scholarly journals Time-Dependent Apparent Increase in dd-cfDNA Percentage in Clinically Stable Patients Between One and Five Years Following Kidney Transplantation

2020 ◽  
Vol 66 (10) ◽  
pp. 1290-1299 ◽  
Author(s):  
Ekkehard Schütz ◽  
Thomas Asendorf ◽  
Julia Beck ◽  
Verena Schauerte ◽  
Nina Mettenmeyer ◽  
...  

Abstract Background Donor-derived cell-free DNA (dd-cfDNA) is reportedly a valuable tool for graft surveillance following kidney transplantation (KTx). Possible changes in dd-cfDNA(%) reference values over time have not been evaluated. For long-term monitoring after KTx, changes in host cfDNA might represent a biasing factor in dd-cfDNA(%) determinations. Methods Plasma samples were obtained (n = 929) 12–60 months after engraftment in a cross-sectional cohort of 303 clinically stable KTx recipients. Total cfDNA(copies/mL), dd-cfDNA(%), and dd-cfDNA(copies/mL) were determined using droplet-digital PCR. Stability of threshold values in these stable KTx recipients over time was assessed by 80th, 85th, and 90th quantile regression. Results Upper percentiles of total cfDNA showed a significant decline of −1902, −3589, and −4753 cp/mL/log(month) (P = 0.014, <0.001, and 0.017, respectively), resulting in increasing dd-cfDNA(%) percentiles by 0.25, 0.46, and 0.72%/log(month) (P = 0.04, 0.001, and 0.002, respectively), with doubling of the 85th percentile value by 5 years. In contrast, dd-cfDNA(cp/mL) was stable during the observation period (P = 0.52, 0.29, and 0.39). In parallel increasing white blood cell counts and decreasing tacrolimus concentrations over time were observed. After 5 years, the median total cfDNA was still 1.6-fold (P < 0.001) higher in KTx recipients than in healthy controls (n = 135) and 1.4-fold (P < 0.001) higher than patients with other medical conditions (n = 364). Conclusions The time-dependent decrease of host cfDNA resulted in an apparent increase of dd-cfDNA fraction in stable KTx patients. For long-term surveillance, measurement of absolute dd-cfDNA concentrations appears to be superior to percentages to minimize false positive results.

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1478
Author(s):  
Lorenzo G. T. M. Segabinazzi ◽  
Giorgia Podico ◽  
Michael F. Rosser ◽  
Som G. Nanjappa ◽  
Marco A. Alvarenga ◽  
...  

In light of PRP’s increasing popularity in veterinary practice, this study aimed to compare three manual methods to prepare and cool equine PRP. The blood of 18 clinically healthy mares was collected via venipuncture in a blood transfusion bag (method 1), blood tubes (method 2), and a syringe (method 3). In method 1, samples were double centrifuged; method 2 involved one centrifugation, and in method 3 the syringe was kept in an upright position to sediment for 4 h. After processing with three methods, PRP and platelet-poor plasma (PPP) were extracted and assessed for red (RBC) and white blood cell counts (WBC), platelet counts, and viability. In a subset of mares (n = 6), samples were processed with the three methods, and PRP was evaluated at 6 and 24 h postcooling at 5 °C. Method 1 resulted in the highest and method 3 in the lowest platelet concentration (p < 0.05), and the latter also had greater contamination with WBC than the others (p < 0.001). Platelet viability was similar across treatments (p > 0.05). Cooling for 24 h did not affect platelet counts in all methods (p > 0.05); however, platelet viability was reduced after cooling PRP produced by method 3 (p = 0.04), and agglutination increased over time in all methods (p < 0.001). The three methods increased (1.8–5.6-fold) platelet concentration in PRP compared to whole blood without compromising platelet viability. In conclusion, all three methods concentrated platelets and while cooling affected their viability. It remains unknown whether the different methods and cooling would affect PRP’s clinical efficacy.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 115-115
Author(s):  
Charles Teyssier ◽  
Magali Quivrin ◽  
Julie Blanc ◽  
Aurelie Petitfils ◽  
Fabienne Bidault ◽  
...  

115 Background: Prostate brachytherapy with iodine seeds has a lasting dose delivery due to a long half life of I125 (i.e. 2 months). To assess changes in dose metrics over time in low-dose rate prostate brachytherapy with iodine seeds and its relationship with rectal distension. Methods: One hundred and twenty-one post-implant CT scans performed every 2 weeks over 2 months after the treatment procedure were analyzed for dosimetry. Each CT-scan was performed without and with rectal enema. The following rectal parameters were collected to evaluate the influence of rectal distension over time: rectal volume, cross-sectional surface area (CSA) and relative CSA calculated from the first CT-scan chosen as reference (CTref). Results: Mean V150% and V200% of the prostate volume increased significantly over time (p < 0.0001) and were significantly higher on postimplant CT scan performed at day 45 (CT45) (p = 0.024 and p = 0.003, respectively) and CT scan performed at day 60 (CT60) (p = 0.0005 and p < 0.0001, respectively) compared with CTref. All dosimetric parameters for the rectum were significantly increased over time. No rectal parameters were significantly different after rectal enema and there was no difference in doses delivered to the prostate and the rectum after rectal emptying. Conclusions: Increased hot spots in the prostate and the rectum during the 2 months following the procedure with iodine seeds may be related to prostate shrinkage rather than rectal distension. We hypothesize that radioelements with shorter half-life (Pd103 or Cs131) or HDR may give less toxicity, as dose distribution is less time-dependent.


2006 ◽  
Vol 189 (5) ◽  
pp. 399-404 ◽  
Author(s):  
Anja Busse ◽  
Matthias C. Angermeyer ◽  
Steffi G. Riedel-Heller

BackgroundStudies of conversion from mild cognitive impairment to dementia suggest a linear progression over time. Conversion rates during lifetime may extend to 80–90%.AimsThis study examines the time-dependent evolution from mild cognitive impairment to dementia. Current assumptions regarding yearly and lifetime conversion rates are challenged.MethodA community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing based on 6 years of observation.ResultsApproximately 60–65% of people with mild cognitive impairment develop clinical dementia during their life. Progression from mild cognitive impairment to dementia appears to be time dependent, occurring primarily within the initial 18 months.ConclusionsFurther long-term studies are needed to examine the time-dependent evolution from mild cognitive impairment to dementia and to establish age-specific conversion rates during lifetime.


2006 ◽  
Vol 80 (1) ◽  
pp. 236-245 ◽  
Author(s):  
Vincent Dioszeghy ◽  
Kadija Benlhassan-Chahour ◽  
Benoit Delache ◽  
Nathalie Dereuddre-Bosquet ◽  
Celine Aubenque ◽  
...  

ABSTRACT Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.


1986 ◽  
Vol 20 (10) ◽  
pp. 783-785 ◽  
Author(s):  
Keith Henry ◽  
Irving Steinberg ◽  
Kent B. Crossley

A case of vancomycin-associated neutropenia occurring during long-term outpatient therapy with vancomycin is described. Pharmacokinetic studies demonstrated that the patient's vancomycin serum levels were within an acceptable range during treatment. Eighteen other reported cases of vancomycin-associated leukopenia are discussed in brief. An immunologic mechanism has been proposed but a clear understanding is lacking. Patients receiving long-term vancomycin therapy should have their white blood cell counts periodically monitored.


2017 ◽  
Vol 44 (3) ◽  
pp. 176-188 ◽  
Author(s):  
Arthur Shiyovich ◽  
Harel Gilutz ◽  
Ygal Plakht

We evaluated the association between white blood cell counts and long-term mortality rates in 2,129 patients (mean age, 65.3 ± 13.5 yr; 69% men) who had survived acute myocardial infarction. We obtained white blood cell counts and differential counts of white blood cell subtypes within the first 72 hours of hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years after acute myocardial infarction. In regard to death in the long term, we found significant negative linear associations (lymphocytes), positive linear associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear U-shaped associations (basophils, eosinophils, monocytes, and total white blood cell count). After multivariate adjustment for the Soroka Acute Myocardial Infarction risk score, lymphocytes (strongest association), neutrophil-to-lymphocyte ratio, and eosinophils were independently associated with death for up to 10 years after hospital discharge. The independent associations weakened over time. We conclude that lymphocyte count, neutrophil-to-lymphocyte ratio, and eosinophil count are independently and incrementally associated with death in the long term after acute myocardial infarction.


Author(s):  
Vijitashwa Pandey ◽  
Zissimos P. Mourelatos ◽  
Annette Skowronska

Many repairable systems degrade with time and are subjected to time-varying loads. Their characteristics may change over time considerably, making the assessment of their performance and hence their design difficult. To address this issue, we introduce in this paper the concept of flexible design of repairable systems under time-dependent reliability considerations. In flexible design, the system can be modified in the future to accommodate uncertain events. As a result, regardless of how uncertainty resolves itself, a modification is available that will keep the system close to optimal provided failure events have been properly characterized. We discuss how flexible design of repairable systems requires a fundamentally new approach and demonstrate its advantages using the design of a hydrokinetic turbine. Our results show that long-term metrics are improved when time-dependent characteristics and flexibility are considered together.


2019 ◽  
Vol 184 (16) ◽  
pp. 503-503 ◽  
Author(s):  
Babak Faramarzi ◽  
Lon Rich

Foals’ haematological values change constantly during their first year of life. The use of updated age-based reference intervals (RIs) is imperative for providing accurate diagnosis and optimum care for sick foals. The authors' objective was to provide updated RIs for 13 haematological values in 2, 7, 14, 30, 90, 180 and 365-day-old foals and to investigate the changes over time in each measured value. Venous blood was collected at those ages from clinically healthy foals. Thirteen haematological values were analysed. The 95% RIs were reported using a bootstrapping method. Differences over time were examined using Friedman test. RIs for each of the measured values were calculated. Results showed noticeable trends in changes over time in several values. Nevertheless, white blood cell counts significantly increased between day 2 and day 90 (P=0.011) while lymphocyte counts increased from day 2 up to day 180 (P=0.033). The mean corpuscular haemoglobin and mean corpuscular volume (P=0.011) significantly decreased between day 2 and day 90. Normal haematological values in foals not only differ from those in adult horses but also change throughout the first year of life; thus, it is critical that clinicians use age-based RIs when treating sick foals.


2010 ◽  
Vol 40 (1) ◽  
pp. 48-54 ◽  
Author(s):  
David B. Lindenmayer ◽  
Jeff T. Wood

Large trees with hollows are an important component of stand structural complexity worldwide. Understanding their population dynamics is needed to manage cavity-dependent biota. We quantified long-term rates of collapse of 302 measured trees with hollows in 1939-aged regrowth mountain ash ( Eucalyptus regnans F. Muell.) forest in southeastern Australia. We identified time-dependent dynamics in which the collapse rates of trees slowed from ∼4% annually between 1983 and 1993 to ∼2.2% between 1993 and 2007. Transitions of trees between different decay states (forms) also slowed over time. Nevertheless, during the 24-year period of our study, over half of our marked and measured trees had fallen, but there was no recruitment of new trees with hollows. Under current projections, few trees with hollows will occur on our field sites by ∼2050, although more had been forecast in earlier investigations. Such a paucity of trees with hollows in extensive areas of regrowth mountain ash forests will lead to a shortage of nesting and sheltering sites for cavity-dependent biota. We suggest a short–medium (10- to 100-year) focus on the conservation of old growth and multi-aged stands will be needed to maintain populations of those species strongly associated with trees with hollows in mountain ash forests.


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