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Acute interstitial pneumonitis requiring extracorporeal membrane oxygenation and lung transplantation in an adolescent patient.

Mon, 10/02/2017 - 12:45

Acute interstitial pneumonitis requiring extracorporeal membrane oxygenation and lung transplantation in an adolescent patient.

J Thorac Cardiovasc Surg. 2017 Aug 24;:

Authors: Spratt JR, Racila E, Shumway SJ

PMID: 28964491 [PubMed - as supplied by publisher]

Pediatric lung transplantation.

Mon, 10/02/2017 - 12:45

Pediatric lung transplantation.

Semin Pediatr Surg. 2017 Aug;26(4):213-216

Authors: Bryant R, Morales D, Schecter M

Abstract
Pediatric lung transplantation is a highly specialized clinical endeavor. Since the late 1980's, there have only been slightly more than 2200 implants reported to the International Society for Heart and Lung transplantation registry. This review will discuss the historical aspects of pediatric lung transplantation. It will familiarize the reader with the current indications for transplant and the referral and listing process. The current state of lung assist devices as a bridge to pediatric lung transplantation is discussed in addition to the technical aspects of the transplant procedure. Finally, posttransplant outcomes, including anticipated morbidity and the role of retransplantation, are clarified.

PMID: 28964476 [PubMed - in process]

Organ allocation and utilization in pediatric transplantation.

Mon, 10/02/2017 - 12:45

Organ allocation and utilization in pediatric transplantation.

Semin Pediatr Surg. 2017 Aug;26(4):186-192

Authors: Andrews WS, Kane BJ, Hendrickson RJ

Abstract
Pediatric transplant candidates include heart, lung, liver, pancreas, small intestine, and kidney. The purpose of this article is to review the history and current methods for determining priority of the above-mentioned transplantable organs. The methods used by the authors involved the review of historical and current manuscripts and UNOS policy documents. We summarized the findings in order to create a concise review of the current policies and wait times for transplantation in pediatric transplant patients.

PMID: 28964472 [PubMed - in process]

Continued Successful Evolution of Extended Criteria Donor Lungs for Transplantation.

Mon, 10/02/2017 - 12:45

Continued Successful Evolution of Extended Criteria Donor Lungs for Transplantation.

Ann Thorac Surg. 2017 Sep 27;:

Authors: Kotecha S, Hobson J, Fuller J, Paul E, Levvey BJ, Whitford H, Paraskeva M, McGiffin D, Snell GI, Westall GP

Abstract
BACKGROUND: In an era of increasing ex vivo lung perfusion (EVLP) use, it remains important to describe what outcomes can be achieved without EVLP, by taking an aggressive approach to donor use to maximize lung transplantation.
METHODS: Data for all lung transplant donor referrals to the Alfred Hospital in Melbourne, Australia were collected for 2012 to 2013. Donor variables were analyzed and calculated into a previously validated lung donor score. Lung transplant recipient outcome data included the following: primary graft dysfunction; duration of mechanical ventilation; need for cardiopulmonary bypass extracorporeal membrane oxygenation; intensive care and hospital length of stay; 30-day, 1-year, and 3- to 4-year survival rates; rates of acute rejection and chronic lung allograft dysfunction; and peak and 12-month lung function (forced expiratory volume in 1 second).
RESULTS: Of the 318 lung donor offers, 129 resulted in successful lung transplantation, with an overall donor use rate of 41%. There was no correlation between donor score and any of the recipient outcomes, and excellent short-term and longer-term survival was achieved.
CONCLUSIONS: Future studies examining lung transplantation outcomes with EVLP must consider the excellent results that can be achieved by using marginal lungs and conventional donor management. It is important to consider that adopting a strategy of perioperative lung donor evaluation and intervention allows use of what are considered marginal lungs to achieve promising results.

PMID: 28964417 [PubMed - as supplied by publisher]

Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation.

Mon, 10/02/2017 - 12:45

Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation.

Ann Thorac Surg. 2017 Sep 27;:

Authors: Miyoshi R, Chen-Yoshikawa TF, Takahagi A, Oshima Y, Hijiya K, Motoyama H, Aoyama A, Date H

Abstract
BACKGROUND: Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation.
METHODS: Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less.
RESULTS: The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02).
CONCLUSIONS: Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating postoperative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes.

PMID: 28964412 [PubMed - as supplied by publisher]

A novel Tropheryma species in a lung biopsy of a kidney transplant patient.

Sun, 10/01/2017 - 12:45

A novel Tropheryma species in a lung biopsy of a kidney transplant patient.

Clin Microbiol Infect. 2017 Sep 26;:

Authors: Vankeerberghen A, Jonckheere S, De Raeve H, Caluwe R, Beenhouwer H

Abstract
OBJECTIVES: A kidney transplant recipient suffering of recurrent pleuritis underwent an open lung biopsy showing multiple nodular infiltrates. The Grocott and PAS staining were positive. Fungal and Tropheryma whipplei PCR were, however, negative. Further identification was needed.
METHODS: FFPE extraction was performed using the FFPE extraction kit (Qiagen). T. whipplei was searched for using a real time PCR targeting the non-coding repeat specific for T. whipplei. Identification of the bacteria in the extract was done using 16S rDNA and 23s rDNA sequencing and Blast analysis (ncbi). ITS2 PCR was used for fungal DNA identification.
RESULTS: The FFPE extract was negative for fungi and T. whipplei. 16S rDNA sequence analysis of a 1375 bp fragment gave T. whipplei as the best match with 26 mismatches resulting in only 98% agreement. Sequence analysis of the 23S rDNA gene gave T. whipplei again as the best match but only with 91% agreement. A pan-Tropheryma 16S rDNA real time PCR was developed and both the biopsy and a respiratory sample of the patient were strongly positive. The patient received antimicrobial treatment targeting T. whipplei with good clinical outcome.
CONCLUSIONS: 16S and 23S rDNA sequencing gave T. whipplei as the best hit albeit with limited agreement. These findings might suggest that a novel Tropheryma species that lacks the non-coding repeat, most frequently used for molecular detection of Whipple's disease, might be the cause of the pulmonary disease. Adaptation of current PCR protocols is warranted in order to detect all Tropheryma species.

PMID: 28962995 [PubMed - as supplied by publisher]

Important Technical Details During Uniportal Video-Assisted Thoracoscopic Major Resections.

Sun, 10/01/2017 - 12:45

Important Technical Details During Uniportal Video-Assisted Thoracoscopic Major Resections.

Thorac Surg Clin. 2017 Nov;27(4):357-372

Authors: Gonzalez-Rivas D, Sihoe ADL

Abstract
Since it was first performed in 2010, lobectomy via a single port-uniportal video-assisted thoracoscopic surgery (VATS)-has become increasingly popular among surgeons. However, this most minimally invasive surgical approach requires a different skill set compared with even conventional multiportal VATS. For those beginning to learn uniportal VATS, the technical challenges can seem considerable. This article shares some tips and tricks from experienced uniportal VATS practitioners that will help those wishing to learn the approach, and covers the principles of operative setup and instrumentation as well as specific pointers on surgery for each lung lobe.

PMID: 28962708 [PubMed - in process]

Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells.

Sun, 10/01/2017 - 12:45

Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells.

Stem Cell Res Ther. 2017 Sep 29;8(1):208

Authors: Martinez VG, Ontoria-Oviedo I, Ricardo CP, Harding SE, Sacedon R, Varas A, Zapata A, Sepulveda P, Vicente A

Abstract
BACKGROUND: Human dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as other MSCs. Hypoxia-preconditioning and hypoxia-inducible factor 1 (HIF-1) alpha overexpression significantly improves MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression.
METHODS: Human dental MSCs were stably transduced with green fluorescent protein (GFP-MSCs) or GFP-HIF-1 alpha lentivirus vectors (HIF-MSCs). A hypoxic-like metabolic profile was confirmed by mitochondrial and glycolysis stress test. Capacity of HIF-MSCs to modulate T-cell activation, dendritic cell differentiation, monocyte migration, and polarizations towards macrophages and natural killer (NK) cell lytic activity was assessed by a number of functional assays in co-cultures. The expression of relevant factors were determined by polymerase chain reaction (PCR) analysis and enzyme-linked immunosorbent assay (ELISA).
RESULTS: While HIF-1 alpha overexpression did not modify the inhibition of T-cell activation by MSCs, HIF-MSCs impaired dendritic cell differentiation more efficiently. In addition, HIF-MSCs showed a tendency to induce higher attraction of monocytes, which differentiate into suppressor macrophages, and exhibited enhanced resistance to NK cell-mediated lysis, which supports the improved therapeutic capacity of HIF-MSCs. HIF-MSCs also displayed a pro-angiogenic profile characterized by increased expression of CXCL12/SDF1 and CCL5/RANTES and complete loss of CXCL10/IP10 transcription.
CONCLUSIONS: Immunomodulation and expression of trophic factors by dental MSCs make them perfect candidates for cell therapy. Overexpression of HIF-1 alpha enhances these features and increases their resistance to allogenic NK cell lysis and, hence, their potential in vivo lifespan. Our results further support the use of HIF-1 alpha-expressing dental MSCs for cell therapy in tissue injury and immune disorders.

PMID: 28962641 [PubMed - in process]

Pulmonary Hypertension and Primary Graft Dysfunction in Lung Transplant Recipients: We Still Have a Long Way to Go.

Sat, 09/30/2017 - 12:45

Pulmonary Hypertension and Primary Graft Dysfunction in Lung Transplant Recipients: We Still Have a Long Way to Go.

Ann Am Thorac Soc. 2017 Oct;14(10):1504-1505

Authors: Singer JP

PMID: 28961030 [PubMed - in process]

Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

Sat, 09/30/2017 - 12:45

Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

Transfusion. 2017 Sep 28;:

Authors: Colavecchia AC, Cohen DA, Harris JE, Thomas JM, Lindberg S, Leveque C, Salazar E

Abstract
BACKGROUND: Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization.
STUDY DESIGN AND METHODS: This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias.
RESULTS: During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively).
CONCLUSION: The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation did not reduce intraoperative blood product requirements at a single institution.

PMID: 28960322 [PubMed - as supplied by publisher]

Twenty-years of lung transplantation in Taiwan: Effects of cumulative institutional experience on early outcomes.

Sat, 09/30/2017 - 12:45
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Twenty-years of lung transplantation in Taiwan: Effects of cumulative institutional experience on early outcomes.

J Formos Med Assoc. 2017 Sep 25;:

Authors: Yang SM, Huang SC, Kuo SW, Huang PM, Hsiao PN, Chen KC, Lin MW, Pan SC, Lin JH, Cheng YJ, Lee JM, Hsu HH

Abstract
BACKGROUND/PURPOSE: Lung transplantation in Taiwan began in 1991, but the experience was limited and diverse in the early years. We examined the cumulative institutional experience of the largest lung transplant cohort in Taiwan.
METHODS: A retrospective review of lung transplantations performed at a single institution from December 1995 through August 2016 was conducted. For comparative purposes, the cohort was divided into halves, with an early group (undergoing lung transplantation in the first decade) vs a late group (undergoing lung transplantation in the second decade). Standardized donor selection, organ procurement, and preservation protocols for brain-dead donors were applied. The outcomes measured were 30-day mortality and actuarial survival using the Kaplan-Meier method.
RESULTS: The cohort included 50 recipients in the early group and 42 recipients in the late group. Compared with the early group, recipients in the late group were significantly older (38.8 ± 11.6 vs 44.8 ± 13.4 years, p = 0.024) and more of them required mechanical ventilation before transplant (26.0% vs 66.7%, p < 0.001). There were more female donors (12.0% vs 33.3%, p = 0.021) and gender-matched donors (34.0% vs 61.9%, p = 0.012) in the late group. A total of 87 recipients (94.6%) had cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) support during transplant, and CPB was used significantly less in the late group. Graft procedures (14.0% vs 47.6%, p < 0.001), delayed chest closure (0% vs 21.4%, p < 0.001), and early tracheostomy (24.0% vs 52.4%, p = 0.005) were performed more in the late group. The durations of hospital and ICU stays were comparable in both groups, but the 30-day mortality was significantly lower in the late group (30.0% vs 2.4%, p = 0.001).
CONCLUSION: Although the results were undesirable in the first decade of the transplant program, the cumulative institutional experience led to significantly improved outcomes in the second decade of the transplant program.

PMID: 28958705 [PubMed - as supplied by publisher]

Modulation of Roquin Function in Myeloid Cells Reduces Mycobacterium tuberculosis-Induced Inflammation.

Sat, 09/30/2017 - 12:45
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Modulation of Roquin Function in Myeloid Cells Reduces Mycobacterium tuberculosis-Induced Inflammation.

J Immunol. 2017 Sep 01;199(5):1796-1804

Authors: Nagalingam G, Vinuesa CG, Britton WJ, Saunders BM

Abstract
Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation; however, its role in immunity to M. tuberculosis is unknown. To address this, we infected mice with a point mutation in Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control of M. tuberculosis infection associated with delayed bacterial dissemination and upregulated TNF production in the lungs after 2 wk. However, this early control of infection was not maintained, and by 8 wk postinfection sanroque mice demonstrated an increased bacterial burden and dysregulated inflammation in the lungs. As the inflammation in the lungs of the sanroque mice could have been influenced by emerging autoimmune conditions that are characteristic of the mice aging, the function of Roquin was examined in immune cell subsets in the absence of autoimmune complications. M. bovis bacillus Calmette-Guérin-primed sanroque T cells transferred into Rag1(-/-) mice provided equivalent protection in the spleen and liver. Interestingly, the transfer of mycobacteria-specific (P25 CD4(+) TCR transgenic) wild-type spleen cells into sanroqueRag1(-/-) mice actually led to enhanced protection with reduced bacterial load, decreased chemokine expression, and reduced inflammation in the lungs compared with transfers into Rag1(-)(/-) mice expressing intact Roquin. These studies suggest that modulation of Roquin in myeloid cells may reduce both inflammation and bacterial growth during the chronic phase of M. tuberculosis infection.

PMID: 28747346 [PubMed - indexed for MEDLINE]

Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination.

Sat, 09/30/2017 - 12:45
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Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination.

Cancer Res. 2017 Jul 15;77(14):3894-3907

Authors: Jiang H, Rivera-Molina Y, Gomez-Manzano C, Clise-Dwyer K, Bover L, Vence LM, Yuan Y, Lang FF, Toniatti C, Hossain MB, Fueyo J

Abstract
Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor, and reactivate antitumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune costimulator OX40 ligand (OX40L). Like its predecessor Delta-24-RGD, Delta-24-RGDOX induced immunogenic cell death and recruit lymphocytes to the tumor site. Compared with Delta-24-RGD, Delta-24-RGDOX exhibited superior tumor-specific activation of lymphocytes and proliferation of CD8(+) T cells specific to tumor-associated antigens, resulting in cancer-specific immunity. Delta-24-RGDOX mediated more potent antiglioma activity in immunocompetent C57BL/6 but not immunodeficient athymic mice, leading to specific immune memory against the tumor. To further overcome the immune suppression mediated by programmed death-ligand 1 (PD-L1) expression on cancer cells accompanied with virotherapy, intratumoral injection of Delta-24-RGDOX and an anti-PD-L1 antibody showed synergistic inhibition of gliomas and significantly increased survival in mice. Our data demonstrate that combining an oncolytic virus with tumor-targeting immune checkpoint modulators elicits potent in situ autologous cancer vaccination, resulting in an efficacious, tumor-specific, and long-lasting therapeutic effect. Cancer Res; 77(14); 3894-907. ©2017 AACR.

PMID: 28566332 [PubMed - indexed for MEDLINE]

Five-year results of patients supported by HeartMate II: outcomes and adverse events.

Fri, 09/29/2017 - 12:45
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Five-year results of patients supported by HeartMate II: outcomes and adverse events.

Eur J Cardiothorac Surg. 2017 Sep 02;:

Authors: Hanke JS, Rojas SV, Mahr C, Schmidt AF, Zoch A, Dogan G, Feldmann C, Deniz E, Molitoris U, Bara C, Strüber M, Haverich A, Schmitto JD

Abstract
OBJECTIVES: Improved outcomes over the past decade have increased confidence of physicians and patients in extended duration of left ventricular assist device (LVAD) support. This single-centre cohort study reports 5-year outcomes with the HeartMate II (HMII) LVAD.
METHODS: We describe a cohort of 89 patients who received a HMII LVAD between February 2004 and December 2010. The causes of death and adverse events were assessed by examination of medical records. A total of 202.74 patient-years were analysed.
RESULTS: After 5 years, of the 89 patients, 15 patients remained on device therapy, 39 patients died, 28 patients underwent heart transplantation and 7 patients underwent explantation of the HMII for recovery. One year after the HMII implantation, there was a survival of 71% in the study cohort. In the following years, the survival rate was 65% in the 2nd year, 63% in the 3rd year, 56% in the 4th year and 54% after 5 years of LVAD support. Ten LVAD exchanges were performed in 8 (11%) patients. Currently (March 2017), 12 patients still remain on their original device. The longest ongoing patient on the HMII has been supported for over 11 years (4097 days). The most common adverse events were bleeding (68%; 1.5837 events per patient-year) and LVAD infection [49%; 1.0666 events per patient-year]. Seven cases of pump thrombosis were described (8%; 0.1131 events per patient-year).
CONCLUSIONS: This is the first single-cohort study to describe a 5-year survival of HMII patients on extended duration of support. A 5-year survival of 54% was observed in this single-centre cohort.

PMID: 28958073 [PubMed - as supplied by publisher]

Previous lung volume reduction surgery does not negatively affect survival after lung transplantation.

Fri, 09/29/2017 - 12:45
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Previous lung volume reduction surgery does not negatively affect survival after lung transplantation.

Eur J Cardiothorac Surg. 2017 Sep 08;:

Authors: Inci I, Iskender I, Ehrsam J, Caviezel C, Hillinger S, Opitz I, Schneiter D, Weder W

Abstract
OBJECTIVES: Lung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx.
METHODS: We reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test.
RESULTS: One hundred and seventeen patients (66 men; mean age 56 ± 7 years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRS + LTx). The mean time from LVRS to LTx was 45 ± 31 months. Patients were slightly older and had extensive smoking history in the LVRS + LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS ( P  = 0.8). The median survival for the LTx-only and LVRS + LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137) months, respectively ( P  = 0.6).
CONCLUSIONS: Previous LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.

PMID: 28957998 [PubMed - as supplied by publisher]

MicroRNAs in right ventricular remodelling.

Fri, 09/29/2017 - 12:45
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MicroRNAs in right ventricular remodelling.

Cardiovasc Res. 2017 Oct 01;113(12):1433-1440

Authors: Batkai S, Bär C, Thum T

Abstract
Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases.

PMID: 28957533 [PubMed - in process]

"Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma.

Fri, 09/29/2017 - 12:45
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"Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma.

PLoS One. 2017;12(9):e0184451

Authors: Clawson GA, Matters GL, Xin P, McGovern C, Wafula E, dePamphilis C, Meckley M, Wong J, Stewart L, D'Jamoos C, Altman N, Imamura Kawasawa Y, Du Z, Honaas L, Abraham T

Abstract
Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploidy, and immunophenotypic characterizations showed that the MTFs express markers characteristic of PDAC and stem cells, as well as M2-polarized macrophages. Single cell RNASeq analyses showed that the MTFs express many transcripts implicated in cancer progression, LINE1 retrotransposons, and very high levels of several long non-coding transcripts involved in metastasis (such as MALAT1). When cultured MTFs were transplanted orthotopically into mouse pancreas, they grew as obvious well-differentiated islands of cells, but they also disseminated widely throughout multiple tissues in "stealth" fashion. They were found distributed throughout multiple organs at 4, 8, or 12 weeks after transplantation (including liver, spleen, lung), occurring as single cells or small groups of cells, without formation of obvious tumors or any apparent progression over the 4 to 12 week period. We suggest that MTFs form continually during PDAC development, and that they disseminate early in cancer progression, forming "niches" at distant sites for subsequent colonization by metastasis-initiating cells.

PMID: 28957348 [PubMed - in process]

Mechanisms of Lung Cancer Caused By Cooking Fumes Exposure: A Minor Review(△).

Fri, 09/29/2017 - 12:45
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Mechanisms of Lung Cancer Caused By Cooking Fumes Exposure: A Minor Review(△).

Chin Med Sci J. 2017 Sep 27;32(3):193-197

Authors: Wang CY, Liu LF, Liu XL, Chen WJ, He GP

Abstract
Cooking fumes (CFs) are mixtures of many toxic components, such as aldehydes, heterocyclic amines, polycyclic aromatic hydrocarbons, fat aerosols and particulate matters. CFs exposure has been proven to be associated with many diseases. Lung cancer takes the leading place among the diseases being reported caused by CFs exposure. Molecular and biochemical studies have found that CFs exposure may lead to lung cancer by gene damage, formation of reactive oxygen species, blockage of related proteins' function, and even cell death. However, reviews about the mechanisms of how CFs exposure leads to lung cancer are still lacking. Elucidation of the mechanisms of lung cancer caused by CFs exposure may provide a new insight into the prevention of lung cancer caused by CFs exposure, as well as laying the foundation for the toxicity study of CFs. In this minor review, the mechanisms of how CFs exposure leads to lung cancer were summarized and discussed.

PMID: 28956747 [PubMed - in process]

Diagnosing filamentous fungal infections in immunocompromised patients applying computed tomography-guided percutaneous lung biopsies: a 12-year experience.

Fri, 09/29/2017 - 12:45
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Diagnosing filamentous fungal infections in immunocompromised patients applying computed tomography-guided percutaneous lung biopsies: a 12-year experience.

Infection. 2017 Sep 27;:

Authors: Lass-Flörl C, Aigner M, Nachbaur D, Eschertzhuber S, Bucher B, Geltner C, Bellmann R, Lackner M, Orth-Höller D, Würzner R, Weiss G, Glodny B

Abstract
BACKGROUND: Invasive fungal diseases (IFD) are an important cause of morbidity and mortality in immunocompromised patients, and early diagnosis and management are a challenge. We evaluated the clinical utility of computed tomography (CT)-guided percutaneous lung biopsies in diagnosing IFD.
METHODS: Between 2003 and 2014, we analyzed 2671 CT-guided lung biopsies, from which 157 were IFD associated; we aimed to determine microbiological-based diagnostic accuracy of calcofluor white staining (CFWS), culture, Aspergillus antigen detection (GM), broad-range fungal PCR, and Aspergillus PCR per sample.
RESULTS: 127 (81%) specimens were microscopically positive for any fungal elements, 30 (19%) negative. Aspergillus and non-Aspergillus like hyphae were obtained in 85 (67%) and 42 (33%) specimens, respectively. CFWS positivity was defined as proof of infection. Sensitivity, specificity, and positive (PPV) and negative predictive (NPV) values for CT scan were 100, 44, 80, and 100%, for Aspergillus PCR 89, 58, 88, and 58%, for broad-range fungal PCR 90, 83, 95, and 90%, and for GM 94, 83, 95, and 90%. The most common CT features were patchy opacifications with central necrosis (78%) or cavern defects (50%), less common were air bronchograms (39%) or ground glass halos (39%), and all other features were rare. The overall pneumothorax rate subsequent to biopsy was 19%, but in only 2% of all cases the placement of a chest tube was indicated. One case of fatal air embolism occurred.
CONCLUSIONS: CT-guided lung biopsies have high diagnostic accuracy in terms of microscopic examination, and complication rates are low. Molecular-based and antigen tests applied on fungal hyphae-positive specimens showed comparable results.

PMID: 28956284 [PubMed - as supplied by publisher]

Severe idiopathic pulmonary fibrosis: what can be done?

Fri, 09/29/2017 - 12:45
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Severe idiopathic pulmonary fibrosis: what can be done?

Eur Respir Rev. 2017 Sep 30;26(145):

Authors: Caminati A, Cassandro R, Torre O, Harari S

Abstract
Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients.

PMID: 28954763 [PubMed - in process]

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