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Article ; Online: Blood phenylalanine fluctuation in phenylketonuric children treated by BH4 or low-phenylalanine diet from birth.

Theron, Maurane / Jeannesson, Elise / Canton, Marie / Namour, Farès / Oussalah, Abderrahim / Feillet, François / Wiedemann, Arnaud

Scientific reports

2023 Volume 13, Issue 1, Page(s) 9559

Abstract: The prognosis of phenylketonuria (PKU) is related to the quality of metabolic control all life-long. PKU treatment is based on a low-Phe diet, 6R-tetrahydrobiopterin (BH4) treatment for the BH4-responsive PKU patients or enzyme replacement therapy. ... ...

Abstract	The prognosis of phenylketonuria (PKU) is related to the quality of metabolic control all life-long. PKU treatment is based on a low-Phe diet, 6R-tetrahydrobiopterin (BH4) treatment for the BH4-responsive PKU patients or enzyme replacement therapy. Fluctuations in blood phenylalanine (Phe) concentrations may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). The aim of this work is to study the fluctuation of Blood Phe in patients treated by BH4 from birth in comparison with patients treated by low-Phe diet. We conducted a retrospective study in a national reference center for PKU management. We compared mean phenylalanine blood concentration and its fluctuation in 10 BH4-responder patients (BH4R) and in 10 BH4 non-responder patients (BH4NR) treated from birth. The mean blood Phe concentration is similar between the two groups before 10 years of age (290 ± 135 (BH4R) vs. 329 ± 187 µmol/L, p = 0.066 (BH4NR)) while it is lower in the BH4R group after 10 years of age. (209 ± 69 vs. 579 ± 136 µmol/L, p = 0.0008). Blood Phe fluctuation is significantly lower in the BH4R group compared to the BH4NR group (70.2 ± 75.6 vs. 104.4 ± 111.6 µmol/L, p < 0.01) before 6 years of age. There are no significant differences observed on nutritional status, growth, and neuropsychological tests between the two groups. BH4 introduced in the neonatal period is associated with less blood Phe fluctuation before 6 years. Additional time and patients are required to determine if the decrease in Phe fluctuation would positively impact the long-term outcome of PKU patients.
MeSH term(s)	Infant, Newborn ; Pregnancy ; Female ; Humans ; Child ; Retrospective Studies ; Parturition ; Phenylalanine ; Phenylketonurias ; Diet
Chemical Substances	Phenylalanine (47E5O17Y3R)
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-36550-1
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Article ; Online: Stemness of Normal and Cancer Cells: The Influence of Methionine Needs and SIRT1/PGC-1α/PPAR-α Players.

Siblini, Youssef / Namour, Farès / Oussalah, Abderrahim / Guéant, Jean-Louis / Chéry, Céline

Cells

2022 Volume 11, Issue 22

Abstract: Stem cells are a population of undifferentiated cells with self-renewal and differentiation capacities. Normal and cancer stem cells share similar characteristics in relation to their stemness properties. One-carbon metabolism (OCM), a network of ... ...

Abstract	Stem cells are a population of undifferentiated cells with self-renewal and differentiation capacities. Normal and cancer stem cells share similar characteristics in relation to their stemness properties. One-carbon metabolism (OCM), a network of interconnected reactions, plays an important role in this dependence through its role in the endogenous synthesis of methionine and S-adenosylmethionine (SAM), the universal donor of methyl groups in eukaryotic cells. OCM genes are differentially expressed in stem cells, compared to their differentiated counterparts. Furthermore, cultivating stem cells in methionine-restricted conditions hinders their stemness capacities through decreased SAM levels with a subsequent decrease in histone methylation, notably H3K4me3, with a decrease in stem cell markers. Stem cells' reliance on methionine is linked to several mechanisms, including high methionine flux or low endogenous methionine biosynthesis. In this review, we provide an overview of the recent discoveries concerning this metabolic dependence and we discuss the mechanisms behind them. We highlight the influence of SIRT1 on SAM synthesis and suggest a role of PGC-1α/PPAR-α in impaired stemness produced by methionine deprivation. In addition, we discuss the potential interest of methionine restriction in regenerative medicine and cancer treatment.
MeSH term(s)	Methionine/metabolism ; Sirtuin 1 ; PPAR alpha ; Racemethionine ; S-Adenosylmethionine/metabolism ; Neoplastic Stem Cells/metabolism ; Neoplasms
Chemical Substances	Methionine (AE28F7PNPL) ; Sirtuin 1 (EC 3.5.1.-) ; PPAR alpha ; Racemethionine (73JWT2K6T3) ; S-Adenosylmethionine (7LP2MPO46S)
Language	English
Publishing date	2022-11-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11223607
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Article ; Online: Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials.

Guéant, Jean-Louis / Guéant-Rodriguez, Rosa-Maria / Oussalah, Abderrahim / Zuily, Stéphane / Rosenberg, Irwin

Thrombosis and haemostasis

2022 Volume 123, Issue 3, Page(s) 270–282

Abstract: Thromboembolic manifestations are relatively frequent in patients with intermediate/severe hyperhomocysteinemia (>30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15-30 µmol/ ...

Abstract	Thromboembolic manifestations are relatively frequent in patients with intermediate/severe hyperhomocysteinemia (>30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15-30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice.Homocysteine-lowering trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half of the cases and related to B12 and/or folate deficiency and Addison/Biermer disease in 55% of these cases.In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for B vitamin deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the effect of lowering homocysteine according to hyperhomocysteinemia categories at baseline.
MeSH term(s)	Humans ; Cardiovascular Diseases/drug therapy ; Hyperhomocysteinemia/diagnosis ; Hyperhomocysteinemia/drug therapy ; Hyperhomocysteinemia/etiology ; Folic Acid/therapeutic use ; Vitamin B 12/therapeutic use ; Risk Factors ; Homocysteine
Chemical Substances	Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204) ; Homocysteine (0LVT1QZ0BA)
Language	English
Publishing date	2022-09-28
Publishing country	Germany
Document type	Review ; Journal Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/a-1952-1946
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Uh III Zs.192: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Correction: A transgenic mice model of retinopathy of cblG‑type inherited disorder of one‑carbon metabolism highlights epigenome‑wide alterations related to cone photoreceptor cells development and retinal metabolism.

Matmat, Karim / Conart, Jean-Baptiste / Graindorge, Paul-Henri / El Kouche, Sandra / Hassan, Ziad / Siblini, Youssef / Umoret, Rémy / Safar, Ramia / Baspinar, Okan / Robert, Aurélie / Alberto, Jean-Marc / Oussalah, Abderrahim / Hergalant, Sébastien / Coelho, David / Guéant, Jean-Louis / Guéant-Rodriguez, Rosa-Maria

Clinical epigenetics

2024 Volume 16, Issue 1, Page(s) 23

Language	English
Publishing date	2024-02-08
Publishing country	Germany
Document type	Published Erratum
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-024-01636-8
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Article ; Online: Epigenome alterations in food allergy: A systematic review of candidate gene and epigenome-wide association studies.

Safar, Ramia / Oussalah, Abderrahim / Mayorga, Lina / Vieths, Stefan / Barber, Domingo / Torres, Maria Jose / Guéant, Jean-Louis

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2023 Volume 53, Issue 3, Page(s) 259–275

Abstract: Objective: The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA).: Design: A systematic review of the literature and meta-analysis were carried out ... ...

Abstract	Objective: The aim of this study was to systematically review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA). Design: A systematic review of the literature and meta-analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated. Data sources: PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022. Eligibility criteria: We included targeted and epigenome-wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations. Results: Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene-targeted studies found associations in Th1/Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll-like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow's milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene-functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP-X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen-induced cytokine storm signalling pathway and dendritic cell maturation. Conclusion: This review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome-based biomarkers for FA.
MeSH term(s)	Female ; Animals ; Cattle ; Epigenome ; Cell Line, Tumor ; Transcription Factors ; DNA-Binding Proteins ; Food Hypersensitivity ; Milk Hypersensitivity
Chemical Substances	Transcription Factors ; DNA-Binding Proteins
Language	English
Publishing date	2023-02-09
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14277
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Article: Usefulness of procalcitonin at admission as a risk-stratifying biomarker for 50-day in-hospital mortality among patients with community-acquired bloodstream infection: an observational cohort study.

Oussalah, Abderrahim / Callet, Jonas / Manteaux, Anne-Elisabeth / Thilly, Nathalie / Jay, Nicolas / Guéant, Jean-Louis / Lozniewski, Alain

Biomarker research

2023 Volume 11, Issue 1, Page(s) 4

Abstract: Purpose: To assess the association between plasma procalcitonin concentration at hospital admission and the risk of 50-day in-hospital mortality among patients with community-acquired bloodstream infections.: Methods: We carried out a retrospective, ... ...

Abstract	Purpose: To assess the association between plasma procalcitonin concentration at hospital admission and the risk of 50-day in-hospital mortality among patients with community-acquired bloodstream infections. Methods: We carried out a retrospective, observational cohort study with all consecutive patients with bacteriologically confirmed community-acquired bloodstream infections hospitalized between 2006 and 2012. We aimed to assess the association between plasma procalcitonin at admission and 50-day in-hospital mortality. Patients were included in the analysis if they had undergone a blood culture test within 48 hours of hospitalization with a concomitant procalcitonin assay (time < 12 hours between the two tests). Inclusion in the study began on the day of hospital admission, and each patient was followed until death, discharge from the hospital, or last known follow-up in the 50 days following hospital admission. The endpoint was the occurrence of all-cause in-hospital mortality during the 50 days following hospital admission. Results: During the 7-year study period, 1593 patients were admitted to one of the healthcare facilities of the University Hospital of Nancy from home or through the emergency department and had positive blood cultures and concomitant procalcitonin assays. Among the patients, 452 met the selection criteria and were analyzed. In ROC analysis, procalcitonin at baseline was significantly associated with 50-day in-hospital mortality, with an optimal threshold > 4.24 ng/mL. A baseline procalcitonin > 4.24 ng/mL was independently associated with an increased risk of in-hospital mortality (multivariable logistic regression: odds ratio, 2.58; 95% CI, 1.57-4.25; P = 0.0002; Cox proportional hazard regression: hazard ratio, 2.01; 95% CI, 1.30-3.11; P = 0.002). In sensitivity analyses, baseline procalcitonin quartiles were independently associated with 50-day in-hospital mortality (multivariable logistic regression: odds ratio, 1.47; 95% CI, 1.17-1.85; P = 0.001; Cox proportional hazard regression: hazard ratio, 1.31; 95% CI, 1.07-1.60; P = 0.008). The independent associations between baseline procalcitonin and the risk of 50-day in-hospital mortality were maintained after adjusting for C-reactive protein and sepsis status at admission. Conclusion: Our data provide the first evidence of the usefulness of plasma procalcitonin at admission as a risk-stratifying biomarker for predicting 50-day in-hospital mortality among patients with community-acquired bloodstream infections.
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2699926-2
ISSN	2050-7771
ISSN	2050-7771
DOI	10.1186/s40364-023-00450-3
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Article ; Online: Un long ARN non codant régule l’activité de la phénylalanine hydroxylase, l’enzyme responsable de la phénylcétonurie.

Wiedemann, Arnaud / Lin, Chunru / Oussalah, Abderrahim / Namour, Bernard / Jeannesson, Élise / Guéant, Jean-Louis / Feillet, François

Medecine sciences : M/S

2022 Volume 38, Issue 1, Page(s) 12–14

Title translation	A long non-coding RNA regulates the activity of phenylalanine hydroxylase, the key enzyme of phenylketonuria.
MeSH term(s)	Biopterins ; Humans ; Phenylalanine Hydroxylase/genetics ; Phenylketonurias/genetics ; RNA, Long Noncoding
Chemical Substances	RNA, Long Noncoding ; Biopterins ; Phenylalanine Hydroxylase (EC 1.14.16.1)
Language	French
Publishing date	2022-01-21
Publishing country	France
Document type	News
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2021237
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Article ; Online: Le dépistage de la phénylcétonurie en France.

Wiedemann, Arnaud / Jeannesson, Élise / Oussalah, Abderrahim / Guéant, Jean-Louis / Guéant-Rodriguez, Rosa-Maria / Feillet, François

Medecine sciences : M/S

2021 Volume 37, Issue 5, Page(s) 468–473

Abstract: Phenylketonuria is the most common inborn error of metabolism and causes irreversible mental retardation if left untreated. Its newborn screening was made possible by the technique of blood collection on filter paper developed by Robert Guthrie. Neonatal ...

Title translation	Newborn screening of phenylketonuria in France.
Abstract	Phenylketonuria is the most common inborn error of metabolism and causes irreversible mental retardation if left untreated. Its newborn screening was made possible by the technique of blood collection on filter paper developed by Robert Guthrie. Neonatal PKU screening began in France in the early 1970s. It was initially carried out by a bacteriological method, then by fluorometry, and finally, since 2020, by tandem mass spectrometry. More than 35 million newborns have been screened to date. This resulted in the diagnosis of more than 3,500 children with PKU or mild hyperphenylalaninemia. The management of these children has improved over time, in particular thanks to the techniques of biochemistry and molecular genetics which lead to an accurate diagnosis and the arrival of drug treatment by sapropterin. Thanks to this screening, which allows for early management, the prognosis of PKU has been transformed and, although neurological or behavioral problems may arise, these patients are living normally today.
MeSH term(s)	Child ; France/epidemiology ; Humans ; Infant, Newborn ; Neonatal Screening ; Phenylketonurias/diagnosis ; Phenylketonurias/epidemiology
Language	French
Publishing date	2021-05-18
Publishing country	France
Document type	Journal Article
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2021061
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Article: Multiparametric renal function assessment in cirrhotic patients shows high prevalence of medically actionable changes in multiple modules.

Belmonte, Richard / Silva-Rodriguez, Maël / Barbé, Françoise / Bensenane, Mouni / Haghenejad, Vincent / Vrillon, Isabelle / Alla, Asma / Flahault, Adrien / Kormann, Raphael / Corbel, Alice / Aitdjafer, Zakia / Quilliot, Didier / Derain-Dubourg, Laurence / Namour, Farès / Guéant, Jean-Louis / Bronowicki, Jean-Pierre / Oussalah, Abderrahim

Hepatology research : the official journal of the Japan Society of Hepatology

2024

Abstract: Aim: Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters ... ...

Abstract	Aim: Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers. Methods: We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43-multiparametric renal function assessment between January 1, 2021, and June 30, 2023. Results: All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte-free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m Conclusions: This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute-free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.
Language	English
Publishing date	2024-04-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1387041-5
ISSN	1386-6346 ; 0928-4346
ISSN	1386-6346 ; 0928-4346
DOI	10.1111/hepr.14050
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Article ; Online: Accuracy of procalcitonin for diagnosing peripheral blood culture contamination among patients with positive blood culture for potential contaminants.

Berthezène, Clémence / Aissa, Nejla / Manteaux, Anne Elisabeth / Guéant, Jean-Louis / Oussalah, Abderrahim / Lozniewski, Alain

Infection

2021 Volume 49, Issue 6, Page(s) 1249–1255

Abstract: Purpose: Blood culture contamination is still a frequently observed event and may lead to unnecessary antibiotic prescriptions and additional hazards and costs. However, in patients hospitalized in tertiary care, true bacteremias for pathogens that are ... ...

Abstract	Purpose: Blood culture contamination is still a frequently observed event and may lead to unnecessary antibiotic prescriptions and additional hazards and costs. However, in patients hospitalized in tertiary care, true bacteremias for pathogens that are classically considered as contaminants can be observed. We assessed the diagnostic accuracy of procalcitonin for differentiating blood culture contamination from bacteremia in patients with positive blood cultures for potential contaminants. Methods: We carried out a retrospective, cross-sectional, observational study on consecutive patients hospitalized between January 2016 and May 2019 at the University Hospital of Nancy and who had a positive peripheral blood culture for a pathogen classically considered as a potential contaminant. Results: During the study period, 156 patients were screened, and 154 were retained in the analysis. Among the variables that were significantly associated with a diagnosis of blood culture contamination in univariate analyses, four were maintained in multivariate logistic regression analysis: a number of positive blood culture bottles ≤ 2 (OR 23.76; 95% CI 1.94-291.12; P = 0.01), procalcitonin < 0.1 ng/mL (OR 14.88; 95% CI 1.62-136.47; P = 0.02), non-infection-related admission (OR 13.00; 95% CI 2.17-77.73; P = 0.005), and a percentage of positive blood culture bottles ≤ 25% (OR 12.15; 95% CI 2.02-73.15; P = 0.006). Conclusions: These data provide new evidence on the usefulness of plasma procalcitonin as a reliable diagnostic biomarker in the diagnostic algorithm of peripheral blood culture contamination among patients hospitalized in tertiary care. Clinical trial: ClinicalTrials.gov #NCT04573894.
MeSH term(s)	Bacteremia/diagnosis ; Blood Culture ; Cross-Sectional Studies ; Humans ; Procalcitonin ; Retrospective Studies
Chemical Substances	Procalcitonin
Language	English
Publishing date	2021-09-15
Publishing country	Germany
Document type	Journal Article ; Observational Study
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-021-01697-4
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