Standardizing Opioids Prescribed at Discharge in Trauma Surgery.

INTRODUCTION: Excessive opioid use after sustaining trauma has contributed to the opioid epidemic. Standardizing the quantity of opioids prescribed at discharge can improve prescribing behavior. We hypothesized that adopting new electronic medical record order sets would be associated with decreased morphine milligram equivalents (MME) prescribed at discharge for trauma patients. METHODS: This was a quasi-experimental study examining opioid prescribing practices at a Level 1 Trauma Center. All patients ages 18-89 admitted to the Trauma Service from January 2017 through March 2021 and hospitalized for at least 2 d were included. In November 2020, new trauma admission and discharge order sets were implemented with recommended discharge opioid quantity based on inpatient opioid usage the day prior to discharge multiplied by five. Postintervention prescribing practices were compared to historical controls. The primary outcome was MME at discharge. RESULTS: Baseline characteristics between preintervention and postintervention cohorts were comparable. There was a significant reduction in median MME prescribed at discharge postintervention (112.5 versus 75.0, P < 0.0001). Median inpatient MME usage also significantly reduced postintervention (184.1 versus 160.5; P < 0.0001). There were trends toward increased ideal prescribing per order set recommendation and a reduction in overprescribing. Patients receiving the recommended opioid quantity at discharge had the lowest opioid refill prescription rate (under: 29.6%, ideal: 7.3%, over: 19.7%, P < 0.0001). CONCLUSIONS: For trauma patients requiring inpatient opioid therapy, a pragmatic and individualized intervention was associated with a reduced quantity of discharge opioids without negative outcomes. Reduction in inpatient opioid use was also associated with standardizing prescribing practices of surgeons with electronic medical record order sets.

Issues and Strategies in Training Left-Handed Surgeons.

Left-hand dominance in surgery is a trait historically regarded as disadvantageous to both the trainee and trainer. The aim of this editorial was to identify challenges faced by left-handed trainees and trainers across multiple surgical specialties and to propose strategies that could be implemented during surgical training. Multiple themes were identified including left-handed surgeons experiencing discrimination due to their handedness. Additionally, a higher incidence of ambidexterity among left-handed trainees was noted, suggesting that left-handed surgeons may be adapting to a lack of accommodations for left-hand trainees. Also explored were the effects of handedness in training vs practice and the effects of handedness across subspecialties including orthopedic surgery, cardiothoracic surgery, and plastic surgery. Solutions discussed involved teaching both right-handed and left-handed surgeons' ambidexterity, pairing left-handed surgeons with left-handed trainees, having left-handed instruments available, adapting the surgical environment to the operating surgeon, communicating laterality, utilizing simulation centers or virtual reality, and encouraging prospective research looking at best-practices.

Efficacy and Safety of Anti-Xa-Guided Versus Fixed Dosing of Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Trauma Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Trauma patients are at high risk of venous thromboembolism (VTE). We summarize the comparative efficacy and safety of anti-Xa-guided versus fixed dosing for low molecular weight heparin (LMWH) for the prevention of VTE in adult trauma patients. METHODS: We searched Medline and Embase from inception through June 1, 2022. We included randomized controlled trials or observational studies comparing anti-Xa-guided versus fixed dosing of LMWH for thromboprophylaxis in adult trauma patients. We incorporated primary data from 2 large observational cohorts. We pooled effect estimates using a random-effects model. We assessed risk of bias using the ROBINS-I tool for observational studies and assessed certainty of findings using GRADE methodology. RESULTS: We included 15 observational studies involving 10,348 patients. No randomized controlled trials were identified. determined that, compared to fixed LMWH dosing, anti-Xa-guided dosing may reduce deep vein thrombosis [adjusted odds ratio (aOR); 0.52, 95% CI: 0.40-0.69], pulmonary embolism (aOR: 0.48, 95% CI: 0.30-0.78) or any VTE (aOR: 0.54, 95% CI: 0.42-0.69), though all estimates are based on low certainty evidence. There was an uncertain effect on mortality (aOR: 1.06, 95% CI: 0.85-1.32) and bleeding events (aOR: 0.84, 95% CI: 0.50-1.39), limited by serious imprecision. We used several sensitivity and subgroup analyses to confirm the validity of our assumptions. CONCLUSION: Anti-Xa-guided dosing may be more effective than fixed dosing for prevention of deep vein thrombosis, pulmonary embolism, and VTE for adult trauma patients. These promising findings justify the need for a high-quality randomized study with the potential to deliver practice changing results.

Enoxaparin titrated by anti-Xa levels reduces venous thromboembolism in trauma patients.

BACKGROUND: Trauma is a major risk factor for the development of a venous thromboembolism (VTE). After observing higher than expected VTE rates within our center's Trauma Quality Improvement Program data, we instituted a change in our VTE prophylaxis protocol, moving to enoxaparin dosing titrated by anti-Xa levels. We hypothesized that this intervention would lower our symptomatic VTE rates. METHODS: Adult trauma patients at a single institution meeting National Trauma Data Standard criteria from April 2015 to September 2019 were examined with regards to VTE chemoprophylaxis regimen and VTE incidence. Two groups of patients were identified based on VTE protocol-those who received enoxaparin 30 mg twice daily without routine anti-Xa levels ("pre") versus those who received enoxaparin 40 mg twice daily with dose titrated by serial anti-Xa levels ("post"). Univariate and multivariate analyses were performed to define statistically significant differences in VTE incidence between the two cohorts. RESULTS: There were 1698 patients within the "pre" group and 1406 patients within the "post" group. The two groups were essentially the same in terms of demographics and risk factors for bleeding or thrombosis. There was a statistically significant reduction in VTE rate (p = 0.01) and deep vein thrombosis rate (p = 0.01) but no significant reduction in pulmonary embolism rate (p = 0.21) after implementation of the anti-Xa titration protocol. Risk-adjusted Trauma Quality Improvement Program data showed an improvement in rate of symptomatic pulmonary embolism from fifth decile to first decile. CONCLUSION: A protocol titrating prophylactic enoxaparin dose based on anti-Xa levels reduced VTE rates. Implementation of this type of protocol requires diligence from the physician and pharmacist team. Further research will investigate the impact of protocol compliance and time to appropriate anti-Xa level on incidence of VTE. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

Compliance with the Accreditation Council for Graduate Medical Education duty hours in a general surgery residency program: Challenges and solutions in a teaching hospital.

BACKGROUND: The inception of work hour restrictions for resident physicians in 2003 created controversial changes within surgery training programs. On a recent Accreditation Council for Graduate Medical Education survey at our institution, we noted a discrepancy between low recorded violations of the duty hour restrictions and the surgery resident's perception of poor duty hour compliance. We sought to identify factors that lead to duty hour violations and to encourage accurate reporting among surgery trainees. METHODS: The A3/Lean methodology, an industry-derived, systematic, problem-solving approach, was used to investigate barriers to accurate reporting of duty hours by residents within the Department of Surgery at our academic institution. In partnership with our office of Graduate Medical Education, we encouraged a 6-month period where residents were asked to record duty hour accurately and to provide honest, descriptive explanations of violations without punitive effects on residents or the program. We performed a 6-month before-and-after analysis of duty hours violations after the A3/Lean implementation. Quantitative analysis was used to elucidate trends in violations by post graduate year and rotation. Qualitative evaluation by key thematic areas revealed resident attitudes and opinions about duty hour violations. RESULTS: Residents reported concern for personal and programmatic, punitive measures, desire to retain control of their education, and frustration with the administrative burden after violations as deterrents to honest duty hour reporting. The intervention was successful in changing logging behavior with 10 total violations prior to A3 meeting and 179 violations afterward (P = .003). This change was driven largely from an increase in short break violations (4 vs 134, P = .021). Analysis of violations revealed trends by post-graduate year, rotation, and weekend cross-coverage. Key findings including less than anticipated violations of the 80-hour work week despite high rates of short break violations. The ability to participate in procedures voluntarily and a sense of professional responsibility emerged as the prevailing themes among surgery residents describing violations. CONCLUSION: Systematic evaluation of duty hour reporting within a surgery training program can identify structural and cultural barriers to accurate reporting of duty hours. Accurate reporting can identify program-specific trends in duty hour violations that can be addressed though programmatic intervention.

Using Interdisciplinary Workgroups to Educate Surgery Residents in Systems-Based Practice.

BACKGROUND: Meaningful education of residents in systems-based practice is notoriously challenging, despite its recognition as 1 of the 6 Accreditation Council for Graduate Medical Education core competencies. To address this challenge, surgery residents and other members of the health care team were organized into interdisciplinary workgroups that were tasked with developing solutions to "systems issues" confronted on a daily basis. The project's goals included providing more meaningful, hands-on educational experience for residents in system-based practice, while also generating practical solutions to workflow issues through interprofessional collaboration. PROJECT DESIGN: Project participants included all surgery residents at the University of Virginia in Charlottesville, VA, as well as surgical health care professionals across all disciplines. Participants were organized into workgroups. Over the course of 3 sessions, each of 1-hour, each workgroup identified commonly encountered systems issues, chose 1 issue to address, and determined an implementable solution for this issue. In total, 140 participants were divided among 13 workgroups. PROJECT EXECUTION: Workgroup topics ranged from improving paging etiquette to standardizing interdisciplinary communication. In total, 9 of the 13 proposals have been piloted or fully implemented as standard practice at our institution, either within a single unit or over the entire health system. DISCUSSION: This project demonstrates an innovative approach toward resident education in system-based practice, providing residents with a hands-on experience in problem solving from a systems perspective. These interdisciplinary workgroups generated effective solutions to issues that were meaningful to frontline health care providers. Interdisciplinary collaboration within the workgroups served as a valuable team-building exercise to improve relations between the disciplines. This project can serve as a model for other institutions desiring meaningful education in the Accreditation Council for Graduate Medical Education competency of systems-based practice.

Rapamycin prevents bronchiolitis obliterans through increasing infiltration of regulatory B cells in a murine tracheal transplantation model.

OBJECTIVE: B lymphocytes are generally considered to be activators of the immune response; however, recent findings have shown that a subtype of B lymphocytes, regulatory B lymphocytes, play a role in attenuating the immune response. Bronchiolitis obliterans remains the major limitation to modern-day lung transplantation. The role of regulatory B lymphocytes in bronchiolitis obliterans has not been elucidated. We hypothesized that regulatory B lymphocytes play a role in the attenuation of bronchiolitis obliterans. METHODS: We performed a standard heterotopic tracheal transplant model. Tracheas from Balb/c mice were transplanted into C57BL/6 recipients. Rapamycin treatment and dimethyl sulfoxide control groups were each treated for the first 14 days after the transplant. Tracheas were collected on days 7, 14, and 28 post-transplantation. Luminal obliteration was evaluated by hematoxylin-eosin staining and Picrosirius red staining. Immune cell infiltration and characteristics, and secretion of interleukin-10 and transforming growth factor-ß1 were accessed by immunohistochemistry. Cytokines and transforming growth factor-ß1 were measured using the Luminex assay (Bio-Rad, Hercules, Calif). RESULTS: The results revealed that intraperitoneal injection of rapamycin for 14 days after tracheal transplantation significantly reduced luminal obliteration on day 28 when compared with the dimethyl sulfoxide control group (97.78% ± 3.63% vs 3.02% ± 2.14%, P < .001). Rapamycin treatment markedly induced regulatory B lymphocytes (B220(+)IgM(+)IgG(-)IL-10(+)TGF-ß1(+)) cells when compared with dimethyl sulfoxide controls. Rapamycin treatment inhibited interleukin-1ß, 6, 13, and 17 on days 7 and 14. Rapamycin also greatly increased interleukin-10 and transforming growth factor-ß1 production in B cells and regulatory T lymphocytes infiltration on day 28. CONCLUSIONS: Mammalian target of rapamycin inhibition decreases the development of bronchiolitis obliterans via inhibition of proinflammatory cytokines and increasing regulatory B lymphocytes cell infiltration, which subsequently produces anti-inflammatory cytokines and upregulates regulatory T lymphocyte cells.

Risk Factors for Urinary Tract Infections in Cardiac Surgical Patients.

BACKGROUND: Risk factors for catheter-associated urinary tract infections (CAUTIs) in patients undergoing non-cardiac surgical procedures have been well documented. However, the variables associated with CAUTIs in the cardiac surgical population have not been clearly defined. Therefore, the purpose of this study was to investigate risk factors associated with CAUTIs in patients undergoing cardiac procedures. METHODS: All patients undergoing cardiac surgery at a single institution from 2006 through 2012 (4,883 patients) were reviewed. Patients with U.S. Centers for Disease Control (CDC) criteria for CAUTI were identified from the hospital's Quality Assessment database. Pre-operative, operative, and post-operative patient factors were evaluated. Univariate and multivariable analyses were used to identify significant correlations between perioperative characteristics and CAUTIs. RESULTS: There were 55 (1.1%) documented CAUTIs in the study population. On univariate analysis, older age, female gender, diabetes mellitus, cardiogenic shock, urgent or emergent operation, packed red blood cell (PRBC) units transfused, and intensive care unit length of stay (ICU LOS) were all significantly associated with CAUTI [p<0.05]. On multivariable logistic regression, older age, female gender, diabetes mellitus, and ICU LOS remained significantly associated with CAUTI. Additionally, there was a significant association between CAUTI and 30-d mortality on univariate analysis. However, when controlling for common predictors of operative mortality on multivariable analysis, CAUTI was no longer associated with mortality. CONCLUSIONS: There are several identifiable risk factors for CAUTI in patients undergoing cardiac procedures. CAUTI is not independently associated with increased mortality, but it does serve as a marker of sicker patients more likely to die from other comorbidities or complications. Therefore, awareness of the high-risk nature of these patients should lead to increased diligence and may help to improve peri-operative outcomes. Recognizing patients at high risk for CAUTI may lead to improved measures to decrease CAUTI rates within this population.

Construct validation of a cost-effective vessel ligation benchtop simulator.

OBJECTIVE: Many benchtop surgical simulators assess laparoscopic proficiency, yet few address core open surgical skills. The purpose of this study is to describe a cost-effective benchtop vessel ligation simulator and provide construct validation. DESIGN: A prospective comparison of blinded proficiency assessments among participants performing a benchtop vessel ligation simulation task. Evaluations were performed using Objective Structured Assessments of Technical Skills. SETTING: This study took place at the University of Virginia, School of Medicine: a large academic medical institution. PARTICIPANTS: The participants included fourth-year medical students participating in a focused surgical elective course (n = 16), postgraduate year 2 to 3 surgery residents (n = 6), and surgical faculty (n = 5). RESULTS: The total fixed costs of the vessel ligation simulator was $30. Flexible costs of operation were less than $0.20 per attempt. The median task-specific checklist scores among the medical students, residents, and faculty were 4.83, 7.33, and 7.67, respectively. Median global rating scores across the 3 groups were 2.29, 4.43, and 4.76, respectively. Significant proficiency differences were noted between the students and the residents/faculty for both the metrics (p < 0.001). CONCLUSIONS: A cost-effective benchtop simulator can effectively measure proficiency with basic open surgical techniques such as vessel ligation. Among the junior surgical trainees, this tool can identify learning gaps and improve operative skills in a preclinical setting.

Cost analysis of endovascular versus open repair in the treatment of thoracic aortic aneurysms.

OBJECTIVE: For descending thoracic aortic aneurysms (TAAs), it is generally considered that thoracic endovascular aortic repairs (TEVARs) reduce operative morbidity and mortality compared with open surgical repair. However, long-term differences in survival of patients have not been demonstrated, and an increased need for aortic reintervention has been observed. Many assume that TEVAR becomes less cost-effective through time because of higher rates of reintervention and surveillance imaging. This study investigated midterm outcomes and hospital costs of TEVAR compared with open TAA repair. METHODS: This was a retrospective, single-institution review of elective TAA repairs between 2005 and 2012. Patient demographics, operative outcomes, reintervention rates, and hospital costs were assessed. The literature was also reviewed to determine commonly observed complication and reintervention rates for TEVAR and open repair. Monte Carlo simulation was used to model and to forecast hospital costs for TEVAR and open TAA repair up to 3 years after intervention. RESULTS: Our cohort consisted of 131 TEVARs and 27 open repairs. TEVAR patients were significantly older (67.2 vs 58.7 years old; P = .02) and trended toward a more severe comorbidity profile. Operative mortality for TEVAR and open repair was 5.3% and 3.7%, respectively (P = 1.0). There was a trend toward more complications in the TEVAR group, although not statistically significant (all P > .05). In-hospital costs were significantly greater in the TEVAR group ($52,008 vs $37,172; P = .001). However, cost modeling by use of reported complication and reintervention rates from the literature overlaid with our cost data produced a higher cost for the open group in-hospital ($55,109 vs $48,006) and at 3 years ($58,426 vs $52,825). Interestingly, TEVAR hospital costs, not reintervention rates, were the most significant driver of cost in the TEVAR group. CONCLUSIONS: Our institutional data showed a trend toward lower mortality and complication rates with open TAA repair, with significantly lower costs within this cohort compared with TEVAR. These findings were likely, at least in part, to be due to the milder comorbidity profile of these patients. In contrast, cost modeling by Monte Carlo simulation demonstrated lower costs with TEVAR compared with open repair at all time points up to 3 years after intervention. Our institutional data show that with appropriate selection of patients, open repair can be performed safely with low complication rates comparable to those of TEVAR. The cost model argues that despite the costs associated with more frequent surveillance imaging and reinterventions, TEVAR remains the more cost-effective option even years after TAA repair.

Treatment with placenta-derived mesenchymal stem cells mitigates development of bronchiolitis obliterans in a murine model.

OBJECTIVE: Bone marrow-derived mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury. Recently, placenta-derived human mesenchymal stem cells (PMSCs) have shown similarities with bone marrow-derived MSCs in terms of regenerative capabilities and immunogenicity. This study investigates the hypothesis that treatment with PMSCs reduces the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model. METHODS: A murine heterotopic tracheal transplant model was used to study the continuum from acute to chronic rejection. In the treatment groups, PMSCs or PMSC-conditioned medium (PMSCCM) were injected either locally or intratracheally into the allograft. Phosphate-buffered saline (PBS) or blank medium was injected in the control groups. Tracheal luminal obliteration was assessed on sections stained with hematoxylin and eosin. Infiltration of inflammatory and immune cells and epithelial progenitor cells was assessed using immunohistochemistry and densitometric analysis. RESULTS: Compared with injection of PBS, local injection of PMSCs significantly reduced luminal obliteration at 28 days after transplantation (P = .015). Intratracheal injection of PMSCs showed similar results to local injection of PMSCs compared with injection of PBS and blank medium (P = .022). Tracheas treated with PMSC/PMSCCM showed protection against the loss of epithelium on day 14, with an increase in P63+CK14+ epithelial progenitor cells and Foxp3+ regulatory T cells. In addition, injection of PMSCs and PMSCCM significantly reduced the number of neutrophils and CD3+ T cells on day 14. CONCLUSIONS: This study demonstrates that treatment with PMSCs is protective against the development of bronchiolitis obliterans in an heterotopic tracheal transplant model. These results indicate that PMSCs could provide a novel therapeutic option to reduce chronic rejection after lung transplant.

Donor risk index predicts graft failure reliably but not post-transplant infections.

BACKGROUND: The Donor Risk Index (DRI) is used to predict graft survival following liver transplantation, but has not been used to predict post-operative infections in graft recipients. We hypothesized that lower-quality grafts would result in more frequent infectious complications. METHODS: Using a prospectively collected infection data set, we matched liver transplant recipients (and the respective allograft DRI scores) with their specific post-transplant infectious complications. All transplant recipients were organized by DRI score and divided into groups with low-DRI and high-DRI scores. RESULTS: We identified 378 liver transplants, with 189 recipients each in the low-DRI and high-DRI groups. The mean DRI scores for the low- and high-DRI-score groups were 1.14±0.01 and 1.74±0.02, respectively (p<0.0001 for the difference). The mean Model for End-Stage Liver Disease (MELD) scores were 26.25±0.53 and 24.76±0.55, respectively (p=0.052), and the mean number of infectious complications per patient were 1.60±0.19 and 1.94±0.24, respectively (p=0.26). Logistic regression showed only length of hospital stay and a history of vascular disease as being associated independently with infection, with a trend toward significance for MELD score (p=0.13). CONCLUSION: We conclude that although DRI score predicts graft-liver survival, infectious complications depend more heavily on recipient factors.

Short-course rapamycin treatment preserves airway epithelium and protects against bronchiolitis obliterans.

BACKGROUND: Damage to airway epithelium is closely related to the development of bronchiolitis obliterans (BO) in pulmonary transplantation. Rapamycin protects against BO development in a murine model, but its use in patients undergoing lung transplantation is limited by its side effects. We hypothesized that short-course rapamycin dosing could be used to prevent airway epithelium loss and protect against BO development in a murine model. METHODS: A total alloantigenic mismatch, murine, heterotopic tracheal transplant model of BO was used. Animals were treated with either rapamycin or dimethyl sulfoxide (controls) according to one of three treatment regimens: (1) days 1 through 14 after transplantation, (2) days 3 through 7 after transplantation, or (3) days 14 through 28 after transplantation. Epithelial loss was assessed by use of hematoxylin and eosin stains 14 and 28 days after transplantation. Tracheal luminal obliteration was assessed at 28 days. RESULTS: Early rapamycin treatment was protective against epithelial loss 14 days after transplantation in comparison with control animals (p < 0.001). Rapamycin treatment from days 1 to 14 was more effective at epithelial preservation (p = 0.002) and reducing luminal obliteration (p < 0.001) at 28 days than was rapamycin treatment from days 3 to 7. Late rapamycin treatment (days 14 to 28) allowed for recovery of the previously denuded epithelium at 28 days (92.5% epithelial loss to 35.6%) and a reduction in BO (p < 0.001). CONCLUSIONS: Short-course rapamycin treatment protects against airway epithelium loss and subsequent development of BO in a murine model. Because of its immunosuppressive and antifibrotic effects, rapamycin may prove to be the ideal medication to prevent chronic rejection and BO in patients undergoing lung transplantation.

Predictors of operative mortality in cardiac surgical patients with prolonged intensive care unit duration.

BACKGROUND: Several systems have been developed to predict mortality after intensive care unit (ICU) admission in medical and surgical patients. However, a similar tool specific to cardiac surgical patients with prolonged ICU duration does not exist. The purpose of the current study was to identify independent perioperative predictors of operative mortality among cardiac surgical patients with prolonged ICU duration. STUDY DESIGN: From 2003 to 2008, a total of 13,105 cardiac surgical patients with ICU durations >48 hours were identified within a statewide database. Perioperative factors, including Society of Thoracic Surgeons Predicted Risk of Mortality, were evaluated. Univariate and multivariate analyses identified significant correlates of operative mortality and their relative strength of association as determined by the Wald chi-square statistic. RESULTS: Mean patient age was 66.8 ± 11.2 years, median ICU duration was 76.5 hours (range 56.0 to 124.0 hours), and mean Society of Thoracic Surgeons predicted risk of mortality was 4.4% ± 6.2%. Among preoperative and operative factors, intra-aortic balloon pump use, patient age, immunosuppressive therapy, hemodialysis requirement, cardiopulmonary bypass time, and heart failure proved to be the strongest correlates of mortality (all p < 0.05) on risk-adjusted multivariate analysis. Type of cardiac procedure had no significant association with mortality after risk adjustment. Among postoperative complications, cardiac arrest, prolonged mechanical ventilation (>24 hours), and stroke were the strongest predictors of risk-adjusted mortality (all p < 0.001). CONCLUSIONS: Operative mortality can be predicted by select risk factors for cardiac surgical patients with prolonged ICU duration. Patient age, preoperative intra-aortic balloon pump, postoperative cardiac arrest, prolonged ventilation, and stroke have the strongest association with mortality. Identification of these factors in the perioperative setting can enhance resource use and improve mortality after cardiac surgery.

Rapamycin blocks fibrocyte migration and attenuates bronchiolitis obliterans in a murine model.

BACKGROUND: Fibrocytes are integral in the development of fibroproliferative disease. The CXCL12/CXCR4 chemokine axis has been shown to play a central role in fibrocyte migration and the development of bronchiolitis obliterans (BO) after lung transplantation. Inhibition of the mammalian target of rapamycin (mTOR) pathway with rapamycin has been shown to decrease expression of both CXCR4 and its receptor agonist CXCL12. Thus, we hypothesized that rapamycin treatment would decrease fibrocyte trafficking into tracheal allografts and prevent BO. METHODS: A total alloantigenic mismatch murine heterotopic tracheal transplant (HTT) model of BO was used. Animals were either treated with rapamycin or dimethyl sulfoxide (DMSO) for 14 days after tracheal transplantation. Fibrocyte levels were assessed by flow cytometry, and allograft neutrophil, CD3(+) T-cell, macrophage, and smooth muscle actin (SMA) levels were assessed by immunohistochemistry. Tracheal luminal obliteration was assessed on hematoxylin and eosin (H&E) stains. RESULTS: Compared with DMSO-treated controls, rapamycin-treated mice showed a significant decrease in fibrocyte levels in tracheal allografts. Fibrocyte levels in recipient blood showed a similar pattern, although it was not statistically significant. Furthermore, animals treated with rapamycin showed a significant decrease in tracheal allograft luminal obliteration compared with controls. Based on immunohistochemical analyses, populations of α-SMA-positive (α-SMA(+)) cells, neutrophils, CD3(+) T cells, and macrophages were all decreased in rapamycin-treated allografts versus DMSO controls. CONCLUSIONS: Rapamycin effectively reduces recruitment of fibrocytes into tracheal allografts and mitigates development of tracheal luminal fibrosis. Further studies are needed to determine the cellular and molecular mechanisms that mediate the protective effect of rapamycin against BO.

Influence of hemodialysis on clinical outcomes after lung transplantation.

BACKGROUND: Chronic renal failure after lung transplantation is associated with significant morbidity. However, the significance of acute kidney injury (AKI) after lung transplantation remains unclear and poorly studied. We hypothesized that hemodialysis (HD)-dependent AKI after lung transplantation is associated with significant mortality. MATERIALS AND METHODS: We performed a retrospective review of all patients undergoing lung transplantation from July 1991 to July 2009 at our institution. Recipients with AKI (creatinine > 3 mg/dL) were identified. We compared recipients without AKI versus recipients with and without HD-dependent AKI. Kaplan-Meier survival curves were compared by log rank test. RESULTS: Of 352 lung transplant recipients reviewed at our institution, 17 developed non-HD-dependent AKI (5%) and 16 developed HD-dependent AKI (4.6%). Cardiopulmonary bypass was significantly higher in patients with HD-dependent AKI. None of the recipients who required HD had recovery of renal function. The 30-day mortality was significantly greater in recipients requiring HD (63% versus 0%; P < 0.0001). One-year mortality after transplantation was significantly increased in recipients with HD-dependent AKI compared with those with non-HD-dependent AKI (87.5% versus 17.6%; P < 0.001). CONCLUSIONS: Hemodialysis is associated with mortality after lung transplantation. Fortunately, AKI that does not progress to HD commonly resolves and has a better overall survival. Avoidance, if possible, of cardiopulmonary bypass may attenuate the incidence of AKI. Aggressive measures to identify and treat early postoperative renal dysfunction and prevent progression to HD may improve outcomes after lung transplantation.