Can we safely expand the donation after circulatory death donor heart pool by extending the donor age limit?

OBJECTIVE: This study evaluates the impact of donor age on outcomes following donation after circulatory death heart transplantation. METHODS: The United Network for Organ Sharing registry was queried to analyze adult recipients who underwent isolated donation after circulatory heart transplantation from January 1, 2019, to September 30, 2023. The cohort was stratified into 2 groups according to donor age, where advanced donor age was defined as 40 years or more. Outcomes were 90-day and 1-year post-transplant survival. Propensity score matching was performed. Subgroup analysis was performed to evaluate the effects of recipient age on 90-day survival among the recipients with advanced-age donors. RESULTS: A total of 994 recipients were included in the study period, and 161 patients (17.1%) received allografts from advanced-age donors. During the study period, the annual incidence of donation after circulatory heart transplantation with advanced-age donors substantially increased. The recipients with advanced-age donors had similar 90-day and 1-year post-transplant survivals compared with the recipients with younger donors. The comparable 90-day survival persisted in a propensity score-matched comparison. In the subgroup analysis among the recipients with advanced-age donors, the recipients aged 60 years or more had significantly reduced 90-day survival compared with the recipients aged less than 60 years. CONCLUSIONS: The use of appropriately selected donation after circulatory donors aged 40 years or more has similar survival compared with that of younger donors. With careful candidate risk stratification and selection, consideration of using donation after circulatory donors aged more than 40 years may further ameliorate ongoing organ shortage with comparable early post-transplant outcomes.

Predictors of acute incisional hernia incarceration at initial hernia diagnosis on computed tomography.

BACKGROUND: Acute incisional hernia incarceration is associated with high morbidity and mortality yet there is little evidence to guide which patients will benefit most from prophylactic repair. We explored baseline computed tomography (CT) characteristics associated with incarceration. METHODS: A case-control study design was utilized to explore adults (≥18 years) diagnosed with an incisional hernia between 2010 and 2017 at a single institution with a 1-year minimum follow-up. Computed tomography imaging at the time of initial hernia diagnosis was examined. Following propensity score matching for baseline characteristics, multivariable logistic regression was performed to identify independent predictors associated with acute incarceration. RESULTS: A total of 532 patients (27.26% male, mean 61.55 years) were examined, of whom 238 experienced an acute incarceration. Between two well-matched cohorts with and without incarceration, the presence of small bowel in the hernia sac (odds ratio [OR], 7.50; 95% confidence interval [CI], 3.35-16.38), increasing sac height (OR, 1.34; 95% CI, 1.10-1.64), more acute hernia angle (OR, 0.98 per degree; 95% CI, 0.97-0.99), decreased fascial defect width (OR, 0.68; 95% CI, 0.58-0.81), and greater outer abdominal fat (OR, 1.28; 95% CI, 1.02-1.60) were associated with acute incarceration. Using threshold analysis, a hernia angle of <91 degrees and a sac height of >3.25 cm were associated with increased incarceration risk. CONCLUSION: Computed tomography features present at the time of hernia diagnosis provide insight into later acute incarceration risk. Improved understanding of acute incisional hernia incarceration can guide selection for prophylactic repair and thereby may mitigate the excess morbidity associated with incarceration. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Improved waitlist and comparable post-transplant outcomes in simultaneous heart-kidney transplantation under the 2018 heart allocation system.

OBJECTIVE: This study aimed to investigate the clinical trends and the impact of the 2018 heart allocation policy change on both waitlist and post-transplant outcomes in simultaneous heart-kidney transplantation in the United States. METHODS: The United Network for Organ Sharing registry was queried to compare adult patients before and after the allocation policy change. This study included 2 separate analyses evaluating the waitlist and post-transplant outcomes. Multivariable analyses were performed to determine the 2018 allocation system's risk-adjusted hazards for 1-year waitlist and post-transplant mortality. RESULTS: The initial analysis investigating the waitlist outcomes included 1779 patients listed for simultaneous heart-kidney transplantation. Of these, 1075 patients (60.4%) were listed after the 2018 allocation policy change. After the policy change, the waitlist outcomes significantly improved with a shorter waitlist time, lower likelihood of de-listing, and higher likelihood of transplantation. In the subsequent analysis investigating the post-transplant outcomes, 1130 simultaneous heart-kidney transplant recipients were included, where 738 patients (65.3%) underwent simultaneous heart-kidney transplantation after the policy change. The 90-day, 6-month, and 1-year post-transplant survival and complication rates were comparable before and after the policy change. Multivariable analyses demonstrated that the 2018 allocation system positively impacted risk-adjusted 1-year waitlist mortality (sub-hazard ratio, 0.66, 95% CI, 0.51-0.85, P < .001), but it did not significantly impact risk-adjusted 1-year post-transplant mortality (hazard ratio, 1.03; 95% CI, 0.72-1.47, P = .876). CONCLUSIONS: This study demonstrates increased rates of simultaneous heart-kidney transplantation with a shorter waitlist time after the 2018 allocation policy change. Furthermore, there were improved waitlist outcomes and comparable early post-transplant survival after simultaneous heart-kidney transplantation under the 2018 allocation system.

Donation after circulatory death improves probability of heart transplantation in waitlisted candidates and results in post-transplant outcomes similar to those achieved with brain-dead donors.

OBJECTIVE: To quantitate the impact of heart donation after circulatory death (DCD) donor utilization on both waitlist and post-transplant outcomes in the United States. METHODS: The United Network for Organ Sharing database was queried to identify all adult waitlisted and transplanted candidates between October 18, 2018, and December 31, 2022. Waitlisted candidates were stratified according to whether they had been approved for donation after brain death (DBD) offers only or also approved for DCD offers. The cumulative incidence of transplantation was compared between the 2 cohorts. In a post-transplant analysis, 1-year post-transplant survival was compared between unmatched and propensity-score-matched cohorts of DBD and DCD recipients. RESULTS: A total of 14,803 candidates were waitlisted, including 12,287 approved for DBD donors only and 2516 approved for DCD donors. Overall, DCD approval was associated with an increased sub-hazard ratio (HR) for transplantation and a lower sub-HR for delisting owing to death/deterioration after risk adjustment. In a subgroup analysis, candidates with blood type B and status 4 designation received the greatest benefit from DCD approval. A total of 12,238 recipients underwent transplantation, 11,636 with DBD hearts and 602 with DCD hearts. Median waitlist times were significantly shorter for status 3 and status 4 recipients receiving DCD hearts. One-year post-transplant survival was comparable between unmatched and propensity score-matched cohorts of DBD and DCD recipients. CONCLUSIONS: The use of DCD hearts confers a higher probability of transplantation and a lower incidence of death/deterioration while on the waitlist, particularly among certain subpopulations such as status 4 candidates. Importantly, the use of DCD donors results in similar post-transplant survival as DBD donors.

Infectious complications following contemporary left ventricular assist device implantation.

BACKGROUND: The aim of this study is to evaluate the source of infectious complications following contemporary left ventricular assist device (LVAD) implantation and to determine the impact of infections on patient outcomes. METHODS: All patients who underwent centrifugal LVAD implantation between 2014 and 2020 at a single center were retrospectively reviewed. Postimplant infections were categorized as VAD-specific, VAD-related, or non-VAD according to previously published definitions. Postoperative survival and freedom from readmission were assessed using Kaplan-Meier analysis. Univariable and multivariable analyses were performed to determine the risk factors for postoperative infectious complications. RESULTS: A total of 212 patients underwent centrifugal LVAD implantation (70 HeartMate 3, 142 HeartWare HVAD) during the study period. One hundred and two patients (48.1%) developed an infection, including 34 VAD-specific, 11 VAD-related, and 57 non-VAD. Staphylococcus species were the most common source of postoperative infection (n = 57, 33.7%). In multivariable analysis, diabetes significantly impacted overall postoperative infection rate. At 12 and 24 months, respectively, Kaplan-Meier survival was 81.1% and 61.6% in the infection group and 83.4% and 78.1% in the noninfection group (p = 0.006). Within the total cohort, 12- and 24-month freedom from infection were 46.2% and 31.9%, respectively. Patients with infectious complication had significantly lower rate of transplantation (16.4% vs. 43.6%; p < 0.001), increased overall mortality (46.3% vs. 17.3%, p < 0.001), and increased rates of noncardiac readmission (58.2% vs. 37.3%, p = 0.007). CONCLUSIONS: Infections are common following contemporary LVAD implantation and are most commonly non-VAD related. Patients with postoperative infectious complications have significantly reduced rates of transplantation, survival, and freedom from noncardiac readmission.

Hyperlactatemia as a prognostic indicator for contemporary left ventricular assist device implantation.

BACKGROUND: This study evaluates the impact of early post-operative hyperlactatemia on outcomes after left ventricular assist device (LVAD) implantation. METHODS: Adults undergoing contemporary LVAD implantation between 2009 to 2018 were included. Peak post-operative (within 24-h) lactate level was analyzed. The cohort was stratified into patients with and without post-operative hyperlactatemia, which was defined as peak > 3.5 mMol/L. The primary outcome was survival, and secondary outcomes included post-implant adverse events. Sub-analysis was performed to evaluate the impact of time for lactate normalization, define as lactate < 2 mMol/L. Multivariable cox regression was used for risk-adjustment. RESULTS: A total of 190 patients were included. 49.5% experienced early post-operative hyperlactatemia. Patients with post-operative hyperlactatemia had significantly higher rates of post-implant complications including re-operation, renal failure, and hepatic dysfunction (all, p ≤ 0.05). The post-operative hyperlactatemia group also had significantly higher 90-day and 1-year mortality rates following LVAD implantation (both, p ≤ 0.05). In multivariable analysis, post-operative hyperlactatemia (HR 1.69, 95% CI 1.09-2.60, p = 0.02) was an independent predictor of overall mortality following LVAD implantation. Increased time for normalization of lactate also adversely impacted risk-adjusted overall mortality following implantation as a continuous variable (HR 1.02, 95% CI 1.01-1.03, p < .001). CONCLUSIONS: This study demonstrates early post-operative hyperlactatemia is associated with increased morbidity and mortality following LVAD implantation. Even early post-operative lactate trends within the first 24 post-operative hours appear to have a useful role in predicting longitudinal survival following implantation. Careful monitoring of post-operative lactate with measures to normalize levels should be considered in the early care of LVAD patients.

Safety and benefit of ad libitum feeding following laparoscopic pyloromyotomy: retrospective comparative trial.

PURPOSE: In this study, we evaluated the impacts of ad libitum feedings on outcomes following laparoscopic pyloromyotomy in patients with infantile hypertrophic pyloric stenosis. METHODS: Pediatric patients with infantile hypertrophic pyloric stenosis who underwent laparoscopic pyloromyotomy were included. Patients were stratified into ad libitum and structured feeding groups. Primary outcomes were times from surgery completion to goal feeding and discharge. RESULTS: A total of 336 patients were included in the study with 63 patients (18.8%) in the ad libitum feeding group. The ad libitum feeding group experienced significantly shorter times from surgery completion to both goal feedings (10.7 h vs 18.7 h; p < 0.001) and hospital discharge (21.6 h vs 23.1 h; p = 0.008) compared to the structured protocol group. Postoperative emesis (47.% vs 30.8%; p = 0.011) was higher in the ab libitum cohort, but the rates of return to an emergency department and/or readmission (4.8% vs 2.2%; p = 0.26) were similar. CONCLUSION: Ad libitum feeding after pyloromyotomy decreases time to reach goal feeding and hospital discharge. While it may contribute to a higher incidence of emesis, it does not appear to significantly increase hospital readmission. Ad libitum feeding appears to be a safe and beneficial alternative to structured feeding protocols following pyloromyotomy. LEVEL OF EVIDENCE: III.

Impact of early massive transfusion and blood component ratios in patients undergoing left ventricular assist device implantation.

BACKGROUND: This study evaluates the impact of early massive transfusion and blood component ratios on outcomes following left ventricular assist device (LVAD) implantation. METHODS: Adults undergoing LVAD implantation between 2009 and 2018 at a single institution were included. Transfusions were analyzed during the intraoperative and the initial 24-h postoperative period. Patients were stratified into massive and nonmassive transfusion groups. The primary outcome was survival, and secondary outcomes included postoperative complications. Sub-analyses were performed to evaluate the impact of balanced transfusion. RESULTS: A total of 278 patients were included. A total of 45.3% (n = 126) required massive transfusions. The massive transfusion group experienced significantly higher rates of postimplant adverse events, including reoperation, renal failure, and hepatic dysfunction (all, p ≤ .05). Furthermore, the massive transfusion group had significantly lower 30-day, 90-day, 1-year, 2-year, and overall survival rates following LVAD implantation (all, p < .05). In multivariable analysis, massive transfusion significantly impacted overall risk-adjusted mortality rate (hazard ratio: 2.402, 95% confidence Interval: 1.677-3.442, p < .001). In the sub-analyses evaluating the impact of balanced massive transfusion, balanced fresh frozen plasma to packed red blood cell (pRBC) transfusion did not provide any survival benefit (all, p > .05). However, balanced platelet to pRBC massive transfusion did improve 2-year and overall mortality rates in the massive transfusion cohort (both, p ≤ .05). CONCLUSIONS: This study demonstrates a significant association between early massive transfusion and adverse outcomes following LVAD implantation. Balancing platelet to pRBC transfusion in the early postoperative period may help mitigate some of these detrimental effects of massive transfusion on subsequent survival.

Pre-implant right ventricular free wall strain predicts post-LVAD right heart failure.

BACKGROUND: The aim of this study is to evaluate the predictive utility of preoperative right ventricular (RV) global longitudinal strain (GLS) and free wall strain (FWS) on outcomes following left ventricular assist devices (LVADs) implantation. METHODS: Preoperative transthoracic echocardiograms were retrospectively reviewed in adults undergoing continuous-flow LVAD implantation between 2004 and 2018 at a single center. Patients undergoing pump exchange were excluded. RV GLS and FWS were calculated using commercially available software with the apical four-chamber view. The primary outcome was RV failure as defined by the Interagency Registry for Mechanically Assisted Circulatory Support within 1-year post-LVAD insertion. RESULTS: A total of 333 patients underwent continuous-flow LVAD implantation during the study period and 137 had adequate preoperative studies for RV strain evaluation. RV FWS was found to be a significant predictor of postoperative RV failure in univariate analysis (odds ratio [OR] = 1.12, p = .03), and this finding persisted after risk adjustment in multivariable analysis (OR = 1.14, p = .04). Using the optimal cutoff value of -5.64%, the c-index of FWS in predicting RV failure was 0.65. RV GLS was not associated with post-LVAD RV failure (OR = 1.07, p = .29). PCWP was the only additional significant predictor of RV failure using multivariable analysis (OR = 0.90, p = .02). CONCLUSION: Pre-implant RV FWS is predictive of RV failure in the first postoperative year after LVAD implantation.

Impact of hepatic steatosis on outcomes after left ventricular assist device implantation.

BACKGROUND: This single-center, retrospective study evaluates the impact of hepatic steatosis on outcomes after continuous-flow left ventricular assist device (LVAD) implantation. METHODS: Adults undergoing LVAD implantation between 2004 and 2018 with a preoperative noncontrast-enhanced chest and abdominal computed tomography scan were included in the study. Patients were stratified as with and without radiographic signs of hepatic steatosis. The primary outcome was survival, and secondary outcomes included rates of postimplant adverse events. RESULTS: A total of 203 patients were included in the study. 27.6% (n = 56) had radiographic signs of hepatic steatosis. Hepatic steatosis group had a higher body mass index (30.1 vs. 27.0, p < .01), model for end-stage liver disease excluding international normalized ratio score (16.8 vs. 15.1, p = .05), and incidence of diabetes (53.6% vs. 35.4%, p = .02). The rates of postimplant adverse events, including bleeding, infection, reoperation, renal failure, hepatic dysfunction, stroke, and right ventricular failure, were similar between the groups (all, p > .05). Unadjusted survival was comparable between the groups at 30-days, 90-days, 1-year, and 2-year following LVAD implantation (all, p > .05). In addition, hepatic steatosis did not impact risk-adjusted overall mortality when modeled as a categorical variable (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.46-1.13; p = .15). CONCLUSIONS: This study demonstrates that the presence of preoperative hepatic steatosis on imaging is not predictive of increased morbidity or mortality following LVAD implantation. Despite the association with obesity, metabolic diseases, and heart failure, hepatic steatosis on imaging appears to have a limited role in patient selection or prognostication in LVAD patients.

Gastrointestinal complications after cardiac surgery: Incidence, predictors, and impact on outcomes.

BACKGROUND: The purpose of this study was to investigate the incidence, predictors, and long-term impact of gastrointestinal (GI) complications following adult cardiac surgery. METHODS: Index Society of Thoracic Surgeons (STS) adult cardiac operations performed between January 2010 and February 2018 at a single institution were included. Patients were stratified by the occurrence of postoperative GI complications. Outcomes included early and late survival as well as other associated major postoperative complications. A subanalysis of propensity score-matched patients was also performed. RESULTS: A total of 10,285 patients were included, and the overall rate of GI complications was 2.4% (n = 246). Predictors of GI complications included dialysis dependency, intra-aortic balloon pump, congestive heart failure, chronic obstructive pulmonary disease, and longer aortic cross-clamp times. Thirty-day (2.6% vs. 24.8%), 1- (6.3% vs. 41.9%), and 3-year (11.1% vs. 48.4%) mortality were substantially higher in patients who experienced GI complications (all p < .001). GI complication was associated with a threefold increased hazard for mortality (hazard ratio = 3.1, 95% confidence interval = 2.6-3.7) after risk adjustment, and there was an association between the occurrence of GI complications and increased rates of renal failure (39.4% vs. 2.5%), new dialysis dependency (31.3% vs. 1.5%), multisystem organ failure (21.5% vs .1.0%), and deep sternal wound infections (2.6% vs. 0.2%; all p < .001). These results persisted in propensity-matched analysis. CONCLUSION: GI complications are infrequent but have a profound impact on early and late survival, and often occur in association with other major complications. Risk factor modification, heightened awareness, and early detection and management of GI complications appear warranted.

Concomitant tricuspid valve surgery is beneficial at the time of left-sided valve surgery.

BACKGROUND: This study evaluates the impact of secondary functional tricuspid regurgitation (TR) and concomitant tricuspid valve repair (TVr) at the time of left-sided valve operations. METHODS: Adults undergoing left-sided valve operations between 2010 and 2019 at a multihospital academic institution were included. Patients were stratified into three groups: less-than-moderate TR without TVr (Group 1), moderate-or-greater TR without TVr (Group 2), and moderate-or-greater TR with TVr (Group 3). Primary outcomes included survival and hospital readmissions. Secondary outcomes included major postoperative morbidities. Multivariable logistic regression evaluated risk-adjusted mortality and readmission. RESULTS: About 3444 patients were included in the analysis and were stratified into Group 1 (n = 2612, 75.8%), Group 2 (n = 563, 16.3%), and Group 3 (n = 269, 7.8%). Patients with moderate or greater TR (Groups 2 and 3) had higher rates of mortality, hospital readmissions and major postoperative complications including reoperations, renal failure requiring dialysis, blood transfusions, and prolonged ventilation (all, p < .05). When assessed individually, the Group 3 had substantially higher rates of renal failure requiring dialysis, prolonged ventilation, and reoperations, although the Group 2 had higher rates of 30-day mortality (all, p < .05). These findings persisted in risk-adjusted analysis with the highest hazards for mortality (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.7-2.2) and readmission (HR 1.3, 95% CI 1.2-1.5) appreciated in the Group 2. CONCLUSIONS: In this analysis of 3444 patients, those with moderate-to-severe TR who did not undergo a TVr at the time of their left-sided valve operation had substantially higher risks of mortality and hospital readmissions compared with those who did undergo TV surgery.

Surgical treatment of infective endocarditis: Results in 831 patients from a single center.

INTRODUCTION: This study evaluated surgical outcomes of infective endocarditis (IE), with particular attention to the impact of intravenous drug use (IVDU). METHODS: Adult patients undergoing surgery for IE between 2011 and 2018 at a single center were included and stratified by IVDU. The primary outcome was overall survival. Secondary outcomes included postoperative complications and hospital readmissions. Kaplan-Meier and multivariable Cox regression were utilized for unadjusted and risk-adjusted survival analyses, respectively. Cumulative incidence function curves were compared for hospital readmissions. RESULTS: A total of 831 patients (mean age 55 years, 34.4% female) were operated on for IE, including 318 (38.3%) with IVDU. Cultures were most commonly positive for streptococcus (25.2%), methicillin-sensitive Staphylococcus aureus (17.7%), enterococcus (14.3%), or methicillin-resistant Staphylococcus aureus (8.4%). The most common procedures included isolated aortic valve repair/replacement (18.8%), aortic root replacement (15.9%), mitral valve repair/replacement (26.7%), aortic and mitral valve replacement (8.4%), and tricuspid valve repair/replacement (7.6%). Mean follow-up was 3.4 ± 2.4 years. Overall 5-year survival was 64% and was similar between IVDU and non-IVDU. Multivariable analysis demonstrated that IVDU was not associated with mortality risk. IVDU patients displayed higher rates of all-cause readmission (61.6% vs 53.9%; P = .03), drug-use readmission (15.4% vs 1.4%; P < .001), and recurrent endocarditis readmission (33.0% vs 13.0%; P < .001). CONCLUSIONS: The majority of patients undergoing surgical treatment of IE are alive at 5-years although readmission rates are high. IVDU is not a risk factor for longitudinal mortality although patients with IVDU are at higher overall readmission risk, driven largely by greater readmissions for drug-use and recurrent endocarditis.

Left ventricular assist device implantation in patients with a history of malignancy.

BACKGROUND: This study evaluates the impact of a history of malignancy on outcomes of left ventricular assist device (LVAD) implantation. METHODS: Adult patients with a preimplant history of malignancy who underwent LVAD implantation between 2006 and 2018 were included. The primary outcome was post-LVAD survival. RESULTS: A total of 250 patients underwent LVAD implant during the study period, including 37 (14.8%) patients with a history of malignancy. Of these 37 patients, five (13.5%) had active malignancy at the time of LVAD implantation, and seven had more than one type of cancer. The median disease-free duration before LVAD was 3.5 years (interquartile range [IQR] 1.0-7.75 years). The most common types of malignancy included urologic (n = 20; 45.5%), skin (n = 7, 15.9%), and leukemia or lymphoma (n = 6; 13.6%). Median follow-up was 244 (IQR, 126-571) days and 313 (IQR 127-738) days for those with and without a history of malignancy, respectively (P = .49). Unadjusted post-LVAD survival was reduced in those with a malignancy history (2-year survival 53.4% vs 66.9%; P = .01), a finding that persisted after risk-adjustment (hazard ratio 1.89, 95% confidence interval, 1.13-3.14; P = .01). Only one (2.7%) patient died post-LVAD from their cancer. CONCLUSIONS: Although a history of malignancy is associated with reduced survival after LVAD implantation, more than half of the patients are alive at 2 years. This combined with the fact that most do not die from causes directly related to their cancer suggest that LVAD implantation is reasonable to perform in carefully selected patients with a history of malignancy.

Preoperative prealbumin does not impact outcomes after left ventricular assist device implantation.

BACKGROUND: This single-center, the retrospective study evaluates the impact of preoperative serum prealbumin levels on outcomes after left ventricular assist device (LVAD) implantation. METHODS: Adults undergoing LVAD implantation, with a recorded preoperative prealbumin level, between 2004 to 2018 were included. Primary outcomes included rates of 1-year survival and secondary outcomes included rates of postimplant adverse events. Threshold regression and restricted cubic splines were utilized to identify a cut-point to dichotomize prealbumin level. Prealbumin was also evaluated as a continuous variable. Multivariable logistic regression was used for risk-adjustment. RESULTS: A total of 333 patients were included. Patients were dichotomized according to an optimal prealbumin threshold of 15 mg/dL: 47.4% (n = 158) had levels below and 52.6% (n = 175) had levels above this threshold, respectively. The rates of postimplant adverse events, including bleeding, infection, stroke, renal failure, and right heart failure, were similar between the groups (all P > .05). Furthermore, the rates of cardiac transplantation and device explantation were also similar (all P > .05). Unadjusted survival was comparable between the groups at 30-days, 90-days, and 1-year following LVAD implantation (all P > .05). In addition, lower prealbumin did not impact risk-adjusted 1-year mortality when modeled either as a categorical (OR, 1.08; 95% CI, 0.48-2.12; P = .82) or continuous variable (OR, 1.99; 95% CI, 0.73-2.34; P = .96). CONCLUSIONS: This study demonstrates that lower prealbumin levels were not predictive of increased post-LVAD morbidity or mortality. Although an established marker of nutritional and inflammatory status, the role of prealbumin in patient selection or prognostication appears limited in LVAD patients.

BIRC5 is a target for molecular imaging and detection of human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer mortality with a dismal overall survival rate and an urgent need for detection of minute tumors. Current diagnostic modalities have high sensitivity and specificity for larger tumors, but not for minute PDAC. In this study, we test the feasibility of a precision diagnostic platform for detecting and localizing minute human PDAC in mice. This platform includes: 1) defining BIRC5 as an early PDAC-upregulated gene and utilizing an enhanced BIRC5 super-promoter to drive expression of dual Gaussia luciferase (GLuc) and sr39 thymidine kinase (sr39TK) reporter genes exponentially and specifically in PDAC; 2) utilizing a genetically-engineered AAV2RGD to ensure targeted delivery of GLuc and sr39TK specifically to PDAC; 3) using serologic GLuc and sr39TK microPET/CT imaging to detect and localize minute human PDAC in mice. The study demonstrates feasibility of a precision diagnostic platform using an integrated technology through a multiple-stage amplification strategy of dual reporter genes to enhance the specificity and sensitivity of detection and localization of minute PDAC tumors and currently undetectable disease.