First Report of the Korean Lung Transplantation Registry.

BACKGROUND: The Korean Organ Transplantation Registry (KOTRY) began to register lung transplants in 2015. This is an initial report on the status of patients receiving lung transplants over the past 2 years. METHODS: We analyzed a total of 69 patients who received lung transplants in 2015 and 2016 and who registered with the KOTRY. RESULTS: The 69 patients were treated in 5 institutions. The average (SD) donor age was 39.2 (12.6) years; there were 40 male patients. The average (SD) recipient age was 55.7 (10.0) years, and the number of male recipients was 46. A total of 66 patients underwent bilateral lung transplantation, 3 underwent single-lung transplantation, and 1 underwent simultaneous heart-lung transplantation. The most frequent indication for lung transplantation was idiopathic pulmonary fibrosis (35 patients), followed by connective tissue disease-related interstitial lung disease (9) and acute respiratory failure (8). Prior to transplantation, 23 patients required ventilator care, and 12 required extracorporeal membrane oxygenation while on the waiting list. Episodes of acute rejection during follow-up were reported in 4, 2, 1, and 1 patients at 3, 6, 9, and 12 months, respectively. Infections requiring hospitalization were reported in 27, 10, 4, and 3 patients at 3, 6, 9, and 12 months, respectively. CONCLUSION: The establishment of KOTRY renders it possible to collect nationwide data on lung transplantation, improving research on the topic and clarifying clinical feasibility.

Isolated Acute Appendicitis Caused by Aspergillus in a Patient Who Underwent Lung Transplantation: A Case Report.

Invasive aspergillosis is an important cause of morbidity and mortality in patients who have undergone lung transplantation. Aspergillus infections usually involve the respiratory tract, with vascular invasion and subsequent dissemination. However, acute appendicitis associated with localized aspergillosis is rare, especially among patients who have undergone prophylaxis with voriconazole. We present a case of primary Aspergillus appendicitis diagnosed by histologic examination in a patient who underwent lung transplantation. A 51-year-old woman with dermatomyositis underwent lung transplantation for acute interstitial pneumonitis. According to our institution's protocol, the patient was treated with immunosuppressive therapy and prophylaxis with voriconazole, ganciclovir, and trimethoprim sulfamethoxazole during the post-transplantation period. Twenty-eight days after transplantation, the patient developed mild abdominal pain and paralytic ileus. There was no apparent infection sign. Abdominal computerized tomography indicated a wall defect of the appendix with multifocal fluid collection, mesenteric leave thickening, and pneumoperitoneum. These findings were consistent with perforated appendicitis, and the patient underwent an appendectomy. The histopathology examination of the resected appendix showed inflammation and abscess. Periodic acid-Schiff-positive and Grocott-Gomori methenamine silver-positive fungal hyphae with acute-angle branching were observed, demonstrating muscular invasion. A galactomannan antigen test obtained on the same day had negative results. The trough level of voriconazole was well maintained and was subsequently adjusted through monitoring of circulating drug concentration. Simultaneously, other potential sites of disseminated Aspergillus were considered and examined, but no other site of systemic Aspergillus infection was detected. Voriconazole treatment was maintained for 3 months, and no aspergillosis relapse or other invasive fungal infections were observed.

The impact of multidisciplinary nutritional team involvement on nutritional care and outcomes in a medical intensive care unit.

The aim of this study was to evaluate nutritional care and outcomes in a medical intensive care unit (ICU) following multidisciplinary nutritional team (MNT) involvement. The authors retrospectively reviewed the data of all patients admitted to a medical ICU from April to October 2013 (pre-MNT period) and from April to October 2014 (post-MNT period). In total, 140 patients were included and allocated to the pre-MNT group (n=70) or the post-MNT group (n=70). The post-MNT group was more likely to use enteral nutrition (61.4 vs 37.1%, P=0.002). In terms of total calories and protein provided, the number of nutritional goal-achieved days during stays in ICU was significantly greater in the post-MNT group than in the pre-MNT group (63.7% vs 47.6%, P<0.05 and 44.3% vs 29.9%, respectively, P<0.05). The MNT activities resulted in significant improvements in terms of nutritional provision and adequacy in a medical ICU.

Extracorporeal Life Support as a Bridge to Lung Transplantation in Patients With Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is being used more often as a bridge to transplantation (BTT) in patients with acutely decompensated end-stage lung disease in Korea. ECMO as a BTT may be the only rescue strategy for severe acute respiratory failure, but many centers still consider it to be a relative contraindication to lung transplantation because of its poor outcome. Because there are not enough lung donors, it is important to determine their optimal use. We reviewed and analyzed our experiences with the use of ECMO as a BTT in patients with acute respiratory failure. METHODS: This was a retrospective analysis of all patients with acutely decompensated end-stage lung disease treated with ECMO as a bridge to lung transplantation between March 2012 and February 2016. RESULTS: Of the 194 patients who underwent respiratory ECMO over a 4-year period, a BTT strategy was used for 19 patients (median age, 58 years) on our institution's lung transplantation waiting list (15 veno-venous, 3 veno-veno-arterial, 1 veno-arterial). Fourteen patients (73.7%) were successfully bridged to transplantation; however, 3 died while on the waiting list and 2 returned to their baseline functions without transplantation. The overall in-hospital survival rate was 57.9% (11 of 19), including the 9 (64.3%) patients who underwent transplantation. CONCLUSIONS: Our findings support the view that well-selected candidates with acutely decompensated end-stage lung disease may be safely bridged until a suitable donor is identified. ECMO is not able to reverse the course of patients; however, it could be a life-saving option for patients with acute respiratory failure requiring lung transplantation.

Lysophosphatidylcholine as a prognostic marker in community-acquired pneumonia requiring hospitalization: a pilot study.

Clinical prediction indicators such as the pneumonia severity index (PSI) and CURB-65 score are useful, but they are complex and often not followed. Therefore, biomarkers that improve hospital outcome predictions are emerging. This study evaluated the prognostic value of a new sepsis biomarker, serum lysophosphatidylcholine (LPC) concentrations, in community-acquired pneumonia (CAP) patients. We prospectively collected blood samples from emergency department CAP patients on days 1 and 7 (post-admission) and analyzed their plasma LPC concentrations. We retrospectively reviewed patient medical records and analyzed correlations between plasma LPC concentrations and clinical parameters and hospital outcomes. A total of 56 CAP patients were included in this study; 24 (42.9 %) required intubation and 15 (26.8 %) died. The mean LPC concentrations on days 1 (p = 0.015) and 7 (p = 0.002) of hospitalization were significantly lower in the non-survivors. Day 1 LPC concentrations were inversely correlated with the PSI (ρ = -269) and CURB-65 scores (ρ = -386). For predicting hospital mortality, the day 1 LPC concentration was comparable with the CURB-65 or PSI scores. Day 1 LPC cut-off levels <29.6 µmol/L were associated with hospital CAP outcomes, including the need for mechanical ventilation, vasopressors, intensive care unit admission, and hospital mortality. Additionally, day 7 LPC concentrations were correlated with in-hospital mortality. Initial serum LPC concentrations predicted hospital outcomes in CAP patients requiring hospitalization. These values were correlated with prognostic markers, such as the PSI and CURB-65 scores. Additionally, follow-up LPC measurements predicted the clinical course of CAP patients.

Crystal structure of the hexameric traffic ATPase of the Helicobacter pylori type IV secretion system.

The type IV secretion system of Helicobacter pylori consists of 10--15 proteins responsible for transport of the transforming protein CagA into target epithelial cells. Secretion of CagA crucially depends on the hexameric ATPase, HP0525, a member of the VirB11-PulE family. We present the crystal structure of a binary complex of HP0525 bound to ADP. Each monomer consists of two domains formed by the N- and C-terminal halves of the sequence. ADP is bound at the interface between the two domains. In the hexamer, the N- and C-terminal domains form two rings, which together form a chamber open on one side and closed on the other. A model is proposed in which HP0525 functions as an inner membrane pore, the closure and opening of which is regulated by ATP binding and ADP release.

S2F, a leaf-specific trans-acting factor, binds to a novel cis-acting element and differentially activates the RPL21 gene.

Tissue-specific factors control the differential expression of nuclear genes encoding plastid proteins. To identify some of these factors, the light-independent spinach RPL21 gene encoding the plastid ribosomal protein L21 was chosen as a model. The RPL21 promoter organization was defined by transient and stable transfections of RPL21 promoter deletion mutants fused to a reporter gene. The following results were obtained. (1) We identified a strong core promoter, spanning the transcription start site region, sufficient to drive high levels of gene expression. (2) We identified two non-overlapping positive and negative domains, located upstream from the core promoter region, that modulate core promoter activity independently of light. (3) We found that the positive domain contains a new cis-acting element, the S2 site, related to but different from the light-responsive GT-1 binding site. We show that the S2 site binds a leaf-specific nuclear factor (named S2F). The S2 site is conserved in the promoter region of many nuclear genes encoding plastid proteins. Experiments with transgenic tobacco plants confirmed that the S2 site is critical for positive domain activity in leaf tissues. The S2 site is thus identified as a new tissue-specific, light-independent regulatory element.

Plasmodium falciparum CTP:phosphocholine cytidylyltransferase expressed in Escherichia coli: purification, characterization and lipid regulation.

The Plasmodium falciparum CTP:phosphocholine cytidylyltransferase (PfCCT) has been isolated from an overexpressing strain of Escherichia coli. The plasmid pETPfCCT mediated the overexpression of the full-length polypeptide directly. The recombinant protein corresponded to 6-9% of the total cellular proteins and was found essentially in the insoluble membrane fraction. Urea at 6 M was used to solubilize the recombinant protein from the insoluble fraction. The CCT activity was restored upon the removal of urea, and the protein was subsequently purified to homogeneity on a Q-Sepharose column. Approx. 1.4 mg of pure enzyme was obtained from a 250 ml culture of E. coli. Biochemical properties, including in vitro substrate specificity and enzymic characterization, were assessed. The lipid regulation of the recombinant plasmodial CCT activity was characterized for the first time. The Km values were 0.49+/-0.03 mM (mean+/-S.E.M.) for phosphocholine and 10.9+/-0.5 mM for CTP in the presence of lipid activators (oleic acid/egg phosphatidylcholine vesicles), whereas the Km values were 0.66+/-0.07 mM for phosphocholine and 28.9+/-0.8 mM for CTP in the absence of lipid activators. The PfCCT activity was stimulated to the same extent in response to egg phosphatidylcholine vesicles containing anionic lipids, such as oleic acid, cardiolipin and phosphatidylglycerol, and was insensitive or slightly sensitive to PC vesicles containing neutral lipids, such as diacylglycerol and monoacylglycerol. Furthermore, the stimulated enzyme activity by oleic acid was antagonized by the cationic aminolipid sphingosine. These lipid-dependence properties place the parasite enzyme intermediately between the mammalian enzymes and the yeast enzyme.

Molecular cloning of CTP:phosphocholine cytidylyltransferase from Plasmodium falciparum.

CTP:phosphocholine cytidylyltransferase (CCT) is the rate-limiting and regulatory enzyme in the synthesis of phosphatidylcholine, the major membrane phospholipid, in Plasmodium. The structural gene encoding CCT was isolated from the human malaria parasite Plasmodium falciparum. This was achieved using the PCR to amplify genomic DNA with degenerate primers constructed on the basis of conserved regions identified within yeast and rat liver CCT molecules, and using the PCR product to screen a genomic library. The P. falciparum CCT gene encodes a protein of 370 amino acids (42. 6 kDa) and displays 41-43% similarity (28-29% identity) to CCT molecules of the other organisms cloned to date. The central domain of CCT, proposed as the catalytic domain of the CTP-transfer reaction, shows 68-72% similarity and 48-55% identity among P. falciparum, human, rat and yeast enzymes. This gene is present in a single copy, as determined by Southern-blotting of genomic DNA, and located on chromosome 13 of P. falciparum. Large transcripts were detected by Northern analysis and indicate that this gene is expressed in the asexual intraerythrocytic stages. The coding region of the P. falciparum CCT gene was inserted into an Escherichia coli expression vector to confirm the function of the CCT product. The recombinant CCT expressed in E. coli is catalytically active, as evidenced by the conversion of phosphocholine to CDP-choline.

Infected erythrocyte choline carrier inhibitors: exploring some potentialities inside Plasmodium phospholipid metabolism for eventual resistance acquisition.

We have developed a model for designing antimalarial drugs based on interference with an essential metabolism developed by Plasmodium during its intraerythrocytic cycle, phospholipid (PL) metabolism. The most promising drug interference is choline transporter blockage, which provides Plasmodium with a supply of precursor for synthesis of phosphatidylcholine (PC), the major PL of infected erythrocytes. Choline entry is a limiting step in this metabolic pathway and occurs by a facilitated-diffusion system involving an asymmetric carrier operating according to a cyclic model. Choline transport in the erythrocytes is not sodium dependent nor stereospecific as demonstrated using stereoisomers of alpha and beta methylcholine. These last two characteristics along with distinct effects of nitrogen substitution on transport rate demonstrate that choline transport in the infected erythrocyte possesses characteristics quite distinct from that of the nervous system. This indicates a possible discrimination between the antimalarial activity (inhibition of choline transport in the infected erythrocyte) and a possible toxic effect through inhibition of choline entry in synaptosomes. Apart from the de novo pathway of choline, PC can be synthesized by N-methylation from phosphatidylethanolamine (PE). There is a de novo pathway for PE biosynthesis from ethanolamine in infected cells but phosphatidylserine (PS) decarboxylation also occurs. In addition, PE can be directly and abundantly synthesized from serine decarboxylation into ethanolamine, a pathway which is absent from the host. The variety of the pathways that exist for the biosynthesis of one given PL led us to investigate whether an equilibrium can occur between all PL metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)