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Article: Acquired Hemophilia A after SARS-CoV-2 Infection: A Case Report and an Updated Systematic Review.

Németh, Márton / Mühl, Diána / Csontos, Csaba / Nagy, Ágnes / Alizadeh, Hussain / Szakács, Zsolt

2023 Volume 11, Issue 9

Abstract: The role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been implicated in the pathogenesis of acquired hemophilia A (AHA). The aim of this study is to report our case and to summarize clinical studies on de novo AHA after SARS-CoV-2 ...

Abstract	The role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been implicated in the pathogenesis of acquired hemophilia A (AHA). The aim of this study is to report our case and to summarize clinical studies on de novo AHA after SARS-CoV-2 infection. We performed a systematic search on the association of SARS-CoV-2 with AHA in four medical databases up to 28 May 2023. Eligible studies should include de novo AHA patients who had SARS-CoV-2 infection before or concomitant with the diagnosis of AHA. Findings were synthesized narratively. In addition, we report the case of a 62-year-old female patient, who presented to our clinic with left flank pain 2 weeks after SARS-CoV-2 infection. Clinical investigations confirmed AHA and imaging studies revealed retroperitoneal bleeding. Her hemostasis was successfully secured with bypassing agents; however, despite immunosuppressive therapy, high inhibitor titer persisted. In the systematic review, we identified only 12 relevant cases with a questionable cause-effect relationship between SARS-CoV-2 infection and AHA. Based on the qualitative analysis of the relevant publications, current clinical evidence is insufficient to support a cause-effect relationship. The analysis of data from ongoing AHA registries can serve further evidence.
Language	English
Publishing date	2023-08-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11092400
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Article ; Online: Novel Damage Biomarkers of Sepsis-Related Acute Kidney Injury.

Ragán, Dániel / Horváth-Szalai, Zoltán / Szirmay, Balázs / Mühl, Diána

EJIFCC

2022 Volume 33, Issue 1, Page(s) 11–22

Abstract: Sepsis-related acute kidney injury (AKI) is one of the most common complications of sepsis at the intensive care unit (ICU) with more adverse mortality rates. The early diagnosis and reliable monitoring of sepsis-related AKI are essential in achieving a ... ...

Abstract	Sepsis-related acute kidney injury (AKI) is one of the most common complications of sepsis at the intensive care unit (ICU) with more adverse mortality rates. The early diagnosis and reliable monitoring of sepsis-related AKI are essential in achieving a favorable outcome. Novel serum and urinary biomarkers could yield valuable information during this process. Regarding the widely used Kidney Disease Improving Global Outcomes (KDIGO) classifications, the diagnosis of AKI is still based on the increase of serum creatinine levels and the decrease of urine output; however, these parameters have limitations in reflecting the extent of kidney damage, therefore more sensitive and specific laboratory biomarkers are needed for the early diagnosis and prognosis of sepsis-related AKI. Regarding this, several serum parameters are discussed in this review including presepsin and the most important actin scavenger proteins (gelsolin, Gc-globulin) while other urinary markers are also examined including cell cycle arrest biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), Cystatin C and actin. Novel biomarkers of sepsis-related AKI could facilitate the early diagnosis and monitoring of sepsis-related AKI.
Language	English
Publishing date	2022-04-11
Publishing country	Italy
Document type	Journal Article
ISSN	1650-3414
ISSN (online)	1650-3414
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Article ; Online: Obstetrical aspects of the National Blood Donation and Blood Saving Program

Oláh, Zsolt / Deli, Tamás / Mühl, Diána

Orvosi hetilap

2020 Volume 161, Issue 37, Page(s) 1588–1598

Abstract: The aims of the National Blood Donation and Blood Saving Program are to support the rational and judicious utilization of blood products and abolish irrational transfusion policy to improve patient safety. In addition to the general principles, this ... ...

Title translation	A Nemzeti Véradó és Vérmentő Program szülészeti vonatkozásai.
Abstract	The aims of the National Blood Donation and Blood Saving Program are to support the rational and judicious utilization of blood products and abolish irrational transfusion policy to improve patient safety. In addition to the general principles, this program has got some special obstetrical aspects. Obstetrical, especially the postpartum haemorrhages belong to the leading causes of maternal mortality worldwide. In developed countries, a trend in increasing incidence can be observed. Preparing for delivery includes some important elements such as optimization of hemoglobin level, routinely applied prophylactic or therapeutic iron supplementation and early screening and comprehensive care of patients with high risk of obstetrical bleeding. The main causes of peripartum bleeding are abruptio placentae, placenta praevia, uterine atony, retained tissue in the uterus, trauma during delivery, and haemostatic disorders or their combinations. To prevent postpartum bleeding, it is important to use the active management of the third stage of labour including prophylactic utilization of uterotonics as an essential element. Utilization of blood salvage techniques with adequate indications may be considered in cases of cesarean section or postpartum haemorhage. In cases of obstetrical haemorrhage, management of surgical bleeding has the main priority by the obstetrician. Secondary coagulopathy associated with massive bleeding should be managed by viscoelastic test-guided, individualized and factor concentrate-based algorithm, however, pregnancy-specific reference and target ranges must be used that are different from the non-pregnancy values. Obstetrical bleedings belong to the potentially preventable causes of death. Hopefully, the implementation of the National Blood Donation and Blood Saving Program in the field of obstetrics can decrease the associated morbidity and mortality further. Orv Hetil. 2020; 161(37): 1588-1598.
MeSH term(s)	Blood Donors ; Cesarean Section ; Female ; Humans ; Obstetrics ; Operative Blood Salvage ; Postpartum Hemorrhage/therapy ; Pregnancy
Language	Hungarian
Publishing date	2020-09-07
Publishing country	Hungary
Document type	Journal Article
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/650.2020.31915
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Article ; Online: Measurement of Urinary Gc-Globulin by a Fluorescence ELISA Technique: Method Validation and Clinical Evaluation in Septic Patients-A Pilot Study.

Kőszegi, Tamás / Horváth-Szalai, Zoltán / Ragán, Dániel / Kósa, Brigitta / Szirmay, Balázs / Kurdi, Csilla / Kovács, Gábor L / Mühl, Diána

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 19

Abstract: A major complication of sepsis is the development of acute kidney injury (AKI). In case of acute tubular damage, Gc-globulin, a known serum sepsis marker is increasingly filtrated into the urine therefore, urinary Gc-globulin (u-Gc) levels may predict ... ...

Abstract	A major complication of sepsis is the development of acute kidney injury (AKI). In case of acute tubular damage, Gc-globulin, a known serum sepsis marker is increasingly filtrated into the urine therefore, urinary Gc-globulin (u-Gc) levels may predict septic AKI. We developed and validated a competitive fluorescence ELISA method for u-Gc measurement. Serum and urine samples from septic patients were collected in three consecutive days (T1, T2, T3) and data were compared to controls. Intra- and interassay imprecisions were CV < 14% and CV < 20%, respectively, with a recovery close to 100%. Controls and septic patients differed (
MeSH term(s)	Humans ; Pilot Projects ; Creatinine ; Acute Kidney Injury/etiology ; Biomarkers ; Sepsis ; Enzyme-Linked Immunosorbent Assay ; Globulins
Chemical Substances	Creatinine (AYI8EX34EU) ; Biomarkers ; Globulins
Language	English
Publishing date	2023-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28196864
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Article ; Online: Distinct patterns of serum and urine macrophage migration inhibitory factor kinetics predict death in sepsis: a prospective, observational clinical study.

Toldi, Janos / Kelava, Leonardo / Marton, Sandor / Muhl, Diana / Kustan, Peter / Feher, Zsolt / Maar, Klaudia / Garai, Janos / Pakai, Eszter / Garami, Andras

Scientific reports

2023 Volume 13, Issue 1, Page(s) 588

Abstract: Macrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF ... ...

Abstract	Macrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF are different between males and females. We conducted a single-center prospective, observational study with repeated measurements of MIF in serum and urine on days 0, 2, and 4 from admission to the intensive care unit (ICU) in 50 adult septic patients. We found that in patients who died within 90 days, there was an increase in serum MIF level from day 0 to 4, whereas in the survivors there was rather a decrease (p = 0.018). The kinetics were sex-dependent as the same difference in the pattern was present in males (p = 0.014), but not in females (p = 0.418). We also found that urine MIF was markedly lower in patients who died than in survivors of sepsis (p < 0.050). Urine MIF levels did not show temporal changes: there was no meaningful difference between day 0 and 4. These results suggest that kinetics of serum MIF during the initial days from ICU admission can predict death, especially in male patients. Additionally, lower urine MIF levels can also indicate death without showing meaningful temporal kinetics.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Biomarkers ; Intensive Care Units ; Macrophage Migration-Inhibitory Factors/blood ; Macrophage Migration-Inhibitory Factors/chemistry ; Macrophage Migration-Inhibitory Factors/urine ; Prospective Studies ; Sepsis/complications ; Sepsis/diagnosis
Chemical Substances	Biomarkers ; Macrophage Migration-Inhibitory Factors
Language	English
Publishing date	2023-01-11
Publishing country	England
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-27506-6
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Article: Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study.

Ragán, Dániel / Kustán, Péter / Horváth-Szalai, Zoltán / Szirmay, Balázs / Miseta, Attila / Woth, Gábor / Kőszegi, Tamás / Mühl, Diána

Frontiers in medicine

2023 Volume 10, Page(s) 1126982

Abstract: Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio.: Methods: Blood ... ...

Abstract	Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio. Methods: Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI). Results: In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated ( Conclusion: PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis. Clinical trail registration: NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.
Language	English
Publishing date	2023-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1126982
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Article: Az oxidatív stressz és haemostasis paramétereinek változása életveszélyes tüdoembólia thrombolyticus kezelése során.

Mühl, Diana

Orvosi hetilap

2008 Volume 149, Issue 20, Page(s) 935–948

Abstract: Unlabelled: Acute pulmonary embolism is the third most common cause of cardiovascular mortality. Thrombolytic treatment of massive pulmonary embolism can be complicated with haemorrhage, re-thrombosis and oxidative stress.: Aims: The purpose of this ... ...

Title translation	Changes in oxidative stress and hemostatic parameters in the course of thrombolytic therapy of pulmonary embolism.
Abstract	Unlabelled: Acute pulmonary embolism is the third most common cause of cardiovascular mortality. Thrombolytic treatment of massive pulmonary embolism can be complicated with haemorrhage, re-thrombosis and oxidative stress. Aims: The purpose of this study was to evaluate the changes in platelet aggregation, haemostatic, leukocyte function parameters and oxidative stress in patients with acute pulmonary embolism treated with thrombolytics. Methods: Fifteen patients undergoing thrombolysis with ultra-high dose streptokinase ( n = 8), or alteplase ( n = 7) treatment were studied. Arterial blood samples were taken before (baseline) and after thrombolysis between the 4th and 24th hour at every four hours, on the second day twice a day and daily on the 3rd, 4th, 5th and 30th day. Platelet aggregation was examined as spontaneous and induced aggregation with adrenaline, collagen and adenosine diphosphate. D-dimer and fibrinogen were measured 8 hourly on the first day and later at the same time intervals as above. To analyse oxidative stress, blood samples were collected prior to thrombolysis, and then 8 hours, 1, 3, 5 and 30 days after treatment. Malondialdehyde, reduced glutathion, plasma sulphydryl groups levels, superoxide dismutase and myeloperoxidase enzyme activities were measured in plasma or whole blood for monitoring of the oxidative stress markers. Production of reactive oxygen species in whole blood was measured by luminol dependent chemiluminescence. Flow cytometry was used to determine CD11a, CD18, and CD97 surface antigen expression on leukocytes. Results: In streptokinase group, adrenaline induced platelet aggregation decreased at the 4th and 8th hour ( p < 0.03) and was significantly lower than in the alteplase group at the 36th hour and on the 3rd day. Platelet aggregation induced by adenosine diphosphate was lower at the 4th hour than at baseline in streptokinase group ( p < 0.05). Collagen induced platelet aggregation was lower at the 4th and 8th hour than at baseline ( p < 0.05) in streptokinase group. Compared to baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels elevated significantly in both therapeutic groups at the 8th hour. Spontaneous platelet aggregation was not detectable and major bleeding or re-embolism was not documented. The elevated malondialdehyde, reactive oxygen species and myeloperoxidase, decreased reduced glutathion and plasma sulphydryl levels indicated the presence of oxidative stress in patients with pulmonary embolism. Malondialdehyde significantly increased, reduced glutathion significantly decreased following thrombolysis. Reactive oxygen species production peaked on the 3rd and 5th days. Thrombolysis was accompanied by significant decrease in granulocyte and monocyte CD11a and CD18 as well as in granulocyte CD97 expression ( p < 0.05). Conclusion: Massive/submassive pulmonary embolism and thrombolysis injures inducible platelet aggregation. The changes in fibrinogen levels correlate significantly with the improvement of pulmonary perfusion which shows the effect of thrombolysis. Pulmonary embolism induced oxidative stress was detected on patients before thrombolysis. Thrombolytic treatment of pulmonary embolism augmented the increase of oxidative stress response and leukocyte activation following reperfusion, and these parameters normalised only on the 30th day.
MeSH term(s)	Acute Disease ; Adult ; Aged ; Antigens, CD/blood ; Biomarkers/blood ; CD11a Antigen/blood ; CD18 Antigens/blood ; Female ; Fibrin Fibrinogen Degradation Products/metabolism ; Fibrinogen/metabolism ; Glutathione/blood ; Hemoglobins/metabolism ; Hemostasis/drug effects ; Humans ; Leukocytes/drug effects ; Male ; Malondialdehyde/blood ; Membrane Glycoproteins/blood ; Middle Aged ; Oxidative Stress/drug effects ; Patient Selection ; Peroxidase/blood ; Platelet Aggregation/drug effects ; Pulmonary Embolism/blood ; Pulmonary Embolism/drug therapy ; Pulmonary Embolism/enzymology ; Reactive Oxygen Species/blood ; Streptokinase/administration & dosage ; Superoxide Dismutase/blood ; Thrombolytic Therapy/methods ; Time Factors ; Tissue Plasminogen Activator/administration & dosage
Chemical Substances	ADGRE5 protein, human ; Antigens, CD ; Biomarkers ; CD11a Antigen ; CD18 Antigens ; Fibrin Fibrinogen Degradation Products ; Hemoglobins ; Membrane Glycoproteins ; Reactive Oxygen Species ; fibrin fragment D ; Malondialdehyde (4Y8F71G49Q) ; Fibrinogen (9001-32-5) ; Peroxidase (EC 1.11.1.7) ; Superoxide Dismutase (EC 1.15.1.1) ; Streptokinase (EC 3.4.-) ; Tissue Plasminogen Activator (EC 3.4.21.68) ; Glutathione (GAN16C9B8O)
Language	Hungarian
Publishing date	2008-05-06
Publishing country	Hungary
Document type	Journal Article
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/OH.2008.28356
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Article: Nonconventional Markers of Sepsis.

Kustán, Péter / Horváth-Szalai, Zoltán / Mühl, Diána

EJIFCC

2017 Volume 28, Issue 2, Page(s) 122–133

Abstract: Sepsis still remains a challenging healthcare problem with high mortality rate. To improve outcome, early diagnosis and monitoring of sepsis is of utmost importance. In this process objective laboratory parameters are the most helpful. Procalcitonin and ... ...

Abstract	Sepsis still remains a challenging healthcare problem with high mortality rate. To improve outcome, early diagnosis and monitoring of sepsis is of utmost importance. In this process objective laboratory parameters are the most helpful. Procalcitonin and C-reactive protein are the most commonly used and recommended markers of sepsis however, more than 200 sepsis biomarkers have already been published. This mini review focuses on nonconventional novel possibilities for the recognition of sepsis severity. Presepsin, actin and actin scavenger proteins (gelsolin and Gc-globulin) and orosomucoid are discussed. Besides serum parameters, the urinary levels of these markers are also elaborated, since urinary biomarkers of sepsis provide new diagnostic implications and are helpful for monitoring both the kidney function and the septic process. Increasing serum actin levels and decreasing levels of actin binding proteins seem to be associated with sepsis severity and outcome. Actin can be detected in the urine samples of septic patients as well, and strongly elevated levels of it were found in sepsis-related acute kidney injury. Both serum and urinary orosomucoid might be able to indicate sepsis, however urinary orosomucoid is a more sensitive inflammatory marker. Novel laboratory tests can provide rapid help for clinical decision making because the key point in successful treatment lies in the early diagnosis of sepsis.
Language	English
Publishing date	2017-05-01
Publishing country	Italy
Document type	Journal Article
ISSN	1650-3414
ISSN	1650-3414
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Article ; Online: Urinary actin, as a potential marker of sepsis-related acute kidney injury: A pilot study.

Ragán, Dániel / Kustán, Péter / Horváth-Szalai, Zoltán / Szirmay, Balázs / Bugyi, Beáta / Ludány, Andrea / Miseta, Attila / Nagy, Bálint / Mühl, Diána

PloS one

2021 Volume 16, Issue 7, Page(s) e0255266

Abstract: Introduction: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our ... ...

Abstract	Introduction: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our aims were to measure urinary actin (u-actin) concentrations of septic and control patients and to test if u-actin levels could predict AKI and mortality. Methods: Blood and urine samples were collected from septic and sepsis-related AKI patients at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. Patients with malignancies needing palliative care, end-stage renal disease or kidney transplantation were excluded. Serum and u-actin levels were determined by quantitative Western blot. Patients were categorized by the Sepsis-3 and KDIGO AKI classifications. Results: In our study, 17 septic, 43 sepsis-induced AKI and 24 control patients were enrolled. U-actin levels were higher in septic patients compared with controls during follow-up (p<0.001). At T1, the septic and sepsis-related AKI groups also showed differences (p<0.001), yet this increase was not statistically significant at T2 and T3. We also detected significantly elevated u-actin concentrations in AKI-2 and AKI-3 septic patients compared with AKI-1 septic patients (p<0.05) at T1 and T3, along with a significant increase in AKI-2 septic patients compared with AKI-1 septic patients at T2 (p<0.01). This tendency remained the same when referring u-actin to urine creatinine. Parameters of first-day septic patient samples could discriminate AKI from non-AKI state (AUC ROC, p<0.001): u-actin: 0.876; se-creatinine: 0.875. Derived cut-off value for u-actin was 2.63 μg/L (sensitivity: 86.0%, specificity: 82.4%). Conclusion: U-actin may be a complementary diagnostic biomarker to se-creatinine in sepsis-related AKI while higher u-actin levels also seem to reflect the severity of AKI. Further investigations may elucidate the importance of u-actin release in sepsis-related AKI.
MeSH term(s)	Actins/blood ; Actins/urine ; Acute Kidney Injury/diagnosis ; Acute Kidney Injury/etiology ; Acute Kidney Injury/mortality ; Aged ; Area Under Curve ; Biomarkers/urine ; Case-Control Studies ; Creatinine/blood ; Creatinine/urine ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; ROC Curve ; Sepsis/complications ; Sepsis/diagnosis ; Sepsis/mortality ; Sepsis/pathology ; Severity of Illness Index ; Survival Analysis
Chemical Substances	Actins ; Biomarkers ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2021-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0255266
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Article ; Online: Comparison of the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) during carotid artery stenting (CAS) and carotid endarterectomy (CEA).

Mérei, Ákos / Nagy, Bálint / Woth, Gábor / Lantos, János / Kövér, Ferenc / Bogár, Lajos / Mühl, Diána

BMC neurology

2018 Volume 18, Issue 1, Page(s) 128

Abstract: Background: Our aim was to compare the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) in during carotid endarterectomy (CEA) and carotid artery stenting (CAS).: Methods: In our prospective study, twenty- ... ...

Abstract	Background: Our aim was to compare the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) in during carotid endarterectomy (CEA) and carotid artery stenting (CAS). Methods: In our prospective study, twenty-five patients who were scheduled to undergo CAS were enrolled. We used a matched, historical CEA group as controls. Blood samples were collected at four time points: T1: preoperative; T2: 60 min after stent insertion; T3: first postoperative morning; and T4: third postoperative morning. Plasma MMP-9 and TIMP-1 levels were measured by ELISA. Results: In the CEA group, the plasma levels of MMP-9 were significantly elevated at T3 compared to T1. In the CAS group, there was no significant difference in MMP-9 levels in the perioperative period. MMP-9 levels were significantly higher in the T3 samples of the CEA group compared to the CAS group. Significantly lower TIMP-1 levels were measured in both groups at T2 than at T1 in both groups. MMP-9/TIMP-1 at T3 was significantly higher than that at T1 in the CEA group compared to both T1 and the CAS group. Conclusions: CAS triggers smaller changes in the MMP-9-TIMP-1 system during the perioperative period, which may correlate with a lower incidence of central nervous system complications. Additional studies as well as cognitive and functional surveys are warranted to determine the clinical relevance of our findings. Trial registration: NIH U.S. National Library of Medicine, Clinicaltrials.gov,NCT03410576, 24.01.2018, Retrospectively registered.
MeSH term(s)	Aged ; Carotid Stenosis/surgery ; Endarterectomy, Carotid/adverse effects ; Female ; Humans ; Incidence ; Male ; Matrix Metalloproteinase 9/blood ; Middle Aged ; Perioperative Period ; Prospective Studies ; Retrospective Studies ; Stents ; Time Factors ; Tissue Inhibitor of Metalloproteinase-1/blood ; Treatment Outcome ; United States ; Vascular Surgical Procedures/adverse effects
Chemical Substances	TIMP1 protein, human ; Tissue Inhibitor of Metalloproteinase-1 ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2018-08-29
Publishing country	England
Document type	Comparative Study ; Journal Article
ISSN	1471-2377
ISSN (online)	1471-2377
DOI	10.1186/s12883-018-1133-1
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