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[PMID]: 29524528
[Au] Autor:Sersté T; Cornillie A; Njimi H; Pavesi M; Arroyo V; Putignano A; Weichselbaum L; Deltenre P; Degré D; Trépo E; Moreno C; Gustot T
[Ad] Address:Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Department of Hepatogastroenterology, CHU Saint-Pierre, Bruxelles, Belgium. Electronic address: thomas.serste@skynet.be.
[Ti] Title:The prognostic value of Acute-on-Chronic Liver Failure during the course of severe alcoholic hepatitis.
[So] Source:J Hepatol;, 2018 Mar 07.
[Is] ISSN:1600-0641
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND & AIMS: A better identification of factors predicting death is needed in alcoholic hepatitis. Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF, pACLF) or during follow-up (incidental ACLF, iACLF). This study analyzed the impact of ACLF on outcomes in AH and the role of infection in the onset of ACLF and death. METHODS: Patients admitted from July, 2006 to July, 2015 suffering from biopsy-proven severe (s)AH with a Maddrey discriminant function (mDF) ≥32 were included. Infectious episodes, ACLF, and mortality were assessed during a 168-day follow-up period. Results were validated on an independent cohort. RESULTS: One hundred sixty-five patients were included. Mean mDF was 66.3±20.7 and mean MELD score was 26.8±7.4. The 28-day cumulative incidence of death (CID) was 31% (95%CI, 24-39%). Seventy-nine patients (47.9%) had pACLF. The 28-day CID without pACLF and with pACLF-1, pACLF-2, and pACLF-3 were 10.4% (95%CI, 5.1-18.0), 30.8% (95%CI, 14.3-49.0), 58.3% (95%CI, 35.6-75.5), and 72.4% (95%CI, 51.3-85.5), respectively, p <0.0001. Twenty-nine patients (17.5%) developed iACLF. The 28-day relative risk of death in patients developing iACLF was 41.87 (95%CI, 5.2-335.1, p< 0.001). A previous infection was the only independent risk factor for developing iACLF during the follow-up. Prevalence, incidence, and impact on prognosis of ACLF were confirmed in a validation cohort of 97 patients with probable sAH. CONCLUSIONS: ACLF is frequent during the course of sAH and is associated with high mortality. Infection strongly predicts the development of ACLF in this setting. LAY SUMMARY: In patients with chronic liver disease, an acute deterioration of liver function combined with single or multiple organ failures is known as acute-on-chronic liver failure (ACLF). This study shows that ACLF is frequent during the course of severe alcoholic hepatitis (sAH). In sAH, ACLF is associated with high mortality and frequently occurs secondary to a previous infection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 18127 MEDLINE  
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[PMID]: 29524230
[Au] Autor:Maier CL; Gross PJ; Dean CL; Chonat S; Ip A; McLemore M; El Rassi F; Stowell SR; Josephson CD; Fasano RM
[Ad] Address:Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, Georgia.
[Ti] Title:Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.
[So] Source:Transfusion;, 2018 Mar 09.
[Is] ISSN:1537-2995
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). CASE REPORT: An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission. CONCLUSIONS: Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher
[do] DOI:10.1111/trf.14566

  3 / 18127 MEDLINE  
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[PMID]: 29505517
[Au] Autor:Abulimiti A; Husaiyin A; Sailai Y
[Ad] Address:Department of General Surgery, First Affiliated Hospital of Xinjiang Medical University, Urimqi, China.
[Ti] Title:Evaluation of HVHF for the treatment of severe acute pancreatitis accompanying MODS.
[So] Source:Medicine (Baltimore);97(1):e9417, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Systemic inflammatory response syndrome (SIRS) prevention is key to severe acute pancreatitis (SAP) treatment and the assessment of high-volume hemofiltration (HVHF) for treating SAP accompanying multiple organ dysfunction syndromes.In this prospective controlled study, 40 SAP patients were divided into 2 groups: control (n = 22, treated with fasting, decompression, and intravenous somatostatin) and HVHF (n = 18, HVHF administration in addition to the treatment in the control group) groups; and were assessed for serum and urine amylase, WBC, C-reactive protein (CRP), and hepatic and renal functions. Vital signs and abdominal symptoms were recorded, and complications and mortality were analyzed.APACHE II scores in the HVHF group were significantly lower than in the control group at 3 and 7 days (6.3 ±â€Š1.7 vs 9.2 ±â€Š2.1 and 3.3 ±â€Š0.8 vs 6.2 ±â€Š1.7, respectively). Compared with controls, serum, and urine amylase, WBC, CRP, and organ functions significantly improved after HVHF treatment. Meanwhile, mortality (16.7% vs 31.8%) and complication (11.1% vs 40.9%) rates were significantly reduced.The other clinical parameters were significantly ameliorated by HVHF. HVHF rapidly reduces abdominal symptoms and improves prognosis, reducing mortality in SAP patients; and is likely through systemic inflammatory response syndrome attenuation in the early disease stage.
[Mh] MeSH terms primary: Hemofiltration/statistics & numerical data
Multiple Organ Failure/etiology
Pancreatitis/therapy
[Mh] MeSH terms secundary: APACHE
Adult
Aged
Amylases/blood
Amylases/urine
Blood Urea Nitrogen
C-Reactive Protein/metabolism
Female
Humans
Leukocyte Count
Liver Function Tests
Male
Middle Aged
Multiple Organ Failure/blood
Multiple Organ Failure/urine
Pancreatitis/blood
Pancreatitis/complications
Pancreatitis/urine
Prospective Studies
[Pt] Publication type:CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Name of substance:9007-41-4 (C-Reactive Protein); EC 3.2.1.- (Amylases)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180306
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009417

  4 / 18127 MEDLINE  
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[PMID]: 29332223
[Au] Autor:Togasaki E; Shimizu N; Nagao Y; Kawajiri-Manako C; Shimizu R; Oshima-Hasegawa N; Muto T; Tsukamoto S; Mitsukawa S; Takeda Y; Mimura N; Ohwada C; Takeuchi M; Sakaida E; Iseki T; Yoshitomi H; Ohtsuka M; Miyazaki M; Nakaseko C
[Ad] Address:Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
[Ti] Title:Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia.
[So] Source:Ann Hematol;97(4):655-662, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 10 /L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 10 /L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 10 /L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 10 /L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses.
[Mh] MeSH terms primary: Embolization, Therapeutic
Purpura, Thrombocytopenic, Idiopathic/therapy
Spleen/blood supply
[Mh] MeSH terms secundary: Adolescent
Adrenal Cortex Hormones/therapeutic use
Adult
Aged
Aged, 80 and over
Disease-Free Survival
Drug Resistance
Drug Resistance, Multiple
Embolization, Therapeutic/adverse effects
Female
Follow-Up Studies
Hospitals, University
Humans
Japan
Male
Middle Aged
Organ Size
Purpura, Thrombocytopenic, Idiopathic/diagnostic imaging
Purpura, Thrombocytopenic, Idiopathic/drug therapy
Purpura, Thrombocytopenic, Idiopathic/pathology
Retrospective Studies
Spleen/diagnostic imaging
Spleen/drug effects
Spleen/pathology
Steroids/therapeutic use
Young Adult
[Pt] Publication type:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Name of substance:0 (Adrenal Cortex Hormones); 0 (Steroids)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180115
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3232-x

  5 / 18127 MEDLINE  
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[PMID]: 29521119
[Au] Autor:Liu WJ; Li W; Tang Y; Gao SJ; Fang F; Xu F; Xu Y
[Ad] Address:a Department of Critical Care Medicine , Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders , Chongqing , China.
[Ti] Title:Soft tissue calcifications secondary to Hymenoptera stings: a potential prognostic CT imaging sign in pediatric patients.
[So] Source:Clin Toxicol (Phila);:1-7, 2018 Mar 09.
[Is] ISSN:1556-9519
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:CONTEXT: Soft tissue calcifications (STCs) were incidentally found in some of the Hymenoptera-stung (HS) children when they underwent computed tomography (CT) scans for evaluating complications of vital organs. Afterwards, a predilection of STCs to the children with severe complications was clinically noticed. A hypothesis was then developed that STCs secondary to HS may correlate with poor outcomes. OBJECTIVE: This study aims to firstly characterize the CT findings of STCs in HS children and to confirm our hypothesis that the occurrence of STCs may act as an indicator of poor outcomes in HS children. MATERIALS AND METHODS: Children who received CT scanning after Hymenoptera sting from January 2011 to October 2016 in our hospital were analyzed retrospectively. Shape, location, and distribution of the STCs were described according to the CT findings. Then the enrolled cases were classified into Soft Tissue Calcification Group (STCG) and non-Soft tissue Calcification Group (non-STCG) to conduct prognostic comparisons of Sequential Organ Failure Assessment (SOFA) scores, incidence of main complications (acute liver failure (ALF), acute kidney injury stage III (AKI-III) and multiple organ failure (MOF)), length of hospital days, and in-hospital death, respectively. Pearson correlation was also utilized between the cumulative volume of STCs and the SOFA score. RESULTS: Sixteen cases were enrolled, and STCs' incidence was 56.25% (9/16). Two STCG cases had diffuse nodular calcifications in their swollen subcutaneous tissue, and another seven had symmetrically stripy or patchy calcifications within or along local muscles. The SOFA scores during the first 3 days were all higher in STCG, and rose to the greatest difference at the third day (9.78 ± 2.17 vs. 2.29 ± 2.06, t = 7.009, p < .001); the incidence of ALF, AKI-III and MOF were significantly higher in STCG (66.67% vs. 0, p = .011), (77.78% vs. 0, p = .003) and (77.78% vs. 14.29%, p = .041); and children in STCG were treated with longer hospital durations (26.33 ± 8.41 days vs. 12.29 ± 7.36 days, t = 3.493, p = .004). One child in STCG died of cardiopulmonary failure, and no deaths occurred in non-STCG. No significant correlations presented between STCs cumulative volumes and SOFA score (r = 0.096, p = .806; r = 0.067, p = .863; r = 0.024, p = .950). CONCLUSION: Soft tissue calcifications detected on CT imaging following multiple Hymenoptera stings in pediatric patients may be a potential prognostic indicator of more severe complications and poorer outcomes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1080/15563650.2018.1447121

  6 / 18127 MEDLINE  
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[PMID]: 29517639
[Au] Autor:Ji L; Wang G; Li L; Li YL; Hu JS; Zhang GQ; Chen HZ; Chen H; Kong R; Bai XW; Sun B
[Ad] Address:From the Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
[Ti] Title:Risk Factors for the Need of Surgical Necrosectomy After Percutaneous Catheter Drainage in the Management of Infection Secondary to Necrotizing Pancreatitis.
[So] Source:Pancreas;47(4):436-443, 2018 Apr.
[Is] ISSN:1536-4828
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVES: This study aimed to assess the need of surgical necrosectomy after percutaneous catheter drainage (PCD) for infected necrotizing pancreatitis. METHODS: The clinical data of documented/suspected patients who were treated with a step-up approach were extracted and analyzed. RESULTS: Of the 329 patients enrolled, the initial PCD was performed at 12 (interquartile range, 9-15) days since onset and 35.3% were cured by PCD alone. In the pre-PCD model, mean computed tomographic (CT) density of necrotic fluid collection (NFC; P < 0.001), and multiple-organ failure (MOF; P < 0.001) within 24 hours before the initial PCD were independent risk factors, and a combination of the previously mentioned 2 factors produced an area under the curve of 0.775. In the post-PCD model, mean CT density of NFC (P = 0.041), MOF (P = 0.002), and serum procalcitonin level (P = 0.035) 3 days after the initial PCD were independent risk factors, and a combination of these previously mentioned factors produced an area under the curve of 0.642. CONCLUSIONS: Both mean CT density of NFC and MOF are independent pre- and post-PCD risk factors for the need of necrosectomy after PCD. Post-PCD serum procalcitonin level might be a respondent factor that is correlated with the necessity of necrosectomy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1097/MPA.0000000000001031

  7 / 18127 MEDLINE  
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[PMID]: 29514995
[Au] Autor:Liu JQ; Cai GY; Liang S; Wang WL; Wang SY; Zhu FL; Nie SS; Feng Z; Chen XM
[Ad] Address:Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
[Ti] Title:Characteristics of and risk factors for death in elderly patients with acute kidney injury: a multicentre retrospective study in China.
[So] Source:Postgrad Med J;, 2018 Mar 07.
[Is] ISSN:1469-0756
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE OF THE STUDY: The incidence of acute kidney injury (AKI) with a poor prognosis in the elderly has been increasing each year. This study aimed to investigate the clinical characteristics of and risk factors for death from AKI in the elderly and help improve prognosis. STUDY DESIGN: This study was a retrospective cohort study based on data from adult patients (≥18 years old) admitted to 15 hospitals in China between 1 January 2009 and 31 December 2011. The characteristics of AKI in the elderly were compared with those in younger patients. RESULTS: In elderly patients with AKI, rates of hypertension, cardiovascular disease and multiple organ dysfunction syndrome (MODS) were higher than in younger patients (44.2% vs 31.2%, 16.1% vs 4.6% and 20.9% vs 16.9%, respectively), the length of ICU stay was longer (3.8 days vs 2.7 days, P=0.019) and renal biopsy (1.0% vs 7.13%, P<0.001) and dialysis (9.6% vs 19.2%, P<0.001) were performed less. Hospital-acquired (HA) AKI was more common than community-acquired (CA) AKI (60.3% vs 39.7%), while the most common cause of AKI was pre-renal (53.5%). Multiple logistic regression analysis showed that age (OR 1.041, 95% CI 1.023 to 1.059), cardiovascular disease (OR 1.980, 95% CI 1.402 to 2.797), cancer (OR 2.302, 95% CI 1.654 to 3.203), MODS (OR 3.023, 95% CI 1.627 to 5.620) and mechanical ventilation (OR 2.408, 95% CI 1.187 to 4.887) were significant risk factors for death. CONCLUSIONS: HA-AKI and pre-renal AKI were more common in the elderly. Age, cardiovascular disease, cancer, MODS and mechanical ventilation were independent risk factors for death in the elderly with AKI.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher

  8 / 18127 MEDLINE  
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[PMID]: 29432297
[Au] Autor:McClave SA; Patel J; Bhutiani N
[Ad] Address:Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, Kentucky.
[Ti] Title:Should fecal microbial transplantation be used in the ICU?
[So] Source:Curr Opin Crit Care;24(2):105-111, 2018 Apr.
[Is] ISSN:1531-7072
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE OF REVIEW: Maintaining gut barrier defenses, modulating immune responses, and supporting the role of commensal microbiota are major factors influencing outcome in critical illness. Of these, maintaining a commensal 'lifestyle' and preventing the emergence of a virulent pathobiome may be most important in reducing risk of infection and multiple organ failure. RECENT FINDINGS: The polymeric formulas utilized for enteral nutrition in the ICU are absorbed high in the gastrointestinal tract and may not reach the microbial burden in the cecum where their effect is most needed. The provision of a few select probiotic organisms may be insufficient to refaunate the gut and establish a 'recovery pattern,' propelling the patient toward health and homeostasis. Use of fecal microbial transplantation (FMT) appears to be a more successful strategy for replenishing the intestinal microbiome and maintaining its commensal phenotypic expression. SUMMARY: FMT has become an attractive option to mitigate multiple organ dysfunction in the ICU. This article discusses the physiology, rationale, early experience, and expectations for such therapy in the critically ill patient.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1097/MCC.0000000000000489

  9 / 18127 MEDLINE  
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[PMID]: 29267971
[Au] Autor:Cantaluppi V; Medica D; Quercia AD; Dellepiane S; Figliolini F; Virzì GM; Brocca A; Quaglia M; Marengo M; Olivieri C; Senzolo M; Garzotto F; Della Corte F; Castellano G; Gesualdo L; Camussi G; Ronco C
[Ad] Address:Nephrology, Dialysis and Kidney Transplantation Unit, Maggiore della Carità Hospital-University of Eastern Piedmont, Novara, Italy.
[Ti] Title:Perfluorocarbon solutions limit tubular epithelial cell injury and promote CD133+ kidney progenitor differentiation: potential use in renal assist devices for sepsis-associated acute kidney injury and multiple organ failure.
[So] Source:Nephrol Dial Transplant;, 2017 Dec 16.
[Is] ISSN:1460-2385
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Background: The renal assist device (RAD) is a blood purification system containing viable renal tubular epithelial cells (TECs) that has been proposed for the treatment of acute kidney injury (AKI) and multiple organ failure. Perfluorocarbons (PFCs) are oxygen carriers used for organ preservation in transplantation. The aim of this study was to investigate the effect of PFCs on hypoxia- and sepsis-induced TEC injury and on renal CD133+ progenitor differentiation in a microenvironment similar to the RAD. Methods: TECs were seeded in a polysulphone hollow fibre under hypoxia or cultured with plasma from 10 patients with sepsis-associated AKI in the presence or absence of PFCs and were tested for cytotoxicity (XTT assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay, caspases, enzyme-linked immunosorbent assay, Fas/Fas Ligand pathway activation), mitochondrial activity, cell polarity [transepithelial electrical resistance (TEER)] and adenosine triphosphate production. The effect of PFCs on proliferation and differentiation of human CD133+ progenitors was also studied. Results: n the presence of PFCs, TECs seeded into the polysulphone hollow fibre showed increased viability and expression of insulin-like growth factor 1, hepatocyte growth factor and macrophage-stimulating protein. Plasma from septic patients induced TEC apoptosis, disruption of oxidative metabolism, alteration of cell polarity and albumin uptake, down-regulation of the tight junction protein ZO-1 and the endocytic receptor megalin on the TEC surface. These detrimental effects were significantly reduced by PFCs. Moreover, PFCs induced CD133+ renal progenitor cell proliferation and differentiation towards an epithelial/tubular-like phenotype. Conclusions: PFCs improved the viability and metabolic function of TECs seeded within a polysulphone hollow fibre and subjected to plasma from septic AKI patients. Additionally, PFCs promoted differentiation towards a tubular/epithelial phenotype of CD133+ renal progenitor cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1093/ndt/gfx328

  10 / 18127 MEDLINE  
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[PMID]: 29236952
[Au] Autor:Faller KME; Atzler D; McAndrew DJ; Zervou S; Whittington HJ; Simon JN; Aksentijevic D; Ten Hove M; Choe CU; Isbrandt D; Casadei B; Schneider JE; Neubauer S; Lygate CA
[Ad] Address:Division of Cardiovascular Medicine, Radcliffe Department of Medicine, BHF Centre of Research Excellence at the University of Oxford and the Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
[Ti] Title:Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine.
[So] Source:Cardiovasc Res;114(3):417-430, 2018 Mar 01.
[Is] ISSN:1755-3245
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Aims: Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. Methods and results: Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. Conclusions: Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1093/cvr/cvx242


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