Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

A Rare Case of Orthostasis, Dizziness, and Non-O1, Non-O139 Vibrio cholerae Infection in a Lung Transplant Recipient.

Non-O1, non-O139 Vibrio cholerae are rare strains that are generally nonpathogenic in immunocompetent hosts. However, this pathogen has been shown to cause gastroenteritis, wound infections, or bacteremia in immunocompromised patients and is associated with significant mortality in these hosts. Herein, we describe a case of hemorrhagic enterocolitis in a lung transplant recipient with an atypical presentation of non-O1, non-O139 V. cholerae and ongoing orthostasis. The patient reported recent seafood consumption and was managed appropriately with antibiotic therapy before necessitating esophagogastroduodenoscopy (EGD) for further objective testing.

Corrigendum: Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

[This corrects the article DOI: 10.3389/ti.2022.10433.].

Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series.

Background: Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Methods: Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018. Results: The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 µmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 µmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%. Conclusion: The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.

Effect of mode of intraoperative support on primary graft dysfunction after lung transplant.

OBJECTIVE: To clarify the relationship between the use of extracorporeal life support during lung transplantation and severe primary graft dysfunction (PGD), we developed and analyzed a novel multicenter international registry. METHODS: The Extracorporeal Life Support in Lung Transplantation Registry includes double-lung transplants performed at 8 high-volume centers (>40/year). Multiorgan transplants were excluded. We defined severe PGD as grade 3 PGD (PGD3) observed 48 or 72 hours after reperfusion. Modes of support were no extracorporeal life support (off-pump), extracorporeal membrane oxygenation (ECMO), and cardiopulmonary bypass (CPB). To assess the association between mode of support and PGD3, we adjusted for demographic and intraoperative factors with a stepwise, mixed selection, multivariable regression model, ending with 10 covariates in the final model. RESULTS: We analyzed 852 transplants performed between January 2016 and March 2020: 422 (50%) off-pump, 273 (32%) ECMO, and 157 (18%) CPB cases. PGD3 rates at time point 48-72 were 12.1% (51 out of 422) for off-pump, 28.9% for ECMO (79 out of 273), and 42.7% (67 out of 157) for CPB. The adjusted model resulted in the following risk profile for PGD3: CPB versus ECMO odds ratio, 1.89 (95% CI, 1.05-3.41; P = .033), CPB versus off-pump odds ratio, 4.24 (95% CI, 2.24-8.04; P < .001), and ECMO versus off-pump odds ratio, 2.24 (95% CI, 1.38-3.65; P = .001). CONCLUSIONS: Venoarterial ECMO is increasingly used at high-volume centers to support complex transplant recipients during double-lung transplantation. This practice is associated with more risk of PGD3 than off-pump transplantation but less risk than CPB. When extracorporeal life support is required during lung transplantation, ECMO may be the preferable approach when feasible.

Successful Preoperative Optimization for Lung Transplantation With Transcatheter Mitral Valve Repair.

Surgically treatable valvular heart disease is common in patients with end-stage lung disease. Nevertheless, advanced lung disease is often seen as a contraindication to cardiac surgery, and severe valvular disease is seen as a contraindication to lung transplantation. This report describes the case of a patient presenting with very severe chronic obstructive pulmonary disease and severe mitral regurgitation who was managed with transcatheter mitral valve repair and who subsequently underwent successful lung transplantation. Critical valvular heart disease in patients with chronic respiratory failure may be amenable to transcatheter therapy, which may favorably affect lung transplantation candidacy.

Evaluating resilience as a predictor of outcomes in lung transplant candidates.

BACKGROUND: Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates' resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10). METHODS: Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t test or chi-square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood. RESULTS: Participation was 55.3% (N = 199). Baseline RISC-10 averaged 32.0 ± 5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores < 26.3 (representing > 1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23-5.77; P = .01). CONCLUSION: One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.

Successful bridge to lung transplantation with transcatheter aortic valve replacement.

End-stage lung disease and advanced cardiac conditions are frequently seen together and represent a clinical dilemma. Even though both issues may be amenable to surgical management, combining lung transplant with surgical valve repair is rarely done and theoretically associated with increased morbidity and mortality risks, especially in elderly patients. Here, we describe 2 patients presenting with end-stage lung disease and significant aortic stenosis who were successfully bridged to lung transplant via transcatheter aortic valve replacement. Patient 1 was a 66-year-old man who underwent a double lung transplant 56 days after transcatheter aortic valve replacement. Patient 2 was a 70-year-old man who underwent a single right lung transplant 103 days after transcatheter aortic valve replacement. Both patients had uneventful postoperative courses and are alive at the 1-year time point with excellent performance status. This report suggests that transcatheter aortic valve replacement may favorably impact lung transplant candidacy for patients with end-stage lung disease in the setting of severe aortic stenosis, likely representing a better alternative to concomitant aortic valve replacement and lung transplant in elderly patients.

Impact of Affect on Lung Transplant Candidate Outcomes.

BACKGROUND: We examined the association of adult lung transplant candidates' self-reported affect with transplant-related outcomes, evaluating whether a positive (vs negative) frame of mind might be protective. METHOD: Consenting waitlisted candidates from 6 centers completed the questionnaires including the Positive and Negative Affect Schedule annually and posttransplant. Univariate logistic regression analysis was performed to determine the association of baseline affect with outcomes of death or delisting. Models were subsequently adjusted for age, marital status, and education. RESULTS: Questionnaires were completed by 169 candidates (77.9% participation). Mean positive affect, negative affect, and positive-to-negative affect ratio (positivity ratio) were similar to expected norms. The scores of the questionnaire did not change significantly over time. Fifteen (8.9%) waitlisted participants died. Candidates who died while waiting had lower positivity ratios compared to those who survived (1.82 vs 2.45; P = .02). A more negative affect was associated with increased death on the waiting list (adjusted odds ratio [OR] 1.10; P = .021). Conversely, a higher positivity ratio was associated with decreased death while waiting (adjusted OR: 0.45; P = .027). CONCLUSION: Negative affect may represent a novel risk factor for death on the waitlist. Enhancing positive affect may represent a useful target for psychological optimization in lung transplant candidates.

The Impact of Donor and Recipient Age: Older Lung Transplant Recipients Do Not Require Younger Lungs.

BACKGROUND: Lung transplantation for patients with end-stage lung disease continues to grow worldwide. Increasing demand for this therapy generates significant waitlist mortality, indicating that alternative sources of donor lungs, such as older donors, are needed. The effect of the donor-recipient age relationship on outcomes remains unclear. METHODS: A retrospective review of the United Network for Organ Sharing Standard Transplant Analysis and Research database was performed for adult lung recipients from 2005 to 2015. Variables examined included donor age, recipient age, listing diagnosis, episodes of acute cellular rejection in the first year, and survival. Both donors and recipients were stratified according to age ranges. Survival was compared with the log-rank test. Propensity score matching was done stratifying donors younger than 60 years versus older than 60 years for the recipient population of 60 to 69 years. RESULTS: From May 2005 to February 2015, 15,844 patients underwent lung transplantation. Unadjusted comparisons of donor-to-recipient age showed that older donor age appeared to be more relevant for recipients 60 to 69 years old (p = 0.002). Nevertheless, when propensity matching was done based on relevant covariates for recipients in this age range by donors younger or older than 60 years, there were no differences in survival. CONCLUSIONS: Our results suggest that even though donor and recipient age may be important in lung transplantation, the interplay between donor and recipient age alone is not an independent determinant of survival. Careful selection of lungs from donors older than 60 years old should be exercised, taking into consideration the totality of donor demographics and risk factors rather than dismissing lungs based on advanced age alone.

Immunosuppression for Lung Transplantation: Current and Future.

PURPOSE OF THE REVIEW: The number of lung transplantations performed worldwide continues to increase. There is a growing need in these patients for more effective immunosuppressive medications with less toxicity. RECENT FINDINGS: This review article summarizes the recent studies and developments in lung transplant immunosuppression. Novel immunosuppressive medications and strategies used in other solid organ transplantations are being trialed in lung transplantation. This includes the use of co-stimulation blockers like belatacept and mTOR inhibitors like everolimus. Calcineurin sparing regimens have been described in an attempt to minimize nephrotoxicity. Assays to measure the bioactivity of immunosuppressive medications to determine the global immune competence, such as Immuknow assay and Gamma interferon response are gaining traction. SUMMARY: Immunosuppression in lung transplant is evolving with the development of newer drugs and promising strategies to optimize immunosuppression. Further studies with multicenter randomized trials are required to increase the strength of the evidence.

Mycobacterium abscessus disease in lung transplant recipients: Diagnosis and management.

Mycobacterium abscessus complex (MAbsC ) disease in lung transplant recipients is increasingly being recognized as an important cause of graft function decline and suboptimal outcomes. Lung transplant recipients appear to be at the highest risk of MAbsC among solid organ transplant recipients, as they have more intense immunosuppression, and the organisms preferentially inhabit the lungs. MAbsC is the most resistant species of rapidly growing mycobacteria and difficult to treat, causing considerable mortality and morbidity in immunocompetent and immunosuppressed patients. Herein we describe the risk factors, epidemiology, clinical features, diagnostics, and treatment strategies of MAbsC in lung transplant recipients.

Incidence, Predictors, and Outcomes of Early Atrial Arrhythmias After Lung Transplant: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study sought to determine the incidence, predictors, and prognostic implications of early post-lung transplant atrial arrhythmias (AAs). BACKGROUND: Although frequently encountered, the prognostic implications of early AAs after lung transplant remain uncertain. METHODS: A systematic review of MEDLINE and the Cochrane Library was conducted for all studies that reported early post-lung transplant AAs. Random-effects DerSimonian-Laird risk ratios (RRs) were calculated for categorical variables and standardized mean difference (SMD) for continuous variables. RESULTS: A total of 12 studies with 3,203 patients (mean age 57 ± 3 years; 52% males) were included. The incidence of early post-lung transplant AAs during hospitalization was 26.6% at mean follow-up duration of 6.7 days. Predictors of post-lung transplant AAs included advanced age (SMD: 0.50; 95% confidence interval [CI]: 0.35 to 0.64), male gender (RR: 1.37; 95% CI: 1.28 to 1.47), history of smoking (RR: 1.23; 95% CI: 1.05 to 1.46), hypertension (RR: 1.35; 95% CI: 1.13 to 1.59), hyperlipidemia (RR: 1.39; 95% CI: 1.18 to 1.63), coronary artery disease (RR: 1.40; 95% CI: 1.12 to 1.7), left atrial diameter (SMD: 0.25; 95% CI: 0.07 to 0.44), and restrictive lung disease (RR: 1.34; 95% CI: 1.13 to 1.59). Post-lung transplant AAs were associated with increased all-cause mortality (adjusted RR: 1.63; 95% CI: 1.22 to 2.19) at mean follow-up of 27.8 months and length of hospital stay (36.5 ± 16.5 days vs. 26.1 ± 14.3 days; p < 0.001). CONCLUSIONS: Early AAs post-lung transplant are associated with increased mortality and length of hospital stay. Advanced age, male sex, smoking, hypertension, hyperlipidemia, coronary artery disease, increased left atrial diameter, and restrictive lung disease are independent predictors of early AAs in post-lung transplant patients.

A 48-Year-Old Man With Leukopenia, Jaundice, and Skin Rash After Lung Transplantation.

A 48-year-old African-American male subject presented with progressive fatigue, jaundice, and new-onset leukopenia 12 weeks after undergoing bilateral lung transplantation for advanced pulmonary sarcoidosis. His transplant surgery and immediate posttransplantation course were uneventful. Induction immunosuppression included methylprednisolone 500 mg intraoperatively and basiliximab (anti-IL-2 monoclonal antibody) on days 0 and 4 after transplantation. His maintenance immunosuppression posttransplantation was prednisone 20 mg daily, tacrolimus with target tacrolimus levels 10 to 15 ng/mL, and mycophenolate mofetil 750 mg twice daily. Both the donor and recipient were seropositive for cytomegalovirus and Epstein-Barr virus. Infectious disease prophylaxis consisted of valganciclovir, trimethoprim/sulfamethoxazole, and voriconazole. Results of the surveillance bronchoscopy conducted after the lung transplant were negative for acute cellular rejection or infection at 4 and 12 weeks' posttransplantation. Findings on spirometry had continuously improved since transplantation.

Weight loss prior to lung transplantation is associated with improved survival.

BACKGROUND: Obesity is associated with increased mortality after lung transplantation and is a relative contraindication to transplant. It is unknown whether weight reduction prior to transplantation ameliorates this risk. Our objective was to determine whether weight loss prior to lung transplantation improves survival. METHODS: Our investigation was a two-center, retrospective cohort study of lung transplant recipients between January 1, 2000 and November 5, 2010. Change in weight, demographics, transplant details, lung allocation score, length of intensive care and mechanical ventilator days and graft and patient survival were abstracted. Wilcoxon's signed-rank test and the Cox proportional hazard model were used for analysis where appropriate. RESULTS: Three hundred fifty-five patients (55% male, median age 59 years) satisfied inclusion and exclusion criteria. After adjusting for standard demographic and clinical measures, a 1-unit reduction in BMI pre-transplant was associated with a reduced risk of death with a hazard ratio 0.89 (95% confidence interval 0.82 to 0.96; p = 0.004). This survival benefit persisted in the group with baseline BMI ≥ 25 kg/m(2) (overweight and obese) and hazard ratio 0.85 (95% CI 0.77 to 0.95; p = 0.003), but not in those with a BMI ≤ 24.9 kg/m(2). The 1-unit reduction in BMI was also associated with a 6.1% decrease in median mechanical ventilator days (p = 0.02) and a trend toward decreased intensive care unit length of stay (p = 0.06). CONCLUSIONS: A reduction in BMI prior to lung transplantation was associated with a reduction in the risk of death and mechanical ventilator days. A greater reduction in BMI was associated with a greater survival benefit.

Pulmonary morbidity improves after autologous stem cell transplantation in POEMS syndrome.

BACKGROUND: POEMS syndrome is a plasma cell disorder manifested by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Pulmonary morbidity includes restriction, decreased diffusing capacity for carbon monoxide (DLCO), respiratory muscle weakness, abnormal imaging, and pulmonary hypertension. Autologous peripheral blood stem cell transplantation (aPBSCT) is an effective treatment for POEMS syndrome. It is unknown if aPBSCT improves pulmonary morbidity. We hypothesize pulmonary morbidity will improve following aPBSCT. METHODS: Retrospective cohort study of POEMS syndrome aPBSCT recipients from 2000 to 2010. Demographic, pulmonary function test (PFT), echocardiogram, cytokine, and imaging data at baseline and after aPBSCT were abstracted. Pre- and post-transplant data were compared using Wilcoxon signed-rank and McNemar's tests. RESULTS: 53 patients met criteria. Median improvements in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) after transplant were 180, 315 and 350 ml respectively (median follow-up of 1.1 years). DLCO, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) improved by a median of 11, 12.5 and 10% predicted respectively. RVSP and chest imaging also improved. Vascular endothelial growth factor and IL-6 decreased by a median of 334 and 2 pg/ml respectively. All comparisons were statistically significant. Longitudinal data demonstrated stability in FEV1, MEP, and TLC and continued improvement in FVC, MIP and DLCO on subsequent PFTs (median follow-up 26.5 months). CONCLUSION: Patients with POEMS syndrome treated with aPBSCT have significant improvement in PFTs, respiratory muscle strength, imaging, and post-transplant IL-6. The improvement in PFTs persists during long-term follow-up.

Postpartum reversible cerebral vasoconstriction syndrome.

Postpartum reversible cerebral vasoconstriction syndrome, also known as postpartum cerebral angiopathy, is clinically characterized by headache and focal neurologic deficits, and angiographically by transient, fully reversible cerebral vasoconstriction. A 26-year-old woman was brought to the emergency room with a 3-day history of confusion, agitation, and headache. She was 2 weeks postpartum. She went on to develop right leg weakness two days after admission. A cerebral angiogram showed diffuse irregularities of all intracerebral vessels, and MRI showed multiple acute infarcts. Her clinical condition improved significantly over the next several days without any intervention, and she was discharged. MRA 3 months after initial presentation was normal. It is important to consider this syndrome in the differential diagnosis in patients presenting with headache and focal neurologic deficits in the postpartum period.