Clinical Utility of Cytomegalovirus Viral Load in Bronchoalveolar Lavage in Lung Transplant Recipients

The utility of cytomegalovirus (CMV) viral load (VL) by quantitative hybrid capture assay (Q-HCA) was investigated in bronchoalveolar lavage (BAL) from lung transplant recipients and compared with BAL cultures and blood VL. Forty-three consecutive BAL samples from 27 lung transplant recipients were analyzed. All samples had shell vial (SV) cultures in addition to Q-HCA. Histopathology was done on all lung tissues, and immunohistochemistry (IHC) in those with positive CMV cultures. Fifteen (56%) lung transplant recipients had both positive BAL SV cultures and BAL VL. Five of 15 had CMV pneumonitis with a VL in BAL >500 000 copies/mL (mean: 1638 450). Ten patients without CMV pneumonitis had VL in BAL <500 000 copies/mL (mean 81 820, p = 0.002). High VL in BAL and blood invariably meant CMV pneumonitis, but 2 patients with CMV pneumonitis had high BAL VL but relatively low blood VL. Initial CMV seronegativity was associated with pneumonitis (4/5 vs. 1/10; p = 0.004) and higher BAL CMV VL (p = 0.03). High CMV BAL or blood VL did not correlate with acute rejection or development of bronchiolitis obliterans syndrome (BOS). High CMV VL in BAL in lung transplant recipients is strongly associated with CMV pneumonitis, and may be more predictive than peripheral blood viral load.     

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report

Initial experience with lung transplant of COVID-19–positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.     

The Perioperative Lung Transplant Virome: Torque Teno Viruses Are Elevated in Donor Lungs and Show Divergent Dynamics in Primary Graft Dysfunction

Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. To date, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 mo after transplant and found that levels of Anellovirus, mainly torque teno viruses (TTVs), were significantly higher than in nontransplanted healthy controls. We used quantitative polymerase chain reaction to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and postreperfusion allografts in PGD and non‐PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were elevated 100‐fold in donor lungs compared with healthy adults (p = 0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from before to after transplant than did control recipients (p = 0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung.     

Donor Age and Early Graft Failure After Lung Transplantation: A Cohort Study

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1‐year graft failure and primary graft dysfunction (PGD). The rate of 1‐year graft failure was similar among recipients of lungs from donors age 18–64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56–64 years had increased rates of 1‐year graft failure (p‐values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1‐year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01–1.50 and adjusted HR 2.15, 95% CI 1.47–3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.     

Impact of Donor Age and Year of Transplant on Graft Survival in Liver Transplant Recipients with Chronic Hepatitis C

Studies suggest donor age and year of transplantation are associated with low graft survival in liver transplant recipients with hepatitis C. We sought to determine if advanced donor age and recent year of transplantation are associated with graft survival in hepatitis C recipients and to determine if the effect of donor age on graft survival is specific to hepatitis C. We analyzed the United Network for Organ Sharing liver transplant database from 1994 to 2002. Six thousand four hundred and four subjects transplanted for end-stage liver disease from chronic hepatitis C met our criteria. One-year graft survival in hepatitis C recipients with organs from donors <40 years old and >or=60 years old was 84% and 73%, p = 0.003, respectively. These rates in recipients with cholestatic liver disease and alcoholic liver disease were 85% and 82%, respectively, p = 0.11 and 82% and 78%, respectively, p = 0.14. Three-year graft survival in hepatitis C recipients transplanted from 1994 to 1995 and 1996 to 1999 was 67% and 69%, respectively, p = 0.10. Graft survival in hepatitis C recipients has not declined in recent years. Older donor age is associated with lower short-term graft survival in recipients with hepatitis C, but not in recipients with cholestatic or alcoholic liver disease.     

Primary Graft Failure After Heart Transplantation: The Importance of Donor Pharmacological Management

Background

Primary graft failure (PGF) remains the strongest determinant of perioperative mortality after heart transplantation (HT). Donor management may play an important role in the incidence of PGF.

Materials and methods

Multivariate analysis was used to identify PGF determinants after HT. Donor and recipient data were analyzed together with preharvest management information and perioperative results. PGF was defined as the need for mechanical circulatory support immediately post-HT.

Results

Isolated HT was performed in 54 consecutive patients from January 2006 to June 2009. PGF occurred in 11 (20%) patients. Upon univariate analysis, preoperative mean pulmonary arterial pressure was significantly higher among patients developing PGF (P = .02). The donors for PGF patients had more often been managed with high inotropic support (dopamine > 10 μg/kg/min and/or alpha agonists > 0.06 μg/kg/min; P = .008). In contrast, death for head trauma was more common among donors for patients who did not develop PGF (P = .02). In-hospital mortality was 13% (7/54); 71% of these deceased patients displayed PGF (5/7). Upon multivariate analysis, preharvest high donor inotropic support was the strongest determinant of PGF (P = .01, odds ratio [OR] = 7.5). Donor death due to head trauma showed a protective effect against PGF (P = .03, OR = 0.1).

Conclusion

PGF remains a lethal perioperative complication despite modern tools for prompt cardiac mechanical assistance. As a result of the organ shortage, many centers accept marginal hearts assuming that donor hemodynamic management shows a reduced impact on PGF. We suggest a timely evaluation of the hazards for PGF whenever high inotropic support is used, especially among donors dying for causes other than head trauma.     

Improvements in Extracorporeal Membrane Oxygenation for Primary Graft Failure After Heart Transplant

BackgroundSevere primary graft failure is a life-threatening complication of heart transplantation that may require venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Surgical practices and management strategies regarding VA-ECMO vary between and within centers.MethodsWe performed a single-center retrospective cohort study on adult patients who received VA-ECMO for primary graft failure between 2013 and 2020. Clinical data were obtained from chart review and national databases. Patients were stratified by transplantation before or after 2017, when our center adopted additional objective criteria for VA-ECMO, adopted partial-flow support, and changed from central cannulation to chimney graft arterial cannulation of brachiocephalic, axillary, or aorta. The primary outcome was survival to device weaning. Secondary outcomes were survival to discharge, survival to 1 year, complications on support, and time to sedation weaning and extubation.ResultsFrom 276 heart transplant recipients, 39 severe primary graft failure patients requiring VA-ECMO were identified. Incidence of graft failure was 13% (n = 18 of 135) pre-2017 and 15% (n = 21 of 141) post-2017. Survival at all time points improved significantly after 2017, with greatest difference in survival to device weaning (61% pre-2017 vs 100% post-2017). After controlling for other factors in multivariable Cox regression modeling, transplantation after 2017 was a predictor of reduced mortality (hazard ratio, 0.209; 95% CI, 0.06-0.71; P = .01). Significant differences were not observed in other secondary outcomes of recovery.ConclusionsThe new VA-ECMO strategy displayed reasonable survival and a remarkable improvement from the prior system.     

Herpesviruses Detection by Quantitative Real-Time Polymerase Chain Reaction in Bronchoalveolar Lavage and Transbronchial Biopsy in Lung Transplant: Viral Infections and Histopathological Correlation

The monitoring of herpesvirus infection plays a central role in lung transplantation (LT). Herein we evaluated the prevalence of human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), and Epstein-Barr Virus (EBV) DNA in bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) specimens from LT patients. We associated the findings with the occurrence of interstitial pneumonia, acute rejection, or organizing pneumonia. Viral DNA was detected using real-time polymerase chain reaction (PCR) on 76 paired samples (BAL and TBB) from 27 patients who were receiving a universal combined prophylaxis (cytomegalovirus [CMV] immunoglobulin [Ig] + gancyclovir or valgancyclovir). Histopathological analysis was performed in accordance with the International Society for Heart and Lung Transplantation (ISHLT) criteria. Overall, HCMV results were positive in 25/76 (32.9%) specimens (BAL and/or TBB); HHV-6 in 16 (21.1%); HHV-7 in 40 (52.6%); and EBV in 13 (17.1%). Interstitial pneumonia was diagnosed in 6/76 (7.9%) cases: 5 (83.3%) were positive to HCMV (combined specimens; P < .0001); 5 (83.3%) to HHV-7; and 2 (33.3%) to EBV. An acute rejection episode was diagnosed in 19/76 (25%) cases: 7 (36.8%) were positive to HCMV; 5 (26.3%) to HHV-6; 10 (52.6%) to HHV-7, and 3 (15.8%) to EBV. No significant association was observed between virus detection or load and acute rejection. Organizing pneumonia was diagnosed in 4/76 (5.3%) cases: 1 (25%) positive to HCMV; 4 (100%) to HHV-6 (P < .05); 2 (50%) to HHV-7; and none to EBV. In conclusion, the prevalence of HCMV tended to be lower than that reported in the literature, confirming the importance of universal combined prophylaxis. HCMV was a relevant agent for interstitial pneumonia; although the small numbers limit the statistical analysis, our data did not support an association between herpesviruses and acute rejection episodes, whereas the role of HHV-6 in the pathogenesis of organizing pneumonia deserves further study. Viral detection on TBB could represent an adjunctive tool to complement that on BAL.     

Donor and Recipient Factors Predicting Time to Graft Failure Following Orthotopic Liver Transplantation: A Transplant Risk Index

Introduction

Much of the success of a transplant depends on appropriate matching of donor to recipient.

Methods

We validated the Donor Risk Index formula (DRI) using Mount Sinai Medical Center's 10-year cohort of over 1000 transplants.

Results

The DRI was significantly associated to graft failure with a relative risk (RR) of 1.32. Our cohort had an average DRI of 2.6 with survival of 83% at 3 months, 79% at 1 year, and 70% at 3 years. The low rate of graft failure at a high DRI implies that there are other factors important in transplant pairing that are not considered in the DRI model. To determine these variables and quantify their importance, we constructed a Transplant Risk Index by identifying recipient and donor variables not captured in United Network for Organ Sharing (UNOS) that significantly correlated to graft failure. The most significant independent predictors of time to graft failure were donor age, weight, and peak serum sodium; ischemia time; and recipient creatinine, international normalized ratio, and hepatitis C infection. The coefficients for each of these factors were compiled into a Transplant Risk Index formula. A cutoff of 5 resulted in a graft survival rate of 86% at 3 months, 76% at 1 year, and 62% at 3 years using Kaplan-Meier analysis. The predictive ability of the Transplant Risk Index was greater than the DRI or DMELD (the product of donor age and preoperative MELD) as assessed by the area under the receiver operating curve and the positive and negative predictive values.

Conclusion

The Transplant Risk Index captures recipient factors and donor factors not captured in UNOS. Including these factors may improve the ability to predict good donor–recipient pairing.     

Influence of Bronchoscopic Interventions on Graft Function of Double Lung Transplant Recipients due to Cystic Fibrosis

BackgroundHealing of bronchial anastomoses may sometimes be complicated and require bronchoscopic intervention (BI). The main aim of the study was to assess whether patients who require BI present comparable lung function after reaching 1-year posttransplant survival to those who did not require any BI by means of spirometry and 6-minute walk test (6MWT).MethodsThis retrospective study included an analysis of 44 primary double lung transplant recipients who underwent transplant for end-stage respiratory failure in the course of cystic fibrosis transplanted in a single center between 2018 and 2021. Bronchoscopic intervention is defined as performing endoscopic bronchoplasty through balloon dilatation, cryoprobe, argon plasma, and/or laser treatment. Group 1 (25 patients who required at least 1 BI) presented similar spirometry parameters at qualification as group 2 (no BI).ResultsStatistically significant differences between the groups for the following parameters were reported: forced expiratory volume in 1 second (FEV1), FEV1 (%), Tiffeneau-Pinelli index (FEV1/forced vital capacity percentage of predicted value), oxygen saturation after conclusion of 6MWT (%) and oxygen saturation before 6MWT (%). In each case, the mean for the BI group in the first year was lower. All patients in this group received an average amount of 6.8 ± 4.9 bronchoscopic procedures during the first year (minimum = 1; maximum = 18). Strong negative correlations were observed between the number of balloons in the first year and the FEV1 (%) and FEV1/forced vital capacity percentage of predicted value indicators after the first year.ConclusionsLung transplant recipients who underwent transplant because of cystic fibrosis and required at least 1 BI during the first posttransplant year presented inferior spirometry and 6MWT results in comparison with those who did not require any.     

The Impact of Meeting Donor Management Goals on the Development of Delayed Graft Function in Kidney Transplant Recipients

Many organ procurement organizations (OPOs) utilize preset critical care endpoints as donor management goals (DMGs) in order to standardize care and improve outcomes. The objective of this study was to determine the impact of meeting DMGs on delayed graft function (DGF) in renal transplant recipients. All eight OPOs of the United Network for Organ Sharing Region 5 prospectively implemented nine DMGs in every donor after neurologic determination of death (DNDD). “DMGs met” was defined a priori as achieving any seven of the nine DMGs and this was recorded at the time of consent for donation to reflect donor hospital ICU management, 12–18 h later, and prior to organ recovery. Multivariable analyses were performed to identify independent predictors of DGF (dialysis in the first week after transplantation) with a p < 0.05. A total of 722 transplanted kidneys from 492 DNDDs were included. A total of 28% developed DGF. DMGs were met at consent in 14%, 12–18 h in 32% and prior to recovery in 38%. DGF was less common when DMGs were met at consent (17% vs. 30%, p = 0.007). Independent predictors of DGF were age, Cr and cold ischemia time, while meeting DMGs at consent was significantly protective. The management of potential organ donors prior to consent affects outcomes and should remain a priority in the intensive care unit.     

Raised Endothelin Content in Bronchoalveolar Lavage Fluid During Lung Allograft Rejection in Pigs

Abstract

Objectives. Freedom Solo is a stentless biological aortic valve which is implanted supra-annularly with a single suture line. An increased risk of postoperative thrombocytopenia in the early postoperative period has been reported in recent studies. In our study we evaluated postoperative haemodynamic performance and thrombocyte-levels. Design. Thirty seven patients who underwent valve implantation of the Sorin Freedom Solo stentless valve were included. The haemodynamic performance of the valve was evaluated by transthoracic echocardiography postoperatively at the fourth day (mean) and after a median of 4.2 months. Results. The mean gradient (mmHg) of Freedom Solo was 7.5 at four days and 8.6 at 4.2 months. Postoperatively no patient had more than grade 1 leakage. Seven percent of the patients had a reduction of thrombocytes to less than 20% of the preoperative level. Seventy six percent had a minimum postoperative thrombocyte level less than 100*10⁹/L. The 30 days mortality in our patient material was zero. Conclusions. Implantation of the Freedom Solo valve was uncomplicated in our experience. Favourable transvalvular gradients and no significant leaks were found. In accordance with the literature, we found a high percentage of patients having a postoperative level of thrombocytes less than 100*10⁹/L after implantation of Freedom Solo.