Prolonged Use of the Hemolung Respiratory Assist System as a Bridge to Redo Lung Transplantation.

Although extracorporeal membrane oxygenation (ECMO) has been used frequently as a bridge to primary lung transplantation, active centers are conservative with this approach in patients requiring redo lung transplantation. We report the use of extracorporeal carbon dioxide removal, using the Hemolung respiratory assist system, as a prolonged bridge to lung transplantation, and the first use of the Hemolung as a bridge to redo lung transplantation. Hemolung support improved the patient's clinical status and allowed redo lung transplantation.

Lung transplantation with lungs from older donors: recipient and surgical factors affect outcomes.

BACKGROUND: A shortage of donors has compelled the use of extended-criteria donor organs in lung transplantation. The purpose of this study was to evaluate the impact of using older donors on outcomes after lung transplantation using current protocols. METHODS: From January 2003 to August 2009, 593 lung transplants were performed at our institution. We compared 87 patients (14.7%) who received lungs from donors aged 55 years or older with 506 patients who received lungs from donors less than 55 years old. We also examined risk factors for mortality in recipients of lungs from older donors. RESULTS: The incidence of major complications including severe primary graft dysfunction and early mortality rates were similar between the groups. However, posttransplant peak FEV1 was lower in the patients who received lungs from older donors (71.7% vs. 80.7%, P<0.05). In multivariate analysis, recipient pulmonary hypertension (transpulmonary pressure gradient >20 mm Hg) and prolonged intraoperative cardiopulmonary bypass were significant risk factors for mortality in the recipients of lungs from older donors. CONCLUSIONS: This large, single-center experience demonstrated that transplanting lungs from donors older than 55 years did not yield worse short- or long-term outcomes as compared with transplanting lungs from younger donors. However, transplanting lungs from older donors into recipients with pulmonary hypertension or recipients who required prolonged cardiopulmonary bypass increased the risk for mortality. Although lungs from older donors should not be excluded because of donor age alone, surgeons should carefully consider their patient selection criteria and surgical plans when transplanting lungs from older donors.

Delayed chest closure after lung transplantation: techniques, outcomes, and strategies.

BACKGROUND: Delayed chest closure (DCC) after lung transplantation is a viable option to be taken in the cases of prolonged cardiopulmonary bypass time, prolonged ischemic time, coagulopathic problems or oversized donor lung grafts. Decision-making for DCC in the operating room remains challenging to surgeons, because the impact of DCC on outcomes after lung transplantation has not yet been fully elucidated. METHODS: We performed a retrospective review of 90 lung transplantations with DCC and 783 cases with primary chest closure to clarify the reasons for DCC, complications of DCC, and the risk factors for adverse outcomes. RESULTS: The 30- and 90-day mortality in the DCC group was 7.8% and 9.9%, respectively. Early post-operative bleeding and severe primary graft dysfunction (PGD) were higher in the DCC group (p<0.05). In multivariate analysis, prolonged cardiopulmonary bypass use (>4 hours), post-operative extracorporeal oxygen requirement and use of a DCC technique with open skin and retracted ribs were significantly associated with mortality (p<0.05), whereas prolonged duration of DCC was not. In a matched cohort study to compare the results of a DCC technique with skin closure to similarly matched controls with primary closure, DCC contributed to significantly decreased incidence of severe PGD (9.6% vs. 26%, p<0.05), leading to an improved post-transplant survival and functional status as compared with primary closure. CONCLUSIONS: Our technical approaches to prevent possible problems in DCC cases are described. DCC can be safely performed with acceptable procedure-related risks. DCC should not be considered a sub-optimal option after lung transplantation.

Long-term patient and allograft outcomes of renal transplant recipients undergoing cardiac surgery.

OBJECTIVES: Cardiovascular complications are a major cause of morbidity and mortality among renal transplant recipients. This study assessed perioperative risk factors for mortality and long-term outcomes in renal transplant recipients who underwent cardiac surgery. METHODS: From 1999 to 2010, 92 renal transplant recipients with a functioning allograft underwent cardiac surgery at our institution. Cardiac procedures included coronary artery bypass grafting (43 patients, 46%), isolated valve surgery (17 patients, 18%), combined coronary artery bypass grafting and valve surgery (18 patients, 19%), and aortic procedures (7 patients, 7%). RESULTS: Transient renal failure requiring dialysis occurred in 20 of 92 patients (21%), with 3 not recovering renal function and returning to a permanent dialysis regimen while in the hospital. After cardiac surgery 30-day, 1-year, 5-year, and 8-year survival rates were 89%, 72%, 47%, and 30%, respectively. Freedom from dialysis was 90% after 1 year, 66% after 5 years, and 49% after 8 years. Risk factors for 30-day mortality were age > 65 years, left ventricle ejection fraction < 35%, and a combined cardiac procedure. Pulmonary hypertension and diabetes were risk factors for death from a cardiac cause after discharge. Diabetes, dyslipidemia, preoperative use of an intra-aortic balloon pump, postoperative creatinine > 2 mg/dL, and transient renal failure requiring dialysis were associated with a permanent dialysis requirement after cardiac surgery. CONCLUSIONS: Cardiac surgery in patients receiving renal transplant who have functioning allograft has acceptable outcomes. If combined procedures are required, patients should be carefully considered. Transient postoperative renal impairment, even if resolved at discharge, increases the risk for allograft failure during long-term follow-up.

Lobar lung transplantation: a relevant surgical option in the current era of lung allocation score.

BACKGROUND: With the implementation of the lung allocation score (LAS) system, an increased number of critically ill patients are considered for transplantation. However, LAS does not take size matching between donor and recipient lungs into consideration. Mortality on the waiting list is high (as high as 25%) for short-stature patients and for patients with restrictive lung disease. Here, we review our experience using cadaveric lobar lung transplantation as a surgical option in an attempt to decrease mortality while waiting. METHODS: We retrospectively reviewed patients with end-stage lung diseases and an LAS greater than 70 who underwent cadaveric lobar lung transplantation between 2010 and 2012 (n = 25) at our institution, a high-volume lung transplant center. Anatomic lobectomy was performed on all donor lungs before double lung transplantation. RESULTS: Median LAS was 85.6 (range, 72 to 94). Average waiting time after the patients' LAS was updated to greater than 70 was 10 days (range, 1 to 41). There were 2 in-hospital deaths. The 90-day and 1-year survivals were 88% and 76%, respectively. Patient major comorbidities included severe primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation (7 patients), acute renal insufficiency (4 patients), and bleeding requiring reoperation (4 patients). No technical problems were identified, and repeated bronchoscopy demonstrated satisfactory healing of the bronchial stump after lobectomy. The average posttransplant peak for forced expiratory volume in 1 second was 85%. CONCLUSIONS: Our initial experience supports the option of lobar lung transplantation for critically ill patients whose opportunities for transplant are limited by their stature. Long-term functional studies are warranted.

Lung transplantation after lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery (LVRS) as a bridge to lung transplantation was first advocated in 1995 and published studies have supported the concept but with limited data. The risk-benefit tradeoffs of the combined procedure have not been thoroughly examined, although substantial information regarding LVRS has emerged. METHODS: Of 177 patients who underwent lung transplantation for end-stage emphysema between 2002 and 2009 at our center, 25 had prior LVRS (22 bilateral and 3 unilateral). Lung transplantation was performed 22.9±15.9 months after LVRS. We compared in-hospital morbidity, functional capacity, and long-term outcomes of patients who underwent LVRS before lung transplantation with a matched cohort of patients without prior LVRS to assess the influence of LVRS on posttransplantation morbidity and mortality. RESULTS: The incidence of postoperative bleeding requiring reexploration and the incidence of renal dysfunction requiring dialysis were higher in patients with LVRS before lung transplantation. Posttransplantation peak forced expiratory volume in 1 s was worse in patients with LVRS before lung transplantation (56.7% vs. 78.8%; P<0.05). Five-year survival was not significantly different (59.7% in patients with LVRS before lung transplantation vs. 66.2% in patients with lung transplantation alone). In multivariate analysis, age more than 65 years, prolonged cardiopulmonary bypass time, and severe pulmonary hypertension were significant predictors for mortality (P<0.05). CONCLUSIONS: Although LVRS remains a viable option as a bridge to lung transplantation in appropriately selected patients, LVRS before lung transplantation can impart substantial morbidity and compromised functional capacity after lung transplantation. LVRS should not be easily considered as a bridge to transplantation for all lung transplant candidates.

Efficacy of extracorporeal membrane oxygenation as a bridge to lung transplantation.

BACKGROUND: Preoperative extracorporeal membrane oxygenation (ECMO) is a risk factor for poor outcome and currently considered a contraindication to lung transplantation. The lung allocation score system was introduced in May 2005 and prioritizes lung allocation to those with the greatest respiratory impairment. The purpose of this study is to determine whether ECMO as a bridge to lung transplantation is an acceptable option to support those in respiratory failure until donor lungs become available in the lung allocation score era. METHOD: A retrospective review of 715 consecutive lung transplants performed between May 2005 and September 2011 was conducted using a prospectively collected institutional registry database. Twenty-four lung transplants (3.4%) were performed in the 31 patients with attempted pretransplant ECMO; 7 patients who received ECMO patients did not survive or were deemed unfit for transplantation. These patients were compared with a control group of 691 patients who did not receive pretransplant ECMO. RESULTS: The duration of pretransplant ECMO was 171 ± 242 hours (median, 91 hours). Venovenous ECMO was used for respiratory failure in 15 patients, whereas venoarterial ECMO was used for circulatory collapse due to pulmonary hypertension in 9 patients. Patients in the retransplant ECMO group were younger (46 ± 15 years vs 57 ± 14 years, P < .01) compared with the control group, with no difference in recipient gender (male/female: 10/14 vs 380/311), donor age (33 ± 14 years vs 36 ± 15 years), or donor gender (male/female: 10/14 vs 352/339). Emphysema was less common (1, 4% vs 260, 38%, P < .01), and cystic fibrosis (5, 21% vs 72, 10%, P = .09), redo lung transplant (3, 13% vs 28, 4%, P = .08), and bronchiectasis (2, 8% vs 6, 1%, P = .03) were more common in the pretransplant ECMO group. Patients in the pretransplant ECMO group had a significantly higher lung allocation score (87 ± 9 vs 44 ± 15, P < .01). All patients in the pretransplant ECMO group underwent double lung transplants on pump (cardiopulmonary bypass/ECMO), and single lung transplants were performed in 171 patients (25%) and pump was used in 243 patients (35%) in the control group. The cardiopulmonary bypass time was longer in the pretransplant ECMO group (277 ± 69 minutes vs 225 ± 89 minutes, P = .02), with no difference in ischemic time (343 ± 93 minutes vs 330 ± 98 minutes, P = .54). Cadaveric lobar lung transplants were performed because of the urgency to overcome size mismatch with an oversized donor more frequently in 25% (n = 6, no mortality with the longest follow-up at 6 years) of patients in the pretransplant ECMO group versus 0.3% (n = 2) of patients in the control group (P < .01). Post-transplant ECMO was used for primary graft dysfunction in 13 patients (54%) in the pretransplant ECMO group and 41 patients (6%) in the control group (P < .01). The median hospital stay was 46 days in the pretransplant ECMO group versus 27 days in the control group (P = .16). The actuarial survivals after lung transplants at 1, 3, 6, 12, and 24 months were 96%, 88%, 83%, 74%, and 74%, respectively, in the pretransplant ECMO group, and 97%, 94%, 90%, 83%, and 74%, respectively, in the control group (P = .787). CONCLUSIONS: Although the incidence of primary graft dysfunction requiring post-transplant ECMO is higher and the hospital stay is longer in patients receiving pretransplant ECMO, the graft survival is good (2-year survival, 74%). ECMO is efficacious as a bridge to lung transplantation with good post-lung transplant outcomes.

Donor smoking history and age in lung transplantation: a revisit.

BACKGROUND: When selecting a donor for lung transplantation, it is generally believed that the best outcomes occur when the donor has no smoking history. Because we experienced unexpected adverse outcomes after transplant of lungs from teenaged donors with no smoking history, this study revisited the effects of donor smoking history in relation to age on transplant outcomes. METHODS: We conducted a retrospective review of 532 consecutive lung transplants performed at our institution. Most donors (293, 55%) had a history of smoking; 239 donors were nonsmokers. The smoking donors were further subgrouped based on consumption (<20, 20-40, or >40 pack-years). The nonsmoking donors were subgrouped by age (<20 years or ≥20 years). Recipients' characteristics and outcomes were compared. RESULTS: The recipients of lungs from donors with a smoking history showed better 5-year survival than recipients of lungs from nonsmokers (65.8% vs. 48.3%, P<0.05), but recipients of lungs from heavy smokers (>40 pack-years smoking history) exhibited a significantly higher incidence of severe primary graft dysfunction and higher short- and long-term mortality than the recipients of lungs from donors who smoked less. Surprisingly, recipients of lungs from teenaged donors with no smoking history exhibited a higher morbidity and mortality than recipients of lungs from adult nonsmoking donors but did not exhibit decreased posttransplant forced expiratory volume in 1 sec. CONCLUSIONS: In this large, single-center experience, the absence of smoking history in the donor did not result in better long-term outcomes after lung transplantation. Potential problems with lungs from teenaged donors with no smoking history were suggested.

Lung transplantation for patients with high lung allocation score: single-center experience.

BACKGROUND: The lung allocation score (LAS) assigns organ allocation priority based on medical urgency and the likelihood of posttransplant survival. This study is a review of a single institutional experience for lung transplantation in the era of LAS. METHODS: We performed a retrospective review of 527 consecutive patients, from May 2005 to February 2010, who underwent lung transplant at our institution, comprising a high LAS group (LAS≥50, n=108) and a low LAS group (LAS<50, n=419). Kaplan-Meier and univariate analyses were performed to assess postoperative mortality as a primary outcome, and length of ventilator support and intensive care unit stay as secondary outcomes. Risk factors, including demographics, pulmonary status, and surgical and donor variables, were compared. Predictors of mortality were determined using a Cox proportional hazard model. RESULTS: Survivals after 30 days, 90 days, 1 year, and 3 years were 92.6%, 87.8%, 71.5%, and 52.0%, respectively, in the high LAS group, and 96.9%, 93.5%, 83.2%, and 73.9% in the low LAS group (p<0.001). The incidence of prolonged ventilator support and the need for tracheostomy were higher, and intensive care unit stay was longer in the high LAS group. In the high LAS group, ischemic time greater than 8 hours was an independent predictor for mortality (hazard ratio: 3.080; 95% confidence interval 1.101 to 8.161, p=0.032). CONCLUSIONS: Lung transplant in patients with high a LAS is associated with significantly decreased survival and increased complications compared with patients with a low LAS. Ischemic time greater than 8 hours is a significant predictor of death in patients with a high LAS.

Midterm outcomes of off-pump and on-pump coronary artery revascularization in renal transplant recipients.

OBJECTIVES: Renal transplant recipients have high mortality from cardiac causes and are frequently in need of coronary interventions. Surgical coronary revascularization is associated with significant morbidity and mortality in this patient population. This study was undertaken to evaluate outcomes of on-pump versus off-pump revascularization in renal transplant recipients. METHODS: We retrospectively reviewed 43 renal transplant recipients who underwent surgical coronary revascularization with functioning allografts. Revascularization was performed on-pump [coronary artery bypass grafting (CABG)] in 21 patients and off-pump [off-pump coronary artery bypass (OPCAB)] in 22 patients. RESULTS: Preoperative characteristics did not differ between the two groups except for age and incidence of prior sternotomy. Total operative time and transfusion requirements were similar. The on-pump group received a higher number of bypass grafts (p = 0.03). Overall 30-day, one-year, five-year, and eight-year survival was 90%, 76%, 61%, and 32% for CABG group, and 95%, 86%, 62%, and 48% for OPCAB group (p = 0.53). The postoperative peak creatinine was higher in the CABG patients than in OPCAB patients (p = 0.04). At discharge, there was no difference in mean creatinine between the two groups. The rate of return to permanent dialysis after revascularization was similar (28% for CABG and 22% for OPCAB, p = 0.73). There was no difference in dialysis-free survival up to eight-years postrevascularization (p = 0.63). CONCLUSIONS: Despite higher mortality risk, surgical coronary revascularization can be performed safely in renal transplant recipients. OPCAB resulted in no improvement in patient survival or renal allograft function compared to on-pump revascularization.

Extracorporeal membrane oxygenation for advanced refractory shock in acute and chronic cardiomyopathy.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used to obtain rapid resuscitation and stabilization in advanced refractory cardiogenic shock (CS), but clear strategies to optimize outcomes and minimize futile support have not been established. METHODS: We retrospectively reviewed our experience with ECMO in patients with advanced refractory CS, after an acute myocardial infarct (AMI) compared with patients receiving ECMO after an acute decompensating chronic cardiomyopathy (CCM). RESULTS: Between January 2003 and February 2009, 33 patients required ECMO support for advanced refractory CS secondary to AMI (AMI-CS) and 9 patients were supported by ECMO in the presence of an acutely decompensated CCM (CCM-CS). Survival at 30 days, 1 and 2 years for patients with AMI-CS, was 64%, 48%, and 48% compared with 56%, 11%, and 11% at the same time points for those with CCM-CS (p = 0.05). In the AMI-CS group, 14 of 33 (42%) patients were weaned directly from ECMO after revascularization; 15 of 33 (45%) patients were bridged to ventricular assist device (VAD) support and subsequently either underwent heart transplantation (n = 6), were successfully weaned from VAD (n = 2) or died while on VAD support (n = 7). In the CCM-CS group, 7 patients were bridged to VAD support (77%), with 1 patient surviving after VAD weaning. CONCLUSIONS: Extracorporeal membrane oxygenation in advanced refractory AMI-CS is associated with acceptable outcomes in a well-selected population. The ECMO in patients with an acute decompensation of a chronic CM should be carefully considered, to avoid futile support.

Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm outcomes.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used occasionally as a bridge to lung transplantation. The impact on mid-term survival is unknown. We analyzed outcomes after lung transplant over a 19-year period in patients who received ECMO support. METHODS: From March 1991 to October 2010, 1,305 lung transplants were performed at our institution. Seventeen patients (1.3%) were supported with ECMO before lung transplant. Diagnoses included retransplantation (n = 6), pulmonary fibrosis (n = 6), cystic fibrosis (n = 4), and chronic obstructive pulmonary disease (n = 1). Fifteen patients underwent double lung transplant, one patient had single left lung transplant and one patient had a heart-lung transplant. Venovenous and venoarterial ECMO were implanted in eight and nine cases, respectively. Median duration of support was 3.2 days (range, 1 to 49 days). Mean patient follow-up was 2.3 years. RESULTS: Thirty-day, 1-year, and 3-year survivals were 81%, 74%, and 65%, respectively, for the supported patients and 93%, 78%, and 62% in the control group (p = 0.56). Two-year survival was not affected by ECMO type, with survival of five out of nine patients supported by venoarterial ECMO vs seven out of eight patients supported by venovenous ECMO (p = 0.17). At 1- year follow-up, allograft function for the ECMO-supported patients did not differ from the control group (forced expiratory volume in one second, 2.35 L vs 2.09 L, p = 0.39) (forced vital capacity, 3.06 L vs 2.71 L, p = 0.34). CONCLUSIONS: Extracorporeal membrane oxygenation as a bridge to lung transplantation is associated with higher perioperative mortality but acceptable mid-term survival in carefully selected patients. Late allograft function did not differ in patients who received ECMO support before lung transplant from those who did not receive ECMO.

Five-year outcomes with alemtuzumab induction after lung transplantation.

BACKGROUND: Induction therapy with alemtuzumab, followed by lower than conventional intensity post-transplant immunosuppression (eg, tacrolimus monotherapy), has been associated with reduced morbidity and mortality in abdominal and heart transplantation. We examined 5-year outcomes in lung recipients receiving alemtuzumab in conjunction with reduced-intensity post-transplant immunosuppression (early lower-dose tacrolimus; lower-dose steroids, with or without mycophenolate mofetil), compared with lung recipients receiving other induction agents or no induction in association with post-transplant immunosuppression. METHODS: A retrospective analysis was performed using prospectively collected data from a single-site clinical database of 336 lung recipients (aged ≥ 18) who received allografts between 1998 and 2005, classified by induction type: alemtuzumab, 127; Thymoglobulin, 43; daclizumab, 73; and none, 93. Survival analyses examined patient and graft survival, and freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, obliterative bronchiolitis (OB), bronchiolitis obliterans syndrome (BOS), and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Five-year patient and graft survival differed by group (p = 0.046, p = 0.038, respectively). Alemtuzumab patient/graft survival rates were 59%/59%. Survival rates were 60%/44% for Thymoglobulin, 47%/46% for no induction, and 44%/41% for daclizumab. Freedom from ACR, lymphocytic bronchiolitis, OB, and BOS differed by group (all values, p < 0.008); alemtuzumab recipients showed greater 5-year freedom from each outcome (30%/82%/86%/54%) than Thymoglobulin (20%/54%/62%/27%), daclizumab (19%/55%/70%/43%), and no-induction groups (18%/70%/69%/46%). The groups did not differ in PTLD rates (≥ 94% free of PTLD at 5 years; p = 0.864). Effects were unchanged after controlling for potential covariates. CONCLUSIONS: Alemtuzumab induction may be associated with improved outcomes in lung transplantation. Randomized controlled trials are needed to establish any effects of this agent.

A polymorphism linked to elevated levels of interferon-γ is associated with an increased risk of cytomegalovirus disease among Caucasian lung transplant recipients at a single center.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) associated with active cytomegalovirus (CMV) infections after lung transplantation have not been identified. METHODS: SNPs associated with varying levels of interferon (IFN)-γ (+874T/A), tumor necrosis factor-α (-308G/A), interleukin-10 (-1082G/A, -819C/T, -592C/A) and interleukin-6 (-174G/C) were characterized for 170 Caucasian lung transplant recipients who received alemtuzumab induction and valganciclovir prophylaxis against CMV. RESULTS: Patients were followed for a median of 34 months post-transplant, and 66% (113 of 170), 24% (40 of 170) and 10% (17 of 170) had no CMV infection, CMV viremia and CMV disease, respectively. Median times to CMV viremia and disease were 7 and 10 months, respectively. For each gene, there was no significant deviation from Hardy-Weinberg equilibrium. Independent risk factors for the development of CMV disease were IFN-γ +874 T/T genotype (associated with high levels of IFN-γ production), CMV donor-positive/recipient-negative (D(+)/R(-)) serostatus and acute cellular rejection requiring augmented immunosuppression (p = 0.001, 0.003 and 0.049, respectively). The association between IFN-γ +874 T/T genotype and CMV disease was most striking among R(+) patients (p = 0.02). D(+)/R(-) serostatus was also a significant risk factor for CMV viremia (p = 0.0005). IFN-γ +874 T/T genotype was associated with significantly lower peak CMV viral loads (p = 0.03). There were no associations between tumor necrosis factor-α, interleukin-10 or interleukin-6 SNPs and CMV infections. CONCLUSION: A genetic predisposition to elevated IFN-γ levels may play a dual role in controlling active CMV infection among lung transplant recipients receiving alemtuzumab induction and valganciclovir prophylaxis, limiting the extent of viral replication in serum but increasing the risk of CMV disease.

Plasma inflammatory mediators associated with bone metabolism in COPD.

ABSTRACT The association of osteoporosis with COPD is well established, but the relationship between systemic inflammatory mediators and bone metabolism has not been explored. Plasma samples from 40 COPD patients awaiting lung transplantation were analyzed for 27 inflammatory mediators using a multiplex protein array. C-telopeptide type I collagen (CTx), a marker of bone resorption, was measured with ELISA, and N-terminal procollagen propeptide (P1NP), a marker of bone formation, was ascertained with a radioimmunoassay. Associations between inflammatory mediators versus CTx and P1NP with adjustments for steroid and bisphosphonate use were determined. Mean age was 59 years (+/- 6) and FEV(1) was 23.5% (+/- 8.3%) predicted. Ninety-five percent of the subjects had low bone mineral density measured by dual x-ray absorptiometry (DXA). Tumor necrosis factor alpha and interleukin 4 were positively associated with CTx and P1NP. RANTES and eotaxin were inversely associated with CTx and P1NP. Interleukin 2 and interferon gamma were also directly associated with P1NP. Biologically plausible systemic mediators are associated with bone metabolism in patients with severe COPD, offering potential insight into risk factors and underlying mechanisms of bone disease. Furthermore, they may be useful in monitoring disease activity, and serve as targets for biological therapy.

Impact of abdominal complications on outcome after mechanical circulatory support.

BACKGROUND: Mechanical circulatory support (MCS) is life sustaining for patients with end-stage heart failure. Most devices require abdominal wall transgression, creating a potential for abdominal complications. The incidence and impact of these relatively underreported complications are unknown. METHODS: A retrospective review was performed on 179 patients who received MCS therapy from 1999 to 2008. Abdominal complications were grouped as abdominal wall, gastrointestinal tract, and solid organ. RESULTS: Ninety-eight patients (55%) experienced 157 abdominal complications. These involved the abdominal wall in 69 (44%), the gastrointestinal tract in 52 (33%), and the solid organs in 36 (23%). Surgical intervention was required in 36% of patients with abdominal wall complications, 19% of patients with gastrointestinal tract complications, and 14% of patients with solid organ complications. Multivariate analysis identified diabetes mellitus (p < 0.001), emergent device placement (p = 0.019), and preimplant mechanical ventilation (p = 0.045) as independent risk factors for developing an abdominal complication. Kaplan-Meier survival while receiving MCS was significantly reduced for patients with abdominal complications versus those without (p = 0.0142). Multivariate analysis identified only solid organ abdominal complications (p = 0.001) as an independent risk factor for death while receiving device support. CONCLUSIONS: Abdominal complications are common in patients supported with MCS devices and significantly reduce survival. Surgical intervention is more frequently required for complications related to the abdominal wall compared with other complications. Patients with significant comorbidities (diabetes mellitus, respiratory failure) requiring urgent or emergent device placement are at higher risk for the development of abdominal complications with an attendant reduction in device-related survival.

Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection.

BACKGROUND: Lung transplants, in particular, have the highest rate of infections among solid organ transplant recipients. However, there is no existing objective measure to predict the development of infections. We report the correlation between Cylex ImmuKnow (ng/mL ATP) values and various infectious syndromes in a large prospective cohort of lung transplant recipients. METHODS: We followed up 175 lung transplants that developed 129 infectious episodes. Multiple logistic regression analysis was performed; generalized estimating equations were used to determine the odds ratio for infections. RESULTS: The median ImmuKnow values in cytomegalovirus disease (49.3 ng/mL ATP), viral infection (70 ng/mL ATP), and bacterial pneumonia (92 ng/mL ATP) were significantly different from stable state (174.8 ng/mL ATP). The median ImmuKnow values of fungal disease (85 ng/mL ATP) and tracheobronchitis (123 ng/mL ATP) had a tendency to be lower than stable state (P=0.10), whereas patients with fungal colonization had comparable ImmunKnow values (167 vs. 174.8 ng/mL ATP). Of the patients colonized with fungus who subsequently developed fungal disease within 100 days, the median value of ImmuKnow was significantly lower than in those who did not develop fungal disease (22.5 vs. 183.5 ng/mL ATP; P<0.0001). Generalized estimating equation regression analysis showed ImmuKnow values less than or equal to 100 ng/mL ATP to be an independent predictor of infections (odds ratio 2.81). CONCLUSIONS: Cylex ImmuKnow assay monitoring has the potential to identify the patients at risk of developing infection and those colonized with fungus that are at risk of developing disease.

Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival.

BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation is a major cause of morbidity and mortality. Venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) allows lung recovery; however, the optimal approach and impact on long-term survival are unknown. We analyzed outcomes after ECMO use for PGD after lung transplantation at a single center over a 15-year period and assessed long-term survival. METHODS: From March 1991 to March 2006, 763 lung or heart-lung transplants were performed at our center. Fifty-eight patients (7.6%) required early (0 to 7 days after transplant) ECMO support for PGD. Venovenous or venoarterial ECMO was implemented (32 and 26 cases) depending on the patient's hemodynamic stability, surgeon's preference, and the era of transplantation. Mean duration of support was 5.5 days (range, 1 to 20). Mean follow-up was 4.5 years. RESULTS: Thirty-day and 1- and 5-year survivals were 56%, 40%, and 25%, respectively, for the entire group. Thirty-nine patients were weaned from ECMO, 21 venovenous and 18 venoarterial (53.8% and 46.2%), with 1- and 5-year survivals of 59% and 33%, inferior to recipients not requiring ECMO (p = 0.05). Survival at 30 days and at 1 and 5 years was similar for the patients supported with venoarterial or venovenous ECMO (58% versus 55%, p = 0.7; 42% versus 39%, p = 0.8; 29% versus 22%, p = 0.6). CONCLUSIONS: Extracorporeal membrane oxygenation can provide acceptable support for PGD irrespective of the method used. Long-term survival of patients with primary graft dysfunction requiring ECMO (overall and weaned) was inferior to that of patients who did not require ECMO.

Anti-human leukocyte antigen antibodies, vascular C4d deposition and increased soluble c4d in broncho-alveolar lavage of lung allografts.

BACKGROUND: The hallmark of humoral rejection is the presence of subendothelial C4d in the allograft. A simultaneous determination of vascular C4d with soluble C4d in broncho-alveolar lavage fluid (BAL) and circulating anti-human leukocyte antigen (HLA) antibodies (HLA-Ab) has not been reported in lung transplantation. METHODS: Forty-two consecutive lung-transplant patients were included in this cross-sectional study. The presence and specificity of HLA-Ab was determined at the same frequency with transbronchial biopsies. Soluble C4d levels were measured by enzyme-linked immunosorbent assay in all 42 patients. In a subgroup of 32 patients with available timely matched paraffin-embedded tissue sections, the vascular C4d deposition was also assessed. RESULTS: The presence of HLA-Ab in 16 patients was associated with biopsy-proven acute rejection (10/16 vs. 3/16, P<0.01) and increased immunosuppression (13/16 vs. 4/16, P<0.005). Pulmonary function was also decreased in patients with HLA-Ab (mean forced expiratory volume in 1 second=49%) when compared with the control group (mean forced expiratory volume in 1 second=66%, P<0.05). Nine patients exhibited specific vascular C4d deposition and in eight of nine (89%) cases HLA-Ab were detected, versus 8 of 23 (35%) in C4d-negative patients (P<0.05). Soluble C4d in BAL was highly (>0.5 microg/mL) elevated in patients with HLA-Ab and vascular C4d and was moderately (0.2 microg/mL) increased in patients with antibodies but C4d-negative. In contrast, only a slight elevation of soluble C4d (<0.1 microg/mL) was detected in patients without HLA-specific antibodies. CONCLUSIONS: The association of HLA-specific antibodies with vascular C4d deposition and soluble C4d in BAL, in addition to the reduced pulmonary function, might constitute a diagnostic triad for antibody-mediated rejection in lung transplant patients.