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Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation.

Wed, 08/21/2013 - 10:08
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Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation.

Int J Oncol. 2013 Apr;42(4):1390-8

Authors: Zhang MH, Hu YD, Xu Y, Xiao Y, Luo Y, Song ZC, Zhou J

Abstract
Currently, some evidence suggests that human multipotential mesenchymal stems cells (hMSCs) aid tumor growth and metastasis. Nutrient deprivation and oxygen deficiency are representative characteristics of solid tumor microenvironment during the cancer development. Because the effects of hMSCs on tumors under stressful conditions have not been determined, we investigated the survival mechanisms used by stressed stromal cells on A549 and SPC-1 lung carcinoma cell lines in vitro and in vivo. An indirect culture system was used to investigate the effects of hMSCs on viability and apoptosis in starved carcinoma cells and focused on the role of autophagy in regulating the survival of carcinoma cells. The results showed that A549 and SPC-1 cells had higher viability when co-cultured with hMSCs and that this was mainly attributed to decreased apoptosis. Autophagosomes were analyzed using GFP-LC3 and electron microscopy, which showed that autophagy was significantly activated in the starved co-culture groups. However, the inhibition of autophagy by the autophagic inhibitor 3-MA significantly abrogated the apoptosis reduction in either single groups or co-culture groups under serum deprivation, which implied that the hMSCs protected against apoptosis by enhancing autophagy in lung carcinoma cells in vitro. We also observed that hMSCs promoted tumor initiation and growth in vivo. In conclusion, our study demonstrates that hMSCs can protect carcinoma cells from nutrient deprivation-induced apoptosis and promote tumor initiation and growth, and, interestingly, autophagy plays an important role in the survival of cancer cells.

PMID: 23403920 [PubMed - indexed for MEDLINE]

Long-term in vivo imaging of multiple organs at the single cell level.

Wed, 08/21/2013 - 10:08
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Long-term in vivo imaging of multiple organs at the single cell level.

PLoS One. 2013;8(1):e52087

Authors: Chen BJ, Jiao Y, Zhang P, Sun AY, Pitt GS, Deoliveira D, Drago N, Ye T, Liu C, Chao NJ

Abstract
Two-photon microscopy has enabled the study of individual cell behavior in live animals. Many organs and tissues cannot be studied, especially longitudinally, because they are located too deep, behind bony structures or too close to the lung and heart. Here we report a novel mouse model that allows long-term single cell imaging of many organs. A wide variety of live tissues were successfully engrafted in the pinna of the mouse ear. Many of these engrafted tissues maintained the normal tissue histology. Using the heart and thymus as models, we further demonstrated that the engrafted tissues functioned as would be expected. Combining two-photon microscopy with fluorescent tracers, we successfully visualized the engrafted tissues at the single cell level in live mice over several months. Four dimensional (three-dimensional (3D) plus time) information of individual cells was obtained from this imaging. This model makes long-term high resolution 4D imaging of multiple organs possible.

PMID: 23300962 [PubMed - indexed for MEDLINE]

Design, synthesis, and evaluation of a water-soluble antofine analogue with high antiproliferative and antitumor activity.

Wed, 08/21/2013 - 10:08
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Design, synthesis, and evaluation of a water-soluble antofine analogue with high antiproliferative and antitumor activity.

Bioorg Med Chem. 2013 Feb 15;21(4):1006-17

Authors: Kwon Y, Song J, Lee B, In J, Song H, Chung HJ, Lee SK, Kim S

Abstract
New water soluble antofine C-13a analogues were designed, synthesized, and evaluated for antiproliferative activity against cancer cells. Particularly, (-)-(R)-13a-hydroxymethylantofine ((-)-(R)-4b) demonstrated notable growth inhibition against a panel of human cancer cell lines. This growth inhibition was associated with the arrest of the cell cycle in the G0/G1 phases and suppression of mTOR signaling in human lung A549 cancer cells. Compound (-)-(R)-4b also overcame paclitaxel-resistance in human lung cancer cells (A549-Pa) by suppressing P-glycoprotein expression. Furthermore, compound (-)-(R)-4b significantly inhibited the tumor growth of A549 and A549-Pa xenografts in a nude mouse model, which suggests it is a promising novel antitumor agent with sufficient aqueous solubility.

PMID: 23294831 [PubMed - indexed for MEDLINE]

The red cell distribution width as a prognostic indicator in idiopathic pulmonary fibrosis.

Wed, 08/21/2013 - 10:08
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The red cell distribution width as a prognostic indicator in idiopathic pulmonary fibrosis.

Chest. 2013 Jun;143(6):1692-8

Authors: Nathan SD, Reffett T, Brown AW, Fischer CP, Shlobin OA, Ahmad S, Weir N, Sheridan MJ

Abstract
BACKGROUND: The course of idiopathic pulmonary fibrosis (IPF) is characterized by variable patterns of disease progression. The red cell distribution width (RDW) is a parameter that is routinely reported with all CBC counts. We sought to test the prognostic usefulness of this parameter in a well-defined cohort of patients with IPF.
METHODS: CBCs, demographics, and pulmonary function data from patients with IPF evaluated between January 1997 and June 2011 were collated. Patient outcomes were ascertained from the program's database and the Social Security Death Index.
RESULTS: There were 319 patients with IPF evaluated in whom baseline CBCs were available. The range in the RDW was 11.9 to 21.9 (median 14.1). There were 228 subjects with RDW values ≤ 15 (normal) and 91 patients with RDW values > 15. Patients with normal RDW values had a median survival of 43.1 months compared with 16.3 months for those whose RDW was > 15 (P = .001). There were 198 patients with available serial RDW data. Those patients who had a change in the RDW of less or greater than +0.010/mo had median survivals of 43.0 and 23.9 months, respectively (P = .0246).
CONCLUSIONS: The RDW is a readily available laboratory test result that may provide important, independent prognostic information at baseline and follow-up in patients with IPF. Further studies are warranted to validate this as a biomarker for IPF outcomes, as well as to define the biologic basis for this association.

PMID: 23238641 [PubMed - indexed for MEDLINE]

A placebo-controlled, randomized trial of mesenchymal stem cells in COPD.

Wed, 08/21/2013 - 10:08
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A placebo-controlled, randomized trial of mesenchymal stem cells in COPD.

Chest. 2013 Jun;143(6):1590-8

Authors: Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP

Abstract
BACKGROUND: COPD is a devastating disease affecting millions worldwide. As disease pathogenesis includes both chronic pulmonary and systemic inflammation, antiinflammatory effects of systemically administered mesenchymal stem cells (MSCs) may decrease inflammation, resulting in improved lung function and quality of life. The goal of this study was to assess safety and to perform an initial evaluation of the potential efficacy of systemic MSC administration to patients with moderate to severe COPD.
METHODS: Sixty-two patients at six sites were randomized to double-blinded IV infusions of either allogeneic MSCs (Prochymal; Osiris Therapeutics Inc) or vehicle control. Patients received four monthly infusions (100 × 10⁶ cells/infusion) and were subsequently followed for 2 years after the first infusion. End points included comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, 6MWT, and assessments of systemic inflammation.
RESULTS: All study patients completed the full infusion protocol, and 74% completed the 2-year follow-up. There were no infusional toxicities and no deaths or serious adverse events deemed related to MSC administration. There were no significant differences in the overall number of adverse events, frequency of COPD exacerbations, or worsening of disease in patients treated with MSCs. There were no significant differences in PFTs or quality-of-life indicators; however, an early, significant decrease in levels of circulating C-reactive protein (CRP) was observed in patients treated with MSCs who had elevated CRP levels at study entry.
CONCLUSIONS: Systemic MSC administration appears to be safe in patients with moderate to severe COPD and provides a basis for subsequent cell therapy investigations.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00683722; URL: www.clinicaltrials.gov.

PMID: 23172272 [PubMed - indexed for MEDLINE]

Response of CFTR-deficient mice to long-term chronic Pseudomonas aeruginosa infection and PTX3 therapy.

Wed, 08/21/2013 - 10:08
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Response of CFTR-deficient mice to long-term chronic Pseudomonas aeruginosa infection and PTX3 therapy.

J Infect Dis. 2013 Jul;208(1):130-8

Authors: Paroni M, Moalli F, Nebuloni M, Pasqualini F, Bonfield T, Nonis A, Mantovani A, Garlanda C, Bragonzi A

Abstract
BACKGROUND:  In cystic fibrosis (CF) patients, chronic lung infection and inflammation due to Pseudomonas aeruginosa contribute to the decline of lung function. The increased prevalence of multidrug resistance among bacteria and the adverse effects of antiinflammatory agents highlight the need for alternative therapeutic approaches that should be tested in a relevant animal model.
METHODS:  Gut-corrected CF and non-CF mice were chronically infected with a multidrug-resistant P. aeruginosa strain and treated with the long pentraxin PTX3. Body weight, bacterial count, inflammation, and lung pathology were evaluated after 12 days. PTX3 localization in CF sputum specimens was analyzed by immunofluorescence.
RESULTS:  Chronic P. aeruginosa infection developed similarly in CF and non-CF mice but differed in terms of the inflammatory response. Leukocyte recruitment in the airways, cytokine levels, and chemokine levels were significantly higher in CF mice, compared with non-CF mice. PTX3 treatment, which facilitates phagocytosis of pathogens, reduced P. aeruginosa colonization and restored airway inflammation in CF mice to levels observed in non-CF mice. The presence of PTX3 in CF sputum, in leukocytes, or bound to P. aeruginosa macrocolonies, as well as previous data on PTX3 polymorphisms in colonized CF patients, confirm the relevance of this molecule.
CONCLUSIONS:  These findings represent a step forward in demonstrating the therapeutic potential of PTX3 in CF.

PMID: 23087427 [PubMed - indexed for MEDLINE]

Hepatopulmonary syndrome: favorable outcomes in the MELD exception era.

Wed, 08/21/2013 - 10:08
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Hepatopulmonary syndrome: favorable outcomes in the MELD exception era.

Hepatology. 2013 Jun;57(6):2427-35

Authors: Iyer VN, Swanson KL, Cartin-Ceba R, Dierkhising RA, Rosen CB, Heimbach JK, Wiesner RH, Krowka MJ

Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long-term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2 ) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5-year P = 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post-LT survival of 19/21 patients and one wait-list death. Conclusion: Long-term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis. (HEPATOLOGY 2012).

PMID: 22996424 [PubMed - indexed for MEDLINE]

Successful surgical intervention in an unusual case of Aspergillus endocarditis with acute myeloid leukemia.

Fri, 08/16/2013 - 10:09

Successful surgical intervention in an unusual case of Aspergillus endocarditis with acute myeloid leukemia.

Acta Med Iran. 2013;51(7):506-8

Authors: Ansari Aval Z, Mirhosseini SM, Fakhri M, Mozaffary A, Adimi Naghan P, Behzadnia N, Ahmadi ZH

Abstract
Endocarditis due to Aspergillus infection is a rare complication in patients with hematological malignancies. Here, we present a case of aspergillus endocarditis in a patient with acute myeloid leukemia (AML) successfully treated with antifungal therapy and surgical treatment. The patient was a 51 years old male, a known case of AML who was admitted to our medical center for evacuating his valvular vegetations and repairing his atrial septal defect. He underwent an open heart surgery to relinquish his thromboses and also received an antifungal regimen. The patient tolerated the procedure well and eight months after his surgery, the patient remains asymptomatic. Successful treatment of this severe case of aspergillus endocarditis justifies a multidisciplinary method to be as a safe and effective approach to manage these patients.

PMID: 23945898 [PubMed - in process]

Stiff skin syndrome and myeloma successfully treated with autologous haematopoietic stem cell transplantation (HSCT).

Fri, 08/16/2013 - 10:09

Stiff skin syndrome and myeloma successfully treated with autologous haematopoietic stem cell transplantation (HSCT).

Clin Exp Rheumatol. 2013 Mar-Apr;31(2 Suppl 76):181-3

Authors: Bandinelli F, Saccardi R, Salvadorini G, Bosi A, Gozzini A, Matucci Cerinic M

Abstract
Stiff skin syndrome (SSS) is a rare scleroderma-like syndrome characterised by stone hard skin, joint limitation and progressive restriction of chest that may lead to death. We describe the efficacy of haematopoietic autologous stem cell transplantation (HSCT) in a case of SSS secondary to a smouldering myeloma (SM), with severe joint disability, lung interstitial disease and oesophageal dysfunction. The patient was evaluated at 1, 12 and 18 months after HSCT, clinically (joint motility, HAQ and NYHA for dyspnoea) and instrumentally (DLCO, chest HRCT, oesophagus x-ray). After 18 months since HSCT, we observed a high improvement, contemporaneously to SM remission, of HAQ, joint motility, lung (at DLCO and HRCT) and oesophageal abnormalities.

PMID: 23910622 [PubMed - in process]

Glucocorticoids in systemic sclerosis: weighing the benefits and risks - a systematic review.

Fri, 08/16/2013 - 10:09

Glucocorticoids in systemic sclerosis: weighing the benefits and risks - a systematic review.

Clin Exp Rheumatol. 2013 Mar-Apr;31(2 Suppl 76):157-65

Authors: Iudici M, van der Goes MC, Valentini G, Bijlsma JW

Abstract
OBJECTIVES: To identify indications for which different dosages of glucocorticoids (GCs) have been prescribed in systemic sclerosis (SSc), and to assess the efficacy and safety of GCs in SSc.
METHODS: A literature search focusing on experimental studies, observational studies, and case reports describing GC use in SSc was conducted using PubMed, EMBASE and Cochrane databases. Information about the study population, GC therapy and its effects was recorded. Available data have been summarised, and efficacy and safety of GCs have been assessed for different indications and dosages.
RESULTS: Forty-four studies and 93 case reports were included in this review. GCs were applied in the treatment of interstitial lung disease (ILD), diffuse cutaneous disease, myopathy, painful hands and cardiac involvement, or accompanying anti-thymocyte globulin to prevent serum sickness in the context of stem cell transplantation. GCs were used in different dosages, predominantly in combination with other immunosuppressive treatments. Monotherapy with GCs led to inconsistent results. Most adverse events recorded were infections. Twenty-three cases of scleroderma renal crisis (SRC) have been reported, mainly in patients with early diffuse disease (n=10) or with anti-thymocyte treatment (n=10). These patients were treated with low to medium dose GCs (n=10), high-dose GCs (n=11) and pulse therapy (n=2).
CONCLUSIONS: Evidence of a beneficial role of GCs in SSc is limited. GCs have been part of the therapeutic strategy in the management of ILD, diffuse cutaneous disease or myositis. Awareness for the risk of SRC should persist, especially in patients with diffuse disease who are also treated with possibly nephrotoxic drugs.

PMID: 23910618 [PubMed - in process]

TNFα, TGFβ, pseudomonas and classically activated macrophages conspire to reprogram the airways in obliterative bronchiolitis.

Fri, 08/16/2013 - 10:09
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TNFα, TGFβ, pseudomonas and classically activated macrophages conspire to reprogram the airways in obliterative bronchiolitis.

Am J Transplant. 2013 Mar;13(3):537-8

Authors: Neujahr DC

PMID: 23332019 [PubMed - indexed for MEDLINE]

Clinical Manifestations and Management of Left Ventricular Assist Device-Associated Infections.

Thu, 08/15/2013 - 12:45

Clinical Manifestations and Management of Left Ventricular Assist Device-Associated Infections.

Clin Infect Dis. 2013 Aug 13;

Authors: Nienaber JJ, Kusne S, Riaz T, Walker RC, Baddour LM, Wright AJ, Park SJ, Vikram HR, Keating MR, Arabia FA, Lahr BD, Sohail MR, for the Mayo Cardiovascular Infections Study Group

Abstract
Background. Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADI) are limited by single center experiences and use of non-standardized definitions. Methods. We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADI were defined using the International Society for Heart and Lung Transplantation criteria. Results. We identified 101 episodes of LVADI in 78 (32%) patients from this cohort. Mean age was 57 (±15) years. The majority underwent Heartmate II (94%) implantation, with 62% placed as destination therapy. The most common type of LVADI were driveline infections (47%), followed by bloodstream infections (24% VAD-related, 22% non-VAD related). Most common causative pathogens include gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. Average duration of LVAD support was 1.5 (±1.0) years. At 2-year follow-up, the cumulative incidence for all-cause mortality was estimated at 43%. Conclusion. Clinical manifestations of LVADI vary based on the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.

PMID: 23943820 [PubMed - as supplied by publisher]

Screening guidelines for non-AIDS defining cancers in HIV-infected individuals.

Thu, 08/15/2013 - 12:45

Screening guidelines for non-AIDS defining cancers in HIV-infected individuals.

Curr Opin Oncol. 2013 Sep;25(5):518-25

Authors: Mani D, Aboulafia DM

Abstract
PURPOSE OF REVIEW: The growing burden of non-AIDS defining malignancies (non-ADMs) among people living with HIV/AIDS (PLWHA) highlights the need for cancer prevention and early detection. In this article, we propose screening guidelines for non-ADMs in PLWHA.
RECENT FINDINGS: A number of recent findings may help direct cancer screening guidelines in PLWHA. Screening for lung cancer with low-dose helical chest computerized tomography (LDCT) in the National Lung Screening Trial data demonstrated a decrease in lung cancer and all-cause mortality. Recent studies have demonstrated a favorable experience among PLWHA with liver transplantation. Overdiagnosis is common with breast and prostate cancer screening. Anal cancer rates were substantially higher for HIV-infected MSM, other men and women than for HIV-uninfected individuals.
SUMMARY: Screening recommendations for the general population can be applied to PLWHA patients for breast, colon and prostate cancer. Screening for lung cancer with LDCT could be considered in PLWHA at risk. American Association for the Study of Liver Diseases screening recommendations with biennial ultrasonography may be applied to at-risk PLWHA for hepatocellular carcinoma. All HIV-infected adults should be offered anal cancer screening as part of clinical care at specialized centres.

PMID: 23942295 [PubMed - in process]

The effects of storage and sterilization on de-cellularized and re-cellularized whole lung.

Thu, 08/15/2013 - 12:45
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The effects of storage and sterilization on de-cellularized and re-cellularized whole lung.

Biomaterials. 2013 Apr;34(13):3231-45

Authors: Bonenfant NR, Sokocevic D, Wagner DE, Borg ZD, Lathrop MJ, Lam YW, Deng B, Desarno MJ, Ashikaga T, Loi R, Weiss DJ

Abstract
Despite growing interest on the potential use of de-cellularized whole lungs as 3-dimensional scaffolds for ex vivo lung tissue generation, optimal processing including sterilization and storage conditions, are not well defined. Further, it is unclear whether lungs need to be obtained immediately or may be usable even if harvested several days post-mortem, a situation mimicking potential procurement of human lungs from autopsy. We therefore assessed effects of delayed necropsy, prolonged storage (3 and 6 months), and of two commonly utilized sterilization approaches: irradiation or final rinse with peracetic acid, on architecture and extracellular matrix (ECM) protein characteristics of de-cellularized mouse lungs. These different approaches resulted in significant differences in both histologic appearance and in retention of ECM and intracellular proteins as assessed by immunohistochemistry and mass spectrometry. Despite these differences, binding and proliferation of bone marrow-derived mesenchymal stromal cells (MSCs) over a one month period following intratracheal inoculation was similar between experimental conditions. In contrast, significant differences occurred with C10 mouse lung epithelial cells between the different conditions. Therefore, delayed necropsy, duration of scaffold storage, sterilization approach, and cell type used for re-cellularization may significantly impact the usefulness of this biological scaffold-based model of ex vivo lung tissue regeneration.

PMID: 23380353 [PubMed - indexed for MEDLINE]

Therapeutic drug monitoring of ciclosporin A and tacrolimus in heart lung transplant patients using dried blood spots.

Wed, 08/14/2013 - 12:45

Therapeutic drug monitoring of ciclosporin A and tacrolimus in heart lung transplant patients using dried blood spots.

Ann Clin Biochem. 2013 Aug 12;

Authors: Hinchliffe E, Adaway J, Fildes J, Rowan A, Keevil BG

Abstract
BACKGROUND: Therapeutic drug monitoring of ciclosporin A (CsA) and tacrolimus is traditionally performed using venous whole blood sampling. A number of reports have described development of ultra high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for the quantitation of CsA and tacrolimus from dried blood spots (DBS), which may offer a convenient alternative. As yet, no such reports have validated this methodology using fingerprick capillary DBS samples collected from transplant patients.
METHODS: Capillary fingerprick DBS were collected from heart and lung transplant patients in a specialist cardiothoracic transplant centre. We utilized our previously published method for the extraction and simultaneous quantitation of CsA and tacrolimus from DBS using UPLC-MS/MS. Drug concentrations measured from DBS were compared to concentrations measured in venous whole blood by our routine clinical UPLC-MS/MS assay.
RESULTS: In total, 91 heart or lung transplant patients were enrolled onto the study; 46 patients were on CsA therapy and 45 on tacrolimus therapy. Passing-Bablock analysis demonstrated excellent agreement between capillary fingerprick DBS samples and venous whole blood samples. There was a mean positive bias of 2.6 µg/L (95% confidence interval (CI) -2.2 to 7.5 µg/L) for CsA (n = 45) and mean negative bias of -0.7 µg/L (95% CI -1.1 to -0.3 µg/L) for tacrolimus (n = 42).
CONCLUSIONS: We demonstrate utility of DBS for serial monitoring of CsA and tacrolimus using UPLC-MS/MS in heart and lung transplant patients. This may offer significant advantages for these patients including the ability to take capillary DBS samples in the community prior to clinic visits.

PMID: 23939194 [PubMed - as supplied by publisher]

Continuous-flow left ventricular assist device exchange: Clinical outcomes.

Wed, 08/14/2013 - 12:45

Continuous-flow left ventricular assist device exchange: Clinical outcomes.

J Heart Lung Transplant. 2013 Aug 9;

Authors: Ota T, Yerebakan H, Akashi H, Takayama H, Uriel N, Colombo PC, Jorde UP, Naka Y

Abstract
BACKGROUND: A percentage of patients with a left ventricular assist device (LVAD) require device exchange. Although this is an important clinical entity, there are only a handful of relevant studies on this topic in the literature.
METHODS: From 2004 to 2012, 30 device exchanges (HeartMate II to HeartMate II) were performed. Since June 2011, we have employed the subcostal approach for device exchange if indicated. Sixteen patients underwent device exchange through a subcostal approach (S group), whereas 14 patients had devices exchanged through a full sternotomy (F group). Pre- and post-operative data were retrospectively reviewed.
RESULTS: There was no difference in baseline patient characteristics between the two groups. Overall, mean duration between primary surgery and device exchange was 425 ± 407 days. Surgical indications included device thrombus/hemolysis (N = 19), device malfunction (N = 9) and infection (N = 2). Cardiopulmonary bypass time was significantly shorter in the S group (S: 40 ± 23 minutes, F: 105 ± 84 minutes; p < 0.05), and post-operative bleeding within 24 hours after surgery was less in the S group (S: 362 ± 367 ml, F: 1,286 ± 971 ml; p < 0.05). Length of ICU stay was significantly shorter in the S group (S: 4.6 ± 1.8 days, F: 8.2 ± 4.9 days; p < 0.05). There was no difference in post-operative complications, except for prolonged intubation (F: N = 6 [43%], S: N = 1 [6.3%]; p < 0.05). There were 3 deaths in the F group and 0 in the S group, with no statistical difference (p = 0.09). Also, there was no significant difference in other outcomes, including transplantation, device explantation and ongoing LVAD support.
CONCLUSIONS: A subcostal approach may be preferred for HeartMate II device exchange if indicated.

PMID: 23937885 [PubMed - as supplied by publisher]

Tissue Doppler imaging for rejection surveillance in pediatric heart transplant recipients.

Wed, 08/14/2013 - 12:45

Tissue Doppler imaging for rejection surveillance in pediatric heart transplant recipients.

J Heart Lung Transplant. 2013 Aug 9;

Authors: Lunze FI, Colan SD, Gauvreau K, Perez-Atayde AR, Smith RN, Blume ED, Singh TP

Abstract
BACKGROUND: Most transplant centers perform serial cardiac biopsies for rejection surveillance in pediatric heart transplant (HT) recipients. We sought to assess tissue Doppler imaging (TDI) findings during biopsy specimen-proven rejection in pediatric HT recipients and to develop TDI criteria for absence of rejection with high predictive accuracy.
METHODS: We included the 122 HT recipients in follow-up at our center (median age at HT, 8.7 years). We identified all echocardiograms with adequate TDI data performed within 24 hours of a cardiac biopsy during 2005 to 2011. Rejection was defined as Grade ≥ 2R cellular rejection or antibody-mediated rejection. Paired comparisons of TDI velocities were made using patients' baseline velocities as the control.
RESULTS: Overall, 647 specimen-pairs were identified where there was no rejection at baseline. In 24 of these, the second biopsy specimen demonstrated rejection. Using receiver operating characteristic curve analysis of percentage change from baseline, we identified < 15% decline in left ventricular (LV) S' velocity and < 5% decline in LV A' velocity to individually predict non-rejection with > 99% accuracy. When joint criteria were used, the predictive accuracy was 100%, and no rejection event was misclassified. More than 75% of TDI pairs met these criteria for non-rejection.
CONCLUSIONS: Biopsy specimen-proven rejection is associated with a significant decline in biventricular TDI velocities from baseline in pediatric HT recipients. By using well-defined TDI criteria to predict non-rejection, a substantial proportion of planned biopsies may be deferred or avoided at minimal risk to pediatric HT recipients.

PMID: 23937884 [PubMed - as supplied by publisher]

Aortic valve opening and thrombotic events with continuous-flow left ventricular assist devices.

Wed, 08/14/2013 - 12:45

Aortic valve opening and thrombotic events with continuous-flow left ventricular assist devices.

J Heart Lung Transplant. 2013 Aug 9;

Authors: Saeed O, Maybaum S, Alessandro DD, Goldstein DJ, Patel SR

PMID: 23937883 [PubMed - as supplied by publisher]

Fondaparinux: An effective bridging strategy in heparin-induced thrombocytopenia and mechanical circulatory support.

Wed, 08/14/2013 - 12:45

Fondaparinux: An effective bridging strategy in heparin-induced thrombocytopenia and mechanical circulatory support.

J Heart Lung Transplant. 2013 Aug 9;

Authors: Gellatly RM, Leet A, Brown KE

PMID: 23937882 [PubMed - as supplied by publisher]

[Lung transplantation in sporadic lymphangioleiomyomatosis: Study of 7 cases.]

Wed, 08/14/2013 - 12:45

[Lung transplantation in sporadic lymphangioleiomyomatosis: Study of 7 cases.]

Med Clin (Barc). 2013 Aug 9;

Authors: Ansótegui Barrera E, Mancheño Franch N, Peñalver Cuesta JC, Vera-Sempere F, Padilla Alarcón J

Abstract
BACKGROUND AND OBJECTIVE: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare disease that affects only women. It is characterized by an abnormal proliferation of immature smooth muscle cells (LAM cells) that grow in an aberrant manner in the airway, parenchymal lung lymph and blood vessels, determining the onset of pulmonary cystic lesions. The disease has no treatment, progressing to respiratory failure, and lung transplantation (LT) may be a treatment option at this stage. Our goal was to study 7 patients undergoing LT for S-LAM.
MATERIAL AND METHOD: We studied a series of clinical and demographic characteristics, diagnostic modality and post-transplant outcomes. We performed a descriptive analysis of the series. The Kaplan-Meier method was used to estimate survival.
RESULTS: The mean age of onset of symptoms was 35 years, the diagnosis of 37 years and that of LT 38 years. The most common symptom was dyspnea. Four patients had a history of pneumothorax and pleural effusion. The mean forced expiratory volume in one second was 32.7% and the diffusing capacity for carbon monoxide was 29%. All patients were subjected to LT and survival was 100, 85.7 and 57.1% at one, 3 and 5 years, respectively. Three died of bronchiolitis obliterans and 2 necropsies did not show evidence of disease recurrence.
CONCLUSIONS: LT is a therapeutic option in patients with S-LAM with an advanced respiratory functional impairment.

PMID: 23937818 [PubMed - as supplied by publisher]

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