In this study, we tested the hypothesis that endogenous expression of specialized pro-resolving lipid mediators (SPMs) that facilitate the resolution of inflammation, specifically Resolvin D1and -D2, as well as Maresin1 (MaR1), can impact abdominal aortic aneurysm (AAA) formation and progression in a sex-specific manner.SPM expression was quantified in aortic tissue from human AAA samples and from a murine in vivo AAA model via liquid chromatography-tandem mass spectrometry. mRNA expression for SPM receptors FPR2, LGR6, and GPR18 were quantified by real-time polymerase chain reaction. A Student t test with nonparametric Mann-Whitney or Wilcoxon test was used for pair-wise comparisons of groups. One-way analysis of variance after post hoc Tukey test was used to determine the differences among multiple comparative groups.Human aortic tissue analysis revealed a significant decrease in RvD1 levels in male AAAs compared with controls, whereas FPR2 and LGR6 receptor expressions were downregulated in male AAAs compared with male controls. In vivo studies of elastase-treated mice showed higher levels of RvD2 and MaR1 as well as the SPM precursors, omega-3 fatty acids DHA and EPA, in aortic tissue from males compared with females. FPR2 expression was increased in elastase-treated females compared with males.Our findings demonstrate that specific differences in SPMs and their associated G-protein coupled receptors exist between sexes. These results indicate the relevance of SPM-mediated signaling pathways in sex differences impacting the pathogenesis of AAAs.

  View details for DOI 10.1016/j.jvssci.2023.100107

  View details for Web of Science ID 001395991300004

  View details for PubMedID 37292185

  View details for PubMedCentralID PMC10245328

• Resolution of inflammation via RvD1/FPR2 signaling mitigates Nox2 activation and ferroptosis of macrophages in experimental abdominal aortic aneurysms FASEB JOURNAL Filiberto, A. C., Ladd, Z., Leroy, V., Su, G., Elder, C. T., Pruitt, E. Y., Hensley, S. E., Lu, G., Hartman, J. B., Zarrinpar, A., Sharma, A. K., Upchurch, G. R. 2022; 36 (11): e22579

  Abstract

  Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. Resolvin D1 (RvD1) is derived from ω-3 polyunsaturated fatty acids and is involved in the resolution phase of chronic inflammatory diseases. The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating abdominal aortic aneurysms (AAA). The elastase-treatment model of AAA in C57BL/6 (WT) mice and human AAA tissue was used to confirm our hypotheses. Elastase-treated FPR2-/- mice had a significant increase in aortic diameter, proinflammatory cytokine production, immune cell infiltration (macrophages and neutrophils), elastic fiber disruption, and decrease in smooth muscle cell α-actin expression compared to elastase-treated WT mice. RvD1 treatment attenuated AAA formation, aortic inflammation, and vascular remodeling in WT mice, but not in FPR2-/- mice. Importantly, human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to non-aneurysm human aortas. Mechanistically, RvD1/FPR2 signaling mitigated p47phox phosphorylation and prevented hallmarks of ferroptosis, such as lipid peroxidation and Nrf2 translocation, thereby attenuating HMGB1 secretion. Collectively, this study demonstrates RvD1-mediated immunomodulation of FPR2 signaling on macrophages to mitigate ferroptosis and HMGB1 release, leading to resolution of aortic inflammation and remodeling during AAA pathogenesis.

  View details for DOI 10.1096/fj.202201114R

  View details for Web of Science ID 000862995400001

  View details for PubMedID 36183323

  View details for PubMedCentralID PMC11137679

• Psoas Muscle Area as a Prognostic Factor for Survival in Patients Undergoing Endovascular Aneurysm Repair Conversion Jacobs, C. R., Scali, S. T., Filiberto, A., Anderson, E., Fazzone, B., Back, M. R., Cooper, M., Upchurch, G. R., Huber, T. S. ELSEVIER SCIENCE INC. 2022: 1-12

  Abstract

  Endovascular aneurysm repair conversion (EVAR-c) is increasingly reported and known to be technically complex and physiologically demanding. It has been proposed that pragmatic anthropomorphic measures such as psoas muscle area (PMA) may reliably quantify levels of preoperative frailty and be used to inform point of care clinical decision-making and patient discussions for a variety of complex operations. To date, there is mixed data supporting use of PMA as a prognostic factor in fenestrated endovascular and open abdominal aortic aneurysms (AAA) repairs; however, no literature exists evaluating the impact of preoperative PMA on EVAR-c results. Therefore, the purpose of this study was to review our EVAR-c experience and evaluate the association of PMA with perioperative and long-term mortality outcomes.A retrospective single-center review of all AAA repairs was performed (2002-2019) and EVAR-c procedures were subsequently analyzed (n = 153). Cross-sectional PMA at the mid-body of the L3 vertebrae was measured. The lowest PMA tertile was used as a threshold value to designate patients as having "low" PMA (n = 51) and this cohort was subsequently compared to subjects with "normal" PMA (n = 102). Cox proportional hazards modeling was used to estimate covariate association with all-cause mortality.Patients with low PMA were older (77 vs. 72 years; P = 0.002), more likely to be female (27% vs. 5%; P < 0.001), and had reduced body mass index (26 vs. 29 kg/m2; P = 0.002). Time to conversion, total number of endovascular aneurysm repair (EVAR) reinterventions prior to conversion and elective EVAR-c presentation incidence were similar; however, patients with low PMA had larger aneurysms (8.3 vs. 7.5 cm; P = 0.01) and increased post-EVAR sac growth (2.3 vs. 1 cm; P = 0.005). Unadjusted inpatient mortality was significantly greater for low PMA patients (16% vs. normal PMA, 5%, P = 0.02). Similarly, the total number of complications was higher among low PMA subjects (1.5 ± 1.9 vs. normal PMA, 0.9 ± 1.5; P = 0.02). Although frequency of major adverse cardiovascular events and new onset inpatient hemodialysis were similar, low PMA patients had a more than four-fold increased likelihood of having persistent requirement of hemodialysis at discharge (18% vs. 4%,P = 0.01). The low PMA group had decreased survival at 1 and 5 years, respectively (77 ± 5%, 65 ± 6% vs. normal PMA, 86 ± 3%, 82% ± 5%; log-rank P = 0.03). Low PMA was an independent predictor of mortality with every 100 mm2 increase in PMA being associated with a 15% reduction in mortality (hazard ratio: 0.85,95% confidence interval:, 0.74-0.97; P = 0.02).Among EVAR-c patients, subjects with low preoperative PMA had higher rates of postoperative complications and worse overall survival. PMA assessments may be a useful adjunct to supplement traditional risk-stratification strategies when patients are being considered for EVAR-c.

  View details for DOI 10.1016/j.avsg.2022.08.001

  View details for Web of Science ID 000917245200001

  View details for PubMedID 36058454

• Sex-based differences in patients undergoing thoracic endovascular aortic repair for acute complicated type B dissection Filiberto, A. C., Pruitt, E. Y., Hensley, S. E., Weaver, M., Shah, S., Scali, S. T., Neal, D., Huber, T. S., Upchurch, G. R., Cooper, M. MOSBY-ELSEVIER. 2022: 1198-+

  Abstract

  Sex-based differences in outcomes for patients undergoing degenerative aortic aneurysm repair have been well described, with female patients having worse early and long-term outcomes compared with male patients. However, differences between men and women after thoracic endovascular aortic repair (TEVAR) of acute complicated type B aortic dissection (TBAD) have not been well characterized. Therefore, the objective of the present study was to assess the sex-based differences in clinical presentation, time to repair, morbidity, and mortality for patients undergoing TEVAR for TBAD.All TEVAR procedures performed for acute complicated TBAD from a single academic medical center from August 2005 to January 2020 were analyzed. The clinical presentation, time to repair, and outcomes were compared by sex. The primary outcome was 30-day mortality. The secondary outcomes were in-hospital complications, reintervention, aorta-related death, and out of hospital survival. The predictors of mortality, including sex, were determined using multivariable logistic regression.A total of 159 patients (38 women [24%]) were included in the analysis. No sex-based differences were found in clinical presentation or comorbidity prevalence between the female and male patients. The female patients had had a longer overall time from initial symptom onset to TEVAR (female patients: median, 3.5 days [interquartile range (IQR), 1-10 days]; male patients: median, 1 day [IQR, 1-3]; P = .007). However, no differences were found in the time to repair after admission to the academic medical center (female patients: median, 1 day [IQR, 0-5 days]; male patients: median, 1 day [IQR, 0-3]; P = .176). No differences were found in the unadjusted aortic-related, in-hospital, or 30-day death between the female and male patients. Similarly, the risk-adjusted analysis revealed that sex was not associated with adverse outcomes. The 1- and 5-year freedom from aortic-related mortality were 82% ± 4% and 87% ± 6% and 79% ± 4% and 80% ± 8% for the men and women, respectively.We found no differences between the female and male patients with acute complicated TBAD who had undergone TEVAR in the clinical presentation or comorbidities. The female patients had undergone TEVAR after a longer duration of symptoms, but this was not associated with sex-based differences in early or late morbidity or mortality.

  View details for DOI 10.1016/j.jvs.2022.06.088

  View details for Web of Science ID 000898561400011

  View details for PubMedID 35788367

• Personalized decision-making for acute cholecystitis: Understanding surgeon judgment FRONTIERS IN DIGITAL HEALTH Filiberto, A. C. C., Efron, P. A. A., Frantz, A., Bihorac, A., Upchurch, G. R. R., Loftus, T. J. J. 2022; 4: 845453

  Abstract

  There is sparse high-level evidence to guide treatment decisions for severe, acute cholecystitis (inflammation of the gallbladder). Therefore, treatment decisions depend heavily on individual surgeon judgment, which is highly variable and potentially amenable to personalized, data-driven decision support. We test the hypothesis that surgeons' treatment recommendations misalign with perceived risks and benefits for laparoscopic cholecystectomy (surgical removal) vs. percutaneous cholecystostomy (image-guided drainage).Surgery attendings, fellows, and residents applied individual judgement to standardized case scenarios in a live, web-based survey in estimating the quantitative risks and benefits of laparoscopic cholecystectomy vs. percutaneous cholecystostomy for both moderate and severe acute cholecystitis, as well as the likelihood that they would recommend cholecystectomy.Surgeons predicted similar 30-day morbidity rates for laparoscopic cholecystectomy and percutaneous cholecystostomy. However, a greater proportion of surgeons predicted low (<50%) likelihood of full recovery following percutaneous cholecystostomy compared with cholecystectomy for both moderate (30% vs. 2%, p < 0.001) and severe (62% vs. 38%, p < 0.001) cholecystitis. Ninety-eight percent of all surgeons were likely or very likely to recommend cholecystectomy for moderate cholecystitis; only 32% recommended cholecystectomy for severe cholecystitis (p < 0.001). There were no significant differences in predicted postoperative morbidity when respondents were stratified by academic rank or self-reported ability to predict complications or make treatment recommendations.Surgeon recommendations for severe cholecystitis were discordant with perceived risks and benefits of treatment options. Surgeons predicted greater functional recovery after cholecystectomy but less than one-third recommended cholecystectomy. These findings suggest opportunities to augment surgical decision-making with personalized, data-driven decision support.

  View details for DOI 10.3389/fdgth.2022.845453

  View details for Web of Science ID 001034025100001

  View details for PubMedID 36339515

  View details for PubMedCentralID PMC9632988

• Endothelial pannexin-1 channels modulate macrophage and smooth muscle cell activation in abdominal aortic aneurysm formation NATURE COMMUNICATIONS Filiberto, A. C., Spinosa, M. D., Elder, C. T., Su, G., Leroy, V., Ladd, Z., Lu, G., Mehaffey, J., Salmon, M. D., Hawkins, R. B., Ravichandran, K. S., Isakson, B. E., Upchurch, G. R., Sharma, A. K. 2022; 13 (1): 1521

  Abstract

  Pannexin-1 (Panx1) channels have been shown to regulate leukocyte trafficking and tissue inflammation but the mechanism of Panx1 in chronic vascular diseases like abdominal aortic aneurysms (AAA) is unknown. Here we demonstrate that Panx1 on endothelial cells, but not smooth muscle cells, orchestrate a cascade of signaling events to mediate vascular inflammation and remodeling. Mechanistically, Panx1 on endothelial cells acts as a conduit for ATP release that stimulates macrophage activation via P2X7 receptors and mitochondrial DNA release to increase IL-1β and HMGB1 secretion. Secondly, Panx1 signaling regulates smooth muscle cell-dependent intracellular Ca2+ release and vascular remodeling via P2Y2 receptors. Panx1 blockade using probenecid markedly inhibits leukocyte transmigration, aortic inflammation and remodeling to mitigate AAA formation. Panx1 expression is upregulated in human AAAs and retrospective clinical data demonstrated reduced mortality in aortic aneurysm patients treated with Panx1 inhibitors. Collectively, these data identify Panx1 signaling as a contributory mechanism of AAA formation.

  View details for DOI 10.1038/s41467-022-29233-4

  View details for Web of Science ID 000771678500001

  View details for PubMedID 35315432

  View details for PubMedCentralID PMC8938517

• Machine Learning in Clinical Decision-Making FRONTIERS IN DIGITAL HEALTH Filiberto, A. C., Leeds, I. L., Loftus, T. J. 2021; 3: 784495

  View details for DOI 10.3389/fdgth.2021.784495

  View details for Web of Science ID 001031839500001

  View details for PubMedID 34870273

  View details for PubMedCentralID PMC8636718

• Treatment and Outcomes of Aortic Graft Infections Using a Decision Algorithm Filiberto, A. C., Scali, S. T., Patterson, S., Neal, D., Elder, C. T., Shah, S. K., Shahid, Z., Upchurch Jr, G. R., Huber, T. S., Back, M. R. ELSEVIER SCIENCE INC. 2021: 254-268

  Abstract

  Aortic graft infection (AGI) is a rare but devastating complication requiring both explant of the infected prosthesis and lower extremity revascularization. Despite a variety of methods to treat AGI, there is a paucity of evidence that describes comparative outcomes. Moreover, controversy exists surrounding what the optimal repair strategy is with limited descriptions of how these techniques should be employed in this complex group of patients. Therefore, the purpose of this analysis was to review our experience with AGI management while highlighting a practice philosophy that can achieve acceptable outcomes.All AGI patients between 2002-2019 were reviewed. The primary end-point was 30-day mortality. Secondary end-points included complications, re-infection, unplanned re-operation and all-cause mortality. Kaplan-Meier methodology was used to estimate time to events. Cox regression models were employed to identify association between patient factors and operative strategy with survival. Subgroup analysis included outcome comparison among four different operative approaches(extra-anatomic bypass with aortic ligation [EAB] and in-situ reconstruction [ISR] using either NAIS, cryopreserved allograft [Cryo], or antibiotic-soaked prosthetic grafts [Other]).142 patients (male-69%, mean age 67 ± 11 years) were reviewed. Median time to AGI presentation was 52 (IQR 16-128) months. ISR was performed in 70% (n = 99)[ISR: NAIS-49% (n = 49), Cryo, 33% (n = 33) and Other-23% (n = 23)]. EAB was used in 26% (n = 37), of which 57% (n = 21) were staged repairs[no reconstruction, 4%: intraoperative death-2, AGI removal without reconstruction-2]. A graft enteric erosion/fistula was identified in 39% (n = 55). Mean follow-up time was 14 ± 27 (median 2.2[IQR 0.1-16]) months. Overall, 30-day mortality was 21% and 69% (n = 98) experienced a complication. The most common complications were pulmonary (35%;n = 50), vascular (28%;n = 39), gastrointestinal (22%;n = 31) and renal (21%;n = 30). Freedom from re-infection at one and three years was 78 ± 5% and 73 ± 6% while freedom from unplanned re-operation was 50 ± 5% and 40 ± 6%, respectively. Corresponding one- and five-year freedom from all-cause mortality was 67 ± 4% and 53 ± 4%. When stratified by the four different repair strategies, unadjusted rates of postoperative complications and mortality were not different. However, EAB patients had more renal complications. All-cause mortality predictors included age (HR 1.04, 95%CI 1.01-1.1; P = 0.003), CHF (HR 2.7, 1.3-5.7; P = 0.01), and graft enteric erosion/fistula (HR 2.2, 1.3-3.8;P = 0.005) while total graft excision was protective (HR 0.34, 0.2-0.7; P = 0.003).AGI repair, regardless of operative strategy, results in significant early morbidity, and mortality. The need for unplanned re-operation is common; however, long-term survival is acceptable in appropriately selected patients. Re-infection risk mandates life-long surveillance and consideration of indefinite anti-microbial suppression in certain subgroups. Due to the complexity and intensity of care, all AGI should be treated, when possible, at centers performing high-volume aortic surgery.

  View details for DOI 10.1016/j.avsg.2021.04.047

  View details for Web of Science ID 000726775700031

  View details for PubMedID 34182116

• Maresin 1 activates LGR6 signaling to inhibit smooth muscle cell activation and attenuate murine abdominal aortic aneurysm formation FASEB JOURNAL Elder, C. T., Filiberto, A. C., Su, G., Ladd, Z., Leroy, V., Pruitt, E. Y., Lu, G., Jiang, Z., Sharma, A. K., Upchurch, G. R. 2021; 35 (8): e21780

  Abstract

  The specialized pro-resolving lipid mediator maresin 1 (MaR1) is involved in the resolution phase of tissue inflammation. It was hypothesized that exogenous administration of MaR1 would attenuate abdominal aortic aneurysm (AAA) growth in a cytokine-dependent manner via LGR6 receptor signaling and macrophage-dependent efferocytosis of smooth muscle cells (SMCs). AAAs were induced in C57BL/6 wild-type (WT) mice and smooth muscle cell specific TGF-β2 receptor knockout (SMC-TGFβr2-/- ) mice using a topical elastase AAA model. MaR1 treatment significantly attenuated AAA growth as well as increased aortic SMC α-actin and TGF-β2 expressions in WT mice, but not SMC-TGFβr2-/- mice, compared to vehicle-treated mice. In vivo inhibition of LGR6 receptors obliterated MaR1-dependent protection in AAA formation and SMC α-actin expression. Furthermore, MaR1 upregulated macrophage-dependent efferocytosis of apoptotic SMCs in murine aortic tissue during AAA formation. In vitro studies demonstrate that MaR1-LGR6 interaction upregulates TGF-β2 expression and decreases MMP2 activity during crosstalk of macrophage-apoptotic SMCs. In summary, these results demonstrate that MaR1 activates LGR6 receptors to upregulate macrophage-dependent efferocytosis, increases TGF-β expression, preserves aortic wall remodeling and attenuate AAA formation. Therefore, this study demonstrates the potential of MaR1-LGR6-mediated mitigation of vascular remodeling through increased efferocytosis of apoptotic SMCs via TGF-β2 to attenuate AAA formation.

  View details for DOI 10.1096/fj.202100484R

  View details for Web of Science ID 000678975300036

  View details for PubMedID 34320253

  View details for PubMedCentralID PMC9170188

• Optimizing predictive strategies for acute kidney injury after major vascular surgery SURGERY Filiberto, A. C., Ozrazgat-Baslanti, T., Loftus, T. J., Peng, Y., Datta, S., Efron, P., Upchurch Jr, G. R., Bihorac, A., Cooper, M. A. 2021; 170 (1): 298-303

  Abstract

  Postoperative acute kidney injury is common after major vascular surgery and is associated with increased morbidity, mortality, and cost. High-performance risk stratification using a machine learning model can inform strategies that mitigate harm and optimize resource use. It is hypothesized that incorporating intraoperative data would improve machine learning model accuracy, discrimination, and precision in predicting acute kidney injury among patients undergoing major vascular surgery.A single-center retrospective cohort of 1,531 adult patients who underwent nonemergency major vascular surgery, including open aortic, endovascular aortic, and lower extremity bypass procedures, was evaluated. The validated, automated MySurgeryRisk analytics platform used electronic health record data to forecast patient-level probabilistic risk scores for postoperative acute kidney injury using random forest models with preoperative data alone and perioperative data (preoperative plus intraoperative). The MySurgeryRisk predictions were compared with each other as well as with the American Society of Anesthesiologists physical status classification.Machine learning models using perioperative data had greater accuracy, discrimination, and precision than models using either preoperative data alone or the American Society of Anesthesiologists physical status classification (accuracy: 0.70 vs 0.64 vs 0.62, area under the receiver operating characteristics curve: 0.77 vs 0.68 vs 0.61, area under the precision-recall curve: 0.70 vs 0.58 vs 0.48).In predicting acute kidney injury after major vascular surgery, machine learning approaches that incorporate dynamic intraoperative data had greater accuracy, discrimination, and precision than models using either preoperative data alone or the American Society of Anesthesiologists physical status classification. Machine learning methods have the potential for real-time identification of high-risk patients who may benefit from personalized risk-reduction strategies.

  View details for DOI 10.1016/j.surg.2021.01.030

  View details for Web of Science ID 000667298800045

  View details for PubMedID 33648766

  View details for PubMedCentralID PMC8276529

• Intraoperative hypotension and complications after vascular surgery: A scoping review SURGERY Filiberto, A. C., Loftus, T. J., Elder, C. T., Hensley, S., Frantz, A., Efron, P., Ozrazgat-Baslanti, T., Bihorac, A., Upchurch Jr, G. R., Cooper, M. A. 2021; 170 (1): 311-317

  Abstract

  Intraoperative hypotension during major surgery is associated with adverse health outcomes. This phenomenon represents a potentially important therapeutic target for vascular surgery patients, who may be uniquely vulnerable to intraoperative hypotension. This review summarizes current evidence regarding the impact of intraoperative hypotension on postoperative complications in patients undergoing vascular surgery, focusing on potentially modifiable procedure- and patient-specific risk factors.A scoping review of the literature from Embase, MEDLINE, and PubMed databases was conducted from inception to December 2019 to identify articles related to the effects of intraoperative hypotension on patients undergoing vascular surgery.Ninety-two studies met screening criteria; 9 studies met quality and inclusion criteria. Among the 9 studies that defined intraoperative hypotension objectively, there were 9 different definitions. Accordingly, the reported incidence of intraoperative hypotension ranged from 8% to 88% (when defined as a fall in systolic blood pressure of >30 mm Hg or mean arterial pressure <65). The results demonstrated that intraoperative hypotension is an independent risk factor for longer hospital length of stay, myocardial injury, acute kidney injury, postoperative mechanical ventilation, and early mortality. Vascular surgery patients with comorbid conditions that confer increased vulnerability to hypoperfusion and ischemia appear to be susceptible to the adverse effects of intraoperative hypotension.There is no validated, consensus definition of intraoperative hypotension or other hemodynamic parameters associated with increased risk for adverse outcomes. Despite these limitations, the weight of evidence suggests that intraoperative hypotension is common and associated with major postoperative complications in vascular surgery patients.

  View details for DOI 10.1016/j.surg.2021.03.054

  View details for Web of Science ID 000667298800047

  View details for PubMedID 33972092

  View details for PubMedCentralID PMC8318382

• Prevalence and extent of industry support for program directors of surgical fellowships in the United States (vol 168, pg 1101, 2020) SURGERY Balch, J. A., Cooper, L., Filiberto, A. C., Chan, P. E., Riner, A. N., Sarosi, G. A., Tan, S. A. 2021; 169 (6): 1564

  View details for DOI 10.1016/j.surg.2021.02.047

  View details for Web of Science ID 000655418800004

  View details for PubMedID 33789814

• Cardiovascular and Renal Disease in Chronic Critical Illness JOURNAL OF CLINICAL MEDICINE Loftus, T. J., Filiberto, A. C., Ozrazgat-Baslanti, T., Gopal, S., Bihorac, A. 2021; 10 (8)

  Abstract

  With advances in critical care, patients who would have succumbed in previous eras now survive through hospital discharge. Many survivors suffer from chronic organ dysfunction and induced frailty, representing an emerging chronic critical illness (CCI) phenotype. Persistent and worsening cardiovascular and renal disease are primary drivers of the CCI phenotype and have pathophysiologic synergy, potentiating one another and generating a downward spiral of worsening disease and clinical outcomes manifest as cardio-renal syndromes. In addition to pharmacologic therapies (e.g., diuretics, beta adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and blood pressure control), special consideration should be given to behavioral modifications that avoid the pitfalls of polypharmacy and suboptimal renal and hepatic dosing, to which CCI patients may be particularly vulnerable. Smoking cessation, dietary modifications (e.g., early high-protein nutrition and late low-sodium diets), and increased physical activity are advised. Select patients benefit from cardiac re-synchronization therapy or renal replacement therapy. Coordinated, patient-centered care bundles may improve compliance with standards of care and patient outcomes. Given the complex, heterogeneous nature of cardiovascular and renal disease in CCI and the dismal long-term outcomes, further research is needed to clarify pathophysiologic mechanisms of cardio-renal syndromes in CCI and develop targeted therapies.

  View details for DOI 10.3390/jcm10081601

  View details for Web of Science ID 000644446600001

  View details for PubMedID 33918938

  View details for PubMedCentralID PMC8070314

• Performance Improvement With Implementation of a Surgical Skills Curriculum JOURNAL OF SURGICAL EDUCATION Loftus, T. J., Filiberto, A. C., Upchurch, G. R., Hall, D. J., Mira, J. C., Taylor, J., Shaw, C. M., Tan, S. A., Sarosi, G. A. 2021; 78 (2): 561-569

  Abstract

  To assess the efficacy of an intern surgical skills curriculum involving a boot camp for core open and laparoscopic skills, self-guided practice with positive and negative incentives, and semiannual performance evaluations.Longitudinal cohort study.Academic tertiary care center.Intervention group (n = 15): residents who completed the intern surgical skills curriculum and had performance evaluations in fall of intern year, spring of intern year, and fall of second year. Control group (n = 8): second-year residents who were 1 year ahead of the intervention group in the same residency program, did not participate in the curriculum, and had performance evaluations in fall of second year.In fall of second year of residency, the intervention group had better performance (presented as median values with interquartile ranges) than the control group on one-hand ties (left hand: 9.1 [6.3-10.1] vs 14.6 [13.5-15.4] seconds, p = 0.007; right hand: 8.7 [8.5-9.6] vs 11.5 [9.9-16.8] seconds, p = 0.039). The intervention group also had better performance on all open suturing skills, including mattress suturing (vertical: 33.4 [30.0-40.0] vs 55.8 [50.0-67.6] seconds, p = 0.001; horizontal: 28.7 [27.3-39.9] vs 52.7 [40.7-57.8] seconds, p = 0.003), and a water-filled glove clamp, divide, and ligate task (28.0 [25.0-31.0] vs 59.1 [53.0-93.0] seconds, p < 0.001). Finally, the intervention group had better performance on all laparoscopic skills, including peg transfer (66.0 [59.0-82.0] vs 95.2 [87.5-101.5] seconds, p = 0.018), circle cut (82.0 [69.0-124.0] seconds vs 191.8 [155.5-231.5] seconds, p = 0.002), and intracorporeal suturing (195.0 [117.0-200.0] seconds vs 359.5 [269.0-450.0] seconds, p = 0.002).Implementation of a comprehensive surgical skills curriculum was associated with improved performance on core open and laparoscopic skills. Further research is needed to understand and optimize motivational factors for deliberate practice and surgical skill acquisition.

  View details for DOI 10.1016/j.jsurg.2020.08.030

  View details for Web of Science ID 000621119000028

  View details for PubMedID 32888847

  View details for PubMedCentralID PMC7462643

• Metabolomic Profiling for Diagnosis and Prognostication in Surgery: A Scoping Review ANNALS OF SURGERY Khan, T. A., Loftus, T. J., Filiberto, A. C., Ozrazgat-Baslanti, T., Ruppert, M. M., Bandyopadhyay, S., Laiakis, E. C., Arnaoutakis, D. J., Bihorac, A. 2021; 273 (2): 258-268

  Abstract

  This review assimilates and critically evaluates available literature regarding the use of metabolomic profiling in surgical decision-making.Metabolomic profiling is performed by nuclear magnetic resonance spectroscopy or mass spectrometry of biofluids and tissues to quantify biomarkers (ie, sugars, amino acids, and lipids), producing diagnostic and prognostic information that has been applied among patients with cardiovascular disease, inflammatory bowel disease, cancer, and solid organ transplants.PubMed was searched from 1995 to 2019 to identify studies investigating metabolomic profiling of surgical patients. Articles were included and assimilated into relevant categories per PRISMA-ScR guidelines. Results were summarized with descriptive analytical methods.Forty-seven studies were included, most of which were retrospective studies with small sample sizes using various combinations of analytic techniques and types of biofluids and tissues. Results suggest that metabolomic profiling has the potential to effectively screen for surgical diseases, suggest diagnoses, and predict outcomes such as postoperative complications and disease recurrence. Major barriers to clinical adoption include a lack of high-level evidence from prospective studies, heterogeneity in study design regarding tissue and biofluid procurement and analytical methods, and the absence of large, multicenter metabolome databases to facilitate systematic investigation of the efficacy, reproducibility, and generalizability of metabolomic profiling diagnoses and prognoses.Metabolomic profiling research would benefit from standardization of study design and analytic approaches. As technologies improve and knowledge garnered from research accumulates, metabolomic profiling has the potential to provide personalized diagnostic and prognostic information to support surgical decision-making from preoperative to postdischarge phases of care.

  View details for DOI 10.1097/SLA.0000000000003935

  View details for Web of Science ID 000640972700029

  View details for PubMedID 32482979

  View details for PubMedCentralID PMC7704904

• Objective predictors of intern performance BMC MEDICAL EDUCATION Filiberto, A. C., Cooper, L., Loftus, T. J., Samant, S. S., Sarosi, G. A., Tan, S. A. 2021; 21 (1): 77

  Abstract

  Residency programs select medical students for interviews and employment using metrics such as the United States Medical Licensing Examination (USMLE) scores, grade-point average (GPA), and class rank/quartile. It is unclear whether these metrics predict performance as an intern. This study tested the hypothesis that performance on these metrics would predict intern performance.This single institution, retrospective cohort analysis included 244 graduates from four classes (2015-2018) who completed an Accreditation Council for Graduate Medical Education (ACGME) certified internship and were evaluated by program directors (PDs) at the end of the year. PDs provided a global assessment rating and ratings addressing ACGME competencies (response rate = 47%) with five response options: excellent = 5, very good = 4, acceptable = 3, marginal = 2, unacceptable = 1. PDs also classified interns as outstanding = 4, above average = 3, average = 2, and below average = 1 relative to other interns from the same residency program. Mean USMLE scores (Step 1 and Step 2CK), third-year GPA, class rank, and core competency ratings were compared using Welch's ANOVA and follow-up pairwise t-tests.Better performance on PD evaluations at the end of intern year was associated with higher USMLE Step 1 (p = 0.006), Step 2CK (p = 0.030), medical school GPA (p = 0.020) and class rank (p = 0.016). Interns rated as average had lower USMLE scores, GPA, and class rank than those rated as above average or outstanding; there were no significant differences between above average and outstanding interns. Higher rating in each of the ACGME core competencies was associated with better intern performance (p < 0.01).Better performance as an intern was associated with higher USMLE scores, medical school GPA and class rank. When USMLE Step 1 reporting changes from numeric scores to pass/fail, residency programs can use other metrics to select medical students for interviews and employment.

  View details for DOI 10.1186/s12909-021-02487-0

  View details for Web of Science ID 000613648500003

  View details for PubMedID 33499857

  View details for PubMedCentralID PMC7839184

• Fluoroquinolones and Aortic Disease-Is It Time to Broaden the Warning? JAMA SURGERY Filiberto, A. C., Upchurch, G. R. 2021; 156 (3): 273

  View details for DOI 10.1001/jamasurg.2020.6185

  View details for Web of Science ID 000605764000005

  View details for PubMedID 33404599

• Prevalence and extent of industry support for program directors of surgical fellowships in the United States SURGERY Balch, J. A., Cooper, L., Filiberto, A. C., Chan, P. E., Sarosi, G. A., Tan, S. A. 2020; 168 (6): 1101-1105

  Abstract

  Fellowship program directors have a considerable influence on the future practice patterns of their trainees. Multiple studies have demonstrated that industry can also exert substantial influence on the practice patterns of physicians as a whole. The purpose of this study is to quantify industry support of fellowship program directors across surgical subspecialties and to assess the prevalence of this support within specific subspecialties.Fellowship program directors for acute care, breast, burn, cardio-thoracic, critical care, colon and rectal, endocrine, hepato-pancreato-biliary, minimally invasive, plastic, oncologic, pediatric, and vascular surgery for 2017 were identified using a previously described database. The Open Payments Database for 2017 was queried and data regarding general payments, research, associated research payments, and ownership were obtained. The national mean and median payouts to nonfellowship program director surgeons were used to determine subspecialties with substantial industry support.Five hundred and seventy-six fellowship program directors were identified. Of these, 77% of the fellowship program directors had a presence on the Open Payments Database. The subspecialties with the most fellowship program directors receiving any industry payment, regardless of amount, included vascular (93.5%), cardio-thoracic (92.8%), minimally invasive surgery (90.5%), plastics (85.3%), and colon and rectal (81.0%). The subspecialty with the greatest mean payment was minimally invasive surgery (21,175 US dollars); the greatest median payment was vascular (1,871 US dollars). The 3 most common types of payments were for general compensation (31.4%), consulting fees (28.7%), and travel and lodging (14.7%). Vascular surgery had the greatest percentage of fellowship program directors receiving research payments (48%). The greatest amount paid to any individual fellowship program director was 382,368 US dollars. Excluding outliers, fellowship program directors received substantially more payments than those received on average by general surgeons.The majority of fellowship program directors receive some industry support. Most payments are for compensation for noncontinuing medical education related services and consulting fees. Certain specialties were more likely to have industry payments than others. Overall, only a minority of fellowship program directors received research support from industry. We advocate for transparent discussions between fellowship program directors and their trainees to help foster healthy academic-industry collaborations.

  View details for DOI 10.1016/j.surg.2020.07.035

  View details for Web of Science ID 000594548300025

  View details for PubMedID 32943202

• Opportunities for machine learning to improve surgical ward safety AMERICAN JOURNAL OF SURGERY Loftus, T. J., Tighe, P. J., Filiberto, A. C., Balch, J., Upchurch, G. R., Rashidi, P., Bihorac, A. 2020; 220 (4): 905-913

  Abstract

  Delayed recognition of decompensation and failure-to-rescue on surgical wards are major sources of preventable harm. This review assimilates and critically evaluates available evidence and identifies opportunities to improve surgical ward safety.Fifty-eight articles from Cochrane Library, EMBASE, and PubMed databases were included.Only 15-20% of patients suffering ward arrest survive. In most cases, subtle signs of instability often occur prior to critical illness and arrest, and underlying pathology is reversible. Coarse risk assessments lead to under-triage of high-risk patients to wards, where surveillance for complications depends on time-consuming manual review of health records, infrequent patient assessments, prediction models that lack accuracy and autonomy, and biased, error-prone decision-making. Streaming electronic heath record data, wearable continuous monitors, and recent advances in deep learning and reinforcement learning can promote efficient and accurate risk assessments, earlier recognition of instability, and better decisions regarding diagnosis and treatment of reversible underlying pathology.

  View details for DOI 10.1016/j.amjsurg.2020.02.037

  View details for Web of Science ID 000577526000025

  View details for PubMedID 32127174

  View details for PubMedCentralID PMC7673643

• Intelligent, Autonomous Machines in Surgery JOURNAL OF SURGICAL RESEARCH Loftus, T. J., Filiberto, A. C., Balch, J., Ayzengart, A. L., Tighe, P. J., Rashidi, P., Bihorac, A., Upchurch, G. R. 2020; 253: 92-+

  Abstract

  Surgeons perform two primary tasks: operating and engaging patients and caregivers in shared decision-making. Human dexterity and decision-making are biologically limited. Intelligent, autonomous machines have the potential to augment or replace surgeons. Rather than regarding this possibility with denial, ire, or indifference, surgeons should understand and steer these technologies. Closer examination of surgical innovations and lessons learned from the automotive industry can inform this process. Innovations in minimally invasive surgery and surgical decision-making follow classic S-shaped curves with three phases: (1) introduction of a new technology, (2) achievement of a performance advantage relative to existing standards, and (3) arrival at a performance plateau, followed by replacement with an innovation featuring greater machine autonomy and less human influence. There is currently no level I evidence demonstrating improved patient outcomes using intelligent, autonomous machines for performing operations or surgical decision-making tasks. History suggests that if such evidence emerges and if the machines are cost effective, then they will augment or replace humans, initially for simple, common, rote tasks under close human supervision and later for complex tasks with minimal human supervision. This process poses ethical challenges in assigning liability for errors, matching decisions to patient values, and displacing human workers, but may allow surgeons to spend less time gathering and analyzing data and more time interacting with patients and tending to urgent, critical-and potentially more valuable-aspects of patient care. Surgeons should steer these technologies toward optimal patient care and net social benefit using the uniquely human traits of creativity, altruism, and moral deliberation.

  View details for DOI 10.1016/j.jss.2020.03.031

  View details for Web of Science ID 000550908900041

  View details for PubMedID 32339787

  View details for PubMedCentralID PMC7594619

• Decision analysis and reinforcement learning in surgical decision-making SURGERY Loftus, T. J., Filiberto, A. C., Li, Y., Balch, J., Cook, A. C., Tighe, P. J., Efron, P. A., Upchurch, G. R., Rashidi, P., Li, X., Bihorac, A. 2020; 168 (2): 253-266

  Abstract

  Surgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted response to treatment. Decision analysis and techniques of reinforcement learning theoretically can mitigate these challenges but are poorly understood and rarely used clinically. This review seeks to promote an understanding of decision analysis and reinforcement learning by describing their use in the context of surgical decision-making.Cochrane, EMBASE, and PubMed databases were searched from their inception to June 2019. Included were 41 articles about cognitive and diagnostic errors, decision-making, decision analysis, and machine-learning. The articles were assimilated into relevant categories according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.Requirements for time-consuming manual data entry and crude representations of individual patients and clinical context compromise many traditional decision-support tools. Decision analysis methods for calculating probability thresholds can inform population-based recommendations that jointly consider risks, benefits, costs, and patient values but lack precision for individual patient-centered decisions. Reinforcement learning, a machine-learning method that mimics human learning, can use a large set of patient-specific input data to identify actions yielding the greatest probability of achieving a goal. This methodology follows a sequence of events with uncertain conditions, offering potential advantages for personalized, patient-centered decision-making. Clinical application would require secure integration of multiple data sources and attention to ethical considerations regarding liability for errors and individual patient preferences.Traditional decision-support tools are ill-equipped to accommodate time constraints and uncertainty regarding diagnoses and the predicted response to treatment, both of which often impair surgical decision-making. Decision analysis and reinforcement learning have the potential to play complementary roles in delivering high-value surgical care through sound judgment and optimal decision-making.

  View details for DOI 10.1016/j.surg.2020.04.049

  View details for Web of Science ID 000554926800019

  View details for PubMedID 32540036

  View details for PubMedCentralID PMC7390703

• Performance advantages for grit and optimism AMERICAN JOURNAL OF SURGERY Loftus, T. J., Filiberto, A. C., Rosenthal, M. D., Arnaoutakis, G. J., Sarosi, G. A., Dimick, J. B., Upchurch, G. R. 2020; 220 (1): 10-18

  Abstract

  Unsustainable surgeon burnout rates and moral imperatives for performance improvement suggest an urgent need to understand and apply rationales and methods for cultivating grit and optimism in surgery.Embase, MEDLINE, and PubMed articles.Passivity in response to negative events is the default human response, but the presence of control activates the prefrontal cortex-the brain region controlling executive function-promoting effort toward solutions. Challenges, failures, and traumatic events perceived as inescapable, permanent, pervasive, and irreparable lead to debility and attrition; grit and optimism shift the human response toward growth, strength, and improved performance. Methods for realizing these advantages include maintaining positivity, pursuing major challenges that match personal skills, engaging in deliberate practice to improve skills, persisting in hard work, and pursuing higher meaning and purpose in work and life. Grit and optimism are difficult to teach; selecting gritty, optimistic surgical residency applicants may also be effective.

  View details for DOI 10.1016/j.amjsurg.2020.01.057

  View details for Web of Science ID 000545562900007

  View details for PubMedID 32098653

• Artificial Intelligence and Surgical Decision-making JAMA SURGERY Loftus, T. J., Tighe, P. J., Filiberto, A. C., Efron, P. A., Brakenridge, S. C., Mohr, A. M., Rashidi, P., Upchurch, G. R., Bihorac, A. 2020; 155 (2): 148-158

  Abstract

  Surgeons make complex, high-stakes decisions under time constraints and uncertainty, with significant effect on patient outcomes. This review describes the weaknesses of traditional clinical decision-support systems and proposes that artificial intelligence should be used to augment surgical decision-making.Surgical decision-making is dominated by hypothetical-deductive reasoning, individual judgment, and heuristics. These factors can lead to bias, error, and preventable harm. Traditional predictive analytics and clinical decision-support systems are intended to augment surgical decision-making, but their clinical utility is compromised by time-consuming manual data management and suboptimal accuracy. These challenges can be overcome by automated artificial intelligence models fed by livestreaming electronic health record data with mobile device outputs. This approach would require data standardization, advances in model interpretability, careful implementation and monitoring, attention to ethical challenges involving algorithm bias and accountability for errors, and preservation of bedside assessment and human intuition in the decision-making process.Integration of artificial intelligence with surgical decision-making has the potential to transform care by augmenting the decision to operate, informed consent process, identification and mitigation of modifiable risk factors, decisions regarding postoperative management, and shared decisions regarding resource use.

  View details for DOI 10.1001/jamasurg.2019.4917

  View details for Web of Science ID 000517986100010

  View details for PubMedID 31825465

  View details for PubMedCentralID PMC7286802

• Gender differences among surgical fellowship program directors Filiberto, A. C., Le, C. B., Loftus, T. J., Cooper, L. A., Shaw, C., Sarosi, G. A., Iqbal, A., Tan, S. A. MOSBY-ELSEVIER. 2019: 735-737

  Abstract

  Although women are increasingly represented in American surgery, data regarding sex and academic rank of the leadership of fellowship programs are lacking.Demographics and academic ranks for fellowship program directors were analyzed for 811 surgery fellowship programs across 14 specialties. Associations between academic rank and sex were assessed using a χ2 independence test. Correlation between subspecialty compensation and percentage of female fellowship program directors was assessed using Pearson r.Women represented 18% of all fellowship program directors. Eighteen percent of fellowship program directors were assistant professors (25% women vs 17% men, P = .049), 36% were associate professors (39% women vs 35% men, P = .379), and 46% were full professors (36% women vs 48% men, P = .018). The percentage of women program directors was greatest in breast surgery (65%) and least in minimally invasive surgery (6%). There was a negative correlation between subspecialty compensation and percentage of female fellowship program directors (r = -0.62, P = .04).Women are underrepresented among surgery fellowship program directors. Female fellowship program directors had lesser academic ranks compared with males. It remains unclear whether women surgeons achieve program director appointments at lesser academic ranks or if promotion among fellowship program directors is influenced by sex.

  View details for DOI 10.1016/j.surg.2019.05.017

  View details for Web of Science ID 000493584600004

  View details for PubMedID 31256855

• Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women HUMAN REPRODUCTION Matyas, R. A., Mumford, S. L., Schliep, K. C., Ahrens, K. A., Sjaarda, L. A., Perkins, N. J., Filiberto, A. C., Mattison, D., Zarek, S. M., Wactawski-Wende, J., Schisterman, E. F. 2015; 30 (7): 1714-1723

  Abstract

  Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women?Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders.Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear.The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles.Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo.During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH.Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women.The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function.This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose.

  View details for DOI 10.1093/humrep/dev099

  View details for Web of Science ID 000359741800023

  View details for PubMedID 25954035

  View details for PubMedCentralID PMC4472321

• Usual dietary isoflavone intake and reproductive function across the menstrual cycle FERTILITY AND STERILITY Filiberto, A. C., Mumford, S. L., Pollack, A. Z., Zhang, C., Yeung, E. H., Schliep, K. C., Perkins, N. J., Wactawski-Wende, J., Schisterman, E. F. 2013; 100 (6): 1727-1734

  Abstract

  To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women.Prospective cohort study.University.Participants included 259 healthy regularly menstruating women aged 18-44 years.None.Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women.Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6-78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02-0.16), compared with the first quartile (Q1: 0.0-0.3 mg/d).Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32-1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility.

  View details for DOI 10.1016/j.fertnstert.2013.08.002

  View details for Web of Science ID 000327533000046

  View details for PubMedID 23998910

  View details for PubMedCentralID PMC3867935

• A Gene-Specific Method for Predicting Hemophilia-Causing Point Mutations JOURNAL OF MOLECULAR BIOLOGY Hamasaki-Katagiri, N., Salari, R., Wu, A., Ql, Y., Schiller, T., Filiberto, A. C., Schisterman, E. F., Komar, A. A., Przytycka, T. M., Kimchi-Sarfaty, C. 2013; 425 (21): 4023-4033

  Abstract

  A fundamental goal of medical genetics is the accurate prediction of genotype-phenotype correlations. As an approach to develop more accurate in silico tools for prediction of disease-causing mutations of structural proteins, we present a gene- and disease-specific prediction tool based on a large systematic analysis of missense mutations from hemophilia A (HA) patients. Our HA-specific prediction tool, HApredictor, showed disease prediction accuracy comparable to other publicly available prediction software. In contrast to those methods, its performance is not limited to non-synonymous mutations. Given the role of synonymous mutations in disease and drug codon optimization, we propose that utilizing a gene- and disease-specific method can be highly useful to make functional predictions possible even for synonymous mutations. Incorporating computational metrics at both nucleotide and amino acid levels along with multiple protein sequence/structure alignment significantly improved the predictive performance of our tool. HApredictor is freely available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/HA_Predict/index.htm.

  View details for Web of Science ID 000326257100011

  View details for PubMedID 23920358

• Habitual Dietary Isoflavone Intake Is Associated with Decreased C-Reactive Protein Concentrations among Healthy Premenopausal Women JOURNAL OF NUTRITION Filiberto, A. C., Mumford, S. L., Pollack, A. Z., Zhang, C., Yeung, E. H., Perkins, N. J., Wactawski-Wende, J., Schisterman, E. F. 2013; 143 (6): 900-906

  Abstract

  Isoflavones have been associated with lower cardiovascular disease risk, but existing research focused on very high isoflavone intakes, as seen in Asian populations, as well as on risk factor reductions primarily in postmenopausal women. We investigated whether habitual low isoflavone intake among premenopausal women was associated with serum C-reactive protein (CRP) concentration, a commonly used biomarker associated with prediction of cardiovascular disease risk in healthy women. Between 2005 and 2007, 259 healthy, regularly menstruating women were enrolled in the BioCycle Study, and followed for up to 2 menstrual cycles. CRP was measured in serum at up to 16 clinic visits, timed to phases of the women's menstrual cycle. Diet was assessed up to 4 times per cycle by using 24-h recalls. Marginal structural models with inverse probability of exposure weights estimated the association between CRP and quartiles of isoflavone intake adjusted for age, race, BMI, cycle phase, total energy intake, total fiber, total whole grains, and phase-specific hormone concentrations including estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone. Compared with the lowest quartile of total isoflavone intake, women in the highest quartile had, on average, 27% lower serum CRP concentrations (95% CI: -35, -21%). Our results suggest that dietary isoflavone intakes at levels characteristic of the U.S. population are associated with decreased serum CRP concentrations, a factor associated with beneficial effects on inflammation, and subsequently may have the potential to improve health status among young women.

  View details for DOI 10.3945/jn.112.173187

  View details for Web of Science ID 000319306200020

  View details for PubMedID 23616515

  View details for PubMedCentralID PMC3652886

• The Utility of Menstrual Cycle Length as an Indicator of Cumulative Hormonal Exposure JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Mumford, S. L., Steiner, A. Z., Pollack, A. Z., Perkins, N. J., Filiberto, A. C., Albert, P. S., Mattison, D. R., Wactawski-Wende, J., Schisterman, E. F. 2012; 97 (10): E1871-E1879

  Abstract

  Associations between menstrual cycle length and chronic diseases are hypothesized to be due to differences in underlying hormonal patterns.The aim of the study was to evaluate the association between menstrual cycle length and the hormonal profile and anovulation.We conducted a prospective cohort study at the University at Buffalo from 2005 to 2007.We recruited 259 healthy, regularly menstruating women aged 18-44 yr.Cycle length was observed for up to two cycles. Serum estradiol, progesterone, LH, and FSH were measured up to eight times per cycle for up to two cycles.Women with short cycles (<26 d) had higher FSH concentrations during menses and in the late luteal phase, higher follicular estradiol concentrations, and lower LH concentrations across the cycle. Among women with longer cycles (>35 d), estradiol and LH peaks occurred on average about 3 d later, and FSH peaks about 1 d later compared to women with normal-length cycles. Both short and long cycles, compared with normal-length cycles, had an increased probability of anovulation. In general, per-cycle exposure to hormones was less in short cycles based on the area under the curve, although over time the cumulative exposure to estradiol would be greater for women with short cycles.Short ovulatory cycles were associated with higher follicular phase estradiol, an earlier rise in FSH, and an increased risk of anovulation. These results suggest that menstrual cycle length may be a relevant indicator of estradiol exposure and risk of anovulation among regularly cycling women.

  View details for DOI 10.1210/jc.2012-1350

  View details for Web of Science ID 000309664400006

  View details for PubMedID 22837188

  View details for PubMedCentralID PMC3674299

• Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta EPIGENETICS Filiberto, A. C., Maccani, M. A., Koestler, D., Wilhelm-Benartzi, C., Avissar-Whiting, M., Banister, C. E., Gagne, L. A., Marsit, C. J. 2011; 6 (5): 566-572

  Abstract

  Birthweight has been associated with a number of health outcomes throughout life. Crucial to proper infant growth and development is the placenta, and alterations to placental gene function may reflect differences in the intrauterine environment which functionally contribute to infant growth and may ultimately affect the child's health. To examine if epigenetic alteration to the glucocorticoid receptor (GR) gene was linked to infant growth, we analyzed 480 human placentas for differential methylation of the GR gene exon 1F and examined how this variation in methylation extent was associated with fetal growth. Multivariable linear regression revealed a significant association (p < 0.0001) between differential methylation of the GR gene and large for gestational age (LGA) status. Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function.

  View details for DOI 10.4161/epi.6.5.15236

  View details for Web of Science ID 000290203600006

  View details for PubMedID 21521940

  View details for PubMedCentralID PMC3121971