Lactate dehydrogenase to carboxyhemoglobin ratio as a biomarker of heme release to heme processing is associated with higher tricuspid regurgitant jet velocity and early death in sickle cell disease.
Ontology highlight
ABSTRACT:
SUBMITTER: van Vuren AJ
PROVIDER: S-EPMC8453521 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Introduction: The American College of Emergency Physicians (ACEP) recommends that Emergency Medicine physicians with advanced training can evaluate right ventricular (RV) pressures via point-of-care ultrasound (POCUS) by measuring a tricuspid regurgitant jet (TRJ). We were unable to find a published curriculum to deliver education for this at any skill level. Therefore, we developed, delivered, and evaluated a curriculum for the assessment of TRJ for novice physician sonographers. Methods: We designed an educational intervention for novice physician sonographers. The curriculum was created using a modified Delphi methodology. All novice sonographers participated in the educational intervention which consisted of a didactic lecture followed by hands-on-deliberate practice on healthy medical student volunteers with expert feedback in a simulated setting. Sonographer’s knowledge was assessed at 3 time points: pre-intervention, immediately post-intervention, and 3 months post-intervention (retention assessment) by multiple choice exam. Results: Nine novice physician sonographers participated in the intervention. Mean exam performance increased from 55.6% [standard deviation (SD) 11.3%] on the pre-intervention exam to 94.4% (SD 7.3%) on the post-intervention exam and 92.9% (SD 12.5%) on the retention exam. The mean improvement between the pre- and post- exam was +38.9% (95% CI 31.8 – 46.0), and between the pre-exam and retention exam +37.1% (95% CI 22.3 – 52.0). Conclusion: Sonographer knowledge of TRJ assessment improved following a brief educational intervention as measured by exam performance. Given the expanding role of POCUS it is increasingly important to provide effective resources for teaching these skills. This work establishes the basis for further study and implementation of our TRJ curriculum.
| S-EPMC9316333 | biostudies-literature
Project description:Elevated tricuspid regurgitant velocity (TRV) ≥2.5 m/s is a predictor of disease severity in adults and children with sickle cell anemia (SCA), but how disease-modifying therapies (DMTs) affect this biomarker is incompletely understood. We investigated the effect of DMTs on TRV elevation in children. In a prospective single-center study, 204 subjects with HbSS or HbSβ0 thalassemia (mean age, 10.6 years; range, 5-18) had echocardiograms with assessment of TRV, with repeat evaluations after 2 years of observation. One-hundred and twelve participants received DMTs (hydroxyurea, n = 72; monthly erythrocyte transfusions, n = 40), 58 did not receive any DMT, and 34 were begun on hydroxyurea during this observation period. In the entire cohort, an increase in hemoglobin of 1.0 g/dL was associated with a 0.03-m/s decrease in TRV (P = .024), and a decrease in absolute reticulocyte count of 1.0 × 106/mL was associated with a 0.34-m/s decrease in TRV (P = .034). Compared with baseline, hydroxyurea exposure (continuous or newly started) was associated with an average 5% decline in mean TRV at the 2-year evaluation. Among participants newly started on hydroxyurea (mean treatment duration 1.2 ± 0.6 years), an increase in hemoglobin of 1.0 g/dL was associated with a 0.06-m/s decrease in TRV (P = .05). We conclude that hydroxyurea therapy may mitigate TRV elevation in children with SCA, possibly as a result of a reduction in hemolysis and improvement in anemia.
| S-EPMC7805333 | biostudies-literature
Project description:BackgroundPeak tricuspid regurgitant velocity (TRV) on transthoracic echocardiography (TTE) is a commonly obtained parameter and robust predictor of subsequent adverse clinical outcomes.ObjectivesThe purpose of this study was to determine the predictors and clinical significance of TRV progression.MethodsWe retrospectively linked consecutive outpatient TTE reports from our institution to 2005 to 2017 Medicare claims. Individuals with prior tricuspid surgery, endocarditis, tricuspid stenosis, missing TRV values, TTEs performed during inpatient hospitalization, or <2 TTEs were excluded.ResultsA total of 4,572 patients (mean age 67.8 ± 11.9 years, 50.4% female) received 13,273 TTEs over a median follow-up of 7.4 (IQR: 4.5-6.9) years. TRV increased by a mean of 0.23 (95% CI: 0.22 to 0.23 m/s/y, P < 0.001) (range, 0.01-0.80 m/s/y). Older age, depressed left ventricular ejection fraction, diabetes, hypertension, hyperlipidemia, atrial fibrillation, heart failure, and chronic kidney disease were associated with faster progression (all P < 0.05). Accounting for 23 demographic, clinical, and TTE variables, faster TRV progression was associated with a stepwise increased risk of all-cause mortality (TRV progression quartile 4 vs 1; adjusted HR: 2.17; 95% CI: 1.74-2.71; P < 0.001). Those with regression of TRV (n = 384 [8.4%]) had a lower mortality risk (adjusted HR: 0.40; 95% CI: 0.28-0.57; P < 0.001).ConclusionsIn this large, multidecade study of Medicare beneficiaries with serial TTEs performed in the outpatient setting, the mean rate of TRV progression was 0.23 m/s/y. Older age, left heart disease, and adverse metabolic features were associated with faster progression. Faster progression was associated with a graded risk for all-cause mortality.
| S-EPMC10583835 | biostudies-literature
Project description:An elevated tricuspid regurgitant jet velocity (TRV) is associated with hemolysis and early mortality in sickle cell disease, yet risk factors, clinical parameters, and mortality associated with this biomarker in thalassemia are poorly defined. This report summarizes the prevalence of an elevated TRV in 325 patients screened by Doppler echocardiography in the Thalassemia Clinical Research Network. A documented TRV was reported in 148 of 325 (46%) of patients. Average age was 25.9 years (range, 5-56 years) and 97% were transfusion-dependent. Mean TRV was 2.3 ± 0.4 m/s (range, 0.2-3.5 m/s). An abnormal TRV ? 2.5 m/s was identified in 49 of 148 (33%) of patients with a documented TRV, 5% (8/148), with a TRV ? 3.0 m/s, suggesting significant PH risk. Older age was strongly associated with a high TRV; however, 16% of children had a TRV ? 2.5 m/s. A history of splenectomy, hepatitis C, smoking, or high white blood cell count was associated with TRV elevation. In summary, an elevated TRV is noted in one-third of transfusion-dependent thalassemia patients with a documented value and develops in both children and adults. Age, splenectomy, hepatitis C, and smoking are significant univariate risk factors, with splenectomy surfacing as the dominant risk factor over time. Mortality was low in this cohort. Prospective longitudinal studies are needed. This study is registered at http://www.clinicaltrials.gov as NCT00661804.
| S-EPMC3193260 | biostudies-literature
Project description:Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi-level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S') and diastole (E'), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty-eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional-hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end-organ failure. On Cox proportional-hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S' results in a 91% increase, and 1 cm/s decrease in E' results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.
| S-EPMC7746595 | biostudies-literature
Project description:RationaleAn increased tricuspid regurgitation jet velocity (TRV > 2.5 m/s) and pulmonary hypertension defined by right heart catheterization both independently confer increased mortality in sickle cell disease (SCD).ObjectivesWe explored the usefulness of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated TRV in SCD.MethodsTwenty-seven patients with SCD underwent echocardiography and peripheral blood mononuclear cell isolation for expression profiling and 112 patients with SCD were genotyped for single-nucleotide polymorphisms.Measurements and main resultsGenome-wide gene and miRNA expression profiles were correlated against TRV, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of patients with SCD without (n = 10) and with pulmonary hypertension (n = 10, 90% accuracy). Increased TRV-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n = 49) versus normal (n = 63) TRV revealed five significant single-nucleotide polymorphisms within GALNT13 (P < 0.005), four trans-acting (P < 2.1 × 10(-7)) and one cis-acting (P = 0.6 × 10(-4)) expression quantitative trait locus upstream of the adenosine-A2B receptor gene (ADORA2B).ConclusionsThese studies validate the clinical usefulness of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in SCD-associated elevated TRV.
| S-EPMC3443809 | biostudies-literature
Project description:Purpose: We aimed to determine if lactate dehydrogenase to albumin ratio (LAR) might play a prognostic role for patients with operable colorectal cancer (CRC). Patients and Methods: 1334 operable CRC patients in Wuhan Union Hospital Between July 2013 and September 2017 were enrolled in this study and were randomly appointed them into training (n=954) and validation (n=380) sets. The relationship between LAR and overall survival (OS) and disease-free survival (DFS) were determined by restricted cubic splines (RCS) with Cox regression models. LAR was then divided into three categories based on the RCS and compared to the well-known TNM stage system. Finally, survival nomograms were developed by compounding the LAR and other clinical factors. Results: Baseline LAR values and the all-cause mortality were U shaped, which slowly decreased until around 4.50 and then started to increase rapidly when the LAR ranged from 4.50-6.68 and then became flat thereafter (P for non-linearity <0.001). LAR was superior to TNM stage for OS as well as DFS and LAR plus TNM stage could add more net benefit than clinical model alone. Moreover, the survival nomograms based on LAR achieved great predictive ability for OS and DFS in operable CRC patients. Conclusions: LAR could be served as a reliable prognostic factor for OS as well as DFS, with more accurate prognostic prediction than current TNM stage for patients with operable CRC.
| S-EPMC9254365 | biostudies-literature
Project description:At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes are implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely aging mtDNA mutator mice to establish a molecular link between mitochondrial dysfunction and abnormal metabolism in the aging process. Using proton magnetic resonance spectroscopy and HPLC, we found that brain lactate levels were increased twofold in both normally and prematurely aging mice during aging. To correlate the striking increase in lactate with tissue pathology, we investigated the respiratory chain enzymes and detected mitochondrial failure in key brain areas from both normally and prematurely aging mice. We used in situ hybridization to show that increased brain lactate levels were caused by a shift in transcriptional activities of the lactate dehydrogenases to promote pyruvate to lactate conversion. Separation of the five tetrameric lactate dehydrogenase (LDH) isoenzymes revealed an increase of those dominated by the Ldh-A product and a decrease of those rich in the Ldh-B product, which, in turn, increases pyruvate to lactate conversion. Spectrophotometric assays measuring LDH activity from the pyruvate and lactate sides of the reaction showed a higher pyruvate ? lactate activity in the brain. We argue for the use of lactate proton magnetic resonance spectroscopy as a noninvasive strategy for monitoring this hallmark of the aging process. The mtDNA mutator mouse allows us to conclude that the increased LDH-A/LDH-B ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes.
| S-EPMC2993405 | biostudies-literature
Project description:BACKGROUND:COVID-19 (Coronavirus Disease-2019) is a pandemic disease, infecting more than 26.5 million people. Since there is no specific and effective treatment; early diagnosis and optimal isolation of the patient are of vital importance. Real-time polymerase chain reaction-based (RT-PCR) analyses do not achieve sufficient sensitivity in the diagnosis of the disease. METHODS:The data from 2217 patients diagnosed as COVID-19 between March 2020 and June 2020 and hospitalized or discharged with home isolation were retrospectively analyzed. Demographic data, comorbidities, PCR results, initial computed tomography (CT), laboratory values, Lactate Dehydrogenase (LDH)/Lymphocyte ratio, initial treatments and last status were recorded. The diagnostic sensitivity of LDH/Lymphocyte ratio, which is the main purpose of the study, was analyzed statistically. RESULTS:In order to test the effectiveness of LDH/Lymphocyte ratio for COVID-19 for diagnostic purposes, CT results were considered as gold standard. The area under the curve (AUC) was found to be 0.706 (p < 0.001; cut-off > 0.06) (Sensitivity: 76.4, specificity: 59.60). For the evaluation of LDH/Lymphocyte ratio in terms of survival, AUC was found to be 0.749 (p < 0.001; cut-off > 0.21) (Sensitivity: 70.59, specificity: 73.88). CONCLUSION:Studies based on radiological findings have demonstrated that CT involvement has higher sensitivity. LDH/Lymphocyte ratio was analyzed in terms of diagnosis and mortality with using specific CT involvement as gold standard method which was found to be a more sensitive due to PCR false negativity; 0.06 and 0.21 were obtained as cut off values for diagnosis and mortality.
| S-EPMC7526632 | biostudies-literature
Project description:AbstractThis study was performed to verify whether lactate dehydrogenase to albumin (LDH/ALB) ratio could be used as an independent prognostic factor in patients with severe infection requiring intensive care.We reviewed electronic medical records of patients hospitalized to the intensive care unit via the emergency department with a diagnosis of infection between January 2014 and December 2019. From the collected data, ALB-based ratios (LDH/ALB, blood urea nitrogen to albumin, C-reactive protein to albumin, and lactate to albumin ratios) and some severity scores (modified early warning score, mortality in emergency department sepsis score [MEDS], and Acute Physiology And Chronic Health Evaluation II [APACHE II] score) were calculated. LDH/ALB ratio for predicting the in-hospital mortality was compared with other ALB-based ratios and severity scales by univariable and receiver-operating characteristics curve analysis. Modified severity scores by LDH/ALB ratio and multivariable logistic regression were used to verify the independence and usefulness of the LDH/ALB ratio.The median LDH/ALB ratio was higher in non-survivors than survivors (166.9 [interquartile range: 127.2-233.1] vs 214.7 [interquartile range: 160.2-309.7], P < .001). The area under the receiver-operating characteristics curve of the LDH/ALB ratio (0.642, 95% confidence interval: 0.602-0.681, P < .001) was not lower than that of other ALB-based ratios and severity scores. From multivariable logistic regression, LDH/ALB ratio was independently associated with in-hospital mortality (odds ratio = 1.001, 95% confidence interval: 1.000-1.002, P = .047). Area under the receiver-operating characteristics curves of MEDS and APACHE II scores were improved by modification with LDH/ALB ratio (MEDS: 0.643 vs 0.680, P < .001; APACHE II score: 0.675 vs 0.700, P = .003).LDH/ALB ratio may be useful as the prognostic factor in patients with severe infection requiring intensive care.
| S-EPMC8519202 | biostudies-literature