Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy

2019 ◽  
Vol 74 (8) ◽  
pp. 2341-2346 ◽  
Author(s):  
E Furfaro ◽  
A Signori ◽  
C Di Grazia ◽  
A Dominietto ◽  
A M Raiola ◽  
...  
Keyword(s):  
Roc Curve ◽  
Liver Function Tests ◽  
Fixed Time ◽  
High Serum ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Roc Curve Analysis ◽  
Blood Concentrations ◽  
Length Of Treatment ◽  
Days Of Therapy

Abstract Background Isavuconazole is the newest triazole antifungal approved for the treatment of invasive aspergillosis (IA) and invasive mucormycosis in adult patients. Objectives To characterize the assessment of the blood levels of isavuconazole and their association with efficacy and toxicity. Methods From January 2017 to May 2018, blood samples obtained from patients receiving isavuconazole were analysed for therapeutic drug monitoring. Factors influencing the blood concentrations of isavuconazole, such as weight, length of treatment, route of administration and results of selected liver function tests, were analysed in univariate and multivariate models. The receiver operating characteristic (ROC) curve was analysed to detect the best cut-off for isavuconazole toxicity. Results A total of 264 isavuconazole blood concentrations in 19 patients were analysed. The median value of isavuconazole concentration in all patients during the first 30 days of therapy was 3.69 mg/L (range 0.64–8.13 mg/L). A linear increase of 0.032 mg/L (range 0.023–0.041 mg/L) for each day of treatment (P = 0.002) was observed. In multivariate analysis the association between the length of treatment and higher levels of isavuconazole (P < 0.001) and higher serum GGT and lower isavuconazole levels (P = 0.001) was confirmed. Adverse events, mainly gastrointestinal, were reported in six patients (31.6%). Based on time-dependent and fixed-time ROC curve analysis, 4.87 mg/L and 5.13 mg/L, respectively, were the identified thresholds for toxicity. Conclusions Isavuconazole was efficacious and well tolerated. Side effects, mainly gastrointestinal, were associated with prolonged administration and high serum levels.

scholarly journals 788. Therapeutic Drug Monitoring for Pyrazinamide During Tuberculosis Treatment: What Is the Diagnostic Accuracy?

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S282-S283
Author(s):  
Ginger Anderson ◽  
Christopher Vinnard
Keyword(s):  
High Risk ◽  
Therapeutic Drug Monitoring ◽  
Diagnostic Accuracy ◽  
Roc Curve ◽  
Drug Monitoring ◽  
Sparse Sampling ◽  
Blood Sampling ◽  
Successful Outcome ◽  
Therapeutic Drug ◽  
Blood Levels

Abstract Background Pyrazinamide (PZA) is a key drug for both drug-sensitive and drug-resistant tuberculosis (TB). Patients co-infected with TB and human immunodeficiency virus (HIV) are more likely to have low blood levels of PZA, associated with inferior outcomes. Therapeutic drug monitoring (TDM) with sparse blood sampling is recommended for high-risk groups, including HIV/TB patients, but the accuracy is uncertain. We performed a pharmacokinetic (PK) simulation study to estimate the diagnostic accuracy of TDM for PZA among HIV/TB patients. Methods We recently performed a population PK study among HIV/TB patients in Botswana, identifying a 1-compartment model with first-order elimination. In the current work, we performed an intensive PK simulation (n = 10,000 patients) to determine the accuracy of sparse blood sampling in identifying HIV/TB patients with low PZA blood levels, as defined by the AUC in a dosing interval (AUC0-24) predictive of successful outcome (363 mg*hr/L). PZA dosing followed WHO guidelines with weight-based dosing bands. In secondary analysis, we examined the peak concentration (Cmax) target predictive of 2-month sputum conversion (58 mg/L). To determine the accuracy of sparse sampling (2- and 6-hours), we performed receiver-operating-characteristic (ROC) analysis, with bootstrapping (n = 1,000) for 95% confidence intervals (CI), and defined accuracy as the area under the ROC curve. Results In this simulation PK study of PZA among HIV/TB patients, the PZA AUC0-24 fell below the target in 29% of patients, while in 71% of patients the PZA Cmax was below the target. For the AUC0-24 target, the area under the ROC curve was 0.69 (95% CI 0.68–0.70) for a single 2-hour sample, increasing to 0.75 (95% CI 0.74–0.76) for 2- and 6-hour samples. For the Cmax target, diagnostic accuracy was similar for a 2-hour sample (0.87, 95% CI 0.86–0.87) and 2- and 6-hour samples (0.88, 95% CI 0.88–0.89). Conclusion We observed modest diagnostic accuracy of TDM for identifying in silico HIV/TB patients with low PZA AUC0-24, and higher accuracy for low Cmax. By identifying diagnostic performance characteristics of sparse sampling strategies, including optimal cut-offs, the ROC framework can support wider implementation of TDM in high-risk TB populations. Disclosures All authors: No reported disclosures.

scholarly journals P723 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: Results from the GO-LEVEL study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
M Samaan ◽  
G Cunningham ◽  
G Tamilarasan ◽  
K Rawstron ◽  
K Hawash ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Disease Activity ◽  
Induction Therapy ◽  
Roc Curve ◽  
Curve Analysis ◽  
Therapeutic Drug ◽  
Response Relationship ◽  
Roc Curve Analysis ◽  
Exposure Response ◽  
Therapeutic Threshold

Abstract Background The exposure–response relationship associated with the use of golimumab for UC has been previously demonstrated in the PURSUIT trial programme. A significant association between serum golimumab concentrations (SGC) and favourable outcomes was observed during both induction and maintenance therapy. However, data regarding the optimal therapeutic SGC threshold is limited. Methods GO-LEVEL was an open-label, phase IV, investigator initiated study (NCT03124121) which included a prospective cohort of UC patients commencing golimumab induction therapy, as well as a cross-sectional cohort receiving maintenance treatment (&gt;18 weeks from initiation). Patients commencing induction therapy all had disease activity objectively confirmed and were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare, or during stable remission. Clinical disease activity was evaluated using SCCAI and PRO2, and biochemical activity using FC and CRP. Combined clinical-biochemical remission was defined as SCCAI&lt;3 as well as FC&lt;250ug/g. SGC and anti-golimumab antibodies (AGA) were measured using a drug-sensitive ELISA (LISATRACKER, Theradiag). Fishers exact or Mann–Whitney U were used to compare groups, ROC analysis to identify therapeutic thresholds and Spearman’s rank coefficient (rs) for correlations. Results Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined remission at week 6. The median SGC of those in combined remission was significantly higher than those who were not (5.0 vs. 3.1 μg/ml, respectively, p = 0.03). ROC curve analysis demonstrates 3.8 μg/ml as the optimal therapeutic threshold to achieve combined remission at week 6 (sensitivity 0.71, specificity 0.65, AUC 0.72). Significant, inverse correlations were also observed between week 6 SGC and PRO2, CRP and FC (rs −0.41 (p = 0.01), −0.47 (p = 0.004) and −0.40 (p = 0.02), respectively). However, week 6 SGC did not predict outcomes at week 10 or 14. Sixty-four patients were included in the maintenance cohort; 32 (50%) were in combined remission, 32 were not. The median SGC of those in combined remission was significantly higher (3.0 vs. 2.1 μg/ml, respectively, p = 0.003). ROC curve analysis demonstrates 2.4 μg/ml as the optimal therapeutic threshold to achieve combined remission (sensitivity 0.73, specificity 0.66, AUC 0.71). No AGA were detected in either cohort. Conclusion GO-LEVEL offers further evidence of the exposure-response relationship with golimumab. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested SGC therapeutic thresholds of 3.8 μg/ml at week 6 and 2.4 μg/ml during maintenance.

scholarly journals Importance of Therapeutic Drug Monitoring to Detect Drug Interaction between Pazopanib and Warfarin: A Case Report

2020 ◽  
Vol 23 ◽  
pp. 200-205
Author(s):  
Shinya Takasaki ◽  
Hisanobu Adachi ◽  
Yoshihide Kawasaki ◽  
Masafumi Kikuchi ◽  
Akihiro Ito ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Liver Dysfunction ◽  
Kinase Inhibitor ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Close Monitoring ◽  
Blood Concentrations ◽  
Patients At Risk

Pazopanib is an orally available multi-tyrosine kinase inhibitor and has been used to treat renal cell carcinoma (RCC). Here, we report the case of a patient with RCC with an increased prothrombin time-international normalized ratio (PT-INR) due to pazopanib therapy. In addition, we have reported the change in the blood levels of pazopanib. A 75-year-old man underwent a left nephrectomy for RCC. Four years later, his cancer recurred and pazopanib therapy was initiated. He was also taking warfarin for atrial fibrillation and his PT-INR was constant at approximately 2. His warfarin dose was reduced from 3.5 mg/day to 3.0 mg/day on day 10 because his PT-INR increased from 2.19 to 3.07 compared to that before starting pazopanib. On day 28, his PT-INR further increased to 4.34, and his aspartate aminotransferase, alanine transaminase, and alkaline phosphatase levels increased. The target concentration of pazopanib was 20.5 to 50.3 µg/mL, but his blood concentrations were 92.1 µg/mL on day 6 and 93.7 µg/mL on day 13. Therefore, both pazopanib and warfarin were discontinued. One week later, his laboratory tests recovered, and hence, warfarin treatment was resumed. However, pazopanib therapy was terminated due to concerns about liver dysfunction. His hepatic dysfunction and increased PT-INR were considered to be due to pazopanib treatment. Pazopanib has been reported to have no effect on the pharmacokinetics of warfarin in clinical patients. In this case, blood levels of pazopanib were abnormally high, possibly causing liver dysfunction and drug interactions, leading to his PT-INR prolongation. TDM monitoring, in addition to the recommended monitoring for pazopanib hepatotoxicity, may help identify patients at risk for drug interactions. For patients receiving concomitant pazopanib and warfarin, close monitoring of PT-INR is warranted.

scholarly journals Buprenorphine–cannabis interaction in patients undergoing opioid maintenance therapy

2020 ◽  
Author(s):  
Christopher Vierke ◽  
Brigitte Marxen ◽  
Michael Boettcher ◽  
Christoph Hiemke ◽  
Ursula Havemann-Reinecke
Keyword(s):  
Maintenance Therapy ◽  
Illicit Drugs ◽  
Cannabis Use ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Opioid Agonist ◽  
Blood Concentrations ◽  
Opioid Maintenance Therapy ◽  
Regular Control ◽  
Pharmacologically Active

AbstractBuprenorphine is a partial μ-opioid agonist widely used for opioid maintenance therapy (OMT). It is mainly metabolized to pharmacologically active norbuprenorphine by the cytochrome P450 (CYP) isozyme 3A4. This may give rise to drug–drug interactions under combinations with inhibitors or inducers of CYP3A4. Cannabis is a potential inhibitor of CYP3A4, and there is a large degree of concomitant cannabis use among OMT patients. We performed a retrospective analysis on liver healthy OMT patients substituted with buprenorphine, either with (n = 15) or without (n = 17) concomitant use of cannabis. Patients with additional illicit drugs or medications affecting CYP3A were excluded. Measured blood concentrations of buprenorphine and norbuprenorphine were compared between the two groups. Cannabis users and non-users received similar doses, but users had 2.7-fold higher concentrations of buprenorphine (p < 0.01) and 1.4-fold for norbuprenorphine (1.4-fold, p = 0.07). Moreover, the metabolite-to-parent drug ratio was 0.98 in non-users and 0.38 in users (p = 0.02). Female gender did not produce significant effects. These findings indicate that cannabis use decreases the formation of norbuprenorphine and elevates buprenorphine and norbuprenorphine concentrations in blood most probably by inhibition of CYP3A4. The pharmacokinetic interaction may give rise to enhanced or altered opioid activity and risk of intoxications. Physicians should inform patients about this risk and supervise cannabis users by regular control of buprenorphine blood levels, i.e., by therapeutic drug monitoring.

Prediction of Post spinal anesthesia hypotension in patients undergoing cesarean section using Perfusion index

2020 ◽  
Vol 5 (3) ◽  
pp. 1241-1245
Author(s):  
Kumud Pyakurel ◽  
Lalit Kumar Rajbanshi ◽  
Ramesh Bhattarai ◽  
Sonia Dahal
Keyword(s):  
Spinal Anesthesia ◽  
Cesarean Delivery ◽  
Supine Position ◽  
Roc Curve ◽  
Anesthetic Management ◽  
College Teaching ◽  
Perfusion Index ◽  
Sensory Level ◽  
Roc Curve Analysis ◽  
Group I

Introduction: Spinal anesthesia induced hypotension frequently complicates Cesarean delivery. This is usually due to sudden sympatholysis causing decreased venous return which can be aggravated by physiological changes of pregnancy leading to change in baseline peripheral vascular tone. Strategies to prevent hypotensive episodes should be the primary aim of anesthetic management. A simple noninvasive measurement of perfusion index derived from pulse oximeter predicting hypotension during the routine intraoperative course could provide a new dynamism to the management and improving the safe execution of anesthesia. Objectives: The primary objective of this study was to compare incidence of hypotension following SAB for LSCS in patients with baseline PI ≤ 3.5 to those with PI > 3.5. The secondary objectives were to compare PI, HR, SBP, MAP at various time intervals and also to study the side effects between the two groups. Methodology: This prospective observational study was conducted at Nobel Medical College Teaching Hospital from to July 2019 to October 2019. 73 Term parturients presenting for elective cesarean delivery were included for the study. Upon arrival in the operation room, standard monitors were attached and baseline HR, SBP, DBP, MAP, PI and SPO2 were recorded in supine position. The patients with baseline PI ≤ 3.5 were enrolled into Group I and those with a PI > 3.5 were enrolled into Group II. Spinal Anesthesia with 10mg of 0.5% heavy Bupivacaine and 20mcg Fentanyl ( total 2.4ml) was given at L3-L4 interspace in sitting position using midline approach. Patient was then returned to supine position with left lateral tilt of 15 degrees to facilitate left uterine displacement. Upper sensory level was checked at 5 minutes using alcohol swab. Once T-6 level was reached, surgery was started. Maternal SBP, DBP, MAP, HR and PI were recorded at 1 minute intervals between spinal injection and delivery and then 3 minutes until end of surgery. Clinically relevant hypotension was defined as the decrease in MAP by 20% or more from baseline value. Results: The incidence of hypotension in Group I was 18.8% (6/30) compared to 81.3% (26/38). This was clinically and statistically highly significant (P = 0.000, odds ratio 0.11). On Spearman’s rank correlation we found highly significant correlation between baseline PI >3.5 and number of episodes of hypotension (rs 0.482, P = 0.000). The sensitivity and specificity of baseline PI with cut-off 3.5 for predicting hypotension were 81.3% and 66.7% respectively. The ROC curve analysis showed 3.53 as appropriate cut‑off for our findings. The area under the ROC curve (AUC) was 0.734 [Figure 6](Lower bound 0.608 and upper bound 0.861, P=0.001).  Conclusion : This study demonstrates that baseline PI of > 3.5 correlates with incidence of hypotension after spinal anesthesia for cesarean delivery in healthy parturients compared to a baseline PI of < 3.5.

Baseline apparent diffusion coefficients: Validation study of new predictor of survival in patients with unresectable hepatocellular carcinoma following chemoembolization

2021 ◽  
pp. 1-10
Author(s):  
Lichao Xu ◽  
Shiqin Wang ◽  
Shengping Wang ◽  
Ying Wang ◽  
Wentao Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Curve ◽  
Cox Regression ◽  
Response To Treatment ◽  
Roc Curve Analysis ◽  
Adc Value ◽  
Apparent Diffusion Coefficients ◽  
Apparent Diffusion ◽  
Response Biomarker ◽  
The Difference

OBJECTIVES: To investigate whether the baseline apparent diffusion coefficient (ADC) can predict survival in the hepatocellular carcinoma (HCC) patients receiving chemoembolization. MATERIALS AND METHODS: Diffusion-weighted MR imaging of HCC patients is performed within 2 weeks before chemoembolization. The ADC of the largest index lesion is recorded. Responses are assessed by mRECIST after the start of the second course of chemoembolization. Receiver operating characteristic (ROC) curve analysis is performed to evaluate the diagnostic performance and determine optimal cut-off values. Cox regression and Kaplan–Meier survival analyses are used to explore the differences in overall survival (OS) between the responders and non-responders. RESULTS: The difference is statistically significant in the baseline ADC between the responders and non-responders (P <  0.001). ROC analyses indicate that the baseline ADC value is a good predictor of response to treatment with an area under the ROC curve (AUC) of 0.744 and the optimal cut-off value of 1.22×10–3 mm2/s. The Cox regression model shows that the baseline ADC is an independent predictor of OS, with a 57.2% reduction in risk. CONCLUSION: An optimal baseline ADC value is a functional imaging response biomarker that has higher discriminatory power to predict tumor response and prolonged survival following chemoembolization in HCC patients.

Acute heart failure: predicting early in-hospital outcomes

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Santos ◽  
S Paula ◽  
I Almeida ◽  
H Santos ◽  
H Miranda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Logistic Regression ◽  
Acute Heart Failure ◽  
Roc Curve ◽  
Real Life ◽  
Study Data ◽  
Curve Analysis ◽  
Older Age ◽  
Invasive Ventilation ◽  
Roc Curve Analysis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (P) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. The Get With The Guidelines Heart Failure score (GWTG-HF) predicts in-hospital mortality (M) of P admitted with AHF. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF and to compare ACTION-ICU to GWTG-HF as predictors of in-hospital M (IHM), early M [1-month mortality (1mM)] and 1-month readmission (1mRA), using real-life data. Methods Based on a single-center retrospective study, data collected from P admitted in the Cardiology department with AHF between 2010 and 2017. P without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used chi-square, non-parametric tests, logistic regression analysis and ROC curve analysis. Results Among the 300 P admitted with AHF included, mean age was 67.4 ± 12.6 years old and 72.7% were male. Systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. ACTION-ICU score was 10.4 ± 2.3 and GWTG-HF was 41.7 ± 9.6. Inotropes’ usage was necessary in 32.7% of the P, 11.3% of the P needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the P were readmitted 1 month after discharge. Older age (p &lt; 0.001), lower SBP (p = 0,035) and need of inotropes (p &lt; 0.001) were predictors of IHM in our population. As expected, patients presenting in KKC 4 had higher IHM (OR 8.13, p &lt; 0.001). Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p &lt; 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the variables were predictive of IV. LVEF (OR 0.924, p &lt; 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p &lt; 0.001, CI 0.971-0.988), higher urea (OR 1.01, p &lt; 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors of inotropes’ usage. Logistic regression showed that GWTG-HF predicted IHM (OR 1.12, p &lt; 0.001, CI 1.05-1.19), 1mM (OR 1.10, p = 1.10, CI 1.04-1.16) and inotropes’s usage (OR 1.06, p &lt; 0.001, CI 1.03-1.10), however it was not predictive of 1mRA, need of IV or NIV. Similarly, ACTION-ICU predicted IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed that GWTG-HF score performed better than ACTION-ICU regarding IHM (AUC 0.774, CI 0.46-0-90 vs AUC 0.731, CI 0.59-0.88) and 1mM (AUC 0.727, CI 0.60-0.85 vs AUC 0.707, CI 0.58-0.84). Conclusion In our population, both scores were able to predict IHM, 1mM and inotropes’s usage.

scholarly journals Blood Micronutrient and Thyroid Hormone Concentrations in the Oldest-Old

2000 ◽  
Vol 85 (6) ◽  
pp. 2260-2265 ◽  
Author(s):  
Giovanni Ravaglia ◽  
Paola Forti ◽  
Fabiola Maioli ◽  
Barbara Nesi ◽  
Loredana Pratelli ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Oldest Old ◽  
Serum Zinc ◽  
Blood Levels ◽  
Elderly Age ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Plasma Retinol ◽  
Age Range

Several micronutrients are involved in thyroid hormone metabolism, but it is unclear whether their marginal deficits may contribute to the alterations in thyroid function observed in extreme aging. The relationships among blood concentrations of thyroid hormones and selenium, zinc, retinol, and α-tocopherol were studied in 44 healthy Northern Italian oldest-old subjects (age range, 90–107 yr), selected by the criteria of the SENIEUR protocol. Control groups included 44 healthy adult (age range, 20–65 yr) and 44 SENIEUR elderly (age range, 65–89 yr) subjects. Oldest-old subjects had higher TSH (P &lt; 0.01) and lower free T3 (FT3)/freeT4 (FT4) ratio, zinc, and selenium serum values (P &lt; 0.001) than adult and elderly control subjects. No significant difference was found for plasma retinol and α-tocopherol values. The associations between micronutrients and thyroid hormones were evaluated by multivariate analysis. In oldest-old subjects, plasma retinol was negatively associated with FT4 (P = 0.019) and TSH serum levels (P = 0.040), whereas serum zinc was positively associated with serum FT3 (P = 0.010) and FT3/FT4 ratio (P = 0.011). In younger subjects, no significant association was found among thyroid variables and micronutrients. In conclusion, blood levels of specific micronutrients are associated with serum iodothyronine levels in extreme aging.

scholarly journals Presepsin values and prognostic nutritional index predict mortality in intensive care unit patients with sepsis: a pilot study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami
Keyword(s):  
Multivariate Analysis ◽  
Roc Curve ◽  
Operating Characteristic ◽  
Prognostic Nutritional Index ◽  
Early Mortality ◽  
Curve Analysis ◽  
Rank Test ◽  
Roc Curve Analysis ◽  
Log Rank Test ◽  
Nutritional Index

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).

scholarly journals Soluble cytotoxic T-lymphocyte–associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiajia Liu ◽  
Xiaoyi Tian ◽  
Yan Wang ◽  
Xixiong Kang ◽  
Wenqi Song
Keyword(s):  
T Lymphocyte ◽  
Roc Curve ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Grade ◽  
Curve Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
High Grade ◽  
Healthy Individuals ◽  
Roc Curve Analysis

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.

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