Video-Assisted Thoracoscopic Surgery Lung Resection in United States Veterans: Trends and Outcomes versus Thoracotomy.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) offers reduced morbidity compared with open thoracotomy (OT) for pulmonary surgery. The use of VATS over time has increased, but at a modest rate in civilian populations. This study examines temporal trends in VATS use and compares outcomes between VATS and OT in the Veterans Health Administration (VHA). METHODS: Patients who underwent pulmonary surgery (wedge or segmental resection, lobectomy, or pneumonectomy) at Veterans Affairs centers from 2008 to 2018 were retrospectively identified using the Veterans Affairs Surgical Quality Improvement Project database. The cohort was divided into OT and VATS and propensity score matched, taking into account the type of pulmonary resection, preoperative diagnosis, and comorbidities. Thirty-day postoperative outcomes were compared. The prevalence of VATS use and respective complications over time was also analyzed. RESULTS: A total of 16,895 patients were identified, with 5,748 per group after propensity matching. VATS had significantly lower rates of morbidity and a 2-day reduction in hospital stay. Whereas 76% of lung resections were performed open in 2008, nearly 70% of procedures were performed using VATS in 2018. While VATS was associated with an 8% lower rate of major complications compared with thoracotomy in 2008, patients undergoing VATS lung resection in 2018 had a 58% lower rate of complications (p < 0.001). CONCLUSIONS: VATS utilization at VHA centers has become the predominant technique used for pulmonary surgeries over time. OT patients had more complications and longer hospital stays compared with VATS. Over the study period, VATS patients had increasingly lower complication rates compared with open surgery.

Dependent functional status rather than age is a better predictor of adverse outcomes after excision of an infected abdominal aortic graft.

OBJECTIVE: The optimal management of infected abdominal aortic grafts is complete surgical excision plus in situ or extra-anatomic revascularization in patients who can tolerate this morbid operation. In addition to using age and the presence of comorbidities for risk assessment, physicians form a global clinical impression when deciding whether to offer excision or to manage conservatively. Functional status is a distinct objective measure that can inform this decision. This study examines the relative impact of age and functional status on outcomes of infected abdominal aortic graft excision to guide surgical decision-making. METHODS: Current Procedural Terminology code 35907 was used to identify patients undergoing excision of infected abdominal aortic graft in the 2005 to 2017 American College of Surgeons - National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified by the upper age quartile (75 years old) as a cutoff, and then by functional status, independent vs dependent (as defined by NSIQIP). The patients were then stratified into four groups: Younger (<75)/Independent, Younger (<75)/Dependent, Older (≥75)/Independent, and Older (≥75)/Dependent. Outcomes measured included 30-day mortality and major organ-system dysfunction. RESULTS: There were 814 patients who underwent infected abdominal aortic graft excision: 508 patients (62%) were Younger/Independent, 89 patients (11%) were Younger/Dependent, 176 patients (22%) were Older/Independent, and 41 patients (5%) were Older/Dependent. There was no statistically significant difference in 30-day mortality for Younger/Dependent (odds ratio [OR], 1.66; 95% confidence interval [CI], 0.90-3.09; P = .536) or Older/Independent (OR, 1.31; 95% CI, 0.78-2.19; P = .311) patients when compared with Younger/Independent patients, which suggests that neither old age nor dependent functional status by itself adversely affects mortality. However, when both factors were present, Older/Dependent patients had three times higher mortality when compared with Younger/Independent patients (41.5% vs 13.4%, respectively; OR, 3.13; 95% CI, 1.46-6.71; P = .003). Furthermore, as long as patients presented with independent functional status, old age by itself did not adversely affect major organ-system dysfunction (ORs for Older/Independent vs Younger/Independent were 0.76 [P = .454], 1.04 [P = .874], and 0.90 [P = .692] for cardiac, pulmonary, and renal complications, respectively). On the contrary, even in younger patients, dependent functional status was significantly associated with higher pulmonary complications (Younger/Dependent vs Younger/Independent: OR, 2.22; 95% CI, 1.33-3.73; P = .002) and higher rates of unplanned reoperation (OR, 2.67; 95% CI, 1.62-4.41; P < .0001). CONCLUSIONS: Dependent functional status has significant association with adverse outcomes after excision of infected abdominal aortic grafts, whereas old age alone does not. Therefore, this procedure could be considered in appropriately selected elderly patients with otherwise good functional status. However, caution should be applied in dependent patients regardless of age due to the risk of pulmonary complications.

Intraoperative transit-time flow measurement and high-frequency ultrasound in coronary artery bypass grafting: impact in off versus on-pump, arterial versus venous grafting and cardiac territory grafted.

OBJECTIVES: Despite society guideline recommendations, intraoperative high-frequency ultrasound (HFUS) and transit-time flow measurement (TTFM) use in coronary artery bypass grafting (CABG) has not been widely adopted worldwide. This retrospective review of the REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study assesses the impact of protocolled high-frequency ultrasound/TTFM use in specific technical circumstances of CABG. METHODS: Three REQUEST study sub-analyses were examined: (i) For off-pump (OPCAB) versus on-pump (ONCAB) procedures: strategy changes from preoperative plans for the aorta, conduits, coronary targets and graft revisions; and for all REQUEST patients, revision rates in: (ii) arterial versus venous grafts; and (iii) grafts to different cardiac territories. RESULTS: Four hundred and two (39.6%) of 1016 patients undergoing elective isolated CABG for multivessel disease underwent OPCAB procedures. Compared to ONCAB, OPCAB patients experienced more strategy changes regarding the aorta [14.7% vs 3.4%; odds ratios (OR) = 4.03; confidence interval (CI) = 2.32-7.20], less regarding conduits (0.2% vs 2.8%; OR = 0.09; CI = 0.01-0.56), with no differences in coronary target changes or graft revisions (4.1% vs 3.5%; OR = 1.19; CI = 0.78-1.81). In all REQUEST patients, revisions were more common for arterial versus venous grafts (4.7% vs 2.4%; OR = 2.05; CI = 1.29-3.37), and inferior versus anterior (5.1% vs 2.9%; OR = 1.77; CI = 1.08-2.89) and lateral (5.1% vs 2.8%; OR = 1.83; CI = 1.04-3.27) territory grafts. CONCLUSIONS: High-frequency ultrasound/TTFM use differentially impacts strategy changes and graft revision rates in different technical circumstances of CABG. Notably, patients undergoing OPCAB experienced 4 times more changes related to the ascending aorta than ONCAB patients. These findings may indicate where intraoperative assessment is most usefully applied. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02385344.

Fenestrated Endovascular Aneurysm Repair Affords Fewer Renal Complications than Open Surgical Repair for Juxtarenal Abdominal Aortic Aneurysms in Patients with Chronic Renal Insufficiency.

OBJECTIVE: Although fenestrated endovascular aneurysm repair (FEVAR) has been associated with lower morbidity and mortality than open surgical repair (OSR) in juxtarenal aneurysms (JAAA), there is a paucity of data in the literature comparing outcomes of the approaches specifically in patients with chronic renal insufficiency (CRI). We hypothesized that benefits of FEVAR over OSR observed in the general patient population may be diminished in CRI patients due to their heightened vulnerability to renal dysfunction stemming from contrast-induced nephropathy. This study compares 30-day outcomes between FEVAR and OSR for JAAA in patients with non-dialysis dependent CRI. METHODS: All adults with estimated glomerular filtration rate (eGFR) < 60 mL/min (but not requiring dialysis) undergoing elective, non-ruptured JAAA repairs were identified in the American College of Surgeons - National Surgical Quality Improvement (ACS-NSQIP) Targeted EVAR and AAA databases from 2012-2018. JAAA were identified by recorded proximal aneurysm extent. FEVAR patients were identified in the Targeted EVAR database as those receiving the "Cook Zenith Fenestrated" endograft. OSR cases were defined as those that required proximal clamp positions "above one renal" or "between SMA & renals." Infra-renal or supra-celiac proximal clamp placement, or cases involving concomitant renal/visceral revascularization were excluded. Thirty-day outcomes including mortality, major adverse cardiovascular events (MACE), pulmonary, and renal complications were compared between FEVAR and OSR groups. RESULTS: There were 284 patients with CRI who underwent elective repair of JAAA (FEVAR: 89; OSR: 195). FEVAR patients were significantly older than those undergoing OSR (77.3±7.2 vs. 74.2±7.7, P=0.001) and less likely to be smokers (25.8% vs 42.1%; P = 0.009). Other baseline demographic and pre-operative parameters were comparable between the two groups.Multivariable analysis revealed no significant difference between FEVAR and OSR in 30-day mortality (4.5% vs 4.6%; OR=1.22; 95% CI=0.35 - 4.22; P=0.753) or unplanned re-operation (4.5% vs 5.1%; OR=0.78; 95% CI=0.22 - 2.70; P=0.693). Patients undergoing FEVAR had significantly fewer pulmonary complications (3.4% vs 18.5%; OR=0.12; 95% CI=0.03 - 0.42; P<0.001) and renal dysfunction (3.4% vs 11.8%; OR 0.24 95% CI=0.07 - 0.86; P=0.029) compared to OSR. FEVAR was also associated with significantly shorter ICU and hospital lengths of stay (ICU stay: 0 days vs 3 days, P<0.0001; hospital stay: 3 days vs 8 days, P<0.0001). CONCLUSION: For patients with chronic renal insufficiency, FEVAR offered improved perioperative renal morbidity compared to OSR without a corresponding mortality benefit. Future studies will be required to determine long term outcomes of this procedure in this vulnerable population.

Intraoperative surgical strategy changes in patients with chronic and end-stage renal disease undergoing coronary artery bypass grafting.

OBJECTIVES: Factors such as more diffuse atherosclerosis, plaque instability and accelerated vascular calcification in patients with chronic and end-stage renal disease (ESRD) can potentially present intraoperative challenges in coronary artery bypass grafting (CABG) procedures. We evaluated whether patients with chronic and ESRD experienced more surgical strategy changes and/or graft revisions than patients with normal renal function when undergoing CABG procedures according to a protocol for intraoperative high-frequency ultrasound and transit-time flow measurement (TTFM). METHODS: Outcomes of CABG for patients with chronic and ESRD and patients with normal renal function enrolled in the multicentre prospective REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study were compared retrospectively. The primary end point was frequency of intraoperative surgical strategy changes. The secondary end point was post-protamine TTFM parameters. RESULTS: There were 95 patients with chronic and ESRD and 921 patients with normal renal function. Patients with chronic and ESRD undergoing CABG according to a protocol for intraoperative high-frequency ultrasound and TTFM had a higher rate of strategy changes overall [33.7% vs 24.3%; odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.01-2.48; P = 0.047] and greater revisions per graft (7.0% vs 3.4%; odds ratio = 2.14; 95% CI = 1.17-3.71; P = 0.008) compared to patients with normal renal function. Final post-protamine graft TTFM parameters were comparable between cohorts. CONCLUSIONS: Patients with chronic and ESRD undergoing CABG procedures with high-frequency ultrasound and TTFM experience more surgical strategy changes than patients with normal renal function while achieving comparable graft flow. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02385344.

Impact of Trainee Involvement on Video-Assisted Thoracoscopic Lobectomy for Cancer.

BACKGROUND: Previous literature in other surgical disciplines regarding the impact of resident and fellow involvement on operative time and outcomes has yielded mixed results. The impact of trainee involvement on minimally invasive thoracic surgery is unknown. This study compared risk-adjusted differences in operative time and outcomes of video-assisted thoracoscopic lobectomy for cancer between cases performed with and without residents and fellows involved. METHODS: All patients undergoing elective video-assisted thoracoscopic lobectomy for cancer between 2008 and 2018 were identified in the Veterans Affairs Surgical Quality Improvement Program database. Patients were stratified into 2 cohorts: cases with residents and fellows involved, and cases performed only by attending surgeons. Primary outcomes included operative time, postoperative hospital length of stay, and composite 30-day morbidity and mortality. Secondary outcomes included factors associated with high and low trainee operative autonomy. RESULTS: A total of 3678 patients met study inclusion criteria. In all, 1780 cases were performed with residents and fellows involved (median postgraduate year, 5; interquartile range, 4-7). Multivariate analysis showed that operative time was significantly shorter in resident- and fellow-involved cases compared with attending-only cases (mean [SD], 3.6 [1.4] versus 3.8 [1.6] hours; P < .001). There were no significant differences in composite 30-day morbidity and mortality (16.0% versus 17.1%; adjusted odds ratio = 0.93; 95% confidence interval, 0.77-1.11; P = .40) or length of stay. Substratification of trainees by postgraduate year resulted in similar findings. Cases performed in July through October and those in the Northeastern United States were associated with low autonomy. CONCLUSIONS: Current training paradigms in thoracic surgery are safe, and the involvement of motivated and skilled trainees with appropriate supervision may benefit operative duration.

Open surgical repair of juxtarenal abdominal aortic aneurysms in the elderly is not associated with increased thirty-day mortality compared with fenestrated endovascular grafting.

OBJECTIVE: Endovascular repair of juxtarenal abdominal aortic aneurysms (JAAAs) with fenestrated grafts (fenestrated endovascular aneurysm repair [FEVAR]) has been reported to decrease operative mortality and morbidity compared with open surgical repair (OSR). However, previous comparisons of OSR and FEVAR have not necessarily included patients with comparable clinical profiles and aneurysm extent. Although FEVAR has often been chosen as the first-line therapy for high-risk patients such as the elderly, many patients will not have anatomy favorable for FEVAR. At present, a paucity of data has examined the operative outcomes of OSR in elderly patients for JAAAs relative to FEVAR. Therefore, we chose to perform a propensity-matched comparison of OSR and FEVAR for JAAA repair in patients aged ≥70 years. METHODS: Patients aged ≥70 years who had undergone elective nonruptured JAAA repairs from 2012 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted endovascular aneurysm repair (EVAR) and AAA databases. Patients who had undergone FEVAR were identified in the targeted EVAR database as those who had received the Cook Zenith Fenestrated endograft (Cook Medical, Bloomington, Ind). Because our study specifically examined JAAAs, those patients who had undergone OSR with supraceliac proximal clamping or concomitant renal/visceral revascularization were excluded. A 1:1 propensity-match algorithm matched the OSR and FEVAR patients by preoperative clinical and demographic characteristics, operative indications, and aneurysm extent. The 30-day outcomes, including mortality, major adverse cardiovascular events, and pulmonary and renal complications, were compared between the propensity-matched OSR and FEVAR groups. RESULTS: A 1:1 propensity match was achieved, and the final analysis included 136 OSR patients and 136 FEVAR patients. No significant differences were found in 30-day mortality (4.4% vs 3.7%; odds ratio [OR], 1.21; 95% confidence interval [CI], 0.36-4.06; P = .759) between the OSR and FEVAR groups. OSR was associated with a higher incidence of major adverse cardiovascular events compared with FEVAR; however, the trend was not statistically significant (8.1% vs 3.7%; OR, 2.31; 95% CI, 0.78-6.82; P = .131). Compared with FEVAR, the OSR group had significantly greater rates of pulmonary complications (19.1% vs 3.7%; OR, 6.19; 95% CI, 2.30-16.67; P < .001) and renal complications (8.1% vs 2.2%; OR, 3.90; 95% CI, 1.06-14.31; P = .040). CONCLUSIONS: In the samples assessed in the present study, the results with OSR of JAAAs in the elderly did not differ from those of FEVAR with respect to 30-day mortality despite a greater incidence of pulmonary and renal complications. Although FEVAR should remain the first-line therapy for JAAAs in elderly patients, OSR might be an acceptable alternative for select patients with anatomy unfavorable for FEVAR.

Thirty-day outcomes of open abdominal aortic aneurysm repair by proximal clamp level in patients with normal and impaired renal function.

OBJECTIVE: Open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) has often been reserved in contemporary practice for complex aneurysms requiring a suprarenal or supraceliac proximal clamp level. The present study investigated the associated 30-day outcomes of different proximal clamp levels in OSR of complex infrarenal/juxtarenal AAA in patients with normal renal function and those with chronic renal insufficiency (CRI). METHODS: All patients undergoing elective OSR of infrarenal and juxtarenal AAA were identified in the American College of Surgeons National Surgical Quality Improvement Program-targeted AAA database from 2012 to 2018. The patients were stratified into two cohorts (normal renal function [estimated glomerular filtration rate, ≥60 mL/min] and CRI [estimated glomerular filtration rate, <60 mL/min and no dialysis]) before further substratification into groups by the proximal clamp level (infrarenal, inter-renal, suprarenal, and supraceliac). The 30-day outcomes, including mortality, renal and pulmonary complications, and major adverse cardiovascular event rates, were compared within each renal function cohort between proximal clamp level groups using the infrarenal clamp group as the reference. Supraceliac clamping was also compared with suprarenal clamping. RESULTS: A total of 1284 patients with normal renal function and 524 with CRI were included in the present study. The proximal clamp levels for the 1808 patients were infrarenal for 1080 (59.7%), inter-renal for 337 (18.6%), suprarenal for 279 (15.4%), and supraceliac for 112 (6.2%). In the normal renal function cohort, no difference was found in 30-day mortality with any clamp level. Increased 30-day acute renal failure was only observed in the supraceliac vs infrarenal clamp level comparison (5.9% vs 1.5%; adjusted odds ratio [aOR], 3.97; 95% confidence interval [CI], 1.04-5.18; P = .044). In the CRI cohort, supraceliac clamping was associated with an increased rate of renal composite complications (22.7% vs 5.6%; aOR, 8.81; 95% CI, 3.17-24.46; P < .001) and ischemic colitis (13.6% vs 3.0%; aOR, 4.78; 95% CI, 1.38-16.62; P = .014) compared with infrarenal clamping and greater 30-day mortality (13.6% vs 2.4%; aOR, 6.00; 95% CI, 1.14-31.55; P = .034) and renal composite complications (22.7% vs 10.8%; aOR, 2.87; 95% CI, 1.02-8.13; P = .047) compared with suprarenal clamping. Suprarenal clamping was associated with greater renal dysfunction (10.8% vs 5.6%; aOR, 2.77; 95% CI, 1.08-7.13; P = .035) compared with infrarenal clamping, with no differences in mortality. No differences were found in 30-day mortality or morbidity for inter-renal clamping compared with infrarenal clamping in either cohort. No differences were found in major adverse cardiovascular events with higher clamp levels in either cohort. CONCLUSIONS: In elective OSR of infrarenal and juxtarenal AAAs for patients with CRI, this study found a heightened mortality risk with supraceliac clamping and increased renal morbidity with suprarenal clamping, though these effects were not present for patients with normal renal function. Every effort should be made to keep the proximal clamp level as low as possible, especially in patients with CRI.

Impact of Timing of Smoking Cessation on 30-Day Outcomes in Veterans Undergoing Lobectomy for Cancer.

The adverse effects of tobacco use on postoperative outcomes are well documented. While smoking cessation is associated with overall improvement in long-term survival for lung cancer patients, the effects of cessation shortly before lung surgery are unclear. This study compares 30-day outcomes after lobectomy between active smokers, recent quitters, and nonsmokers. Patients who underwent lobectomy for cancer at national Veterans Affairs medical centers from 2012 to 2018 were retrospectively identified in the Veterans Affairs Surgical Quality Improvement Program database. The sample was stratified into 3 groups: smokers within 2 weeks of surgery ("active smokers"), those who quit between 2 weeks and 3 months prior to surgery ("recent quitters"), and "nonsmokers." Propensity score matching was performed to compare groups. Of 5715 patients who met inclusion criteria, 2696 were nonsmokers, 774 were recent quitters, and 2245 were active smokers. After propensity matching, 572 patients comprised each group. Compared to recent quitters, active smokers had 48% higher odds of suffering a pulmonary complication (95% confidence interval [CI]: 1.03-2.14; P = 0.035) and 72% higher odds of suffering multiple complications (CI: 1.07-2.76; P = 0.026). Relative to nonsmokers, active smokers had 81% higher odds of pulmonary complications (CI: 1.34-2.65; P = 0.003). No differences were detected in outcomes comparing recent quitters to nonsmokers. Veterans undergoing lobectomy for cancer who quit 2 weeks before surgery had less pulmonary complications than active smokers. Recent quitters have similar outcomes to nonsmokers. Surgeons should therefore encourage patients to quit smoking, including just prior to lung surgery.

Long-Term Outcomes of Coronary Artery Bypass Grafting in Veterans with Ischemic Cardiomyopathy.

BACKGROUND: The Surgical Treatment for Ischemic Heart Failure (STICH) trial showed that surgical revascularization in ischemic cardiomyopathy (ICM) patients improves long-term mortality compared with medical treatment alone. This study examines how veterans with ICM undergoing revascularization fare against patients without ICM; it also examines the outcomes in the veteran population. METHODS: This is a retrospective review of a single-center database. From 2000 to 2018, 1,461 patients underwent isolated coronary artery bypass grafting (CABG). Two-hundred-one patients with an ejection fraction less than 35% were classified as the ICM cohort. The primary outcome was mortality. Secondary outcomes included postoperative complications. Subgroup analysis was performed within the ICM cohort comparing off-pump CABG (OPCAB) versus on-pump CABG (ONCAB). RESULTS: ICM patients had a higher incidence of myocardial infarction (MI), diabetes, chronic kidney disease (CKD), and preoperative intra-aortic balloon pump (IABP) use. The non-ICM cohort was more functionally independent. OPCAB was performed in 80.1% of ICM and 66.3% of non-ICM cohorts. There was no statistical difference between ICM and non-ICM cohorts in 30-day mortality (OR 1.94[0.79 - 4.75], P = .15). The ICM cohort had an increased 5-year mortality (OR 1.75[1.14 - 2.69], P = .01) and 10-year mortality (OR 1.71[1.09 - 2.67], P = .02). The ICM cohort showed improved, although not statistically significant, short-term mortality with OPCAB compared with ONCAB (3.1% versus 12.5%, OR 0.31[0.05 - 1.82], P = .20). CONCLUSION: Veterans with ICM undergoing CABG demonstrated similar short-term survival compared with non-ICM veterans. The long-term survival in the ICM cohort still is inferior to patients without ICM. There is a trend toward improved short-term survival in patients with ICM undergoing OPCAB.

Influence of Age on Cardiac Surgery Outcomes in United States Veterans.

OBJECTIVE: Heart disease is still the leading cause of death for both men and women in the United States, and the rate of cardiovascular disease in veterans is even higher than in civilians. This study examines age-related outcomes for veterans undergoing cardiac surgeries at a single institution. METHODS: We included all veterans undergoing coronary artery bypass grafting (CABG) and/or valve surgery between 1997 to 2017 at a single Veterans Affairs (VA) medical center. We stratified this cohort into 4 age groups: ≤59 years old, 60-69 years old, 70-79 years old, and ≥80 years old. Outcomes in age groups were compared using standard statistical methods with the ≤59 years old group as reference. RESULTS: A total of 2,301 patients underwent open cardiac procedures at our institution. The frequency of simultaneous CABG and valve operations increased with age. Usage of cardiopulmonary bypass versus off-pump CABG and operative time was not associated with age. Increased pulmonary and renal complications as well as rates of postoperative arrhythmias all were associated with increasing age. There was no statistically significant difference in 30-day mortality. However, multivariable analysis adjusted for covariates showed all-cause mortality significantly was increased with older age groups (aHR ≥80 years old: 2.94 [2.07-4.17], P < .01; aHR 70-79 years old: 2.15 [1.63-2.83], P < 0.01, with ≤59 years old as reference). CONCLUSIONS: Older patients may have comparable perioperative mortality as their younger counterparts. However, age still is a significant predictor of all-cause mortality, pulmonary and renal complications, and postoperative arrhythmia, and should be considered as a major factor in preoperative risk assessment.

Prolonged hemodynamic response during incidental facial emotion processing in inter-episode bipolar I disorder.

This fMRI study examined whether hemodynamic responses to affectively-salient stimuli were abnormally prolonged in remitted bipolar disorder, possibly representing a novel illness biomarker. A group of 18 DSM-IV bipolar I-diagnosed adults in remission and a demographically-matched control group performed an event-related fMRI gender-discrimination task in which face stimuli had task-irrelevant neutral, happy or angry expressions designed to elicit incidental emotional processing. Participants' brain activation was modeled using a "fully informed" SPM5 basis set. Mixed-model ANOVA tested for diagnostic group differences in BOLD response amplitude and shape within brain regions-of-interest selected from ALE meta-analysis of previous comparable fMRI studies. Bipolar-diagnosed patients had a generally longer duration and/or later-peaking hemodynamic response in amygdala and numerous prefrontal cortex brain regions. Data are consistent with existing models of bipolar limbic hyperactivity, but the prolonged frontolimbic response more precisely details abnormalities recognized in previous studies. Prolonged hemodynamic responses were unrelated to stimulus type, task performance, or degree of residual mood symptoms, suggesting an important novel trait vulnerability brain dysfunction in bipolar disorder. Bipolar patients also failed to engage pregenual cingulate and left orbitofrontal cortex-regions important to models of automatic emotion regulation-while engaging a delayed dorsolateral prefrontal cortex response not seen in controls. These results raise questions about whether there are meaningful relationships between bipolar dysfunction of specific ventromedial prefrontal cortex regions believed to automatically regulate emotional reactions and the prolonged responses in more lateral aspects of prefrontal cortex.