Textbook Outcome: Definition and Analysis of a Novel Quality Measure in Lung Transplantation.

OBJECTIVE: To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. SUMMARY BACKGROUND DATA: TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. METHODS: Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. RESULTS: Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.

Harry Truman's Complicated Cholecystectomy.

MINI-ABSTRACT: Harry S. Truman, the 33rd President of the United States, developed right-sided abdominal pain the year after he left office. Misdiagnosed with appendicitis, Truman underwent an appendectomy before a cholecystectomy treated the underlying cholecystitis. This error was concealed at the time from the American people. His postoperative course was closely followed by Americans through newspapers and was complicated by a bout of Clostridium difficile colitis. Truman survived this episode to die of heart failure decades later.

Subnormothermic ex vivo lung perfusion attenuates graft inflammation in a rat transplant model.

OBJECTIVE: Ex vivo lung perfusion has emerged as a novel technique to safely preserve lungs before transplantation. Recent studies have demonstrated an accumulation of inflammatory molecules in the perfusate during ex vivo lung perfusion. These proinflammatory molecules, including damage-associated molecular patterns and inflammatory cytokines, may contribute to acute and chronic allograft dysfunction. At present, ex vivo lung perfusion is performed clinically at normothermic temperature (37°C). The effect of lowering temperature to the subnormothermic range during ex vivo lung perfusion has not been reported. In this study, we hypothesized that lower ex vivo lung perfusion temperature will lead to a reduction in allograft inflammation and result in improved post-transplant graft function. METHODS: Lewis rat heart-lung blocs underwent 4 hours of ex vivo lung perfusion in 3 temperature groups: 37°C (MP37), 30°C (MP30), and 25°C (MP25). In the control group, lung grafts were preserved by static cold storage before transplantation. After ex vivo lung perfusion or static cold storage, the left lung was transplanted for 2 hours before the animal was killed. Sera and tissue were collected and analyzed. RESULTS: There were no differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios during 4 hours of ex vivo lung perfusion between temperature groups. Tumor necrosis factor α significantly increased in the MP37 group during ex vivo lung perfusion, whereas this was not seen at lower temperatures. Extracellular DNA and high-mobility group box 1 perfusate concentrations increased significantly during ex vivo lung perfusion in all groups, but the rate of increase was diminished at lower temperature. Two hours post-transplant, there were no significant differences in partial pressure of arterial oxygenation to fraction of inspired oxygen ratios of the lung graft or serum damage-associated molecular pattern levels among groups. On histologic grading after transplantation, greater injury was observed in the MP30 and MP37 groups, but not MP25, when compared with static cold storage. CONCLUSIONS: Subnormothermic ex vivo lung perfusion at 25°C reduces the production of inflammatory mediators during ex vivo lung perfusion and is associated with reduced histologic graft injury after transplantation.

Point-of-Care Assessment of DCD Livers During Normothermic Machine Perfusion in a Nonhuman Primate Model.

Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5 minutes (DCD-5min, n = 4) or 45 minutes (DCD-45min, n = 4) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow-controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8 hours for analysis. DCD-45min livers had greater terminal portal vein pressure (8.5 vs. 13.3 mm Hg, P = 0.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, P = 0.005). During perfusion, DCD-45min livers had equivalent terminal lactate clearance (93% vs. 96%, P = 0.344), greater terminal alanine aminotransferase (163 vs. 883 U/L, P = 0.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7 U/L, P = 0.002). DCD-45min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250 ng/mL, P = 0.029; and 158 vs. 293 ng/mL, P = 0.003; respectively). DCD-5min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD-45min livers did not. On blinded histologic evaluation, DCD-45min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. Conclusion: Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP.

Outcomes in Kidney Transplantation Between Veterans Affairs and Civilian Hospitals: Considerations in the Context of the MISSION Act.

OBJECTIVE: We sought to compare kidney transplantation outcomes between Veterans Affairs (VA) and non-VA transplant centers. SUMMARY BACKGROUND DATA: Transplant care at the VA has previously been scrutinized due to geographic and systematic barriers. The recently instituted MISSION Act entered effect June 6th, 2019, which enables veteran access to surgical care at civilian hospitals if certain eligibility criteria are met. METHODS: We evaluated observed-to-expected outcome ratios (O:E) for graft loss and mortality using the Scientific Registry of Transplant Recipients database for all kidney transplants during a 15-year period (July 1, 2001-June 30, 2016). Of 229,188 kidney transplants performed during the study period, 1508 were performed at VA centers (N = 7), 7750 at the respective academic institutions affiliated with these VA centers, and 227,680 at non-VA centers nationwide (N = 286). RESULTS: Aggregate O:E ratios for mortality were lower in VA centers compared with non-VA centers at 1 month and 1 year (O:E = 0.27 vs 1.00, P = 0.03 and O:E = 0.62 vs 1.00, P = 0.03, respectively). Graft loss at 1 month and 1 year was similar between groups (O:E = 0.65 vs 1.00, P = 0.11 and O:E = 0.79 vs 1.00, P = 0.15, respectively). Ratios for mortality and graft loss were similar between VA centers and their respective academic affiliates. Additionally, a subgroup analysis for graft loss and mortality at 3 years (study period January 1, 2009-December 31, 2013) demonstrated no significant differences between VA centers, VA-affiliates, and all non-VA centers. CONCLUSIONS: Despite low clinical volume, VA centers offer excellent outcomes in kidney transplantation. Veteran referral to civilian hospitals should weigh the benefit of geographic convenience and patient preference with center outcomes.

Palliative Care Consultation Is Underutilized in Critically Ill General Surgery Patients.

BACKGROUND: American College of Surgeons recommends palliative care and surgeons collaborate on the care of patients with poor prognoses. These collaborations are done to discuss symptom management and goals of care. However, contemporary practice patterns of palliative care consultation for surgical patients are poorly defined. We aim to describe the use of palliative care consultation for patients admitted to our institution's surgical services who died during their index hospital admission. METHODS: The Duke Enterprise Data Unified Content Explorer 2014 to 2016 was queried for patients admitted to general surgery services who died during their admission. Secondary measures included length of stay, time spent in consultation, days from consultation to death, and execution of a care plan. RESULTS: Of the 105 patients identified, 6 died on the day of admission, and 39 (37%) received palliative care consultation. Our data showed that patients who received consultation were generally older, white, and insured. Median number of days between palliative consult and death was 3 days (interquartile range: 1-8). Goals-of-care conversations were the indication for consultation in 62.5% of patients. The proposed plan by the consultants was congruent with the primary team in 66.7% of cases. CONCLUSIONS: Palliative care consultations were underutilized in surgical patients who died while admitted to the general surgical service at our institution. When palliative care is consulted, the plan of the primary surgical team and the palliative team align. Identification of barriers to consultation and promotion of the benefits of palliative care among surgical teams is warranted.

A Polyaniline-based Sensor of Nucleic Acids.

Detection of nucleic acids is at the center of diagnostic technologies used in research and the clinic. Standard approaches used in these technologies rely on enzymatic modification that can introduce bias and artifacts. A critical element of next generation detection platforms will be direct molecular sensing, thereby avoiding a need for amplification or labels. Advanced nanomaterials may provide the suitable chemical modalities to realize label-free sensors. Conjugated polymers are ideal for biological sensing, possessing properties compatible with biomolecules and exhibit high sensitivity to localized environmental changes. In this article, a method is presented for detecting nucleic acids using the electroconductive polymer polyaniline. Simple DNA "probe" oligonucleotides complementary to target nucleic acids are attached electrostatically to the polymer, creating a sensor system that can differentiate single nucleotide differences in target molecules. Outside the specific and unbiased nature of this technology, it is highly cost effective.

Utilizing Intrinsic Properties of Polyaniline to Detect Nucleic Acid Hybridization through UV-Enhanced Electrostatic Interaction.

Detection of specific RNA or DNA molecules by hybridization to "probe" nucleic acids via complementary base-pairing is a powerful method for analysis of biological systems. Here we describe a strategy for transducing hybridization events through modulating intrinsic properties of the electroconductive polymer polyaniline (PANI). When DNA-based probes electrostatically interact with PANI, its fluorescence properties are increased, a phenomenon that can be enhanced by UV irradiation. Hybridization of target nucleic acids results in dissociation of probes causing PANI fluorescence to return to basal levels. By monitoring restoration of base PANI fluorescence as little as 10(-11) M (10 pM) of target oligonucleotides could be detected within 15 min of hybridization. Detection of complementary oligos was specific, with introduction of a single mismatch failing to form a target-probe duplex that would dissociate from PANI. Furthermore, this approach is robust and is capable of detecting specific RNAs in extracts from animals. This sensor system improves on previously reported strategies by transducing highly specific probe dissociation events through intrinsic properties of a conducting polymer without the need for additional labels.