Total Cell-Free DNA Predicts Death and Infection Following Pediatric and Adult Heart Transplantation.

BACKGROUND: Elevated total cell-free DNA (TCF) concentration has been associated with critical illness in adults and elevated donor fraction (DF), the ratio of donor specific cell-free DNA to total cell-free DNA present in the recipient's plasma, is associated with rejection following cardiac transplantation. This study investigates relationships between TCF and clinical outcomes after heart transplantation. METHODS: A prospective, blinded, observational study of 87 heart transplantation recipients was performed. Samples were collected at transplantation, prior to endomyocardial biopsy, during treatment for rejection, and at hospital readmissions. Longitudinal clinical data were collected and entered into a RedCAP (Vanderbilt University) database. TCF and DF levels were correlated with endomyocardial biopsy and angiography results, as well as clinical outcomes. Logistic regression for modeling and repeated measures analysis using generalized linear modeling was used. The standard receiver operating characteristic curve, hazard ratios, and odds ratios were calculated. RESULTS: There were 257 samples from 87 recipients analyzed. TCF greater than 50 ng/mL were associated with increased mortality (P = .01, area under the curve 0.93, sensitivity 0.44, specificity 0.97) and treatment for infection (P < .005, area under the curve 0.68, sensitivity 0.45, specificity 0.96). Increased DF was not correlated with treatment for infection. DF was associated with rejection and cardiac allograft vasculopathy (P < .001), but TCF was not. CONCLUSIONS: TCF elevation predicted death and treatment for infection. DF elevation predicted histopathologic acute rejection and cardiac allograft vasculopathy. Surveillance of TCF and DF levels may inform treatment after heart transplantation.

Current status of normothermic ex-vivo perfusion of cardiac allografts.

PURPOSE OF REVIEW: Ex-vivo perfusion has emerged in recent years as an alternative to cold static preservation of organs harvested for transplant. Normothermic ex-vivo perfusion, the subject of this review, maintains the donor heart in a near physiologic state, and allows the transplant team to monitor and control perfusion to the organ prior to implantation. A growing body of evidence has established the safety and viability of this technique, which may improve on current standards of donor management. RECENT FINDINGS: Following initial single-arm studies over a decade ago, ex-vivo perfusion has been studied in a prospective, randomized fashion in standard donor hearts (PROCEED II trial). The short and intermediate-term results demonstrated similar outcomes compared with cold storage with significantly shorter cold ischemic time. Since then, ex-vivo perfusion has been studied in extended-criteria donor hearts, first in observational studies, and currently in randomized, prospective fashion in the recently completed EXPAND-Heart trial, which is anticipated to be reported in 2020. SUMMARY: Normothermic ex-vivo perfusion has an established literature base and holds promise for changing current practices of heart preservation. Results of forthcoming pivotal studies will help determine its role in more widespread clinical adoption.

Early changes in cell-free DNA levels in newly transplanted heart transplant patients.

Heart transplantation is a well-established therapy for end-stage heart failure in children and young adults. The highest risk of graft loss occurs in the first 60 days post-transplant. Donor fraction of cell-free DNA is a highly sensitive marker of graft injury. Changes in cell-free DNA levels have not previously been studied in depth in patients early after heart transplant. A prospective study was conducted among heart transplant recipients at a single pediatric heart center. Blood samples were collected from children and young adult transplant patients at three time points within 10 days of transplantation. DF and total cell-free DNA levels were measured using a targeted method (myTAIHEART ). In 17 patients with serial post-transplant samples, DF peaks in the first 2 days after transplant (3.5%, [1.9-10]%) and then declines toward baseline (0.27%, [0.19-0.52]%) by 6-9 days. There were 4 deaths in the first year among the 10 patients with complete sample sets, and 3 out of 4 who died had a late rise or blunted decline in donor fraction. Patients who died trended toward an elevated total cell-free DNA at 1 week (41.5, [34-65] vs 13.6, [6.2-22] P = .07). Donor fraction peaks early after heart transplant and then declines toward baseline. Patients without sustained decline in donor fraction and/or elevated total cell-free DNA at 1 week may have worse outcomes.

Impact of Donor Diabetes on Outcomes of Lung Transplantation in the United States.

BACKGROUND: Diabetes mellitus is among several factors considered when assessing the suitability of donated organs for transplantation. Lungs from diabetic donors (LDD) are not contraindicated for use as allografts, despite established evidence of diabetes-mediated parenchymal damage. The present study used a national database to assess the impact of donor diabetes on the longevity of lung transplant recipients. METHODS: This retrospective study of the United Network for Organ Sharing database analyzed all adult lung transplant recipients from June 2005 through September 2016. Donor and recipient demographics including the presence of diabetes were used to create a multivariable model. The primary outcome was 5-y mortality, with hazard ratios (HRs) assessed using multivariable Cox regression analysis. Survival curves were calculated using the Kaplan-Meier method. RESULTS: Of the 17,839 lung transplant recipients analyzed, 1203 (6.7%) received LDD. Recipients of LDD were more likely to be female (44.1% versus 40.2%, P < 0.01) and have mismatched race (47.5% versus 42.2%, P < 0.01). Diabetic donors were more likely to have hypertension (74.6% versus 19.0%, P < 0.01). Multivariable analysis revealed LDD to be an independent predictor of mortality at 5 y (HR 1.16 [1.04-1.29], P < 0.01). However, among the subgroup of diabetic recipients, transplantation of LDD showed no independent association with 5-y mortality (HR 0.81 [0.63-1.06], P = 0.12). CONCLUSIONS: Recipients of LDD had a lower 5-y post lung transplantation survival compared with recipients of lungs from nondiabetic donors. LDD allografts did not influence the survival of diabetic recipients.

Side-to-Side Tracheobronchoplasty to Reconstruct Complex Congenital Tracheobronchial Stenosis.

BACKGROUND: Long segment tracheobronchial stenosis is a rare congenital anomaly that can also occur in combination with abnormal bronchial arborization. Long segment tracheal reconstruction in the setting of a supernumerary bridging bronchus has been reported; however, these repairs can be particularly complex. We present our experience using the bridging bronchus to augment long segment tracheal stenosis with a side-to-side tracheobronchoplasty. METHODS: Four patients with complex long segment tracheobronchial stenosis involving a bronchus suis (right upper lobe bronchus) and a bridging bronchus presented with refractory respiratory distress requiring urgent tracheal reconstruction. Patient 1 was initially managed with modified slide tracheoplasty and tracheostomy. Patients 2, 3, and 4 were managed with single-stage procedures. All patients underwent definitive long segment tracheobronchoplasty consisting of a side-to-side anastomosis between the bridging bronchus and the right upper lobe bronchus. RESULTS: Age at surgery was 569, 69, 24, and 142 days, respectively. Weight at surgery was 9.3, 4.3, 2.7, and 5.9 kg. All patients were weaned from mechanical ventilation at 84, 13, 47, and 8 days after side-to-side tracheobronchoplasty. All patients were alive and free from tracheostomy at follow-up of 6.7, 3.8, 2.7, and 0.5 years. CONCLUSIONS: Side-to-side tracheal reconstruction is feasible in severe cases of long segment tracheal stenosis with a right upper lobe bronchus and a bridging bronchus. This technique can be successfully applied in high-risk patients and in the neonatal period and can provide excellent midterm results.

Changes in Thoracic Surgery Experience During General Surgery Residency: A Review of the Case Logs From the Accreditation Council for Graduate Medical Education.

BACKGROUND: Although exposure to thoracic surgery is mandated in general surgery residency, little is known about the mix of cases that residents use to meet this requirement and how this has changed over time. We report the experience of general thoracic surgery among general surgery residents using the Accreditation Council for Graduate Medical Education (ACGME) database. METHODS: We performed a retrospective review of the prospectively maintained ACGME resident case log database from 2003 to 2013. Thoracic cases were categorized by procedure type, year, and level of resident participation. A linear regression model was used to determine if there was a significant trend in case volumes over time. RESULTS: First assist volumes decreased in the 90th (-1.46 cases/year, p = 0.0012), 70th (-0.77 cases/year, p = 0.0005), 50th (-0.46 cases/year, p = 0.0013), and 30th percentiles (-0.16 cases/year, p = 0.0187). Pneumonectomy volumes decreased for surgeons junior (-0.01 cases/year, p = 0.0013) and chief residents (-0.01 cases/year, p = 0.005), as did open lobectomy (surgeon junior, -0.202 cases/year, p < 0.0001; chief, -0.08 cases/year, p ≤ 0.0013). Video-assisted (VATS) lobectomy increased for the surgeons junior (0.22 cases/year, p < 0.0001) and chief residents (0.045 cases/year, p < 0.0001). Surgeons junior also had increased volumes of VATS exploratory thoracoscopy (0.11 cases/year, p = 0.0003) and VATS pleurodeisis (0.13 cases/year, p < 0.0001). CONCLUSIONS: Whereas total thoracic volumes on the whole have not changed significantly, resident participation as a first assistant and in key thoracic cases has decreased over the last 11 years, while participation in VATS and minor cases has increased.

Advances in Surgical Treatment of Congenital Airway Disease.

Tracheobronchomalacia (TBM) is frequently present in infants and children with congenital heart disease (CHD). Infants with CHD and TBM appear to do worse than those without TBM. The principle of operative intervention for TBM is to improve function of the airway and clinical status. When indicated, conventional surgical options include tracheostomy, aortopexy, tracheoplasty, and anterior tracheal suspension. There is no consensus on the optimal treatment of severe tracheobonchomalacia, which can be associated with a mortality rate as high as 80%. Congenital tracheal stenosis is also frequently associated with CHD (vascular rings, atrioventricular canal defects, and septal defects) and may require concomitant repair. Repair of tracheal stenosis is often associated with distal TBM. This article addresses new techniques that can be performed in corrective surgery for both TBM and congenital tracheal stenosis.