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High prevalence of skin cancers and actinic keratoses in lung transplant recipients.

Sat, 12/09/2017 - 13:45
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High prevalence of skin cancers and actinic keratoses in lung transplant recipients.

J Heart Lung Transplant. 2017 Nov 15;:

Authors: Sahebian A, Pandeya N, Chambers DC, Soyer HP, Green AC

PMID: 29217109 [PubMed - as supplied by publisher]

Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era.

Sat, 12/09/2017 - 13:45
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Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era.

J Heart Lung Transplant. 2017 Nov 15;:

Authors: Kristen AV, Kreusser MM, Blum P, Schönland SO, Frankenstein L, Dösch AO, Knop B, Helmschrott M, Schmack B, Ruhparwar A, Hegenbart U, Katus HA, Raake PWJ

Abstract
BACKGROUND: Cardiac amyloidosis, caused most commonly by deposition of light chain (AL) or transthyretin (ATTR) type fibrils, has an extremely poor prognosis. In this retrospective single-center study, we evaluated temporal trends in survival after heart transplantation for cardiac amyloidosis.
METHODS: We analyzed 48 patients with cardiac amyloidosis (AL, n = 32; familial ATTR, n = 16) who underwent heart transplantation from May 2002 to March 2017. Patients were analysed in 2 periods, Era 1 (2002- 2007) and Era 2 (2008- 2017), separated by altered patient selection in both, AL and ATTR amyloidosis, and changed chemotherapy regimens for AL amyloidosis.
RESULTS: The modern era was characterized by a lower number of extracardiac organ involvement for AL (94% isolated cardiac amyloidosis in Era 2 vs 56% in Era 1; p = 0.0221), and more frequent treatment for AL with the proteasome inhibitor bortezomib (94% in Era 2 vs 6% in Era 1; p < 0.0001). AL patients had significantly lower survival than patients with non-amyloid cardiomyopathy after heart transplantation in Era 1, and ATTR patients had numerically lower survival. However, survival in the modern era was comparable to non-amyloid transplants in both cohorts, possibly reflecting a shift in chemotherapy strategies and patient selection, respectively.
CONCLUSIONS: In the current era, use of enhanced chemotherapy regimens for isolated advanced AL cardiac amyloidosis was associated with outcomes comparable to non-amyloid cardiomyopathy. We conclude that heart transplantation in highly selected patients with isolated non-systemic advanced cardiac amyloidosis may be a feasible approach.

PMID: 29217108 [PubMed - as supplied by publisher]

The long and winding road: stem cells for cystic fibrosis.

Sat, 12/09/2017 - 13:45
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The long and winding road: stem cells for cystic fibrosis.

Expert Opin Biol Ther. 2017 Dec 08;:1-12

Authors: Conese M, Beccia E, Castellani S, Di Gioia S, Colombo C, Angiolillo A, Carbone A

Abstract
INTRODUCTION: Cystic fibrosis (CF) is a genetic syndrome with a high mortality rate due to severe lung disease. Despite having several drugs targeting specific mutated CFTR proteins already in clinical trials, new therapies, based on stem cells, are also emerging to treat those patients. Areas covered: The authors review the main sources of stem cells, including embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), gestational stem cells, and adult stem cells, such as mesenchymal stem cells (MSCs) in the context of CF. Furthermore, they describe the main animal and human models of lung physiology and pathology, involved in the optimization of these stem cell-applied therapies in CF. Expert opinion: ESCs and iPSCs are emerging sources for disease modeling and drug discovery purposes. The allogeneic transplant of healthy MSCs, that acts independently to specific mutations, is under intense scrutiny due to their secretory, immunomodulatory, anti-inflammatory and anti-bacterial properties. The main challenge for future developments will be to get exogenous stem cells into the appropriate lung location, where they can regenerate endogenous stem cells and act as inflammatory modulators. The clinical application of stem cells for the treatment of CF certainly warrants further insight into pre-clinical models, including large animals, organoids, decellularized organs and lung bioengineering.

PMID: 29216777 [PubMed - as supplied by publisher]

Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway.

Sat, 12/09/2017 - 13:45
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Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway.

Autophagy. 2017 Jan 02;13(1):187-200

Authors: Liu KK, Qiu WR, Naveen Raj E, Liu HF, Huang HS, Lin YW, Chang CJ, Chen TH, Chen C, Chang HC, Hwang JK, Chao JI

Abstract
Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) for entry into the selective autophagy pathway. NDs are ultimately delivered to lysosomes. Ectopically expressed SQSTM1-green fluorescence protein (GFP) could bind to the Ub-coated NDs. By contrast, the Ub-associated domain mutant of SQSTM1 (ΔUBA)-GFP did not bind to the Ub-coated NDs. Chloroquine, an autophagy inhibitor, prevented the ND-containing autophagosomes from fusing with lysosomes. Furthermore, autophagy receptors OPTN and CALCOCO2/NDP52, involved in the processing of bacteria, were found to be involved in the selective autophagy of NDs. However, ND particles located in the lysosomes of cells did not induce mitotic blockage, senescence, or cell death. Single ND clusters in the lysosomes of cells were observed in the xenografted human lung tumors of nude mice. This study demonstrated for the first time that Ub-coated nanoparticles bind to autophagy receptors for entry into the selective autophagy pathway, facilitating their delivery to lysosomes.

PMID: 27846374 [PubMed - indexed for MEDLINE]

Physiologic Evaluation of Ventilation Perfusion Mismatch and Respiratory Mechanics at Different Positive End-expiratory Pressure in Patients Undergoing Protective One-lung Ventilation.

Fri, 12/08/2017 - 13:45

Physiologic Evaluation of Ventilation Perfusion Mismatch and Respiratory Mechanics at Different Positive End-expiratory Pressure in Patients Undergoing Protective One-lung Ventilation.

Anesthesiology. 2017 Dec 06;:

Authors: Spadaro S, Grasso S, Karbing DS, Fogagnolo A, Contoli M, Bollini G, Ragazzi R, Cinnella G, Verri M, Cavallesco NG, Rees SE, Volta CA

Abstract
BACKGROUND: Arterial oxygenation is often impaired during one-lung ventilation, due to both pulmonary shunt and atelectasis. The use of low tidal volume (VT) (5 ml/kg predicted body weight) in the context of a lung-protective approach exacerbates atelectasis. This study sought to determine the combined physiologic effects of positive end-expiratory pressure and low VT during one-lung ventilation.
METHODS: Data from 41 patients studied during general anesthesia for thoracic surgery were collected and analyzed. Shunt fraction, high V/Q and respiratory mechanics were measured at positive end-expiratory pressure 0 cm H2O during bilateral lung ventilation and one-lung ventilation and, subsequently, during one-lung ventilation at 5 or 10 cm H2O of positive end-expiratory pressure. Shunt fraction and high V/Q were measured using variation of inspired oxygen fraction and measurement of respiratory gas concentration and arterial blood gas. The level of positive end-expiratory pressure was applied in random order and maintained for 15 min before measurements.
RESULTS: During one-lung ventilation, increasing positive end-expiratory pressure from 0 cm H2O to 5 cm H2O and 10 cm H2O resulted in a shunt fraction decrease of 5% (0 to 11) and 11% (5 to 16), respectively (P < 0.001). The PaO2/FIO2 ratio increased significantly only at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). Driving pressure decreased from 16 ± 3 cm H2O at a positive end-expiratory pressure of 0 cm H2O to 12 ± 3 cm H2O at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). The high V/Q ratio did not change.
CONCLUSIONS: During low VT one-lung ventilation, high positive end-expiratory pressure levels improve pulmonary function without increasing high V/Q and reduce driving pressure.

PMID: 29215365 [PubMed - as supplied by publisher]

Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis.

Fri, 12/08/2017 - 13:45

Genetic Variants Contributing to Circulating Matrix Metalloproteinase 8 Levels and Their Association With Cardiovascular Diseases: A Genome-Wide Analysis.

Circ Cardiovasc Genet. 2017 Dec;10(6):

Authors: Salminen A, Vlachopoulou E, Havulinna AS, Tervahartiala T, Sattler W, Lokki ML, Nieminen MS, Perola M, Salomaa V, Sinisalo J, Meri S, Sorsa T, Pussinen PJ

Abstract
BACKGROUND: Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP-8 are associated with the risk for and outcome of cardiovascular diseases (CVDs). The origin of circulating MMP-8 is not completely clear.
METHODS AND RESULTS: We performed a genome-wide association study of serum MMP-8 levels in 2 populations comprising altogether 6049 individuals. Moreover, we studied whether MMP-8-associated variants are linked to increased risk of CVDs and overall mortality in >20 000 subjects. The strongest association with serum MMP-8 was found in locus 1q31.3, containing the gene for complement factor H (lead single nucleotide polymorphism: rs800292; P=2.4×10-35). In functional experiments, activation of the alternative pathway of complement in the carriers of rs800292 minor allele (Ile62 in factor H) led to decreased release of MMP-8 from neutrophils compared with the major allele (Val62 in factor H). Another association was detected in 1q21.3, containing genes S100A8, S100A9, and S100A12 (strongest association: rs1560833; P=5.3×10-15). The minor allele of rs1560833 was inversely associated with CVD (odds ratio [95% confidence interval]: 0.90 [0.82-0.99]; P=0.032) and the time to incident CVD event (hazard ratio [95% confidence interval]: 0.91 [0.84-0.99]; P=0.032) in men but not in women.
CONCLUSIONS: According to our results, the activation of the alternative pathway of the complement system strongly contributes to serum MMP-8 concentration. Genetic polymorphism in S100A9-S100A12-S100A8 locus affects serum and plasma MMP-8 and shows a suggestive association with the risk of CVDs. Our results show that genetic variation determines a significant portion of circulating MMP-8 concentrations.

PMID: 29212897 [PubMed - in process]

Clinical Indices Can Standardize and Monitor Pediatric Care: A Novel Mechanism to Improve Quality and Safety.

Fri, 12/08/2017 - 13:45

Clinical Indices Can Standardize and Monitor Pediatric Care: A Novel Mechanism to Improve Quality and Safety.

J Pediatr. 2017 Dec 04;:

Authors: Crandall W, Davis JT, Dotson J, Elmaraghy C, Fetzer M, Hayes D, Horwitz E, Kogon A, Olshefski R, Patel H, Brilli RJ

Abstract
OBJECTIVE: The Cancer Care Index (CCI), a single metric that sums the number of undesirable patient events in a given time frame (either preventable harm events or missed opportunities to provide optimal care), resulted in a 42% improvement in performance. Our objective was to test the index concept in other service lines to determine whether similar performance improvement occurred.
STUDY DESIGN: Care indices were developed and introduced in 3 additional service lines: Nephrology (Chronic Kidney Disease Care Index; CKDCI), Pulmonology (Lung Transplantation Care Index; LTCI), and Otolaryngology (Tracheostomy Care Index; TCI). After reaching agreement on specific harms to be avoided and elements of optimal care that should be reliably delivered, these items were compiled into indices that were updated monthly. Reports included each element individually and the total for all elements. Baseline performance was calculated retrospectively for the previous year.
RESULTS: Significant improvement in performance occurred in each program following implementation of the clinical indices. The CKDCI was decreased by 63.2% (P < .001), the LTCI was decreased by 89.5% (P < .001), and the TCI was decreased by 53.0% (P < .001). Surveyed staff indicated satisfaction with use of the metric.
CONCLUSIONS: Clinical indices are useful for evaluating and managing the overall reliability of a program's ability to deliver optimal care, and are associated with improved clinical performance and satisfaction by service line staff when incorporated into a program's operation.

PMID: 29212624 [PubMed - as supplied by publisher]

FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice.

Fri, 12/08/2017 - 13:45
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FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice.

Am J Physiol Lung Cell Mol Physiol. 2017 Nov 01;313(5):L781-L795

Authors: Justet A, Joannes A, Besnard V, Marchal-Sommé J, Jaillet M, Bonniaud P, Sallenave JM, Solhonne B, Castier Y, Mordant P, Mal H, Cazes A, Borie R, Mailleux AA, Crestani B

Abstract
Fibroblast growth factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (AdCont) was performed. Mice were euthanized at days 3, 5, and 14 Expression of FGF9 and markers of inflammation and myofibroblastic differentiation was studied by qPCR and immunohistochemistry. In vitro, rat mesothelial cells were stimulated with FGF9 (20 ng/ml), and we assessed its effect on proliferation, survival, migration, and differentiation. FGF9 was expressed by mesothelial cells in human idiopathic pulmonary fibrosis. FGF receptors, mainly FGFR3, were expressed by mesothelial cells in vivo in humans and mice. AdCont instillation induced diffuse pleural thickening appearing at day 5, maximal at day 14 The altered pleura cells strongly expressed α-smooth muscle actin and collagen. AdFGF9 injection induced maximal FGF9 expression at day 5 that lasted until day 14 FGF9 overexpression prevented pleural thickening, collagen and fibronectin accumulation, and myofibroblastic differentiation of mesothelial cells. In vitro, FGF9 decreased mesothelial cell migration and inhibited the differentiating effect of transforming growth factor-β1. We conclude that FGF9 has a potential antifibrotic effect on mesothelial cells.

PMID: 28729349 [PubMed - indexed for MEDLINE]

Single-centre study of therapeutic drug monitoring of posaconazole in lung transplant recipients: factors affecting trough plasma concentrations.

Thu, 12/07/2017 - 13:45

Single-centre study of therapeutic drug monitoring of posaconazole in lung transplant recipients: factors affecting trough plasma concentrations.

J Antimicrob Chemother. 2017 Dec 02;:

Authors: Jeong W, Snell GI, Levvey BJ, Westall GP, Morrissey CO, Wolfe R, Ivulich S, Neoh CF, Slavin MA, Kong DCM

Abstract
Objectives: This study describes therapeutic drug monitoring (TDM) of posaconazole suspension and modified release (MR) tablets in lung transplant (LTx) recipients and evaluates factors that may affect posaconazole trough plasma concentration (Cmin).
Methods: A single-centre, retrospective study evaluating posaconazole Cmin in LTx recipients receiving posaconazole suspension or MR tablets between January 2014 and December 2016.
Results: Forty-seven LTx patients received posaconazole suspension, and 78 received the MR tablet formulation; a total of 421 and 617 Cmin measurements were made, respectively. Posaconazole was concurrently administered with proton pump inhibitor in ≥ 90% of patients. The median (IQR) of initial posaconazole Cmin following 300 mg daily of posaconazole tablet was significantly higher than that of 800 mg daily of posaconazole suspension [1.65 (0.97-2.13) mg/L versus 0.81 (0.48-1.15) mg/L, P < 0.01]. Variability in posaconazole Cmin was apparent regardless of the formulations prescribed and dose adjustments were routinely undertaken to maintain therapeutic Cmin. A clear dose-response relationship was observed in patients receiving posaconazole MR tablets. Non-specific adverse events (fatigue, tremor, lethargy, sweating, nausea/vomiting and weight loss) were reported in 3/78 (4%) patients receiving posaconazole MR tablets. Posaconazole Cmin in these three patients was determined to be 9.6, 6.2 and 2.3 mg/L.
Conclusions: The current study has provided clinically important insights into the TDM of posaconazole in LTx recipients. Routine TDM should be undertaken in LTx recipients receiving posaconazole suspension and/or MR tablets.

PMID: 29211913 [PubMed - as supplied by publisher]

Complement Receptor 3 Has Negative Impact on Tumor Surveillance through Suppression of Natural Killer Cell Function.

Thu, 12/07/2017 - 13:45
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Complement Receptor 3 Has Negative Impact on Tumor Surveillance through Suppression of Natural Killer Cell Function.

Front Immunol. 2017;8:1602

Authors: Liu CF, Min XY, Wang N, Wang JX, Ma N, Dong X, Zhang B, Wu W, Li ZF, Zhou W, Li K

Abstract
Complement receptor 3 (CR3) is expressed abundantly on natural killer (NK) cells; however, whether it plays roles in NK cell-dependent tumor surveillance is largely unknown. Here, we show that CR3 is an important negative regulator of NK cell function, which has negative impact on tumor surveillance. Mice deficient in CR3 (CD11b-/- mice) exhibited a more activated NK phenotype and had enhanced NK-dependent tumor killing. In a B16-luc melanoma-induced lung tumor growth and metastasis model, mice deficient in CR3 had reduced tumor growth and metastases, compared with WT mice. In addition, adaptive transfer of NK cells lacking CR3 (into NK-deficient mice) mediated more efficient suppression of tumor growth and metastases, compared with the transfer of CR3 sufficient NK cells, suggesting that CR3 can impair tumor surveillance through suppression of NK cell function. In vitro analyses showed that engagement of CR3 with iC3b (classical CR3 ligand) on NK cells negatively regulated NK cell activity and effector functions (i.e. direct tumor cell killing, antibody-dependent NK-mediated tumor killing). Cell signaling analyses showed that iC3b stimulation caused activation of Src homology 2 domain-containing inositol-5-phosphatase-1 (SHIP-1) and JNK, and suppression of ERK in NK cells, supporting that iC3b mediates negative regulation of NK cell function through its effects on SHIP-1, JNK, and ERK signal transduction pathways. Thus, our findings demonstrate a previously unknown role for CR3 in dysregulation of NK-dependent tumor surveillance and suggest that the iC3b/CR3 signaling is a critical negative regulator of NK cell function and may represent a new target for preserving NK cell function in cancer patients and improving NK cell-based therapy.

PMID: 29209332 [PubMed]

The need and opportunity for donation after circulatory death worldwide.

Wed, 12/06/2017 - 13:45
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The need and opportunity for donation after circulatory death worldwide.

Curr Opin Organ Transplant. 2017 Dec 04;:

Authors: Manyalich M, Nelson H, Delmonico FL

Abstract
PURPOSE OF REVIEW: The global shortage of organ donors will not be resolved solely by relying on deceased donation following a brain death determination (DBD). Expansion of deceased donation after circulatory death (DCD) will be needed to address the shortfall of organs for transplantation. Approximately 120 000 organ transplants are performed each year; however, the WHO estimates that this number of transplants only resolves 10% of the annual worldwide transplant need.
RECENT FINDINGS: The report addresses the opportunity of DCD expansion by evaluating the DCD potential that is not being realized, the utility of DCD enabling DBD to emerge in some clinical situations, by the effectiveness of a donor registry in achieving DCD, and by the current clinical research of heart, lung, and liver transplantation from DCD.
SUMMARY: The future of deceased donation must include DCD and ex-vivo organ repair if the organ shortage is to be reconciled even partially to the ongoing demand. Although the religious and legal impediments have been overcome to determine brain death, the possibility of DCD has not been addressed. A program of DCD is feasible in all countries with transplantation services. The excellent results following kidney and lung transplantation suggest opportunities of heart and liver transplantation should be the focus of needed DCD accomplishment in the near future.

PMID: 29206661 [PubMed - as supplied by publisher]

Liver-first versus lung-first: A new dilemma in combined organ transplantation.

Wed, 12/06/2017 - 13:45
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Liver-first versus lung-first: A new dilemma in combined organ transplantation.

Transpl Int. 2017 Dec 04;:

Authors: Ceulemans LJ, Vos R, Neyrinck A, Pirenne J, Warnecke G, Van Raemdonck D

Abstract
One-staged combined liver-lung transplantation (cLiLuTx) is a life-saving procedure for patients with dual organ failure[1]. The classic sequence dictates LuTx priority over LiTx, due to the tolerable cold ischemic time, which is considered shorter for the lungs (6-8 hours) than for the liver (8-10 hours). However recent reports describe successful LuTx following longer ischemic time (10-12 hours)[2,3]; and safe extension of the lung out-of-body time by ex-vivo lung perfusion (EVLP)[4]. This article is protected by copyright. All rights reserved.

PMID: 29205539 [PubMed - as supplied by publisher]

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

Wed, 12/06/2017 - 13:45
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Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

Ann Intern Med. 2017 Dec 05;:

Authors: Lata S, Marasa M, Li Y, Fasel DA, Groopman E, Jobanputra V, Rasouly H, Mitrotti A, Westland R, Verbitsky M, Nestor J, Slater LM, D'Agati V, Zaniew M, Materna-Kiryluk A, Lugani F, Caridi G, Rampoldi L, Mattoo A, Newton CA, Rao MK, Radhakrishnan J, Ahn W, Canetta PA, Bomback AS, Appel GB, Antignac C, Markowitz GS, Garcia CK, Kiryluk K, Sanna-Cherchi S, Gharavi AG

Abstract
Background: The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown.
Objective: To study the diagnostic utility of WES in a selected referral population of adults with CKD.
Design: Observational cohort.
Setting: A major academic medical center.
Patients: 92 adults with CKD of unknown cause or familial nephropathy or hypertension.
Measurements: The diagnostic yield of WES and its potential effect on clinical management.
Results: Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most solved cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy.
Limitation: The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population.
Conclusion: Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted.
Primary Funding Source: New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of Health.

PMID: 29204651 [PubMed - as supplied by publisher]

Pulmonary Vein Stenosis Following Single-Lung Transplantation Successfully Treated with Intravascular Ultrasound-Guided Angioplasty and Stent Placement.

Wed, 12/06/2017 - 13:45
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Pulmonary Vein Stenosis Following Single-Lung Transplantation Successfully Treated with Intravascular Ultrasound-Guided Angioplasty and Stent Placement.

Am J Case Rep. 2017 Dec 05;18:1289-1295

Authors: Jobanputra YB, Kapadia SR, Johnston DR, Ahmed V, Jones BM, Budev M, Lane CR, Mehta AC

PMID: 29203761 [PubMed - in process]

Evaluation of Cardiac Index and Extravascular Lung Water After Single-Lung Transplantation Using the Transpulmonary Thermodilution Technique by the PiCCO2 Device.

Wed, 12/06/2017 - 13:45
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Evaluation of Cardiac Index and Extravascular Lung Water After Single-Lung Transplantation Using the Transpulmonary Thermodilution Technique by the PiCCO2 Device.

J Cardiothorac Vasc Anesth. 2017 Dec 01;:

Authors: Tran-Dinh A, Augustin P, Dufour G, Lasocki S, Allou N, Thabut G, Castier Y, Montravers P, Desmard M

Abstract
OBJECTIVES: First evaluation of the transpulmonary thermodilution technique by the PiCCO2 device to assess cardiac index and pulmonary edema during the postoperative course after single-lung transplantation.
DESIGN: Prospective observational study.
SETTINGS: Intensive care unit, university hospital (single center).
PARTICIPANTS: Single-lung transplant patients.
INTERVENTIONS: The authors compared cardiac index measured by PiCCO2 and pulmonary artery catheter and assessed pulmonary edema using extravascular lung water index and pulmonary vascular permeability index measured by PiCCO2.
MEASUREMENTS AND MAIN RESULTS: A Bland-Altman method was used to compare cardiac index measured by PiCCO2 and pulmonary artery catheter. Extravascular lung water index and pulmonary vascular permeability index were compared according to the PaO2/FiO2 ratio with a threshold value of 150 mmHg. Ten single-lung transplant patients were included. Cardiac index measured by PiCCO2 and pulmonary artery catheter were 3.3 L/min/m2 (2.9-3.6) and 2.5 L/min/m2 (2.2-3.0). Bias for cardiac index was 0.71 L/min/m2 (-0.03; 1.44) and limit of agreements were -0.03 and 1.44 L/min/m2. Extravascular lung water index was 12 mL/kg (11-16) and pulmonary vascular permeability index was 2.3 (2.0-3.1), consistent with pulmonary edema. Extravascular lung water index was higher in the group of PaO2/FiO2 ratio ≤150 mmHg compared with the group of PaO2/FiO2 ratio >150 mmHg (17 v 12 mL/kg, p = 0.04), whereas pulmonary vascular permeability index only tended to be higher (3.1 v 2.1, p = 0.06).
CONCLUSION: PiCCO2 device systematically overestimated cardiac index compared with pulmonary artery catheter. However, it might be useful to assess pulmonary edema in acute respiratory failure after single-lung transplantation.

PMID: 29203299 [PubMed - as supplied by publisher]

Examining the role of extracorporeal membrane oxygenation in patients following suspected or confirmed suicide attempts: A case series.

Wed, 12/06/2017 - 13:45
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Examining the role of extracorporeal membrane oxygenation in patients following suspected or confirmed suicide attempts: A case series.

J Crit Care. 2017 Oct 18;:

Authors: Abbasi A, Devers C, Muratore CS, Harrington C, Ventetuolo CE

Abstract
The decision to offer extracorporeal membrane oxygenation (ECMO) is based on a risk/benefit assessment and the likelihood of a treatable underlying condition or the feasibility of destination therapy (durable mechanical support or thoracic organ transplantation) should heart-lung function fail to improve. Patients who present following suspected suicide attempts who fail medical therapy may pose a dilemma for clinicians. An assessment to determine if a patient has a high likelihood of psychiatric recovery such that bridging with ECMO or ultimately destination therapy could or should be offered is not always feasible in the setting of critical illness. This case series reviews our institution's experience with ECMO in the management of five patients who presented following suspected or confirmed suicide attempts. All five patients survived to hospital discharge. Two had subsequent psychiatric admissions, one following a repeat suicide attempt. A discussion of these cases demonstrates the effectiveness of ECMO in supporting this group of patients in the short-term. The self-limited natural history of many psychiatric episodes, poisonings and traumatic injuries makes the use of ECMO a potentially reasonable support strategy. However, careful consideration must be given to psychiatric history and follow-up given the substantial commitment of resources, potential for complications and for stranding patients on extracorporeal therapy without definitive destination therapy.

PMID: 29203213 [PubMed - as supplied by publisher]

Prevalence of Pulmonary Infections Caused by Atypical Pathogens in non-HIV Immunocompromised Patients.

Wed, 12/06/2017 - 13:45
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Prevalence of Pulmonary Infections Caused by Atypical Pathogens in non-HIV Immunocompromised Patients.

Adv Exp Med Biol. 2016;935:1-11

Authors: Grabczak EM, Krenke R, Przybylski M, Kolkowska-Lesniak A, Chazan R, Dzieciatkowski T

Abstract
Although atypical bacteria are important causes of lower airway infections, data on their role in immunocompromised patients are scarce. The aim of the study was to evaluate the prevalence of atypical pulmonary infections in patients with various types of immunosuppression, and to analyze clinical characteristics of these infections. Eighty non-HIV immunocompromised patients with different underlying diseases and clinical and radiological signs of pulmonary infection were enrolled. Due to incomplete data on eight patients, 72 patients were eligible for final analysis (median age 58 years). All patients underwent fiberoptic bronchoscopy and bronchoalveolar lavage. Bronchoalveolar lavage fluid (BALF) fluid samples were sent for direct microscopy, cultures, and fungal antigen detection, when appropriate. Commercial qualitative amplification assay (PNEUMOTRIS oligomix Alert Kit(®)), based on nested PCR method, was used to detect specific DNA sequences of L. pneumophila, C. pneumoniae, and M. pneumoniae in BALF. There were 61 (84.7 %) patients with hematologic diseases, 3 (4.2 %) after solid organ transplantation, and 8 (11.1 %) with miscellaneous diseases affecting immune status. Specific sequences of M. pneumoniae, C. pneumoniae, and L. pneumophila DNA were found in 7 (9.7 %), 2 (2.8 %), and 0 patients, respectively. In 8 of these patients co-infections with different microorganisms were demonstrated. Co-infection with A. baumanii and P. aeruginosa was diagnosed in three patients who died. We conclude that atypical lower airway infections are uncommon in immunocompromised patients. The majority of these infections are co-infections rather than single pathogen infections.

PMID: 27334731 [PubMed - indexed for MEDLINE]

The relationship of SSRI and SNRI usage with interstitial lung disease and bronchiectasis in an elderly population: a case-control study.

Tue, 12/05/2017 - 13:45

The relationship of SSRI and SNRI usage with interstitial lung disease and bronchiectasis in an elderly population: a case-control study.

Clin Interv Aging. 2017;12:1977-1984

Authors: Rosenberg T, Lattimer R, Montgomery P, Wiens C, Levy L

Abstract
Background: The association between interstitial lung disease (ILD) and selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors (SSRI/SNRI) has been previously described in published case reports. However, its prevalence may be more common than expected. We examined the association between SSRI/SNRI usage and presence of ILD and or bronchiectasis (ILD/B) in an elderly population.
Methods: We conducted a retrospective case series and case-control study involving all 296 eligible elderly patients in one primary care geriatric practice in Victoria, BC, Canada. Cases required the presence of ILD/B on computed tomography (CT) or chest X-ray (CXR). Cases were excluded if they had other causes for ILD/B on CXR or CT such as exposure to known pneumotoxic drugs, metastatic cancer, rheumatoid lung disease, sarcoidosis, previous pulmonary tuberculosis, or pneumoconiosis. Data were abstracted from the patients' medical record. The exposure variable was standardized cumulative person-month (p-m) dose of SSRI/SNRI. The study was approved by the Clinical Research Ethics Board of University of British Columbia with a waiver of informed consent.
Results: A total of 12 cases and 273 controls were identified. Their mean ages were 89.0 and 88.7 years, respectively (p=0.862). A total of 10/12 cases and 99/273 controls were exposed to SSRI/SNRI. The odds ratio was 8.79, 95% confidence interval 2.40-32.23 (p=0.001). The median p-m exposure to SSRI/SNRI was 110.0 months for cases and 29.5 for controls (p=0.003).
Conclusion: SSRIs and SNRIs were significantly associated with the risk of ILD/B in this elderly population. Because of their widespread usage, further studies should be done to validate these findings. Prescribers should cautiously monitor patients for development of insidious pulmonary symptoms when these drugs are used.

PMID: 29200837 [PubMed - in process]

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

Tue, 12/05/2017 - 13:45

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

Perfusion. 2017 Dec 01;:267659117746234

Authors: Dennhardt N, Beck C, Boethig D, Heiderich S, Horke A, Tiedge S, Boehne M, Sümpelmann R

Abstract
BACKGROUND: During cardiopulmonary bypass (CPB) in children, anesthesia maintained by sevoflurane administered via the oxygenator is increasingly common. Anesthetic uptake and requirement may be influenced by the non-physiological conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may, therefore, be useful to guide the administration of sevoflurane during this phase.
OBJECTIVE: The objective of this prospective, clinical, observational study was to assess the correlation between body temperature, Narcotrend Index (NI) and administered sevoflurane in children during CPB.
METHODS: Forty-four children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied. On bypass, anesthesia was maintained with sevoflurane administered via the oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10 minutes. Expiratory gas was sampled from the oxygenator's sole expiratory port via a separate connecting line and the MAC was measured by the agent analyzer of the anesthesia machine.
RESULTS: Raw (r = 0.74) and corrected (r = 0.73) r-values show that narcosis depth (as indicated by NI) can primarily be explained by the interaction of MAC and temperature. The analysis of variance (without the interaction term) confirms the significant and independent association of both factors, MAC (p<0.004, 95%CI: 0.19 to 0.46) and temperature (p<0.0001, 95%CI: 0.68 to 0.78), with the NI. During hypothermia, sevoflurane had been reduced significantly (r = 0.41, p<0.0001, 95%CI: 0.33 to 0.48).
CONCLUSION: Perfusionists and anesthetists should be aware of the results of processed electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements differ inter-individually; they may decrease during cooling and increase during rewarming. Therefore, it seems reasonable to include the results of processed EEG monitoring when administering sevoflurane during CPB in children, but further studies are necessary to confirm this thesis.

PMID: 29199541 [PubMed - as supplied by publisher]

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

Tue, 12/05/2017 - 13:45

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

J Heart Lung Transplant. 2017 Nov 15;:

Authors: Ariyamuthu VK, Amin AA, Drazner MH, Araj F, Mammen PPA, Ayvaci M, Mete M, Ozay F, Ghanta M, Mohan S, Mohan P, Tanriover B

Abstract
BACKGROUND: Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED).
METHODS: We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up.
RESULTS: During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71).
CONCLUSION: r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge.

PMID: 29198930 [PubMed - as supplied by publisher]

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