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Journal of Investigative Medicine : the... May 2024Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble...
Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73 m, 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (β coefficient = -0.36 √(ml/min/1.73 m), 95% confidence interval (-0.48 to -0.24), p < 0.001), standardized galectin-3 (-0.14 √(ml/min/1.73 m) (-0.27 to -0.02), p = 0.02), and log NT-proBNP (-0.23 √(ml/min/1.73 m) (-0.31 to -0.15), p < 0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.
PubMed: 38715217
DOI: 10.1177/10815589241249991 -
AME Case Reports 2024Intrabdominal hematoma can be managed with angioembolization, surgical drainage, or percutaneous drainage depending on the patient factors, underlying pathology, and...
BACKGROUND
Intrabdominal hematoma can be managed with angioembolization, surgical drainage, or percutaneous drainage depending on the patient factors, underlying pathology, and size and stability of hematoma. During the past decades, advancements have been made in the percutaneous management of intrapleural fluid collections using fibrinolytics. However, intrabdominal hematoma resolution with the help of fibrinolytic-assisted percutaneous drainage has not been as widely studied as intrapleural fibrinolytics. Our case presents a scenario where effective percutaneous drainage of abdominal fluid collection using fibrinolytics avoided an operative intervention in a patient with a history of multiple abdominal surgeries. This case report in essence can help navigate future studies into exploring non-operative management options in patients with a history of multiple abdominal surgeries.
CASE DESCRIPTION
In this report, we present a 51-year-old female status post hiatal hernia repair with jejunostomy tube (J-tube) exchange complicated by walled off intraabdominal hematoma who presented with persistent abdominal pain and leakage around her J-tube. Due to her past history of multiple abdominal surgeries including multiple hiatal hernia repairs, distal esophagectomy with Roux-en-Y, and revision of the said Roux-en-Y complicated by wound dehiscence, surgical drainage was deferred in favor of trialing fibrinolytic administration via catheters. For this purpose, we employed the protocol for fibrinolytic administration used by the Second Multicenter Intrapleural Sepsis Trial (MIST2).
CONCLUSIONS
Use of tissue plasminogen activator (t-PA) and deoxyribonuclease (DNase) as per MIST2 protocol was safely replicated for intrabdominal walled off hematoma and resulted in a near complete resolution of the hematoma in 1 week. The patient was eventually discharged with no complications. This case highlights safe and efficacious use of fibrinolytics for non-operative management of intrabdominal hematomas.
PubMed: 38711892
DOI: 10.21037/acr-23-178 -
Journal of Clinical Laboratory Analysis May 2024Despite advancements in antibiotic therapy and resuscitation protocols, sepsis and septic shock remain major contributors to morbidity and mortality in children. We...
BACKGROUND
Despite advancements in antibiotic therapy and resuscitation protocols, sepsis and septic shock remain major contributors to morbidity and mortality in children. We aimed to investigate the utility of soluble urokinase plasminogen activator receptor (suPAR) for the early detection of septic shock and to evaluate its accuracy in predicting mortality.
METHODS
A prospective study was conducted in a tertiary pediatric emergency department (ED), enrolling patients diagnosed with the sepsis, severe sepsis, or septic shock. In addition to assessing infection biomarkers such as C-reactive protein and procalcitonin, suPAR levels were quantified upon admission using enzyme-linked immunosorbent assay. The primary outcome measure was 30-day mortality.
RESULTS
Overall 72 patients and 80 healthy children included. Plasma suPAR levels demonstrated a statistically significant elevation in the sepsis, severe sepsis, and septic shock groups compared with the control group (p < 0.001 for all). The septic shock group exhibited the highest suPAR levels upon admission, surpassing both the sepsis and severe sepsis groups (p = 0.009 and 0.042). ROC analysis underscored the promising potential of suPAR with an AUC of 0.832 for septic shock. Analysis of mortality prediction revealed significantly higher suPAR levels in nonsurvivors than survivors (9.7 ng/mL vs. 4.2 ng/mL; p < 0.001). Employing plasma suPAR levels to discriminate between mortality and survival, a threshold of ≥7.0 ng/mL demonstrated a sensitivity of 90.9% and specificity of 71.0%.
CONCLUSION
Plasma suPAR levels have the potential as a biomarker for predicting mortality in children with septic shock. In pediatric septic shock, the presence of plasma suPAR ≥7 ng/mL along with an underlying disease significantly increases the risk of mortality.
Topics: Humans; Receptors, Urokinase Plasminogen Activator; Shock, Septic; Male; Female; Child, Preschool; Child; Biomarkers; Infant; Prospective Studies; ROC Curve; Case-Control Studies
PubMed: 38708489
DOI: 10.1002/jcla.25040 -
Research and Practice in Thrombosis and... Mar 2024A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023....
A State of the Art lecture entitled "Connecting Fibrinolysis and Dyslipidemia" was presented at the International Society on Thrombosis and Haemostasis Congress 2023. Hemostasis balances the consequences of blood clotting and bleeding. This balance relies on the proper formation of blood clots, as well as the breakdown of blood clots. The primary mechanism that breaks down blood clots is fibrinolysis, where the fibrin net becomes lysed and the blood clot dissolves. Dyslipidemia is a condition where blood lipid and lipoprotein levels are abnormal. Here, we review studies that observed connections between impaired fibrinolysis and dyslipidemia. We also summarize the different correlations between thrombosis and dyslipidemia in different racial and ethnic groups. Finally, we summarize relevant and new findings on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress. More studies are needed to investigate the mechanistic connections between impaired fibrinolysis and dyslipidemia and whether these mechanisms differ in racially and ethnically diverse populations.
PubMed: 38706781
DOI: 10.1016/j.rpth.2024.102394 -
Molecular Biology Reports May 2024Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims...
BACKGROUND
Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms.
METHODS AND RESULTS
Thirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-β1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations.
CONCLUSION
Lina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.
Topics: Animals; Male; Rats; Acute Kidney Injury; Connective Tissue Growth Factor; Hypoxia-Inducible Factor 1, alpha Subunit; Immunosuppressive Agents; Kidney; Linagliptin; NF-E2-Related Factor 2; Oxidative Stress; Plasminogen Activator Inhibitor 1; Rats, Sprague-Dawley; Signal Transduction; Tacrolimus; Heme Oxygenase-1
PubMed: 38704766
DOI: 10.1007/s11033-024-09533-2 -
Cellular and Molecular Life Sciences :... May 2024Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine...
BACKGROUND
Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis.
METHODS AND RESULTS
Eight-week-old wild-type male mice (CTSK) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16, p22phox, gp91, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and HO-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation.
CONCLUSIONS
CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.
Topics: Animals; Humans; Male; Mice; ADAMTS13 Protein; Apoptosis; Cathepsin K; Chlorides; Disease Models, Animal; Ferric Compounds; Human Umbilical Vein Endothelial Cells; Mice, Inbred C57BL; Mice, Knockout; Plasminogen Activator Inhibitor 1; Stress, Psychological; Thrombosis; Transcription Factor HES-1
PubMed: 38703204
DOI: 10.1007/s00018-024-05240-0 -
Aging May 2024Although intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis is the most effective early treatment for acute ischemic stroke (AIS), outcomes vary...
BACKGROUND
Although intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis is the most effective early treatment for acute ischemic stroke (AIS), outcomes vary greatly among patients. Left ventricular systolic dysfunction (LVSD) is prone to distant organ ischemia and may be a predictor for poor prognosis in AIS patients undergoing intravenous thrombolysis (IVT). Our aim was to investigate the predictivity of LVSD diagnosis (as measured by left ventricular ejection fraction (LVEF)) on 90-day clinical outcomes in AIS patients undergoing thrombolysis.
METHODS
The current prospective cohort study continuously enrolled 273 AIS patients from the National Stroke Prevention and Treatment Engineering Management Special Database who underwent IVT and completed echocardiography within 24 h of admission between 2021 and 2023. LVSD was examined by evaluation of the echocardiographic LVEF values using Simpson's biplane method of discs in line with international guidelines, and defined as a LVEF value < 50%. Multivariable ordinal logistic regression model was performed to analyze the association between LVEF and functional outcome at 3 months. Restricted cubic spline (RCS) was used to examine the shape of the dose-response association between reduced LVEF and poor functional outcomes. Subgroup analysis was also employed to further verify the reliability and practicability of the results.
RESULTS
Baseline data analysis showed LVSD patients had more comorbidities including on multivariate analyses, LVSD (OR 2.78, 95% CI 1.23 to 6.24, P=0.014), pre-existing diabetes mellitus (OR 2.08, 95% CI 1.11 to 3.90, P=0.023) and NIHSS on arrival (OR 1.31, 95% CI 1.21 to 1.49, P<0.001) were independent predictors of poor functional outcomes (mRS ≥ 3) at 3 months. Multivariable-adjusted spline regression indicated a linear dose-response association between LVEF after IVT and poor functional outcomes (p for linearity < 0.001), with the optimal cutoff values of LVEF being 0.48.
CONCLUSIONS
Our finding indicated that AIS patients with LVSD after IVT had poorer outcomes, suggesting the need to monitor and optimize LVEF in stroke management.
Topics: Humans; Male; Female; Ischemic Stroke; Ventricular Dysfunction, Left; Aged; Middle Aged; Prognosis; Thrombolytic Therapy; Tissue Plasminogen Activator; Prospective Studies; Echocardiography; Fibrinolytic Agents; Administration, Intravenous; Treatment Outcome; Ventricular Function, Left; Stroke Volume
PubMed: 38700495
DOI: 10.18632/aging.205786 -
Haematologica May 2024Not available.
Not available.
PubMed: 38695132
DOI: 10.3324/haematol.2023.284920 -
Scientific Reports May 2024Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for...
Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions.
Topics: Humans; Female; Male; Aged; Retrospective Studies; Middle Aged; Hospitalization; Infarction, Middle Cerebral Artery; Cerebral Hemorrhage; Brain Edema; Risk Factors; Ischemic Stroke
PubMed: 38693282
DOI: 10.1038/s41598-024-60635-0 -
Journal of the American Heart... May 2024Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase.... (Review)
Review
Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.
Topics: Tenecteplase; Humans; Fibrinolytic Agents; Ischemic Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Animals
PubMed: 38686848
DOI: 10.1161/JAHA.123.031692