The Induction of IgM and IgG Antibodies against HLA or MICA after Lung Transplantation

The production of IgG HLA antibodies after lung transplantation (LTx) is considered to be a major risk factor for the development of chronic rejection, represented by the bronchiolitis obliterans syndrome (BOS). It has recently been observed that elevated levels of IgM HLA antibodies also correlates with the development of chronic rejection in heart and kidney transplantation. This study investigates the relationship between IgM and IgG antibodies against HLA and MICA after lung transplantation. Serum was collected from 49 patients once prior to transplantation and monthly for up to 1 year after lung transplantation was analyzed by Luminex to detect IgM and IgG antibodies against HLA and MICA. The presence of either IgM or IgG HLA and/or MICA antibodies prior to or after transplantation was not related to survival, gender, primary disease, or the development of BOS. Additionally, the production of IgG alloantibodies was not preceded by an increase in levels of IgM, and IgM levels were not followed by an increase in IgG. Under current immune suppressive regimen, although the presence of IgM antibodies does not correlate with BOS after LTx, IgM high IgG low HLA class I antibody titers were observed more in patients with BOS compared to patients without BOS

The Autoimmune-Associated Single Nucleotide Polymorphism Within PTPN22 Correlates With Clinical Outcome After Lung Transplantation

Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation, and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be associated with BOS incidence. We selected six SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx. A total of 144 patients and matched donors were included, and individual SNPs and haplotype configurations were analyzed. We found a significant association between patients carrying the heterozygous configuration of rs2476601 and a higher risk for BOS development (p = 0.005, OR: 4.400, 95%CI: 1.563–12.390). Kaplan-Meier analysis showed that heterozygous patients exhibit a lower BOS-free survival compared to patients homozygous for rs2476601 (p = 0.0047). One haplotype, which solely contained the heterozygous risk variant, was associated with BOS development (p = 0.015, OR: 7.029, 95%CI: 1.352–36.543). Our results show that LTx patients heterozygous for rs2476601 are more susceptible for BOS development and indicate a deleterious effect of the autoimmune-related risk factor of PTPN22 in patients on LTx outcome

Impact of donor lung quality on post-transplant recipient outcome in the Lung Allocation Score era in Eurotransplant - a historical prospective study

The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current LAS era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N=3053). Donors used for LTx in countries with high donation rate were younger (42% vs. 33% ≤ 45 years, p<0.0001), were less often smokers (35% vs. 46%, p<0.0001), had more often clear chest X-rays (82% vs. 72%, p<0.0001), had better donor oxygenation ratio's (20% vs. 26% with PaO /FiO ≤ 300 mmHg, p<0.0001) and had better lung donor score values (LDS) (28% vs. 17% with LDS=6, p<0.0001) compared to donors used for LTx in countries with low donation rate. Survival rates for the groups LDS =6 and ≥7 at 5 years were 69.7% and 60.9% (p=0.007). Lung donor quality significantly impacts on long-term patient survival. Countries with a low donation rate are more oriented to using donor lungs with a lesser quality compared to countries with a high donation rate. Instead of further stretching donor eligibility criteria, the full potential of the donor pool should be realized

Выявление понятий и их взаимосвязей в рамках технологии контент-мониторинга

Приведены подходы к решению проблемы выявления фактографической информации из неструктурированных текстовых потоков. Описаны технологические решения, позволяющие извлекать из полнотекстовых документов такие понятия как фирмы, фамилии, географические названия и т.п., а также выявлять силу их взаимосвязей на основе применения двух алгоритмов. Первый из этих алгоритмов основывается на учете совместного вхождения понятий в одни и те же документы, а второй на учете общего для рассматриваемых понятий контекста.Наведено підходи до вирішення проблеми виявлення фактографічної інформації з неструктурованих текстових потоків. Описано технологічні рішення, що дозволяють добути з повнотекстових документів такі поняття як фірми, прізвища, географічні назви тощо, а також виявляти силу їхніх взаємозв’язків на базі застосування двох алгоритмів. Перший з цих алгоритмів базується на врахуванні спільного входження понять до одних і тих самих документів, а другий — на врахуванні загального для понять, що розглядаються, контексту.Approaches to the solution of a problem of revealing factual information from unstructured text flows are given. The technological solutions, allowing to take from text-through documents such concepts as a firm, a surname, place names, etc., and also to reveal force of their interrelations on the basis of application of two algorithms are described. The first of these algorithms is based on the account of joint concepts occurrence in the same documents, and the second one on the account of the context common for considered concepts

Cutaneotrichosporon (Cryptococcus) cyanovorans, a basidiomycetous yeast, isolated from the airways of cystic fibrosis patients

Cystic fibrosis (CF) patients are colonized with a multitude of bacteria and fungi. From respiratory samples of two CF patients in our institute, a difficult to identify yeast was isolated repeatedly. This yeast was eventually identified as Cutaneotrichosporon (Cryptococcus) cyanovorans by internal transcribed spacer (ITS) and ribosomal large subunit (LSU) sequencing. C. cyanovorans is a basidiomycetous yeast originally reported as environmental isolate from South African soil and has not been described before as clinical isolate from CF patients

Cutaneotrichosporon (Cryptococcus) cyanovorans, a basidiomycetous yeast, isolated from the airways of cystic fibrosis patients

Cystic fibrosis (CF) patients are colonized with a multitude of bacteria and fungi. From respiratory samples of two CF patients in our institute, a difficult to identify yeast was isolated repeatedly. This yeast was eventually identified as Cutaneotrichosporon (Cryptococcus) cyanovorans by internal transcribed spacer (ITS) and ribosomal large subunit (LSU) sequencing. C. cyanovorans is a basidiomycetous yeast originally reported as environmental isolate from South African soil and has not been described before as clinical isolate from CF patients

Profiling of peripheral blood mononuclear cells does not accurately predict the bronchiolitis obliterans syndrome after lung transplantation

After lung transplantation (LTx), circulating mononuclear cell composition and their subsets may be predictive for the bronchiolitis obliterans syndrome (BOS). We investigated the cellular composition in patients developing BOS, or not, by analyzing peripheral blood taken at multiple time points after transplantation. PBMCs of 11 BOS and 39 non-BOS patients were analyzed by FACS for monocytes, dendritic cells, NK-, NKT-, B- and T cells as well as B- and T cell subsets. Analysis of blood samples taken monthly during the first year post-LTx showed that circulating NK, NKT and dendritic cell percentages were not indicative of BOS development, whereas increases in T cells, monocytes and lowered fractions of B cells were related to BOS development. B- and T cell subset analysis at month 5 post-LTx indicated that IgM+IgD- memory B cells and central memory CD8+ T cells were decreased, whereas NKT cells were increased in BOS patients compared to non-BOS patients. Prior to BOS diagnosis, the composition of specific mononuclear cells on a group level differs from patients remaining BOS free. However, given the overlap in percentages of cellular frequencies between the patient groups investigated, this analysis does not allow prediction or risk stratification for development of BOS in individual patients

Pulmonary Embolism After Endovascular Aortic Repair, a Retrospective Cohort Study

Objectives: Endovascular aortic repair (EVAR) is associated with an increased risk of pulmonary embolism, which is often clinically silent and therefore difficult to recognise. The aim was to investigate the incidence of pulmonary embolism after EVAR using routinely performed pre- and post-operative aortic computed tomography angiography (CTA), and the association between pulmonary embolism and mortality. Methods: This single centre retrospective cohort study included adult patients who underwent EVAR in the University Medical Centre Utrecht between January 2010 and July 2015 and who had a total aortic, thoracic aortic, or pulmonary CTA within one month post-operatively. Baseline and mortality data were obtained by reviewing hospital and general practitioner records. The primary outcome was pulmonary embolism within one month after surgery. Secondary outcomes were 30 day and six month mortality. Results: During the study period, 526 EVARs were performed. Seventy-four of these procedures were included in the analysis of which there were 40 thoracic and 34 abdominal EVARs. In nine patients (12%, 95% CI 7–22) pulmonary embolism was observed of which one was central, two were segmental, and six were subsegmental. Seven were clinically silent and two were present on the pre-operative CTA. Thirty day mortality was significantly higher in patients with pulmonary embolism (relative risk 14.4, 95% CI 1.4–143, p =.037) though none of the deaths seemed directly attributable to it. Conclusions: This study, although preliminary, suggests that silent pulmonary embolism after EVAR occurs in approximately one in 10 patients, despite routine thrombo-embolism prophylaxis. Pulmonary embolism was associated with a higher 30 day mortality risk yet it was not the cause of death in any of these patients