scholarly journals Pharmacokinetics of Peramivir in an Adolescent Patient Receiving Continuous Venovenous Hemodiafiltration

2017 ◽  
Vol 22 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Ryan C. Dillon ◽  
Robert Witcher ◽  
Jeffrey J. Cies ◽  
Wayne S. Moore ◽  
Arun Chopra

Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration–approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia. She quickly progressed to acute respiratory and renal failure in the setting of viral septic shock as a result of a severe influenza H1N1 infection. On hospital day 3, therapy was switched from oseltamivir (Tamiflu, Roche Laboratories Inc, Nutley, NJ) to peramivir owing to the concern for inadequate enteral absorption. On the third day of peramivir treatment, at a dose of 200 mg daily, peramivir serum concentrations revealed a smaller peak concentration, larger volumes of distribution, similar 24-hour area under the curve, and a shorter half-life as compared to adult patients with normal renal function. This illustrated the significant differences in pharmacokinetics when administered in the setting of CRRT. The patient had resolution of viral infection as evidenced by negative respiratory viral panel polymerase chain reaction at hospital day 14 and was eventually discharged at her baseline.

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Songlin Song ◽  
Feihong Wu ◽  
Yiming Liu ◽  
Hongwei Jiang ◽  
Fu Xiong ◽  
...  

Abstract Background Chest computed tomography (CT) has been widely used to assess pulmonary involvement in COVID-19. We aimed to investigate the correlation between chest CT and clinical features in COVID-19 suspected patients with or without fever. Methods We retrospectively enrolled 211 COVID-19 suspected patients who underwent both chest CT and reverse transcription polymerase chain reaction in Wuhan, China. The performance of CT in patients with relevant onset of symptoms, with fever (n = 141) and without fever (n = 70), was assessed respectively. Results The sensitivity of CT for COVID-19 was 97.3%, with area under the curve (AUC) of 0.71 (95% confidence interval [CI], 0.66–0.76). There were 141 suspected patients with fever and 70 without fever. In the fever group, 4 variables were screened to establish the basic model: age, monocyte, red blood cell, and hypertension. The AUC of the basic model was 0.72 (95% CI, 0.63–0.81), while the AUC of the CT-aided model was 0.77 (95% CI, 0.68–0.85), a significant difference (P < .05). In the nonfever group, only dry cough was screened out to establish the basic model. The AUC was 0.76 (95% CI, 0.64–0.88), which was not significantly different than the CT-aided model (P = .08). Conclusions Chest CT has a high sensitivity in patients with COVID-19, and it can improve diagnostic accuracy for COVID-19 suspected patients with fever during the initial screen, whereas its value for nonfever patients remains questionable.


2019 ◽  
Vol 17 ◽  
pp. 205873921985683
Author(s):  
Meiling Guo ◽  
Yanjie Li ◽  
Haibo Li

To investigate the predictive effects of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) on renal-replacement therapy for traumatic acute kidney injury (TAKI). The urinary NGAL and KIM-1 levels of TAKI patients underwent renal-replacement therapy were assessed. The correlation and predictive model were also analyzed. Short-term (28 days) survival rate of patients were 54.5%. As TAKI stage increased, urinary KIM-1 and NGAL level increased significantly ( P < 0.05). The urinary KIM-1 and NGAL level, negatively correlated with 28-day survial, were all higher in deceased patients than survival patients ( P < 0.05). The Youden index demonstrated the predictive value of urinary NGAL area under the curve (AUC; 0.830) and KIM-1 AUC (0.879) levels in the prognosis of patients in this study. NGAL and KIM-1 can predict the prognosis of patients with TAKI and have significant correlation with the prognosis of patients.


2014 ◽  
Author(s):  
Ιωάννης Χαββάς

Σκοπός της μελέτης είναι να διευκρινιστεί, εάν οι πολυμορφισμοί των γονιδίων C2, C3 και CFB του συμπληρώματος είναι σημαντικοί γενετικοί καθοριστές της ηλικιακής εκφύλισης της ωχράς (AMD ) στον Ελληνικό πληθυσμό. Μέθοδοι. Διεξήχθη μια μελέτη συσχέτισης ασθενών μαρτύρων που περιλάμβανε 120 Έλληνες ασθενείς με πρώιμο και προχωρημένο στάδιο της AMD και 140 ανεξάρτητους μάρτυρες Καυκάσιας προέλευσης. Όλοι οι συμμετέχοντες γονοτυπήθηκαν για τους πολυμορφισμούς rs2230199 (C3 R102G), rs547154 (C2 IVS10), rs641153 (CFB R32Q) και rs12614 (CFB R32W) με έναν συνδυασμό αλυσιδωτής αντίδρασης πολυμεράσης [Polymerase Chain Reaction (PCR)], κατάτμησης με ένζυμα περιορισμού [RFLP] και άμεσης αλληλούχισης DNA. Αποτελέσματα. Η συχνότητα του ‘G’ αλληλίου του SNP του γονιδίου C3 rs2230199 (C3 R102G C>G) [ελάσσονος αλληλίου:minor allele frequency (MAF)], ήταν σημαντικά υψηλότερη στους ασθενείς με AMD σε σύγκριση με τους μάρτυρες (0.34 έναντι 0.22, P=0.0031) και παρόμοια με τη συχνότητα άλλων πληθυσμών που έχουν ήδη δημοσιευτεί. Υπήρχε σημαντική διαφορά στις συχνότητες των rs2230199 γονοτύπων ανάμεσα σε ασθενείς και μάρτυρες (p=0.0055). Ο SNP rs2230199 βρέθηκε να είναι ένας σημαντικός προβλεπτικός παράγοντας για την προχωρημένη AMD (OR=6.41, CI 2.72-15.09, P>0,00001) Area under the Curve (AUC= 0.706, CI 0.61-0.78, P<0.0001). Για τους SNPs rs547154 (C2 IVS10), rs641153 (CFB R32Q) και rs12614 (CFB R32W) των γονιδίων C2/CFB, οι αλληλικές και γονοτυπικές συχνότητες δεν ανέδειξαν στατιστική σημαντικότητα. Η MAF στους μάρτυρες και στους ασθενείς ήταν παρόμοια και πολύ χαμηλότερη από τις συχνότητες που έχουν αναφερθεί σε άλλες μελέτες για άλλους πληθυσμούς. Συμπεράσματα. Οι SNPs rs547154 (C2 IVS10), rs641153 (CFB R32Q) και rs12614 (CFB R32W) των γονιδίων C2/CFB του συμπληρώματος δεν συσχετίστηκαν με την ανάπτυξη AMD σε Έλληνες ασθενείς. Παρόλα αυτά, αυτό το εύρημα πρέπει να αντιμετωπίζεται με προσοχή καθώς οι συγκεκριμένοι πολυμορφισμοί, παρουσιάζονται με πολύ χαμηλές συχνότητες στον ελληνικό πληθυσμό. Τέλος, η αναπαραγωγή των αναφερόμενων συσχετισμών του SNP του C3 rs2230199 (C3 R102G C>G) με την ηλικιακή εκφύλιση της ωχράς κηλίδας, υποδηλώνει ότι η παρουσία του ‘G’ αλληλίου θα μπορούσε ίσως να αποτελεί γενετικό δείκτη υψηλού κινδύνου για την ανάπτυξη της AMD και την εξέλιξη της ασθένειας στο προχωρημένο κλινικό στάδιο και στον Ελληνικό πληθυσμό.


2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  

Abstract Background: Gastric cancer (GC) represents one of the most serious cancers worldwide with the increasing mortality. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), a kind of lncRNAs, has been reported to be involved in the progression of cancers. This study aimed to assess serum expression pattern of MALAT1 and its clinical significance in diagnosis of GC.Methods: Serum specimens were collected from 120 GC patients and 58 healthy individuals. The expression profile of MALAT1 was examined using quantitative real-time polymerase chain reaction (qRT-PCR), and its association with clinical parameters was estimated by chi-square test. The diagnostic value of MALAT1 in GC was evaluated by the receiver operating characteristic (ROC) analysis.Results: Upregulated expression of MALTA1 was found in GC patients compared with the healthy controls (P<0.05). The overexpression of MALAT1 was positively correlated with lymph node metastasis (P=0.041) and TNM stage (P=0.005). An area under the curve (AUC) was 0.897 in ROC analysis, suggesting the high diagnostic value of MALAT1. Conclusion: The expression of MALAT1 was upregulated in GC serum samples, and its expression might serve as a potential diagnostic biomarker in patients with GC.


2018 ◽  
Vol 45 (5-6) ◽  
pp. 204-212 ◽  
Author(s):  
Wei Wang ◽  
Dong-Bin Li ◽  
Ru-Ying Li ◽  
Xia Zhou ◽  
Dong-Ju Yu ◽  
...  

Background: Early and accurate diagnosis of ischaemic stroke (IS) requires the use of an optimized biomarker. Exosomal microRNAs have the potential to serve as biomarkers owing to their stability and specificity. We investigated the expression levels of plasma-derived exosomal microRNA-21-5p and microRNA-30a-5p in the different phases of IS. Methods: One hundred forty-three patients with IS and 24 non-stroke controls were enrolled. The patients were divided into the following 5 groups: 1 group for the hyperacute phase IS (HIS, within 6 h); two for the acute phase IS (AIS, including days 1–3 and days 4–7); one for the subacute phase IS (SIS, days 8–14); and one for the recovery phase IS (RIS, days >14). Plasma exosomes were isolated using a QIAGEN exoRNeasy kit and examined by transmission electron ­microscopy, nanoparticle tracking, and flow cytometry. The expression levels of miRNA-21-5p and miRNA-30a-5p were detected by quantitative real-time polymerase chain reaction. Results: The plasma exosomal miR-21-5p levels in SIS and RIS were significantly higher than that in controls (p < 0.05 and p < 0.01 respectively). The levels of miR-30a-5p in HIS were significantly higher (p < 0.05) and in AIS (days 1–3) were lower than that in controls (p < 0.05). In AIS (days 1–3), both miRNAs were decreased compared with the HIS group (p = 0.053 and 0.001, respectively). The area under the curve (AUC) of the miR-21-5p was 0.714 for SIS (95% CI 0.570–0.859, p = 0.007), 0.734 for RIS (95% CI 0.596–0.871, p = 0.003); the AUC of the miR-30a-5p was 0.826 for HIS (95% CI 0.665–0.988, p = 0.001), 0.438 for AIS (days 1–3; 95% CI 0.240–0.635, p = 0.516). Conclusions: The plasma-derived exosomal miR-21-5p and miRNA-30a-5p in combination are promising biomarkers for diagnosing IS and distinguishing among HIS, SIS, and RIS, especially miRNA-30a-5p for the diagnosis of the HIS phase. Our results provide a new reference for clinicians to apply in early-stage diagnosis and identifies the possible value of biomarkers for IS thrombolysis therapy.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Saban Elitok ◽  
Anja Haase-Fielitz ◽  
Martin Ernst ◽  
Michael Haase

Abstract Background and Aims Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery, however, options for early identification of patients at high-risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the discriminatory power and reclassification indices of NGAL:hepcidin-25-ratio (urinary concentrations of NGAL divided by that of hepcidin-25) within 60 min after end of surgery compare favorably to NGAL alone for identification of high-risk patients after cardiac surgery. We also aimed to determine whether an increased NGAL:hepcidin-25-ratio can detect subclinical AKI (no serum creatinine- or urine output-based criteria for AKI). Method This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and ratio-defined subclinical AKI characterized by increased odds for AKI-RRT or in-hospital mortality. We compared biomarkers’ area-under-the-curve of the receiver-operating-characteristic and performed cross-validated reclassification statistics and regression analysis adjusted to Cleveland risk score/EuroScore, cross-clamp time, age and volume of packed red blood cells. Results Patients with AKI-RRT (n=13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL:hepcidin-25-ratio early after surgery compared to patients without AKI-RRT (Figure 1). The NGAL:hepcidin-25-ratio had higher discriminatory power compared with NGAL for risk of AKI-RRT and in-hospital mortality (area-under-the-curve difference 0.087, 95% CI, 0.036 to 0.138, P&lt;0.001; 0.082, 95% CI, 0.018 to 0.146, P=0.012). The NGAL:hepcidin-25-ratio, but not NGAL, was independently associated with AKI-RRT (adjusted OR per 1-SD higher lnNGAL:hepcidin-25-ratio, 1.524, 95% CI, 1.046 to 2.222, P=0.028). The NGAL:hepcidin-25-ratio increased category-free net-reclassification-improvement for AKI-RRT (0.690, 95% CI, 0.146 to 1.234, P=0.013) and in-hospital mortality (cfNRI 0.744, 95% CI, 0.201 to 1.288, P=0.007). NGAL:hepcidin-25-ratio-positive subclinical AKI was associated with increased AKI-RRT (OR 10.02, 95% CI, 1.59 to 63.39; P&lt;0.001) and in-hospital mortality rates (OR 41.07, 95% CI, 4.31 to 391.40; P&lt;0.001). Conclusion The urinary NGAL:hepcidin-25-ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Also, the urinary NGAL:hepcidin-25 ratio can detect subclinical AKI. Confirmation of our findings in other cardiac surgery centers is now needed.


2015 ◽  
Vol 39 (1-3) ◽  
pp. 246-257 ◽  
Author(s):  
Jose J. Zaragoza ◽  
Gianluca Villa ◽  
Francesco Garzotto ◽  
Aashish Sharma ◽  
Anna Lorenzin ◽  
...  

Introduction: One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT. Methods: A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT. Results: We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT. Conclusions: We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi Yao Ma ◽  
Cherry Sze Yan Chan ◽  
Kam Shing Lau ◽  
Lui Ng ◽  
Yuen Yee Cheng ◽  
...  

AbstractMethylated septin 9 (SEPT9) has been approved for non-invasive screening of colorectal cancer (CRC), but data on monitoring of CRC is sparse. Droplet digital polymerase chain reaction (ddPCR), with higher detection precision and simpler quantification than conventional PCR, has not been applied in SEPT9 detection. We explored the role of SEPT9 ddPCR for CRC detection and to measure serial SEPT9 levels in blood samples of CRC patients before and 3-month after surgery. SEPT9 methylated ratio, methylated abundance, and CEA levels were all higher in CRC patients than normal controls (all P < 0.05). The area under the curve (AUC) for methylated ratio and abundance to detect CRC was 0.707 and 0.710, respectively. There was an increasing trend for SEPT9 methylated abundance from proximal to distal cancers (P = 0.017). At 3-month after surgery, both methylated abundance and ratio decreased (P = 0.005 and 0.053, respectively), especially methylated abundance in stage III and distal cancer (both P < 0.01). We have developed a ddPCR platform for the quantitative detection of plasma SEPT9 in CRC patients. SEPT9 methylated abundance had an early post-operative decline, which may be useful in monitoring of treatment response.


2022 ◽  
Vol 9 (1) ◽  
Author(s):  
Gregory L Damhorst ◽  
Kari J Broder ◽  
Elizabeth C Overton ◽  
Ronelio Rara ◽  
Lindsay M Busch ◽  
...  

Abstract Background Pneumocystis jirovecii polymerase chain reaction (PCR) testing is a sensitive diagnostic tool but does not distinguish infection from colonization. Cycle threshold (CT) may correlate with fungal burden and could be considered in clinical decision making. Clinical use of PCR and significance of CT values have not previously been examined with the DiaSorin Molecular platform. Methods Retrospective review of P jirovecii PCR, CT values and clinical data from 18 months in a multihospital academic health system. The diagnostic performance of PCR with respect to pathology and correlation of CT with severity were examined. Results Ninety-nine of 1006 (9.8%) assays from 786 patients in 919 encounters were positive. Among 91 (9.9%) encounters in which P jirovecii pneumonia (PJP) was treated, 41 (45%) were influenced by positive PCR. Negative PCR influenced discontinuation of therapy in 35 cases. Sensitivity and specificity of PCR were 93% (95% CI, 68%–100%) and 94% (95% CI, 91%–96%) with respect to pathology. CT values from deep respiratory specimens were significantly different among treated patients (P = .04) and those with positive pathology results (P &lt; .0001) compared to patients not treated and those with negative pathology, respectively, and was highly predictive of positive pathology results (area under the curve = 0.92). No significant difference was observed in comparisons based on indicators of disease severity. Conclusions Pneumocystis jirovecii PCR was a highly impactful tool in the diagnosis and management of PJP, and use of CT values may have value in the treatment decision process in select cases. Further investigation in a prospective manner is needed.


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