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Double lung, unlike single lung transplantation might provide a protective effect on mortality and bronchiolitis obliterans syndrome.

Tue, 11/28/2017 - 13:45

Double lung, unlike single lung transplantation might provide a protective effect on mortality and bronchiolitis obliterans syndrome.

J Cardiothorac Surg. 2017 Nov 25;12(1):100

Authors: Fakhro M, Broberg E, Algotsson L, Hansson L, Koul B, Gustafsson R, Wierup P, Ingemansson R, Lindstedt S

Abstract
BACKGROUND: Survival after lung transplantation (LTx) is often limited by bronchiolitis obliterans syndrome (BOS).
METHOD: Survey of 278 recipients who underwent LTx. The endpoint used was BOS (BOS grade ≥ 2), death or Re-lung transplantation (Re-LTx) assessed by competing risk regression analyses.
RESULTS: The incidence of BOS grade ≥ 2 among double LTx (DLTx) recipients was 16 ± 3% at 5 years, 30 ± 4% at 10 years, and 37 ± 5% at 20 years, compared to single LTx (SLTx) recipients whose corresponding incidence of BOS grade ≥ 2 was 11 ± 3%, 20 ± 4%, and 24 ± 5% at 5, 10, and 20 years, respectively (p > 0. 05). The incidence of BOS grade ≥ 2 by major indications ranked in descending order: other, PF, CF, COPD, PH and AAT1 (p < 0. 05). The mortality rate by major indication ranked in descending order: COPD, PH, AAT1, PF, Other and CF (p < 0. 05).
CONCLUSION: No differences were seen in the incidence of BOS grade ≥ 2 regarding type of transplant, however, DLTx recipients showed a better chance of survival despite developing BOS compared to SLTx recipients. The highest incidence of BOS was seen among CF, PF, COPD, PH, and AAT1 recipients in descending order, however, CF and PF recipients showed a better chance of survival despite developing BOS compared to COPD, PH, and AAT1 recipients.

PMID: 29178919 [PubMed - in process]

Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta-analysis.

Tue, 11/28/2017 - 13:45

Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta-analysis.

HLA. 2017 Nov 25;:

Authors: Courtwright A, Diamond JM, Wood I, Guleria I, Milford E, El-Chemaly S, Goldberg HJ

Abstract
There is significant variability in lung transplant centers' approach to HLA (human leukocyte antigen) antibodies, creating heterogeneity regarding their clinical significance. Some institutions use beads coated with multiple HLA to screen candidate sera and then use single antigen beads (SAB) to determine antibody identity if the pre-screen is positive. Other centers do not pre-screen, using SAB alone, which may detect low-level antibodies of unknown significance. The primary objective of this study was to review the current literature to identify sources of heterogeneity in the identification of pre- and post-lung transplant HLA antibodies, particularly regarding antibody detection methods. A random effects model meta-analysis was used to evaluate the relationship between pre-transplant HLA antibodies and the development of de novo donor specific antibodies (dnDSA) and dnDSA and chronic lung allograft dysfunction (CLAD). Each outcome was stratified by method of antibody detection (pre-screen followed by SAB versus SAB alone). We identified 13 cohort studies with a total of 3039 patients. The use of pre-screening followed by SAB testing and the use of induction immunosuppression were associated with lower prevalence of dnDSA. Patients with pre-transplant HLA antibodies were more likely to develop dnDSA (HR=1.49, 95% CI=1.19-1.86, p<0.001). dnDSA was associated with CLAD (HR=2.02, 95% CI=1.37-2.97, p<0.001). When considering studies using SAB alone, however, pre-transplant antibody status was no longer associated with dnDSA and dnDSA was no longer associated with CLAD. Based on the current literature, SAB alone testing may detect less clinically relevant antibodies than pre-screening followed by SAB.

PMID: 29178607 [PubMed - as supplied by publisher]

CD38 modulates respiratory syncytial virus-driven pro-inflammatory processes in human monocyte-derived dendritic cells.

Tue, 11/28/2017 - 13:45

CD38 modulates respiratory syncytial virus-driven pro-inflammatory processes in human monocyte-derived dendritic cells.

Immunology. 2017 Nov 27;:

Authors: Schiavoni I, Scagnolari C, Horenstein AL, Leone P, Pierangeli A, Malavasi F, Ausiello CM, Fedele G

Abstract
Respiratory Syncytial Virus (RSV) is the most common cause of hospitalization due to bronchiolitis in infants. Although the mechanisms behind this association are not completely elucidated, they appear to involve an excessive immune response causing lung pathology. Understanding the host response to RSV infection may help in the identification of targets for therapeutic intervention. We infected in vitro human monocyte-derived dendritic cells (DCs) with RSV and analysed various aspects of the cellular response. We found that RSV induces in DCs the expression of CD38, an ectoenzyme that catalyses the synthesis of cyclic ADPR (cADPR). Remarkably, CD38 was under the transcriptional control of RSV-induced type I interferon (IFN). CD38 and a set of IFN stimulated genes (ISGs) were inhibited by the antioxidant N-acetyl cysteine. When CD38-generated cADPR was restrained by 8-Br-cADPR or Kuromanin, a flavonoid known to inhibit CD38 enzymatic activity, RSV-induced type I / type III IFNs and ISGs were markedly reduced. Taken together these results suggest a key role of CD38 in the regulation of antiviral responses. Inhibition of CD38 enzymatic activity may represent an encouraging approach to reduce RSV-induced hyper-inflammation and a novel therapeutic option to treat bronchiolitis. This article is protected by copyright. All rights reserved.

PMID: 29178427 [PubMed - as supplied by publisher]

Review: The transcripts associated with organ allograft rejection.

Tue, 11/28/2017 - 13:45

Review: The transcripts associated with organ allograft rejection.

Am J Transplant. 2017 Nov 25;:

Authors: Halloran PF, Venner JM, Madill-Thomsen K, Einecke G, Parkes M, Hidalgo LG, Famulski KS

Abstract
The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (e.g. CXCL11; IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (e.g. KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (e.g. CTLA4, IFNG); activated (e.g. ADAMDEC1) or IFNG-induced macrophages (e.g. ANKRD22). ABMR-selective transcripts are expressed in NK cells (e.g. FGFBP2, GNLY) and endothelial cells (e.g. ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity. This article is protected by copyright. All rights reserved.

PMID: 29178397 [PubMed - as supplied by publisher]

Takotsubo Cardiomyopathy Following Induction of Anesthesia for Lung Transplantation, an Unexpected Complication.

Tue, 11/28/2017 - 13:45

Takotsubo Cardiomyopathy Following Induction of Anesthesia for Lung Transplantation, an Unexpected Complication.

J Cardiothorac Vasc Anesth. 2017 Oct 16;:

Authors: Duclos G, Mignon A, Zieleskiewicz L, Kelway C, Forel JM, Thuny F, Thomas PA, Leone M

PMID: 29174749 [PubMed - as supplied by publisher]

Impact of declining renal function on outcomes in pulmonary arterial hypertension: A REVEAL registry analysis.

Tue, 11/28/2017 - 13:45

Impact of declining renal function on outcomes in pulmonary arterial hypertension: A REVEAL registry analysis.

J Heart Lung Transplant. 2017 Nov 06;:

Authors: Chakinala MM, Coyne DW, Benza RL, Frost AE, McGoon MD, Hartline BK, Frantz RP, Selej M, Zhao C, Mink DR, Farber HW

Abstract
BACKGROUND: Renal dysfunction is associated with abnormal cardiopulmonary hemodynamics, in-hospital death and poor survival in patients with pulmonary arterial hypertension (PAH), and thus it may be a prognostic biomarker. In our analysis we assess the relationship between change in estimated glomerular filtration rate (eGFR) and outcomes in PAH patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL).
METHODS: Overall 2,368 patients were classified into chronic kidney disease (CKD) stages based on baseline eGFR: normal or Stages 1 or 2 (n = 1,699); Stage 3a (n = 399); Stage 3b (n = 196); and Stages 4 or 5 (n = 74). We evaluated the relationship between baseline CKD stage and survival, as well as the composite end-point of survival and freedom from all-cause hospitalization. The relationships between change in eGFR at ≥1 year and these clinical end-points were also evaluated.
RESULTS: Patients with a ≥10% decline in eGFR from baseline over ≥1 year had a significantly increased risk of death (hazard ratio 1.66; p < 0.0001) and the composite of all-cause hospitalization and death (hazard ratio 1.33; p = 0.002). This decline predicted survival independently of changes in 6-minute walk distance and functional class. However, a ≥10% increase in eGFR was not significantly associated with either end-point.
CONCLUSION: In REVEAL, a ≥10% decline in eGFR over ≥1 year independently predicted poorer survival. Thus, eGFR may be a simple and economical biomarker in PAH.

PMID: 29174533 [PubMed - as supplied by publisher]

Acute kidney injury and 1-year mortality after left ventricular assist device implantation.

Tue, 11/28/2017 - 13:45

Acute kidney injury and 1-year mortality after left ventricular assist device implantation.

J Heart Lung Transplant. 2017 Nov 06;:

Authors: Muslem R, Caliskan K, Akin S, Sharma K, Gilotra NA, Constantinescu AA, Houston B, Whitman G, Tedford RJ, Hesselink DA, Bogers AJJC, Russell SD, Manintveld OC

Abstract
BACKGROUND: Data on the consequences of acute kidney injury (AKI) after continuous-flow left ventricle assist device (LVAD) implantation are scarce and inconsistent. In this study, we evaluated the incidence, predictors and the impact of AKI on mortality and renal function in the first year after LVAD implantation.
METHODS: A retrospective, multicenter cohort study was conducted, including all patients (age ≥18 years) undergoing LVAD implantation (91% with a HeartMate II device and 9% with a HeartWare device). The definition proposed by the Kidney Disease Improving Global Outcome (KDIGO) criteria was used to define AKI.
RESULTS: Overall, 241 patients (mean age 52.4 ± 12.9 years, 76% males) were included in the study. AKI criteria were met in 169 (70%) patients, of whom 109 (45%) were in AKI Stage I, 22 (9%) in Stage II and 38 (16%) in Stage III. Two factors, the need for pre-operative inotropic support and pre-existent chronic kidney disease Stage ≤II (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2), were independently associated with the development of AKI and the severity of AKI stages. One-year mortality rates in patients without AKI and AKI Stages I, II and III were 18.7%, 26.4%, 23%, and 51%, respectively (log rank, p = 0.001). In the multivariable analysis, AKI Stage ≥II was independently associated with mortality (hazard ratio 2.2 [95% confidence interval 1.1 to 4.5], p = 0.027) and worse renal function (β = -7.4 [95% confidence interval -12.6 to -2.1], p < 0.01) at 1 year.
CONCLUSION: AKI is highly frequent after LVAD implantation. More severe AKI stages are associated with higher mortality rates and impaired renal function at 1 year after LVAD implantation.

PMID: 29174532 [PubMed - as supplied by publisher]

Outcomes of children supported with devices labeled as "temporary" or short term: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support.

Tue, 11/28/2017 - 13:45

Outcomes of children supported with devices labeled as "temporary" or short term: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support.

J Heart Lung Transplant. 2017 Oct 31;:

Authors: Lorts A, Eghtesady P, Mehegan M, Adachi I, Villa C, Davies R, Gossett JG, Kanter K, Alejos J, Koehl D, Cantor RS, Morales DLS

Abstract
BACKGROUND: Historically, the "temporary" or short-term ventricular assist device (VAD) was used only as a quick bridge to recovery for children with an acute process. In the current era, the devices that were originally used for temporary support are now being used to support children for longer durations and for a variety of indications. In this study we aimed to describe the overall use, patients' characteristics and outcomes of "temporary" VAD use in children.
METHODS: The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Institutes of Health-supported national registry for United States Food and Drug Administration-approved VADs in patients <19 years of age at the time of VAD implantation (either durable or temporary VAD). Patients undergoing placement of a device classified as a temporary VAD between September 19, 2012 and June 30, 2016 were included.
RESULTS: Temporary VADs were implanted in 63 patients at 20 centers, accounting for 19% of all pediatric VAD patients entered into PediMACS. The median age at implantation was 3.7 (range <1 day to 18) years. The underlying diseases were: congenital heart disease in 26 (41%), 20 of whom were classified as single ventricle; cardiomyopathy in 25 (40%); and myocarditis/rejection in 12 (19%). Patients were predominately Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1 (51%), and 10 patients (16%) had previously been supported with extracorporeal membrane oxygenation. Median duration of support was 15 (range <1 day to 227) days, with 41 patients (65%) being on support for ≥10 days. The most frequent adverse events were bleeding (29% of patients) and neurologic dysfunction (24% of patients). Overall, 71% (45) achieved a positive outcome (defined as bridge to recovery [30%], transplantation [17%], alive on device [2%] or transition to durable VAD [22%]). Eighty-eight percent (n = 22) of the cardiomyopathy patients and 60% (n = 12) of the single-ventricle patients achieved a favorable outcome.
CONCLUSION: Devices historically classified as "temporary" pumps are being used not only as a short-term mechanical circulatory support strategy but also as a longer term support strategy. In this multi-institutional, high-acuity, complex patient cohort, the use of "temporary" VADs resulted in a positive outcome (bridge to transplant, recovery durable device or alive) in 71% of patients.

PMID: 29174220 [PubMed - as supplied by publisher]

Intraoperative Anesthetic Management of Lung Transplantation: Center-Specific Practices and Geographic and Centers Size Differences.

Tue, 11/28/2017 - 13:45

Intraoperative Anesthetic Management of Lung Transplantation: Center-Specific Practices and Geographic and Centers Size Differences.

J Cardiothorac Vasc Anesth. 2017 May 17;:

Authors: Tomasi R, Betz D, Schlager S, Kammerer T, Hoechter DJ, Weig T, Slinger P, Klotz LV, Zwißler B, Marczin N, von Dossow V

Abstract
OBJECTIVE: Although increasing evidence in lung transplantation (LTx) suggests that intraoperative management could influence outcomes, there are no guidelines available regarding intraoperative management of LTx. The overall goal of the study was to assess geographic and center volume-specific clinical practices in perioperative management.
DESIGN: Prospective data analysis.
SETTING: Online survey from a single-center university hospital.
PARTICIPANTS: European and non-European LTx centers.
INTERVENTIONS: An online survey was sent to 176 centers currently performing LTx procedures. It covered organizational data, general anesthesia considerations, fluid therapy and coagulation, antioxidant and anti-inflammatory therapies, and ventilation strategies.
MEASUREMENTS AND MAIN RESULTS: The response rates were 57.5% (n = 42) from European and 32% (n = 33) from non-European countries. Significant differences between European and non-European countries were use of volatile hypnotics (p = 0.016), use of sufentanil (p < 0.001), inotropic agents (p = 0.001) and colloid infusion (p < 0.001), use of calibrated pulse contour analysis (p = 0.004), use of intraoperative traditional laboratory-based coagulation tests (p = 0.001) and platelet function analysis (p = 0.005), and use of higher peak inspiratory pressure (p = 0.009). Center volume-specific differences were use of fentanyl (p = 0.03) and the use of higher peak inspiratory pressure (p = 0.005) for ventilation. Induction of anesthesia and use of advanced hemodynamic monitoring, therapy for pulmonary hypertension, antioxidant and anti-inflammatory therapies, and ventilation strategies were not different among the centers.
CONCLUSIONS: This survey demonstrated for the first time statistically significant differences among European and non-European centers and among low- versus high-volume centers regarding intraoperative management during LTx. These observations will be of some guidance for the LTx community and may trigger more extensive studies.

PMID: 29174123 [PubMed - as supplied by publisher]

Challenges, diligence, and a breakthrough in donation after circulatory death in heart transplantation.

Tue, 11/28/2017 - 13:45

Challenges, diligence, and a breakthrough in donation after circulatory death in heart transplantation.

J Heart Lung Transplant. 2017 Dec;36(12):1319-1321

Authors: Mehra MR

PMID: 29173395 [PubMed - in process]

Outcome after heart transplantation from donation after circulatory-determined death donors.

Tue, 11/28/2017 - 13:45

Outcome after heart transplantation from donation after circulatory-determined death donors.

J Heart Lung Transplant. 2017 Dec;36(12):1311-1318

Authors: Messer S, Page A, Axell R, Berman M, Hernández-Sánchez J, Colah S, Parizkova B, Valchanov K, Dunning J, Pavlushkov E, Balasubramanian SK, Parameshwar J, Omar YA, Goddard M, Pettit S, Lewis C, Kydd A, Jenkins D, Watson CJ, Sudarshan C, Catarino P, Findlay M, Ali A, Tsui S, Large SR

Abstract
BACKGROUND: The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants.
METHODS: DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation, whereas DPP hearts were removed directly. All hearts were maintained on machine perfusion during transportation. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics, was used as a comparison group. The primary outcome measure of this study (set by the United Kingdom regulatory body) was 90-day survival.
RESULTS: There were 28 DCD heart transplants performed during the 25-month study period. Survival at 90 days was not significantly different between DCD and matched DBD transplant recipients (DCD, 92%; DBD, 96%; p = 1.0). Hospital length of stay, treated rejection episodes, allograft function, and 1-year survival (DCD, 86%; DBD, 88%; p = 0.98) were comparable between groups. The method of retrieval (NRP or DPP) was not associated with a difference in outcome.
CONCLUSIONS: These results suggest that heart transplantation from DCD heart donation provides comparable short-term outcomes to traditional DBD heart transplants and can serve to increase heart transplant activity in well-selected patients.

PMID: 29173394 [PubMed - in process]

The life and the legacy of Hamilton Naki: Experimental heart transplant surgeon and teacher.

Tue, 11/28/2017 - 13:45

The life and the legacy of Hamilton Naki: Experimental heart transplant surgeon and teacher.

J Heart Lung Transplant. 2017 Dec;36(12):1309-1310

Authors: Zühlke L, Mayosi BM

PMID: 29173393 [PubMed - in process]

The role of nurses in understanding and enhancing quality of life: A journey from advanced heart failure to heart transplantation.

Tue, 11/28/2017 - 13:45

The role of nurses in understanding and enhancing quality of life: A journey from advanced heart failure to heart transplantation.

J Heart Lung Transplant. 2017 Dec;36(12):1306-1308

Authors: Grady KL

PMID: 29173392 [PubMed - in process]

Advances in the immunology of heart transplantation.

Tue, 11/28/2017 - 13:45

Advances in the immunology of heart transplantation.

J Heart Lung Transplant. 2017 Dec;36(12):1299-1305

Authors: Madsen JC

PMID: 29173391 [PubMed - in process]

Insurance coverage of heart transplantation in the United States: The dilemma, the debate and the definitive decision that ultimately determined the future of transplantation.

Tue, 11/28/2017 - 13:45

Insurance coverage of heart transplantation in the United States: The dilemma, the debate and the definitive decision that ultimately determined the future of transplantation.

J Heart Lung Transplant. 2017 Dec;36(12):1294-1298

Authors: Evans RW

PMID: 29173390 [PubMed - in process]

The scourge and enigmatic journey of cardiac allograft vasculopathy.

Tue, 11/28/2017 - 13:45

The scourge and enigmatic journey of cardiac allograft vasculopathy.

J Heart Lung Transplant. 2017 Dec;36(12):1291-1293

Authors: Mehra MR

PMID: 29173389 [PubMed - in process]

Clinical trials in heart transplantation: The evolution of evidence in immunosuppression.

Tue, 11/28/2017 - 13:45

Clinical trials in heart transplantation: The evolution of evidence in immunosuppression.

J Heart Lung Transplant. 2017 Dec;36(12):1286-1290

Authors: Kobashigawa J

PMID: 29173388 [PubMed - in process]

Evolutionary perspective of mechanical circulatory support as a bridge to heart transplantation.

Tue, 11/28/2017 - 13:45

Evolutionary perspective of mechanical circulatory support as a bridge to heart transplantation.

J Heart Lung Transplant. 2017 Dec;36(12):1283-1285

Authors: Frazier OH

PMID: 29173387 [PubMed - in process]

The dark early years of heart transplantation: Some lessons learned.

Tue, 11/28/2017 - 13:45

The dark early years of heart transplantation: Some lessons learned.

J Heart Lung Transplant. 2017 Dec;36(12):1279-1282

Authors: English ST

PMID: 29173386 [PubMed - in process]

Conquering the first hurdles in cardiac transplantation: In the footprints of giants.

Tue, 11/28/2017 - 13:45

Conquering the first hurdles in cardiac transplantation: In the footprints of giants.

J Heart Lung Transplant. 2017 Dec;36(12):1276-1278

Authors: Hess ML, Hunt S

PMID: 29173385 [PubMed - in process]

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