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Inhibition of Endoplasmic Reticulum Stress Alleviates Lung Injury Induced by Brain Death.

Sat, 07/29/2017 - 12:45
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Inhibition of Endoplasmic Reticulum Stress Alleviates Lung Injury Induced by Brain Death.

Inflammation. 2017 Jul 27;:

Authors: Tang H, Zhang J, Cao S, Yan B, Fang H, Zhang H, Guo W, Zhang S

Abstract
Brain death (BD) can induce inflammation and injury of organs. Endoplasmic reticulum (ER) stress is associated with a variety of diseases. However, little is known about how ER stress is implicated in brain death (BD)-induced lung injury. In this study, a stable BD rat model was constructed to investigate the role of ER stress on BD-induced lung injury. H&E staining demonstrated that BD can induce lung injury in rats. The results of Western blot and immunohistochemistry showed that apoptosis was observed in the lung tissues of BD rats. And the level of GRP78, p-PERK, p-eIF2α, CHOP, and Caspase-12 was highly expressed in BD rats compared with the control group. Inhibition of ER stress with salubrinal reduced the BD-induced lung inflammation. Moreover, BD-induced increase of NF-κB activity was lowered by inhibition of ER stress. These results suggested that inhibition of ER stress alleviates BD-induced lung inflammation by regulating NF-κB signaling pathway.

PMID: 28752363 [PubMed - as supplied by publisher]

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation.

Sat, 07/29/2017 - 12:45
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Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation.

Front Med. 2017 Jul 28;:

Authors: Gao F, Chen J, Wei D, Wu B, Zhou M

Abstract
Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

PMID: 28752350 [PubMed - as supplied by publisher]

Extracorporeal Membrane Oxygenation Support for Rituximab-Induced Acute Respiratory Distress Syndrome in an ABO-Incompatible Living Donor Liver Transplant Recipient: Successful Management of a Rare Complication and a Review of the Literature.

Sat, 07/29/2017 - 12:45
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Extracorporeal Membrane Oxygenation Support for Rituximab-Induced Acute Respiratory Distress Syndrome in an ABO-Incompatible Living Donor Liver Transplant Recipient: Successful Management of a Rare Complication and a Review of the Literature.

Ann Transplant. 2017 Jul 28;22:463-467

Authors: Li PC, Thorat A, Hsu SC, Poon KS, Yang HR, Chen TH, Yeh CC, Jeng LB

Abstract
BACKGROUND Rituximab is commonly used to reduce the agglutinin titer in ABO-incompatible liver transplant recipients. Although well-tolerated, rituximab infusion therapy may result in severe pulmonary adverse effects such as drug-induced pneumonitis, leading to acute respiratory distress syndrome (ARDS), which has a high mortality rate. Management of such rare cases in an ABO-incompatible patient has never been described before. Herein, we present successful use of extracorporeal membrane oxygenation (ECMO) support for rituximab-induced ARDS in an ABO-incompatible living donor liver transplantation (LDLT) recipient. CASE REPORT A 57-year-old man patient presented with acute-on-chronic hepatic failure. Due to worsening clinical condition and unavailability of a deceased donor organ, ABO-incompatible LDLT was considered. The patient received rituximab therapy and plasmapheresis 1 week before the transplantation to reduce the B cell count. However, he suddenly developed acute respiratory distress-like symptoms, with a chest X-ray suggesting organized pneumonia. Infectious etiology was excluded as evidenced from negative sputum and blood culture, which were repeated after 48 h. LDLT was performed and ECMO support was instituted in the immediate postoperative period due to worsening of the ARDS. The pulmonary signs improved, with a chest X-ray showing clear lung fields on the 5th postoperative day. The patient recovered well and was discharged with normal liver functions in the 4th postoperative month. CONCLUSIONS This is first reported experience of successful use of ECMO in an ABO-incompatible liver transplant recipient with rituximab-induced ARDS. This experience shows the feasibility and effectiveness of ECMO support in liver transplant recipients with poor respiratory functions.

PMID: 28751632 [PubMed - in process]

Persistent air leak after pulmonary transplantation.

Sat, 07/29/2017 - 12:45
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Persistent air leak after pulmonary transplantation.

BMJ Case Rep. 2017 Jul 27;2017:

Authors: Pearmain L, Krysiak P, Blaikley J, Alaloul M

Abstract
A 59-year-old man with bilateral apical emphysema underwent a double lung transplant for end-stagechronic obstructive pulmonary disease leaving remnant right apical native tissue due to pleural adhesions. Initial postoperative course was uneventful until the chest drains were removed. This revealed a small pneumomediastinum, which progressively increased in size causing gross surgical emphysema. Re-insertion of the chest drain stabilised the patient so that the cause could be identified and corrected. Two bronchoscopies excluded anastomotic dehiscence as a cause. Therefore the subcostal wound was refashioned under video-assisted thoracoscopic surgery in case there was a defect. Unfortunately this also failed to halt the air leak; therefore another cause was sought. A multidisciplinary team meeting review of the radiology revealed that the patient's native bullous tissue was still inflated. Subsequent bronchoscopy revealed a native bronchial communication, due to variant anatomy, proximal to the surgical anastomosis. This was subsequently occluded using a bronchial valve allowing the patient to make a swift recovery.

PMID: 28751430 [PubMed - in process]

SERCA2a: A potential non-invasive biomarker of cardiac allograft rejection.

Sat, 07/29/2017 - 12:45
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SERCA2a: A potential non-invasive biomarker of cardiac allograft rejection.

J Heart Lung Transplant. 2017 Jul 05;:

Authors: Tarazón E, Ortega A, Gil-Cayuela C, Sánchez-Lacuesta E, Marín P, Lago F, González-Juanatey JR, Martínez-Dolz L, Portolés M, Rivera M, Roselló-Lletí E

Abstract
BACKGROUND: The detection of heart transplant rejection by non-invasive methods remains a major challenge. Despite the well-known importance of the study of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in the heart, its role as a rejection marker has never been analyzed. Our objective in this study was to determine whether circulating SERCA2a could be a good marker of cardiac rejection.
METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs) and serum samples from adult heart transplant recipients (49 without allograft rejection and 78 with the diagnosis of biopsy allograft rejection, including 48 Grade 1R, 21 Grade 2R and 9 Grade 3R). Serum concentrations of SERCA2a were determined using a specific sandwich enzyme-linked immunosorbent assay. We also analyzed SERCA2a expression changes on EMBs using immunofluorescence.
RESULTS: SERCA2a cardiac tissue and serum levels were decreased in patients with cardiac rejection (p < 0.0001). A receiver-operating characteristic analysis showed that SERCA2a strongly discriminated between patients with and without allograft rejection: normal grafts vs all rejecting grafts (AUC = 0.804); normal grafts vs Grade 1R (AUC = 0.751); normal grafts vs Grade 2R (AUC = 0.875); normal grafts vs Grade 3R (AUC = 0.922); normal grafts vs Grade 2R and 3R (AUC = 0.889), with p < 0.0001 for all comparisons.
CONCLUSIONS: We demonstrated that changes in SERCA2a cardiac tissue and serum levels occur in cardiac allograft rejection. Our findings suggest that SERCA2a concentration assessment may be a relatively simple, non-invasive test for heart transplant rejection, showing a strong capability for detection that improves progressively as rejection grades increase.

PMID: 28750934 [PubMed - as supplied by publisher]

Association between antibody functions and human cytomegalovirus (HCMV) replication after lung transplantation in HCMV-seropositive patients.

Sat, 07/29/2017 - 12:45
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Association between antibody functions and human cytomegalovirus (HCMV) replication after lung transplantation in HCMV-seropositive patients.

J Heart Lung Transplant. 2017 Jul 18;:

Authors: Vietzen H, Görzer I, Honsig C, Jaksch P, Puchhammer-Stöckl E

PMID: 28750933 [PubMed - as supplied by publisher]

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

Sat, 07/29/2017 - 12:45
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Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

J Heart Lung Transplant. 2017 Jul 01;:

Authors: Lankeit M, Krieg V, Hobohm L, Kölmel S, Liebetrau C, Konstantinides S, Hamm CW, Mayer E, Wiedenroth CB, Guth S

Abstract
BACKGROUND: Management and outcome of patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) who underwent pulmonary endarterectomy (PEA) at a large German referral center were investigated.
METHODS: In Germany, 394 PEAs were performed in 2014 and 2015 with an in-hospital mortality rate of 5.8%. Of these, 253 patients (64.2%) were treated at the Kerckhoff Clinic, Bad Nauheim, and 237 (93.7%; median age, 62 years [interquartile range [IQR], 52-72 years]; 46.0% female) were included in the present analysis.
RESULTS: On referral, 52 patients (22.0%) were treated with pulmonary arterial hypertension-specific drugs and 95 (40.4%) were treated with non-vitamin K-dependent oral anticoagulants, and 14 (5.9%) had mean pulmonary artery pressure <25 mm Hg and were classified as having chronic thromboembolic pulmonary vascular disease. PEA was feasible in 236 (99.6%) patients with median duration of surgery of 397 minutes (IQR, 363-431 minutes). Periprocedural (0%) and in-hospital (2.5%) mortality rates were very low. Forty-two patients (17.7%) had intraoperative complications, and 60 (25.3%) had post-operative complications. The duration of surgery was the only predictor of in-hospital mortality (≥500 minutes; odds ratio [OR], 32.0; 95% confidence interval [CI], 5.5-187.6) and the only independent predictor of intraoperative (≥440 minutes; OR, 10.8; 95% CI, 4.4-26.5) and post-operative (≥390 minutes; OR, 2.4; 95%CI, 1.1-5.7) complications. Only intraoperative complications independently predicted a longer duration of surgery (≥397 minutes; OR, 5.0; 95% CI, 2.2-11.2).
CONCLUSIONS: In an experienced center with multidisciplinary diagnostic and therapeutic approaches, PEA is safe. Prognosis was mainly determined by occurrence of intraoperative complications and duration of surgery rather than patients' pre-operative status.

PMID: 28750932 [PubMed - as supplied by publisher]

Diagnosis and Treatment of Mucormycosis in Patients with Hematological Malignancies.

Sat, 07/29/2017 - 12:45
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Diagnosis and Treatment of Mucormycosis in Patients with Hematological Malignancies.

Med Mycol J. 2016;57(4):J155-J162

Authors: Asano-Mori Y

Abstract
The risk of invasive fungal infections (IFIs) is extremely high in patients with hematological malignancies due to the prolonged and profound neutropenia and immunosuppression after chemotherapy and hematopoietic stem cell transplantation. There has been increasing interest in mucormycosis despite its relatively uncommon occurrence, because occasional breakthrough infections have been observed under anti-aspergillus prophylaxis. The aggressive nature of mucormycosis easily leads to high mortality because of delays in diagnosis and incorrect treatment decisions, which are due in part to lack of adjunctive diagnostic tools and having similar clinical and radiological features with aspergillosis. The only currently available antifungals against Mucorales in Japan are amphotericin B formulations. Thus, comprehensive therapeutic strategies, including surgery, should be considered in order to achieve a successful outcome.

PMID: 27904061 [PubMed - indexed for MEDLINE]

Rac1-mediated cytoskeleton rearrangements induced by intersectin-1s deficiency promotes lung cancer cell proliferation, migration and metastasis.

Sat, 07/29/2017 - 12:45
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Rac1-mediated cytoskeleton rearrangements induced by intersectin-1s deficiency promotes lung cancer cell proliferation, migration and metastasis.

Mol Cancer. 2016 Sep 14;15(1):59

Authors: Jeganathan N, Predescu D, Zhang J, Sha F, Bardita C, Patel M, Wood S, Borgia JA, Balk RA, Predescu S

Abstract
BACKGROUND: The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied.
METHODS: Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies. In addition scratch assay with time lapse microscopy and in vivo xenograft tumor and mouse metastasis assays were performed.
RESULTS: ITSN-1s, a prevalent protein of lung tissue, is significantly downregulated in human LC cells and LC tissue. Restoring ITSN-1s protein level decreases LC cell proliferation and clonogenic potential. In vivo studies indicate that immunodeficient mice injected with A549 + ITSN-1s cells develop less and smaller metastatic tumors compared to mice injected with A549 cells. Our studies also show that restoring ITSN-1s protein level increases the interaction between Cbl E3 ubiquitin ligase and Eps8 resulting in enhanced ubiquitination of the Eps8 oncoprotein. Subsequently, downstream unproductive assembly of the Eps8-mSos1 complex leads to impaired activation of the small GTPase Rac1. Impaired Rac1 activation mediated by ITSN-1s reorganizes the cytoskeleton (increased thick actin bundles and focal adhesion (FA) complexes as well as collapse of the vimentin filament network) in favor of decreased LC cell migration and metastasis.
CONCLUSION: ITSN-1s induced Eps8 ubiquitination and impaired Eps8-mSos1 complex formation, leading to impaired activation of Rac1, is a novel signaling mechanism crucial for abolishing the progression and metastatic potential of LC cells.

PMID: 27629044 [PubMed - indexed for MEDLINE]

ErbB2 and p38γ MAPK mediate alcohol-induced increase in breast cancer stem cells and metastasis.

Sat, 07/29/2017 - 12:45
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ErbB2 and p38γ MAPK mediate alcohol-induced increase in breast cancer stem cells and metastasis.

Mol Cancer. 2016 Jul 14;15(1):52

Authors: Xu M, Ren Z, Wang X, Comer A, Frank JA, Ke ZJ, Huang Y, Zhang Z, Shi X, Wang S, Luo J

Abstract
BACKGROUND: Both epidemiological and experimental studies suggest that excessive alcohol exposure increases the risk for breast cancer and enhances metastasis/recurrence. We have previously demonstrated that alcohol enhanced the migration/invasion of breast cancer cells and cancer cells overexpressing ErbB2/HER2 were more sensitive to alcohol exposure. However, the underlying mechanisms remain unclear. This study was designed to investigate the mechanisms underlying alcohol-enhanced aggressiveness of breast cancer. Cancer stem cells (CSCs) play a critical role in cancer metastasis and recurrence.
METHODS: We evaluated the effect of chronic alcohol exposure on mammary tumor development/metastasis in MMTV-neu transgenic mice and investigated the cell signaling in response to alcohol exposure in breast cancer cells overexpressing ErbB2/HER2. RESULTS AND DISCUSSION: Chronic alcohol exposure increased breast cancer stem cell-like CSC population and enhanced the lung and colon metastasis in MMTV-neu transgenic mice. Alcohol exposure caused a drastic increase in CSC population and mammosphere formation in breast cancer cells overexpressing ErbB2/HER2. Alcohol exposure stimulated the phosphorylation of p38γ MAPK (p-p38γ) which was co-localized with phosphorylated ErbB2 and CSCs in the mammary tumor tissues. In vitro results confirmed that alcohol activated ErbB2/HER2 and selectively increased p-p38γ MAPK as well as the interaction between p38γ MAPK and its substrate, SAP97. However, alcohol did not affect the expression/phosphorylation of p38α/β MAPKs. In breast cancer cell lines, high expression of ErbB2 and p-p38γ MAPK was generally correlated with more CSC population. Blocking ErbB2 signaling abolished heregulin β1- and alcohol-stimulated p-p38γ MAPK and its association with SAP97. More importantly, p38γ MAPK siRNA significantly inhibited an alcohol-induced increase in CSC population, mammosphere formation and migration/invasion of breast cancer cells overexpressing ErbB2.
CONCLUSIONS: p38γ MAPK is downstream of ErbB2 and plays an important role in alcohol-enhanced aggressiveness of breast cancer. Therefore, in addition to ErbB2/HER2, p38γ MAPK may be a potential target for the treatment of alcohol-enhanced cancer aggressiveness.

PMID: 27416801 [PubMed - indexed for MEDLINE]

Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability.

Sat, 07/29/2017 - 12:45
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Preparation and Evaluation of Oxaliplatin Thermosensitive Liposomes with Rapid Release and High Stability.

PLoS One. 2016;11(7):e0158517

Authors: Zeng C, Yu F, Yang Y, Cheng X, Liu Y, Zhang H, Zhao S, Yang Z, Li M, Li Z, Mei X

Abstract
Oxaliplatin (OXP) was reported to show low anti-tumor activity when used alone and to display side effects; this low activity was attributed to high partitioning to erythrocytes and low accumulation in tumors. Thermosensitive liposomes (TSL) were considered able to specifically deliver drugs to heated tumors and to resolve the OXP distribution problem. Regretfully, TSL encapsulating doxorubicin did not demonstrate significant improvement in progression-free survival. Drug release below 41°C and significant leakage were considered major reasons for the failure. The purpose of this study was to acquire OXP TSL with rapid release at the triggered temperature and high stability at body temperature and at storage temperatures. A small quantity of poloxamer 188 was introduced into the TSL formulation to stabilize the encapsulated drug. It was shown that the addition of poloxamer 188 had no influence on the TSL characteristics. More than 90% of OXP was released within 10 min at 42°C, and less than 15% was released within 60 min at temperatures below 39°C. TSL were stable at 37°C for 96 h and at 4°C for 6 months. The anti-tumor activity of TSL at the dose of 2.5 mg/kg was certified to be equal to those of OXP injection and non-thermosensitive liposomes (NTSL) at the dose of 5 mg/kg, and significant improvement of tumor inhibition was observed in TSL compared with injection and NTSL at the same dose. It was also shown from the histological transmutation of tumors that TSL had stronger anti-tumor activity. Therefore, it could be concluded that TSL composed of a proper amount of poloxamer had rapid release and high stability, and OXP TSL would be anticipated to exert prominent anti-tumor activity in the clinic.

PMID: 27415823 [PubMed - indexed for MEDLINE]

Solid Organ Transplantation in Sarcoidosis.

Fri, 07/28/2017 - 12:45
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Solid Organ Transplantation in Sarcoidosis.

Semin Respir Crit Care Med. 2017 Aug;38(4):538-545

Authors: Yserbyt J, Wuyts WA, Verleden SE, Verleden GM, Van Raemdonck DE, Verbeken EK, Vanaudenaerde BM, Vos R

PMID: 28750467 [PubMed - in process]

Compensatory lung growth after bilobectomy in emphysematous rats.

Fri, 07/28/2017 - 12:45
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Compensatory lung growth after bilobectomy in emphysematous rats.

PLoS One. 2017;12(7):e0181819

Authors: Almeida FM, Saraiva-Romanholo BM, Vieira RP, Moriya HT, Ligeiro-de-Oliveira AP, Lopes FD, Castro-Faria-Neto HC, Mauad T, Martins MA, Pazetti R

Abstract
Lung volume reduction surgery (LVRS) is an option for emphysematous patients who are awaiting lung transplantation. LVRS reduces nonfunctional portions of lung tissues and favors the compensatory lung growth (CLG) of the remaining lobes. This phenomenon diminishes dyspnea and improves both the respiratory mechanics and quality of life for the patients. An animal model of elastase-induced pulmonary emphysema was used to investigate the structural and functional lung response after LVRS. Bilobectomy was performed six weeks after elastase instillation. Two weeks after bilobectomy, CLG effects were evaluated by lung mechanics and histomorphometric analysis. After bilobectomy, the emphysematous animals presented decreased mean linear intercepts, increased elastic fiber proportion, and increased alveolar surface density, total volumes of airspace, tissue and respiratory region and absolute surface area. We conclude that bilobectomy promoted CLG in emphysematous animals, resulting in alveolar architecture repair.

PMID: 28750097 [PubMed - in process]

Fatal Septic Shock Triggered by Donor Transmitted Varicella Zoster Virus Reinfection 3 Days After Lung Transplantation.

Fri, 07/28/2017 - 12:45
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Fatal Septic Shock Triggered by Donor Transmitted Varicella Zoster Virus Reinfection 3 Days After Lung Transplantation.

Transplantation. 2017 Jul 27;:

Authors: Lehingue S, Rambaud R, Guervilly C, Adda M, Forel J, Cassir N, Zandotti C, Hraiech S, Papazian L

PMID: 28749818 [PubMed - as supplied by publisher]

Case Report: Successful Lung Transplantation from a Donor Seropositive for Trypanosoma cruzi Infection (Chagas Disease) to a Seronegative Recipient.

Fri, 07/28/2017 - 12:45
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Case Report: Successful Lung Transplantation from a Donor Seropositive for Trypanosoma cruzi Infection (Chagas Disease) to a Seronegative Recipient.

Am J Trop Med Hyg. 2017 Jul 24;:

Authors: Salvador F, Sánchez-Montalvá A, Sulleiro E, Berastegui C, Jauregui A, Pont T, Los-Arcos I, Len Ó, Gavaldà J, Molina I

Abstract
The increasing shortage of organs for transplantation has prompted transplant programs to investigate the use of extended criteria donors, such as those with transmissible infectious diseases. Successful cases of organ transplantation (mostly kidney and liver) from Trypanosoma cruzi seropositive donors to seronegative recipients have been reported. We present a case of lung transplantation from a donor serologically positive for Chagas disease to a seronegative recipient, and provide a review of the literature. Left single lung transplantation was performed in a 44-year-old Spanish woman presenting with interstitial lung disease in February 2016. The deceased donor was a Colombian immigrant living in Spain who was serologically positive for Chagas disease. Oral administration of 5 mg/kg/day benznidazole divided in three doses for 60 days was given for specific Chagas disease prophylaxis after transplantation. Periodic follow-up with serological reverse transcription polymerase chain reaction to detect T. cruzi DNA were performed until 6 months after the end of treatment. All results were negative, indicating that transmission of T. cruzi had not occurred. In a review of the literature, two similar cases were identified in Argentina and the United States. In both cases T. cruzi infection was detected posttransplant in the recipients, after which they were treated with benznidazole. The course of the patient described herein confirms that lungs from donors with chronic T. cruzi infection can be used successfully as allografts, and that posttransplant prophylaxis with benznidazole may reduce the probability of transmission of T. cruzi to the recipient.

PMID: 28749767 [PubMed - as supplied by publisher]

Disease-related autoantibody profile in patients with systemic sclerosis.

Fri, 07/28/2017 - 12:45
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Disease-related autoantibody profile in patients with systemic sclerosis.

Autoimmunity. 2017 Jul 27;:1-8

Authors: Liaskos C, Marou E, Simopoulou T, Barmakoudi M, Efthymiou G, Scheper T, Meyer W, Bogdanos DP, Sakkas LI

Abstract
BACKGROUND: Autoantibodies (autoAbs) help in diagnosis and predicting clinical phenotypes in systemic sclerosis (SSc).
AIM OF THE STUDY: To determine the clinical utility of 13 SSc-related autoAbs in SSc patients.
MATERIAL AND METHODS: A total of 131 consecutive patients with SSc (111 female, mean age 58.1 ± 14 years; 49 with diffused cutaneous SSc [dcSSc] and 82 with limited cutaneous SSc [lcSSc]) were analysed by a multiplex line immunoassay (Euroimmun) for autoantibodies (autoAbs) against 13 SSc-related antigens. A total of 22 patients with primary Raynaud phenomenon (RP), and 22 healthy controls were also analysed.
RESULTS: ANA by indirect immunofluorescence was present in 128 (97.7%) patients with SSc. Excluding anti-Ro52, 113 (89.3%) SSc patients were positive for at least one autoAb: anti-Topoisomerase I (anti-Topo) I abs in 54 (41.2%), anti-centromere proteins (anti-CENP) in 37 (28.2%, all reactive with centromere protein-A (CENPA) and centromere protein B (CENPB)), anti-RNA polymerase III(RP11) in 19 (14.5%), anti-RNA polymerase III(RP155) in 13 (9.9%), anti-fibrillarin in 4 (3.1%), anti-Ku in 6 (4.6%), anti-nucleolus-organizing region (anti-NOR90) in 8 (6.1%), anti-PM-Scl100 in 2 (1.5%), and anti-PM-Scl75 in 4 (3.1%). There was no immunoreactivity for Th/To or platelet-derived growth factor receptor (PDGFR). Overall, 102 (77.9%) SSc patients had autoAbs against Topo I, CENPA or CENPB, RP11 or RP155. Anti-Topo I abs were strongly associated with dcSSc, interstitial lung disease (ILD) (p < .001), pulmonary hypertension (PH) (p = .019) and ILD-PH (p = .003). Anti-CENPB abs were associated with lcSSc, and negatively associated with ILD. Anti-RP11 and anti-NOR90 abs were associated with male gender, and anti-NOR90 associated with ILD.
CONCLUSIONS: Anti-Topo I, anti-CENP, and anti-RNA pol III are the most prevalent autoAbs in SSc. Anti-Topo I and anti-NOR90 abs are associated with ILD and/or PAH.

PMID: 28749191 [PubMed - as supplied by publisher]

Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center Experience.

Fri, 07/28/2017 - 12:45
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Long-Term Outcome of Adenosine Deaminase-Deficient Patients-a Single-Center Experience.

J Clin Immunol. 2017 Jul 26;:

Authors: Scott O, Kim VH, Reid B, Pham-Huy A, Atkinson AR, Aiuti A, Grunebaum E

Abstract
PURPOSE: Inherited defects in the adenosine deaminase (ADA) enzyme can cause severe combined immune deficiency (SCID) and systemic abnormalities. Management options for ADA-deficient patients include enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy (GT). Here, we describe the long-term benefits of these treatments.
METHODS: Survival, infections, systemic sequelae, and laboratory assessments were recorded for all ADA-deficient SCID patients, managed at a single center since 1985, who survived 5 or more years following treatment.
RESULTS: Of 20 ADA-deficient patients, the 8 (40%) who survived 5 or more years (range 6-29.5 years, median 14 years) were included in the study. Among the long-term survivors, two patients were treated exclusively with ERT, five underwent HSCT (three from HLA-matched sibling donors, two from HLA-mismatched related donors), and one received GT. The long-term survivors often suffered from recurrent respiratory infections; however, opportunistic infections occurred in only one patient. Systemic sequelae included lung disease such as bronchiectasis and asthma (four patients), neurologic abnormalities (six patients), metabolic disturbances (two patients), allergy and autoimmunity (six patients), and neoplasms (three patients). Normal CD4(+) T cell numbers and function, as well as antibody production, were usually observed after HSCT and GT, but not after ERT. Late deaths occurred in two patients at 15 and 25 years after HSCT, respectively, and were attributed to respiratory failure.
CONCLUSIONS: ADA-deficient patients commonly suffer from long-term complications, emphasizing the need for improved management and for multi-disciplinary follow-up.

PMID: 28748310 [PubMed - as supplied by publisher]

Pathological features of explant lungs with fibrosis in autoimmune pulmonary alveolar proteinosis.

Fri, 07/28/2017 - 12:45
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Pathological features of explant lungs with fibrosis in autoimmune pulmonary alveolar proteinosis.

Respirol Case Rep. 2017 Sep;5(5):e00255

Authors: Ono M, Saito R, Tominaga J, Okada Y, Ohkouchi S, Takemura T

Abstract
Association of fibrosis with autoimmune pulmonary alveolar proteinosis (aPAP) is rare. However, prognoses of such cases are poor and the process of the formation of fibrosis is still unknown. In this study, we report a case of aPAP with progressive fibrosis occurring in a 46-year-old woman. She had undergone several repetitions of whole lung lavage (WLL) for 7 years and granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation for 3 months; however, the progression of fibrosis was not hindered. Eventually, she was treated with bilateral lung transplantation. The computed tomography (CT) image suggested pulmonary fibrotic changes in her lung similar to usual interstitial pneumonia. However, the pathological analyses of explant lungs revealed that the fibrosis was not similar to ordinary interstitial pneumonias and suggested that the dysfunction of alveolar macrophage in removing the excess surfactant of alveolar spaces played an important role in the fibrogenesis in aPAP.

PMID: 28748093 [PubMed]

Author׳s reply: Old age may influence features of pleuroparenchymal fibroelastosis (PPFE): Lessons from a donkey model for PPFE.

Fri, 07/28/2017 - 12:45
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Author׳s reply: Old age may influence features of pleuroparenchymal fibroelastosis (PPFE): Lessons from a donkey model for PPFE.

Respir Investig. 2016 Sep;54(5):382

Authors: Watanabe S, Waseda Y, Kasahara K

PMID: 27566390 [PubMed - indexed for MEDLINE]

Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Fri, 07/28/2017 - 12:45
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Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

PLoS One. 2016;11(6):e0157099

Authors: Liu X, Fang Q, Kim H

Abstract
BACKGROUND: In the last two decades, mesenchymal stem cells (MSCs) have been pre-clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models.
METHODS AND RESULTS: A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). The pooled Hedges's g with 95% confidence intervals (95% CIs) was adopted to assess the effect size. Random effect model was used due to the heterogeneity between the studies. A total of 20 eligible studies were included in the current systematic review. The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges's g = -2.325 ± 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges's g = -3.488 ± 0.504 with 95% CI: -4.476 ~ -2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges's g = 3.249 ± 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges's g = 2.053 ± 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001). The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges's g = -2.956 ± 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges's g = 3.103 ± 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001).
CONCLUSION: This systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment. Although the COPD models may not truly mimic COPD patients, these pre-clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD. The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair.

PMID: 27280283 [PubMed - indexed for MEDLINE]

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