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The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma.

Fri, 09/29/2017 - 12:45
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The effect of immune checkpoint inhibitors on lung metastases of osteosarcoma.

J Pediatr Surg. 2017 Sep 04;:

Authors: Shimizu T, Fuchimoto Y, Fukuda K, Okita H, Kitagawa Y, Kuroda T

Abstract
BACKGROUND/PURPOSE: The prognosis of patients with metastases remains unsatisfactory in certain pediatric solid tumors. In this study, we evaluated the efficacy of immune checkpoint inhibitors against such metastases using a murine model of osteosarcoma.
METHODS: Murine osteosarcoma LM8 cells were transplanted subcutaneously into C3H mice. The primary tumor lesion was surgically resected 11 days after transplantation. Two hundred micrograms of three antibodies (anti-PD-1, anti-PD-L1, and anti-OX-86) or an isotype antibody were administered intraperitoneally on post-transplantation days 11, 14, 18, and 21. Survival curves were plotted by the Kaplan-Meier method and compared with the log-rank test. Computed tomography (CT) scans were performed on day 11 after tumor transplantation (pre-therapy) and on day 25 (post-therapy). For pathology, 3 mice from each group were euthanized on days 11, 22, and 33 after tumor transplantation.
RESULTS: The antibody-treated group had a significantly longer survival time compared with the control group (p = 0.002). Both the CT scan and pathological results revealed suppression of metastatic tumor proliferation in the treatment group as compared with the control group.
CONCLUSIONS: These results suggest that immune checkpoint inhibitors may be an innovative therapy for lung metastases of advanced pediatric solid tumors.

PMID: 28954696 [PubMed - as supplied by publisher]

Improving organ donation rates and transplantation in Australia.

Fri, 09/29/2017 - 12:45
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Improving organ donation rates and transplantation in Australia.

Med J Aust. 2017 Sep 02;207(7):287-288

Authors: Allen RD, Pleass HC

PMID: 28954614 [PubMed - in process]

Untapped potential in Australian hospitals for organ donation after circulatory death.

Fri, 09/29/2017 - 12:45
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Untapped potential in Australian hospitals for organ donation after circulatory death.

Med J Aust. 2017 Sep 02;207(7):294-301

Authors: Rakhra SS, Opdam HI, Gladkis L, Arcia B, Fink MA, Kanellis J, Macdonald PS, Snell GI, Pilcher DV

Abstract
OBJECTIVE: To determine the potential for organ donation after circulatory death (DCD) in Australia by applying ideal and expanded organ suitability criteria, and to compare this potential with actual DCD rates.
DESIGN: Retrospective cohort study. Setting, methods: We analysed DonateLife audit data for patients aged 28 days to 80 years who died between July 2012 and December 2014 in an intensive care unit or emergency department, or who died within 24 hours of discharge from either, in the 75 Australian hospitals contributing data to DonateLife. Ideal and expanded organ donation criteria were derived from international and national guidelines, and from expert opinion. Potential DCD organ donors were identified by applying these criteria to patients who had been intubated and were neither confirmed as being brain-dead nor likely to have met brain death criteria at the official time of death.
RESULTS: 8780 eligible patients were identified, of whom 202 were actual DCD donors. For 193 potential ideal (61%) and 313 potential expanded criteria DCD donors (72%), organ donation had not been discussed with their families; most were potential donors of kidneys (416 potential donors) or lungs (117 potential donors). Potential donors were typically older, dying of non-neurological causes, and more frequently had chronic organ disease than actual donors. Identifying all these potential donors, assuming a consent rate of 60%, would have increased Australia's donation rate from 16.1 to 21.3 per million population in 2014.
CONCLUSIONS: The untapped potential for DCD in Australia, particularly of kidneys and lungs, is significant. Systematic review of all patients undergoing end-of-life care in critical care environments for donor suitability could result in significant increases in organ donation rates.

PMID: 28954604 [PubMed - in process]

MicroRNA-200c inhibits epithelial-mesenchymal transition, invasion, and migration of lung cancer by targeting HMGB1.

Fri, 09/29/2017 - 12:45
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MicroRNA-200c inhibits epithelial-mesenchymal transition, invasion, and migration of lung cancer by targeting HMGB1.

PLoS One. 2017;12(7):e0180844

Authors: Liu PL, Liu WL, Chang JM, Chen YH, Liu YP, Kuo HF, Hsieh CC, Ding YS, Chen WW, Chong IW

Abstract
MicroRNAs (miRs) play critical roles in cancer development, proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration through regulating the expression of oncogenes and tumour suppressor genes. Previous studies have indicated that miR-200c acts as a tumour suppressor in various cancers by downregulating high-mobility group box 1 (HMGB1) and thereby suppressing EMT and metastasis. In addition, miR-200c was reported to be downregulated and correlated with poor outcomes in non-small cell lung cancer (NSCLC). However, its functional role in HMGB1 regulation in NSCLC is still unclear. This study aimed to clarify whether miR-200c acts as a tumour suppressor in NSCLC by downregulating HMGB1, which is associated with EMT, invasion, cytoskeleton rearrangement, and migration in vitro and in vivo. In order to demonstrate HMGB1 downregulation by miR-200c, the NSCLC cell line A549 was transfected with miR-200c mimic or inhibitor. The mimic significantly reduced HMGB1 expression and suppressed EMT, invasion, and migration, while the inhibitor generated the opposite effects. Additionally, using xenograft mouse models, we confirmed that HMGB1 overexpression increased tumour EMT. In summary, our results demonstrated that miR-200c could suppress EMT, invasion, and migration of NSCLC cells by downregulating HMGB1.

PMID: 28727734 [PubMed - indexed for MEDLINE]

Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity.

Fri, 09/29/2017 - 12:45
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Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity.

Cancer Res. 2017 Jul 01;77(13):3632-3643

Authors: Seth P, Csizmadia E, Hedblom A, Vuerich M, Xie H, Li M, Longhi MS, Wegiel B

Abstract
Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86(high) and MCP-1(high) M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis, diminished numbers of PD-L1(+) cancer cells, increased numbers of CD3(+) T cells, and activation status of CD8(+) T cells. Furthermore, it was associated with more pronounced antitumor T-cell immunity via induction of IL17 and IFNγ-producing CD8(+) T (Tc17 and Tc1) cells, likely via suppression of lactate-driven PD-L1 expression. Our results suggest that expressions of LDH-A and lactate by macrophage in the tumor microenvironment are major drivers of T-cell immunosuppression, strongly supporting the concept of targeting stromal LDH-A as an effective strategy to blunt tumoral immune escape. Cancer Res; 77(13); 3632-43. ©2017 AACR.

PMID: 28446465 [PubMed - indexed for MEDLINE]

The donor advocacy team: a risk management program for living organ, tissue, and cell transplant donors.

Fri, 09/29/2017 - 12:45
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The donor advocacy team: a risk management program for living organ, tissue, and cell transplant donors.

Surg Today. 2017 Aug;47(8):980-985

Authors: Eguchi S, Soyama A, Nagai K, Miyazaki Y, Kurihara S, Hidaka M, Ono S, Adachi T, Natsuda K, Hara T, Fujita F, Kanetaka K, Takatsuki M

Abstract
BACKGROUND AND PURPOSE: Although the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program.
METHODS AND RESULTS: We describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor.
DISCUSSION: The purposes of the DAT program are as follows: 1. To disclose official information without delay. 2. To provide physical and psychological care to the patient experiencing impairment and their family. 3. To provide psychological care to the medical staff in charge of the transplant. 4. To standardize the responses of the diagnosis and treatment department staff and other hospital staff. 5. To minimize the damage that the whole medical transplantation system may suffer and leverage the occurrence for improvement. To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

PMID: 28205018 [PubMed - indexed for MEDLINE]

Mechanical Circulatory Support as a Bridge to Lung Transplantation: A Single Canadian Institution Review.

Thu, 09/28/2017 - 12:45
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Mechanical Circulatory Support as a Bridge to Lung Transplantation: A Single Canadian Institution Review.

Can Respir J. 2017;2017:5947978

Authors: Kinaschuk K, Bozso SJ, Halloran K, Kapasi A, Jackson K, Nagendran J

Abstract
BACKGROUND: Lung transplant (LTx) waitlists continue to grow internationally. Consequently, more patients are progressing to require mechanical circulatory support (MCS) as a bridge to transplantation (BTT). MCS strategies include interventional lung assist (iLA) and venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO). We review our series of patients bridged with MCS while listed for LTx.
METHODS: All consecutive patients, listed for LTx requiring MCS as a BTT at the University of Alberta from 2004 to 2015, were included. Patient demographics and outcomes were compared for the 3 groups (iLA, VV-ECMO, and VA-ECMO).
RESULTS: Of the 24 patients supported with MCS devices, 17 were successfully transplanted and 7 died waiting. In total, 25% (n = 6) were bridged with VA-ECMO, 54% (n = 13) with VV-ECMO, and 21% (n = 5) with iLA. Overall, 71% of patients were bridged successfully to LTx. The 1-year survival posttransplantation was 88%.
CONCLUSION: We have demonstrated the feasibility of utilizing the MCS modalities of VA-ECMO, VV-ECMO, and most recently iLA, as a BTT. MCS is a viable strategy for BTT, offering improved survival outcomes for decompensating adult patients awaiting LTx, resulting in excellent survival posttransplantation.

PMID: 28951661 [PubMed - in process]

Transplantation of HGF modified Dental Pulp Stem Cells Prevents Bone Loss in the Early Phase of Ovariectomy-induced Osteoporosis.

Thu, 09/28/2017 - 12:45
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Transplantation of HGF modified Dental Pulp Stem Cells Prevents Bone Loss in the Early Phase of Ovariectomy-induced Osteoporosis.

Hum Gene Ther. 2017 Sep 26;:

Authors: Kong F, Shi X, Xiao F, Yang Y, Zhang X, Wang LS, Wu CT, Wang H

Abstract
Investigations based on mesenchymal stem cells (MSCs) for osteoporosis have been obtained intensive attention recently. MSCs can derive from various tissues, such as bone marrow, adipose, umbilical cord, placenta, dental pulp, etc. Among them, dental pulp derived MSCs (DPSCs) and hepatocyte growth factor (HGF)-modified DPSCs (DPSCs-HGF) highly expressed osteogenic related genes and have stronger osteogenic differentiation capacities. DPSCs have more benefits in treating osteoporosis. The purpose of this study is to investigate the roles of HGF gene modified DPSCs in bone regeneration using a mouse model of ovariectomy (OVX)-induced bone loss. In this study, we transferred the HGF and luciferase gene into human DPSCs respectively by using recombinant adenovirus. These transduced cells were assayed for distribution or bone regeneration assay by transplantation into an OVX-induced osteoporosis model. By using bioluminogenic imaging, we determined that some DPSCs could survive for over one month in vivo. The DPSCs were mainly distributed to lung in early stage and to liver in late stage after administration and scarcely to the bone. The homing efficiency of DPSCs is higher when administrated in the early stage of mouse OVX model. The μCT analysis indicated that DPSCs-Null or DPSCs-HGF transplantation significantly reduces the OVX induced bone loss in the trabecular bone of the distal femur metaphysis, and DPSCs-HGF show stronger capacity in relieving the bone loss. Our data suggested that systemic infusion of DPSCs-HGF is a potential therapeutic approach for OVX-induced bone loss, which might be mediated by paracrine mechanisms.

PMID: 28950723 [PubMed - as supplied by publisher]

Bone marrow stem cells modified with human interleukin 10 attenuate acute rejection in rat lung allotransplantation.

Thu, 09/28/2017 - 12:45
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Bone marrow stem cells modified with human interleukin 10 attenuate acute rejection in rat lung allotransplantation.

Eur J Cardiothorac Surg. 2017 Jul 25;:

Authors: Pieróg J, Tamo L, Fakin R, Kocher G, Gugger M, Grodzki T, Geiser T, Gazdhar A, Schmid RA

Abstract
OBJECTIVES: The aim of this study was to investigate new therapeutic options to attenuate acute rejection in a rat lung allograft model. Cell-based gene therapies have recently been reported as a novel curative option in acute and chronic diseases for which conventional treatments are not available. We studied the effect of human interleukin 10 (hIL-10) on expressing bone marrow-derived mesenchymal stem cells (BMSCs) in combination with cyclosporine A (CsA) on acute rejection of lung allografts in the rat.
METHODS: Lung allotransplantation was performed from male Brown Norway donor to male Fisher (F344) rats. Rat BMSCs were transfected with hIL-10 in vitro and introduced in the graft prior to implantation. Group A ( n  = 5) received CsA intraperitoneally (2.5 mg/kg body weight) for 5 days post-transplant; Group B ( n  = 5) received BMSC and CsA and Group C ( n  = 5) received hIL-10-BMSC before implantation and CsA. Graft function was assessed by blood gas levels only from the graft on day 5; tissue was sampled for histological grading of rejection and measurement of the wet-to-dry ratio.
RESULTS: All Group A control animals showed severe signs of rejection. On Day 5, all grafts in Group C showed improved gas exchange (mean arterial partial pressure of oxygen 222.2 ± 40.38 mmHg vs 92.36 ± 20.92 mmHg in Group B and 42.72 ± 18.07 mmHg in Group A). Histological examination revealed moderate-to-severe rejection in all animals in Group A [International Society for Heart and Lung Transplantation Level III B (ISHLT)] in contrast to low-to-moderate rejection in Group B (II-IIIA) and much improved histological grade in Group C (I-IIA). Moreover, the wet-to-dry ratio was also reduced in Group C (4.8 ± 1.19 compared with 4.78 ± 0.62 in Group B and 9.36 ± 0.90 in Group A).
CONCLUSIONS: The hIL-10 BMSC represent a promising novel method for localized cell-based gene therapy for acute rejection in a rat lung allograft model.

PMID: 28950337 [PubMed - as supplied by publisher]

Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

Thu, 09/28/2017 - 12:45
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Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

Eur J Cardiothorac Surg. 2017 Jul 27;:

Authors: Moser B, Jaksch P, Taghavi S, Muraközy G, Lang G, Hager H, Krenn C, Roth G, Faybik P, Bacher A, Aigner C, Matilla JR, Hoetzenecker K, Hacker P, Lang I, Klepetko W

Abstract
OBJECTIVES: Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept.
METHODS: All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed.
RESULTS: Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P  = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population.
CONCLUSIONS: Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides stable postoperative conditions and seems to further improve the results.

PMID: 28950326 [PubMed - as supplied by publisher]

Repeated Resections of Hepatic and Pulmonary Metastases from Colorectal Cancer Provide Long-Term Survival.

Thu, 09/28/2017 - 12:45
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Repeated Resections of Hepatic and Pulmonary Metastases from Colorectal Cancer Provide Long-Term Survival.

World J Surg. 2017 Sep 25;:

Authors: Bellier J, De Wolf J, Hebbar M, Amrani ME, Desauw C, Leteurtre E, Pruvot FR, Porte H, Truant S

Abstract
BACKGROUND: Liver and lungs are the two most frequent sites of metastatic spread of colorectal cancer (CRC). Complete resection of liver and/or lung metastases is the only chance of cure, and several studies have reported an improved survival after an aggressive treatment. Nevertheless, CRC liver metastases (CLM) have been recognized as a pejorative factor for patients undergoing pulmonary metastasectomy. We report our experience with patients successively operated on for CRC hepatic and pulmonary metastasis (CPM) and seek to identify prognostic factors.
METHODS: All consecutive patients who had resection of CPM and CLM between 2001 and 2014 were enrolled in the study. Clinicopathological and survival data were retrospectively analysed.
RESULTS: Forty-six patients underwent resections of both CLM and CPM. Hepatic resection preceded pulmonary resection in most cases (91.3%). The median intervals between the resection of the primary tumour and the hepatic recurrence and between hepatic and pulmonary recurrences were 12 months [0-72] and 21.5 months [1-84], respectively. The mortality rate following CPM resection was 4.3%. After a median follow-up of 41.5 months [0-126], 35 patients recurred of whom 14 (40%) and 11(31.4%) could benefit from repeated resection of recurrent CLM and CPM, respectively. The median and 5-year overall survivals (OS) were 53 months and 49%, respectively. No prognostic factor was identified.
CONCLUSION: An aggressive management of CLM and CPM, including repeated resections, may provide a long-term survival comparable to survival of patients with unique metastasectomy. The absence of prognostic factor may reflect the highly selected pattern of the eligible patients.

PMID: 28948336 [PubMed - as supplied by publisher]

Contemporary Issues in Lung Transplant Allocation Practices.

Thu, 09/28/2017 - 12:45
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Contemporary Issues in Lung Transplant Allocation Practices.

Curr Transplant Rep. 2017 Sep;4(3):238-242

Authors: Tsuang WM

Abstract
PURPOSE OF REVIEW: To discuss the current state of donor lung allocation in the United States, and future opportunities to increase the efficiency of donor lung allocation.
RECENT FINDINGS: The current donor lung allocation system prioritizes clinical acuity by use of the Lung Allocation Score (LAS) which has reduced waitlist mortality since its implementation in 2005. Access to donor lungs can be further improved through policy changes using broader geographic sharing, and developing new technology such as ex vivo lung perfusion to recover marginal donor lungs.
SUMMARY: The number of lung transplants in the U.S. continues to increase annually. However, the demand for donor lungs continues to be outpaced by an ever growing waitlist. Efficient allocation can be achieved through improved allocation policies and new technology.

PMID: 28948134 [PubMed]

Persistent Unexplained Dyspnea: A Case of Hepatopulmonary Syndrome.

Thu, 09/28/2017 - 12:45
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Persistent Unexplained Dyspnea: A Case of Hepatopulmonary Syndrome.

Case Rep Cardiol. 2017;2017:1469893

Authors: Campanile A, Colombo A, Del Pinto M, Cavallini C

Abstract
Regarding a patient with dyspnea, the history and physical examination often lead to the correct diagnosis. In some circumstances, when more than one underlying disease is present, the diagnostic process can be more challenging. We describe an unusual case of dyspnea and persistent hypoxemia related to a hepatopulmonary syndrome in a 53-year-old patient with known heart failure and chronic liver disease. Initially managed with intravenous diuretic therapy, due to signs of lung and peripheral congestion, our patient did not improve as expected; therefore we performed more advanced studies with a chest-abdomen CT scan and a right heart catheterization. They showed, respectively, no signs of parenchymal and vasculature lung disease, a cirrhotic liver disease, splenomegaly, signs of portal hypertension, and high cardiac output with normal pulmonary vascular resistance. These results, along with the association of hypoxemia and chronic liver disease, suggested a hepatopulmonary syndrome. The diagnosis was confirmed by the demonstration of an intrapulmonary vascular dilatation with right to left shunt during a microbubble transthoracic echocardiography and a lung perfusion scan. Liver transplantation is the only successful treatment for this syndrome; however, the patient became soon unsuitable for this strategy, due to a rapid clinical deterioration.

PMID: 28948051 [PubMed]

Effect of organ donation after circulatory determination of death on number of organ transplants from donors with neurologic determination of death.

Thu, 09/28/2017 - 12:45
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Effect of organ donation after circulatory determination of death on number of organ transplants from donors with neurologic determination of death.

CMAJ. 2017 Sep 25;189(38):E1206-E1211

Authors: Rao V, Dhanani S, MacLean J, Payne C, Paltser E, Humar A, Zaltzman J

Abstract
BACKGROUND: To increase the available pool of organ donors, Ontario introduced donation after circulatory determination of death (DCD) in 2006. Other jurisdictions have reported a decrease in donations involving neurologic determination of death (NDD) after implementation of DCD, with a drop in organ yield and quality. In this study, we examined the effect of DCD on overall transplant activity in Ontario.
METHODS: We examined deceased donor and organ transplant activity during 3 distinct 4-year eras: pre-DCD (2002/03 to 2005/06), early DCD (2006/07 to 2009/10) and recent DCD (2010/11 to 2013/14). We compared these donor groups by categorical characteristics.
RESULTS: Donation increased by 57%, from 578 donors in the pre-DCD era to 905 donors in the recent DCD era, with a 21% proportion (190/905) of DCD donors in the recent DCD era. However, overall NDD donation also increased. The mean length of hospital stay before declaration for NDD was 2.7 days versus 6.0 days before withdrawal of life support and subsequent asystole in cases of DCD. The average organ yield was 3.73 with NDD donation versus 2.58 with DCD (p < 0.001). Apart from hearts, all organs from DCD donors were successfully transplanted. From the pre-DCD era to the recent DCD era, transplant activity in each era increased for all solid-organ recipients, including heart (from 158 to 216), kidney (from 821 to 1321), liver (from 477 to 657) and lung (from 160 to 305).
INTERPRETATION: Implementation of DCD in Ontario led to increased transplant activity for all solid-organ recipients. There was no evidence that the use of DCD was pre-empting potential NDD donation. In contrast to groups receiving other organs, heart transplant candidates have not yet benefited from DCD.

PMID: 28947546 [PubMed - in process]

Interaction of pre-transplant recipient characteristics and renal function in lung transplant survival.

Thu, 09/28/2017 - 12:45
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Interaction of pre-transplant recipient characteristics and renal function in lung transplant survival.

J Heart Lung Transplant. 2017 Aug 12;:

Authors: Banga A, Mohanka M, Mullins J, Bollineni S, Kaza V, Torres F, Tanriover B

Abstract
BACKGROUND: There has been little investigation into the potential interaction of recipient characteristics with the association of pre-transplant renal functions and survival after lung transplantation. In this study we tested the hypothesis that association of pre-transplant renal function and post-transplant mortality varies among recipient subgroups.
METHODS: We queried the United Network for Organ Sharing (UNOS) database for adult patients (≥18 years of age) undergoing lung transplantation between May 2005 and March 2015. The study population (n = 15,540) was split into 3 groups (90 to 150, 60 to 89.9 and 30 to 59.9 ml/min/1.73 m(2)) based on the estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) at the time of listing. We utilized multivariable inverse probability weighted Cox proportional hazard models to compare the association of glomerular filtration rate (GFR) groups with mortality among recipient subgroups.
RESULTS: Overall, there was an independent and graded inverse association between the estimated GFR (eGFR) and mortality, with the hazard of mortality significantly rising with listing eGFR <60 ml/min/1.73 m(2). The association between low eGFR and mortality was more consistent and stronger for older (>45 years), non-African-American and non-diabetic patients as well as those with low lung allocation score (LAS <40). Among the diagnosis groups, patients with vascular diseases had the strongest association between low eGFR and poor survival. Sensitivity analyses conducted using an alternate equation to estimate the GFR (Modification of Diet in Renal Disease) supported these associations.
CONCLUSIONS: Prognostic significance of pre-transplant renal functions varies significantly among recipient subgroups. It may be appropriate to develop a customized approach toward assessing and interpreting renal function to determine transplant candidacy.

PMID: 28947250 [PubMed - as supplied by publisher]

Lungs from older donors may provide a breath of fresh air to patients awaiting lung transplant.

Thu, 09/28/2017 - 12:45
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Lungs from older donors may provide a breath of fresh air to patients awaiting lung transplant.

J Thorac Cardiovasc Surg. 2017 Sep 04;:

Authors: Bermudez CA, Crespo MM

PMID: 28947190 [PubMed - as supplied by publisher]

Management of combined pre- and post-capillary pulmonary hypertension in advanced heart failure with reduced ejection fraction.

Thu, 09/28/2017 - 12:45
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Management of combined pre- and post-capillary pulmonary hypertension in advanced heart failure with reduced ejection fraction.

Respir Med. 2017 Oct;131:94-100

Authors: Sahay S, Khirfan G, Tonelli AR

Abstract
Management of pulmonary hypertension (PH) has remained an unmet need in advanced left heart failure with reduced ejection fraction. In fact, patients are frequently denied heart transplant due to untreated pulmonary hypertension. The availability of mechanically circulatory devices and PH therapies has provided a ray of hope. PH specific therapies are currently not FDA approved for patients with left heart failure with reduced ejection fraction. However, clinicians have used these medications in anecdotal manner. With this review, we want to highlight the expanding use of PH specific therapy and mechanical circulatory devices in the management of PH in the setting of advanced heart failure with reduced ejection fraction.

PMID: 28947049 [PubMed - in process]

Frailty and maximal exercise capacity in adult lung transplant candidates.

Thu, 09/28/2017 - 12:45
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Frailty and maximal exercise capacity in adult lung transplant candidates.

Respir Med. 2017 Oct;131:70-76

Authors: Layton AM, Armstrong HF, Baldwin MR, Podolanczuk AJ, Pieszchata NM, Singer JP, Arcasoy SM, Meza KS, D'Ovidio F, Lederer DJ

Abstract
BACKGROUND: Frail lung transplant candidates are more likely to be delisted or die without receiving a transplant. Further knowledge of what frailty represents in this population will assist in developing interventions to prevent frailty from developing. We set out to determine whether frail lung transplant candidates have reduced exercise capacity independent of disease severity and diagnosis.
METHODS: Sixty-eight adult lung transplant candidates underwent cardiopulmonary exercise testing (CPET) and a frailty assessment (Fried's Frailty Phenotype (FFP)). Primary outcomes were peak workload and peak aerobic capacity (V˙O2). We used linear regression to adjust for age, gender, diagnosis, and lung allocation score (LAS).
RESULTS: The mean ± SD age was 57 ± 11 years, 51% were women, 57% had interstitial lung disease, 32% had chronic obstructive pulmonary disease, 11% had cystic fibrosis, and the mean LAS was 40.2 (range 19.2-94.5). In adjusted models, peak workload decreased by 10 W (95% CI 4.7 to 14.6) and peak V˙O2 decreased by 1.8 mL/kg/min (95% CI 0.6 to 2.9) per 1 unit increment in FFP score. After adjustment, exercise tolerance was 38 W lower (95% CI 18.4 to 58.1) and peak V˙O2 was 8.5 mL/kg/min lower (95% CI 3.3 to 13.7) among frail participants compared to non-frail participants. Frailty accounted for 16% of the variance (R(2)) of watts and 19% of the variance of V˙O2 in adjusted models.
CONCLUSION: Frailty contributes to reduced exercise capacity among lung transplant candidates independent of disease severity.

PMID: 28947046 [PubMed - in process]

Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.

Thu, 09/28/2017 - 12:45
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Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.

Respir Med. 2017 Oct;131:229-235

Authors: Salisbury ML, Tolle LB, Xia M, Murray S, Tayob N, Nambiar AM, Schmidt SL, Lagstein A, Myers JL, Gross BH, Kazerooni EA, Sundaram B, Chughtai AR, Martinez FJ, Flaherty KR

Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF.
METHODS: Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival.
RESULTS: IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p = 0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR = 0.42, CI 95% 0.23-0.78, p = 0.006).
CONCLUSIONS: Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates.

PMID: 28947036 [PubMed - in process]

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

Thu, 09/28/2017 - 12:45
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Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

Respir Med. 2017 Oct;131:215-219

Authors: Ogawa A, Miyaji K, Matsubara H

Abstract
BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are categorized as Group 1' in the clinical classification of pulmonary hypertension. No medical therapy has been proven to be effective in patients with PVOD/PCH. Imatinib is a molecular targeted drug and was expected to be effective in patients with pulmonary arterial hypertension. We evaluated its efficacy and safety in patients with PVOD/PCH.
METHODS: In the present observational study, 9 patients with PVOD/PCH received imatinib. Clinical data including exercise capacity and hemodynamics at baseline and at follow-up were compared. Survival rate of patients treated with imatinib was compared to those of 7 patients who did not treated with imatinib.
RESULTS: Imatinib was prescribed at doses of 100-400 mg/day and was well-tolerated. At follow-up, World Health Organization functional class and brain natriuretic peptide levels significantly improved. Mean pulmonary arterial pressure was significantly reduced (from 56.8 ± 8.3 to 43.7 ± 9.0 mmHg) with preserved cardiac index. Patients were treated with imatinib for 797.2 ± 487.0 days. Seven patients (77.8%) died and 2 patients (22.2%) underwent lung transplantation. Mean survival time in patients treated with imatinib therapy was 1493.7 ± 196.3 days (95% confidence interval, 1108.9-1878.5 days), significantly longer than those without imatinib treatment (713.0 ± 258.1 days, log-rank test, P = 0.04).
CONCLUSIONS: Imatinib improved exercise capacity, hemodynamics and survival in patients with PVOD/PCH. In patients with PVOD/PCH, who have no effective medical therapy available, imatinib might function as a bridge to lung transplantation, and may become a potential therapeutic option to improve their survival.

PMID: 28947033 [PubMed - in process]

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