Mean MPA Research Articles

A Phase 0 Study Assessing the Intracranial Activity of a Metabolic Radiosensitizer in Patients with Glioblastoma

Efforts to overcome treatment resistance in glioblastoma (GBM) have been unsuccessful due to tumor heterogeneity and poor intracranial drug penetration. Targeting altered metabolism is a promising approach to improve GBM therapy despite this heterogeneity. Mycophenolate mofetil (MMF) is an inhibitor of purine synthesis that sensitizes GBM to radiation and temozolomide (TMZ) in vitro and in vivo, but its ability to cross the blood brain barrier and inhibit GBM metabolism in patients is unknown. NCT04477200 is a phase 0/1 dose escalation study of MMF combined with radiation and temozolomide in GBM. Here we report the phase 0 results of this study assessing the intracranial activity of MMF. Purine (GTP and IMP) and mycophenolic acid (MPA, the active metabolite of MMF) concentrations were determined using mass spectrometry in flash-frozen tumor (enhancing and non-enhancing) and normal cortex obtained from 8 patients with recurrent GBM who received MMF (500, 1000, 1500 and 2000 mg BID, N = 2 patients each dose level) for 1 week prior to re-resection and 5 control patients who did not receive MMF prior to re-resection. Plasma MPA concentration was similarly quantified to calculate the enhancing tumor, non-enhancing tumor and normal cortex to plasma MPA ratios. Patients who received MMF had a mean MPA concentration of 2.2 ± 0.7 µM in the enhancing tumor samples, 1.2 ± 0.5 µM in the non-enhancing tumor samples and 1.3 ± 0.5 µM in normal cortex. MPA concentration was negligible in control patients. This corresponded to tissue/plasma MPA ratios of 0.31, 0.17 and 0.10 for enhancing tumor, non-enhancing tumor and normal cortex, respectively. The GTP/IMP ratio was decreased by 75% in enhancing tumor in MMF-treated patients compared to untreated controls (p = 0.009), indicating effective target engagement and inhibition of purine synthesis. The GTP/IMP ratio was also decreased in cortex and non-enhancing tumor, though a paucity of control samples prevented statistical analysis. Twice daily MMF treatment yields intracranial drug concentrations above 1 µM and lowers the GTP/IMP ratio in GBMs, consistent with target engagement. As we have previously observed radiosensitization in vitro with MPA concentrations of 1 µM, these data suggest that MMF may achieve adequate CNS penetration for therapeutic benefit. The Phase 1 component of this study to determine the dose limiting toxicity and maximally tolerated dose of MMF when combined with reirradiation in recurrent GBM and radiation and TMZ in newly diagnosed GBM is ongoing.

Core decompression combined with local DFO administration loaded on polylactic glycolic acid scaffolds for the treatment of osteonecrosis of the femoral head: a pilot study

BackgroundDeferoxamine (DFO) angiogenesis induction potential has been demonstrated in earlier studies, but not in the osteonecrosis of the femoral head (ONFH). In this study, we evaluated the outcome of ONFH treated with combined core decompression and local DFO administration loaded on Polylactic Glycolic Acid (PLGA).Patients and methodsIn a pilot experimental study, six patients (10 hips) with early-stage non-traumatic ONFH were treated by core decompression, and concurrent injection of local DFO loaded on PLGA scaffold into the subchondral femoral head. Outcome measures were evaluated before the surgery and 12 and 24 months after the surgery and included visual analog scale (VAS) for pain, modified Merle d’Aubigné-Postel (MAP) score for hip function by MRI, and rate of osteonecrosis assessed by the modified.ResultsThe mean MPA score was 14.7 ± 1.16 before the surgery and 16.7 ± 1.41 one year after the surgery (P = 0.004). The mean VAS for pain was 4.7 ± 1.25 before the surgery and 1.8 ± 1.03 one year after the surgery (P = 0.005). The mean Kerboul angle was 219 ± 58.64 before the operation and 164.6 ± 41.82 one year after the operation (P < 0.001). Osteonecrosis progression or collapse was not seen in any of the patients at the final follow-up. No postoperative side effect attributed to the DFO was noticed, as well.ConclusionIn short-term follow-up, combined core decompression and local DFO administration not only prevent the progression of ONFH but also reduces the rate of osteonecrosis significantly. However, future controlled studies are required to confirm the present results.Trial registrationIRCT20161121031003N3, 16/04/2019.

326 Sleep Stages Variation in Intracranial Pressure and Pulse Amplitude

INTRODUCTION: It is thought that CSF pulsatility has an important role in brain physiology during sleep. Yet few studies have looked into changes of ICP and pulsatility during sleep. METHODS: A single centre prospective cohort study. Patients undergoing 24 h ICP monitoring for suspected CSF dynamic disorders underwent concomitant polysomnography. Clinical and radiological presentation were derived from the patient’s records. Aggregate mean ICP and pulse amplitude (mPA) values were recorded for each sleep stage. Sleep staging was performed in conformity with the AASM guidelines. Within subject values were compared using repeated-measures, one-way ANOVA. Post-hoc paired t-tests were used to compare sleep stages between groups corrected for multiple comparisons (Benjamini-Hochberg method). RESULTS: A total of 12 patients (10 females, 2 males; mean age 40.8 years, SD+/- 12.9) with complete data were analysed. There were significant differences in mean ICP between sleep stages (F(3,33) = 10.7, p &lt; 0.00001). Post-hoc paired t-tests revealed significant differences between rapid eye movement (REM; mean ICP 14.4 mmHg) and all other sleep stages (mean ICP/N1 = 12.0 mmHg, t = -3.6, p = 0.004; ICP/N2 = 11.8 mmHg, t = -4.3, p = 0.001; ICP/N3 = 12.3 mmHg, t = -3.5, p = 0.004). Significant differences were also found in mPA between sleep stages (F(3,33) = 5.7, p = 0.003) confirmed on post-hoc paired t-tests: REM (mean mPA 5.5 mmHg and all other sleep stages: mPA/N1 = 4.7 mmHg, t = -2.3, p = 0.04; mPA/N2 = 4.3 mmHg, t = -2.7, p = 0.02; mPA/N3 = 4.5 mmHg, t = -2.3, p = 0.04). CONCLUSIONS: REM is characterized by higher ICP and mPA values, result confirmed in near-normal patients included in this cohort.

Axial CT measured main pulmonary artery diameter to predict the presence and degree of pulmonary hypertension

We performed this study to investigate if main pulmonary artery (mPA) diameter measured by axial chest computed tomography (CT) can predict the presence and degree of echocardiography-measured pulmonary hypertension (ePH) among emergency department (ED) patients. This retrospective cross-sectional study enrolled patients who underwent both chest CT and echocardiography within 24 h at the ED. The ePH was estimated using right ventricular systolic pressure (RVSP). RVSP &lt;40 mmHg was classified as normal; 40–49 mmHg, mild ePH; 50–75 mmHg, moderate ePH; and ≥76 mmHg, severe ePH. Among 485 adult patients, 297 (61.2%) had normal RVSP and mean mPA of 30.3 mm. The numbers of patients with mild, moderate and severe ePH were 92 (19.0%), 85 (17.5%) and 11 (2.3%) with corresponding mean mPA diameters of 32.4, 34.5 and 35.9 mm, respectively. The best mPA diameters for predicting mild, moderate and severe ePH were 30.6, 31.8 and 33.8 mm, with area under the receiver operating characteristic curve of 0.697, 0.727 and 0.797 and sensitivities of 72.9%, 71.9% and 81.8%, respectively. Axial CT-measured mPA diameter can predict the presence and degree of ePH among ED patients. If the CT-measured mPA diameter is greater than 30.6 mm, the possibility of pulmonary hypertension should be considered and applied to the patient’s treatment.

Noninvasive testing for mycophenolate exposure in children with renal transplant using urinary metabolomics.

Despite the common use of mycophenolate in pediatric renal transplantation, lack of effective therapeuic drug monitoring increases uncertainty over optimal drug exposure and risk for adverse reactions. This study aims to develop a novel urine test to estimate MPA exposure based using metabolomics. Urine samples obtained on the same day of MPA pharmacokinetic testing from two prospective cohorts of pediatric kidney transplant recipients were assayed for 133 unique metabolites by mass spectrometry. Partial least squares (PLS) discriminate analysis was used to develop a top 10 urinary metabolite classifier that estimates MPA exposure. An independent cohort was used to test pharmacodynamic validity for allograft inflammation (urinary CXCL10 levels) and eGFR ratio (12mo/1mo eGFR) at 1 year. Fifty-two urine samples from separate children (36.5% female, 12.0± 5.3 years at transplant) were evaluated at 1.6± 2.5 years post-transplant. Using all detected metabolites (n= 90), the classifier exhibited strong association with MPA AUC by principal component regression (r= 0.56, p< .001) and PLS (r= 0.75, p< .001). A practical classifier (top 10 metabolites; r= 0.64, p< .001) retained similar accuracy after cross-validation (LOOCV; r= 0.52, p< .001). When applied to an independent cohort (n= 97 patients, 1053 samples), estimated mean MPA exposure over Year 1 was inversely associated with mean urinary CXCL10:Cr (r= -0.28, 95% CI -0.45, -0.08) and exhibited a trend for association with eGFR ratio (r= 0.35, p= .07), over the same time period. This urinary metabolite classifier can estimate MPA exposure and correlates with allograft inflammation. Future studies with larger samples are required to validate and evaluate its clinical application.

Is there a Correlation between Hepatic Venous Indices and Main Pulmonary Artery Diameter?

To search whether there is a correlation between middle hepatic venous indices (HVIs) obtained by pulsed waved doppler ultrasonography (PW-DUS) and the main pulmonary artery (mPA) diameter, calculated by computed tomography (CT). A descriptive cross-sectional study. Department of Radiology, Balikesir University School of Medicine, Turkey, from February to December 2020. After excluding the cases with suspected COVID-19 from the cases sent to the Radiology Department for chest CT exams with the mPA included in the cross-sections, the volunteers were evaluated with PW-DUS. The study group consisted of 66 cases. Two radiologists measured the velocity values of the A, S, and D waves in the recorded PW Doppler spectra. HVIs (A/S, A/S+D, A/A+S+D) were calculated. The mPA diameter was calculated in the axial plane from the pulmonary trunk, 1cm proximally to the bifurcation manually on the workstation. The correlation between the HIVs and mPA diameter was evaluated. Interoperator reliability was also analysed. Thirty-nine males (59%) and 27 (41%) females were included in the study group. The mean HVI values were 0.50 ±0.20, 0.28 ±0.12, and 0.21 ±0.07 for A/S, A/A+S, and A/A+S+D, respectively. The mean mPA diameter was 24.0 ±3.3 mm. Correlation analysis determined that the HVIs were positively correlated with mPA diameter (r=0.730-0.765-0.751, p<0.001). Inter-observer correlation coefficients were found to be compatible between two radiologists. A significant and strong correlation was found between HVIs and mPA diameter. The mPA diameter that reflects the pulmonary artery systolic pressure (PAP) increased as the HVIs increased. Therefore, PW-DUS may be helpful to evaluate PAP as a quantitative method that is cost-effective, easily accessible and radiation-free. Hepatic veins, Pulmonary artery, Multidetector computed tomography, Pulmonary hypertension, Pulsed doppler ultrasonography.

Influence of pretreatments on microtensile bond strength to eroded dentin using a universal adhesive in self-etch mode

To evaluate the influence of pretreatments on microtensile bond strength (μTBS) to eroded dentin when using a universal adhesive in self-etch mode. Forty-eight human molars were randomly assigned to six groups (G1–G6, n = 8) and ground down until dentin exposure. G2–G6 were eroded with citric acid (pH 2.6) for 10 × 2 min (within 12 h) on 5 consecutive days. G1 and G2 served as uneroded and eroded controls and were not pretreated. G3 and G4 were pretreated for 60 s with NaOCl (10% and 5%, respectively). G5 was airborne-particle abraded using Al 2 O 3 for 15 s, and G6 was roughened with a diamond bur. The universal adhesive Scotchbond Universal was applied in self-etch mode. After composite build-up, μTBS was determined. Control group G1 (uneroded) showed higher μTBS than G2 (eroded). The μTBS (mean MPa ±SD) of G5 (airborne-particle abrasion; 11.6 ± 4.6) and G6 (bur-roughening; 11.0 ± 3.3) did not differ significantly from the μTBS of G1 (12.4 ± 4.2). Significantly higher μTBS compared to all other groups was observed in G3 (NaOCl 10%; 17.6 ± 7.6). Pretreatment with NaOCl 5% (G4) achieved significantly lower μTBS (3.5 ± 2.6) than the other groups, except for G2 (8.8 ± 2.0). Pretreatment with 10% NaOCl, diamond bur roughening or airborne-particle abrasion can increase bond strength of the tested adhesive to eroded dentine. Pre-treatment with 5% NaOCl is not recommended.

Examining the effects of acid etching duration on the bond strength between two CAD/CAM materials and one composite resin.

This study aimed to evaluate the effect of three hydrofluoric acid (HF) etching periods on the micro-tensile bond strength between two CAD-CAM ceramic systems [Vita Suprinity (VS) and feldspathic CEREC blocs (CB)] and a composite resin. The ceramics were categorized into six groups based on the surface conditioning protocol used, as follows: G1: CB-HF 5% for 20s; G2: CB-HF 5% for 40s; G3: CB-HF 5% for 60s; G4: VS-HF 5% for 20s; G5: VS-HF 5% for 40s; G6: VS-HF 5% for 60s. Scotchbond Universal was applied onto the pretreated ceramic surfaces and covered with Filtek Z350 XT composite resin. After 24h, the specimens were cut into microbars (n = 16) and a micro-tensile bond strength test (μTBS) was carried out. An optical microscope was used to examine the fractured microbars. The results showed statistically significant differences between the factors tested (p < 0.01). Moreover, the mean MPa of G1(17.27), G2(13.03), G3(12.82), G4(15.83), G5(21.66), and G6(14.50) was seen to significantly differ. The predominant failure type observed was adhesive, and all three periods of HF etching produced satisfactory bonding between the composite resin and CB. An etching time of 40s provided the highest μTBS value for VS.

Effect of number of hours and days of accelerometer use on physical activity estimates in adolescents

The study analyzed the effect of number of hours and days of accelerometer use on estimates of physical activity (PA) time in adolescents. Cross-sectional study of 784 adolescents from 10 to 14 years old (53.9% girls). Overlapping 95% confidence intervals (95%CI) were used to compare mean light (LPA), moderate (MPA), vigorous (VPA) and moderate to vigorous (MVPA) physical activity times and prevalence of sufficient PA levels between different numbers of hours (≥6, ≥8 and ≥10 hours/day) and days (≥3, ≥4, ≥5 and 7 days of use). The criterions of ≥6 hours/day with ≥3, ≥4, ≥5 e 7 days and ≥8 hour/day with ≥3, ≥4 e ≥5 days of accelerometer use underestimated, in average, the LPA time in 23.1 and 12.6 min/day, respectively, compared ≥10 hours/day. There were no significant differences in mean MPA, VPA and MVPA times and prevalence of sufficient PA levels between the number of hours and days of use analyzed. To produce accurate estimates of PA time in teenagers, ≥3 days of accelerometer use was adopted for ≥10 hours/day of LPA and ≥ 6 hours/day of MPA, VPA and MVPA.

A Study of the Pharmacokinetic Comparison between the Generic and Original Form of Mycophenolate Mofetil Among Thai Renal Transplant Patients

BackgroundMycophenolic acid (MPA) is one of the main immunosuppressive regimens used after kidney transplantation (KT). The less expensive, generic form of mycophenolate mofetil (MMF) (Immucept®) is recently available in Thailand. Comparisons of the pharmacokinetic profiles between the original and generic forms of MMF among post-KT patients are limited. MethodsThis prospective cohort study recruited KT patients receiving stable doses of MMF 1000 mg daily along with tacrolimus and steroids. All participants were prescribed CellCept® 500 mg every 12 hours for at least 2 weeks before measuring the MPA area under the curve from 0 to 12 hours (AUC0-12). CellCept® was switched to Immucept® 500 mg every 12 hours for 2 weeks and MPA AUC0-12 was remeasured. ResultsTwenty patients with a median follow-up time of 35.4 (11.13–198.83) months were enrolled. Mean MPA AUC0-12 of Immucept® was higher than CellCept® without statistical significance (48.27 ± 2.31 μg⋅hr/mL vs 42.19±15.20 μg⋅hr/mL; P value = .59). No difference was revealed regarding the minimum measured concentration, maximum measured concentration, and time point with maximum concentration between both drugs. While on CellCept®, 5 patients (25%) had an MPA AUC0-12 < 30.0 μg⋅hr/mL, but 3 patients (15%) had MPA AUC0-12 < 30.0 μg⋅hr/mL when receiving Immucept®. However, 3 (15%) and 6 (30%) patients had MPA AUC0-12 > 60.0 μg⋅hr./mL when treated with CellCept® and Immucept®, respectively. ConclusionGeneric MMF exhibited a comparable pharmacodynamic profile as the original formulation. MPA AUC0-12 was more than 30.0 μg⋅hr/mL among most patients receiving MMF 1000 mg/day.

Depot-medroxyprogesterone acetate reduces genital cell–cell adhesion molecule expression and increases genital herpes simplex virus type 2 infection susceptibility in a dose-dependent fashion

ObjectiveAnalyzing ectocervical biopsy tissue from women before and after they initiated use of depot-medroxyprogesterone acetate (DMPA), we previously reported this progestin reduces levels of the cell–cell adhesion molecule (CCAM) desmoglein-1 and increases genital mucosal permeability. We likewise saw treating mice with 1.0 mg of DMPA reduced vaginal CCAM expression and increased genital pathogen susceptibility. Herein, we used dose–response studies to delimit DMPA doses and serum MPA levels in mice associated with impaired genital mucosal barrier function and enhanced susceptibility to low-dose herpes simplex virus type 2 (HSV-2) infection. Study designWe compared genital CCAM expression, genital mucosal permeability, and susceptibility to genital inoculation with 103 plaque-forming units of HSV-2 among mice in estrus vs. after treatment with 0.01 mg, 0.1 mg, 0.3 mg, or 1.0 mg of DMPA. ResultsCompared to mice in estrus, DMPA treatment in a dose-dependent fashion significantly reduced desmoglein 1α (Dsg1a) and desmocollin-1 (Dsc1) gene expression, reduced DSG1 protein levels, and increased genital mucosal permeability to a low molecular weight molecule. While no mice infected with HSV-2 in estrus died, we respectively saw 50% and 100% mortality in mice administered 0.1 mg or 0.3 mg of DMPA. At time of infection, mean serum MPA levels in mice administered the 0.1 mg or 0.3 mg doses were 3.8 nM and 13.0 nM respectively (values comparable to trough and peak MPA serum levels in women using DMPA). ConclusionsMice with pharmacologically relevant serum MPA concentrations display significant changes in genital CCAM expression, genital mucosal barrier function, and HSV-2 susceptibility.

Prognostic impact of the ratio of the main pulmonary artery to that of the aorta on chest computed tomography in patients with idiopathic pulmonary fibrosis

BackgroundIn many clinical disorders, there is a relationship between the ratio of the diameter of the main pulmonary artery (mPA) to that of the aorta (Ao) on chest computed tomography (CT). The aim of this study was to determine if the mPA/Ao ratio at diagnosis is associated with the clinical characteristics and outcomes in patients with idiopathic pulmonary fibrosis (IPF).MethodsWe retrospectively reviewed the diameters of the pulmonary artery and aorta on chest CT, clinical characteristics, and results of other examinations in 303 patients at the time of initial diagnosis of IPF at our tertiary care center between 2011 and 2015. The primary outcomes were death and lung transplantation. The patients were followed up until June 2017.ResultsOne hundred and eight patients (35.6%) died and 58 (19.1%) underwent lung transplantation during follow-up. The mean mPA and Ao diameters were 28.3 mm and 34.0 mm, respectively, and the mean mPA/Ao ratio was 0.84. Thirty-one patients (10.2%) had an mPA/Ao ratio > 1.0 and 182 (60.1%) had an mPA/Ao ratio > 0.8. Patients with an mPA/Ao ratio > 0.8 had a lower DLco value than those with an mPA/Ao ratio ≤ 0.8. In Kaplan-Meier analysis, patients with an mPA/Ao ratio > 1.0 or > 0.8 had worse outcomes than those with an mPA/Ao ratio ≤ 1.0 and ≤ 0.8, respectively.ConclusionsA higher mPA/Ao ratio based on 1.0 and 0.8 is associated with unfavorable prognosis in patients with IPF.

EVALUATION OF COMPRESSIVE STRENGTH AND RADIOPACITY OF DENOVO SYNTHESIZED CALCIUM SILICATE CEMENT CONTAINING ZINC OXIDE NANOPARTICLES VERSUS COMMERCIAL MATERIALS

This in-vitro study evaluated the compressive strength and radiopacity of denovo synthesized calcium silicate cement containing zinc oxide nanoparticles versus commercial materials. A total of 100 specimens were prepared for this study, 25 of them were prepared for each of the 4 materials group: Synthesized Calcium Silicate Cement (SYNT), Nano Zinc Oxide added to the synthesized calcium silicate cement (NANO), Angelus White Mineral Trioxide Aggregate (MTA) and Theracal (THCL). The 25 specimens of each group was then distributed as follows: 10 were tested for compressive strength (MPa) on day 10, 10 were tested for compressive strength (MPa) on day 30; the last 5 specimens were tested for radiopacity. Data was then recorded, tabulated and statistically analyzed. The mean MPa results on day 10 recorded the highest by THCL-10 (55.35 ± 9.82), while the lowest value was recorded for NANO-10 (4.90 ± 1.61). The mean MPa on day 30 recorded by the NANO-30 (52.66 ± 19.30) was the highest, while the lowest value was recorded for SYNT-30 (21.70 ± 2.55). All subgroups on day 10 compared to those on day 30 showed significant statistical difference at p<0.05; Where the mean MPa of SYNT-30 was less than that of SYNT-10, the same was observed for the THCL subgroups. As for the mean MPa of NANO-30 was higher than that NANO-10, the MTA subgroups expressed the same results. On the other hand, the radiopacity results showed that the highest mean radiopacity value was recorded for THCL (9.43 ± 0.60), followed by MTA (9.38 ± 0.63), then NANO (5.06 ± 0.54), while the lowest value was recorded for SYNT (1.26 ± 0.24). In conclusion, the incorporation of zinc oxide nanoparticles in calcium silicate based enhances the physicomechanical properties of the cement expressed in terms of compressive strength and radiopacity in comparison to commercially available materials such as MTA and theracal.

Evaluation of the Bond Strength of Universal Tray Adhesives on Silicone Impression Materials Using an Acrylic Tray

To evaluate the bond strength of two commercially available universal tray adhesives on polyvinylsiloxane addition silicone and condensation silicone impression materials to an autopolymerizing polymethyl methacrylate acrylic tray material. Sixty flat square specimens were fabricated from autopolymerizing polymethyl methacrylate tray material to which an eye hook was incorporated to serve as the point of attachment to a universal testing machine. A polyvinyl chloride (PVC) pipe of 15 mm diameter and 25 mm long was used to house the impression material, and a metal rod was inserted into two centered holes to provide retention that serves as the second point of attachment to the universal testing machine. The specimens were divided into 4 groups of 15 specimens each. The first and second groups of specimens were applied with Coltene and Zhermack universal tray adhesives and tested with addition silicone impression material. The third and fourth groups were coated with the above-mentioned adhesives, respectively, and tested with condensation silicone. Each specimen was then attached to the universal testing machine. The maximum force at which separation failure occurred was divided by the area of adhesion and recorded as the adhesive strength in MPa. A significant difference was observed between mean MPa values of Zhermack and Colten universal tray adhesives, where the F value of 1314.116 was found to be significant at 0.000 levels indicating that the Zhermack adhesive had higher MPa than Coltene adhesive. Impression material again indicated significant difference (F = 132.514; p = 0.000), where addition silicone had higher MPa value than condensation silicone. Also, the interaction between adhesive and impression material was found to be significant (F = 10.794; p = 0.002). The adhesive bond strength of Zhermack universal tray adhesive was higher compared to that of Coltene universal tray adhesive irrespective of the elastomeric impression material. It was also found that bond strength of Zhermack universal tray adhesive with addition silicone impression material was the highest and Coltene universal tray adhesive with condensation silicone impression material was the least of all the four groups. Tray adhesives need to be applied to the tray to obtain an accurate and consistent impression. If there is a separation of impression materials from the tray, it may results in a distorted impression leading to poor final restorations.

P110 Clinical predictors of donor specific antibody following kidney transplantation

Aim Optimizing immunosuppressive drug therapy for individual patients has been one of the challenges of transplantation. In this study, we attempt to define the relationship between tacrolimus (TAC) and mycophenolate mofetil (MPA) in the development of donor specific antibody (DSA) in patients with kidney transplants. Methods 253 patients underwent kidney transplantation from January 2011 to February 2017. All patients received induction therapy with 2–5 mg/kg of thymoglobulin. Standard immunotherapy after induction consisted of steroids, MPA and tacrolimus. All tacrolimus levels drawn after transplantation were included. A two-hour AUC for the active metabolite, MPA, and the glucuronide, MPAG, was determined 1–5 months following transplantation. Results Patients that developed DSA were compared to those that did not using logistic regression. Variables in the logistic regression included age, mean tacrolimus levels with their standard deviation, MPA area under the curve (AUC) with its standard deviation, MPAG (MPA glucuronide) with its standard deviation (SD). For a given patient the mean of all TAC levels was calculated by using every level obtained following kidney transplantation. See Table 1. The coefficients associated with the variables above suggest that the most predictive variables for the development of DSA were mean TAC level, SD of the mean TAC level, mean MPAG level and age. See Table 2. Conclusions Our data suggests: (1) Mean tacrolimus level and standard deviation of the mean has the highest predictive value for the development of DSA, (2) Mean MPAG AUC and not mean MPA AUC, is almost equally important in forecasting the development of DSA and (3) young age predisposes to the formation of DSA.

Comparison of the Microtensile Bond Strength of a Polyetherketoneketone (PEKK) Tooth Post Cemented with Various Surface Treatments and Various Resin Cements.

The aim of this in-vitro research was to evaluate the microtensile bond strength in the newly introduced PEKK tooth post with various surface treatments and resin cements. A fiberglass tooth post was included in order to compare it with PEKK as a possible post material. The microtensile bond strengths of the fiberglass post (FRC Postec Plus) and the PEKK post (Pekkton®) were tested using three kinds of self-adhesive resin cements (G-CEM LinkAce, Multilink Speed, and RelyX U200) and one self-etching resin cement (PANAVIA F2.0). The surface treatments of the fiberglass posts were processed according to the manufacturer’s recommendations (F1, application of 37% phosphoric acid etching gel and silanization). For the PEKK post groups, various surface treatments were performed like no surface treatment (P1), sandblasting (P2), silica-coating and silanization (P3), and sandblasting with a composite primer (P4). In the surface treatment, PEKK posts with silica coating and silane treatment (P3) showed a significantly higher microtensile bond strength (mean MPa: 18.09, p < 0.05). The highest microtensile bond strength was shown when the PEKK posts were treated with a silica coating and silane treatment and cemented with RelyX U200 (mean MPa: 22.22). The PEKK posts with surface treatments of silica-coating and silanization or sandblasting displayed superior microtensile bond strengths (mean MPa: 18.09 and 16.25, respectively) compared to the conventional fiberglass posts (mean MPa: 14.93, p < 0.05).

Comparison of PETINIA and LC-MS/MS for determining plasma mycophenolic acid concentrations in Japanese lung transplant recipients

BackgroundMycophenolic acid (MPA) treatment requires therapeutic drug monitoring to improve the outcome after organ transplantation. The aim of this study was to compare two methods, a particle enhanced turbidimetric inhibition immunoassay (PETINIA) and a reference liquid chromatography tandem mass spectrometry (LC-MS/MS) for determining plasma MPA concentrations from Japanese lung transplant recipients.MethodsPlasma MPA concentrations were determined from 20 Japanese lung transplant recipients using LC-MS/MS and the PETINIA on the Dimension Xpand Plus-HM analyzer.ResultsThe mean MPA concentration measured by PETINIA was significantly higher than that measured by LC-MS/MS (3.26 ± 2.73 μg/mL versus 2.82 ± 2.71 μg/mL, P < 0.0001). The result of the Passing Bablok analysis was a slope of 1.104 (95% confidence interval [CI], 1.036–1.150) and an intercept of 0.229 (95%CI, 0.144–0.315). Bland–Altman analysis revealed PETINIA overestimates plasma MPA concentration by 26.25% and 95%CI from 21.43 to 31.07%.ConclusionThe measurement of MPA by the PETINIA in Japanese lung transplant patients should evaluate the result with attention to positive bias.

Equivalence Of Self-report And Accelerometer Measures Following A Physical Activity Intervention.

The International Physical Activity Questionnaire (IPAQ) is a validated and widely used self-report physical activity (PA) measure, however findings about validity have been somewhat equivocal. PURPOSE: This study evaluated the agreement of the IPAQ measure with a novel and objective activity monitoring method known as Sojourns Including Posture (SIP). The SIP method is based on the same bout detection method as the more established Sojourn method but incorporates data from the ActivPAL to provide more robust information about transitions between Sedentary and Light activity. The aim was to investigate differences between self-reported moderate (MPA), vigorous (VPA), and sedentary (SED) minutes to SIP data, to inform whether participants were able to accurately self-report PA and SED time. METHODS: A sample of 93 inactive adults (53% female; 42 ± 9.1 mean age) participated in this study. Participants received a wearable device to track PA. Post-intervention, individuals wore accelerometers for 1 week, and self-reported PA and SED via the IPAQ. Minutes of MPA, VPA, and SED from each measure were compared using Pearson correlations, equivalence testing, and Bland-Altman plots, with the SIP method as the criterion. RESULTS: The overall Pearson correlation between the measures was low to moderate (r = 0.37, P < .05). The mean MPA via IPAQ was 96.9 ± 87.8 minutes per day compared to 57.3 ± 24.4 minutes per day measured by SIP. Mean VPA from the IPAQ was 8.99 ± 6.76 minutes, while the SIP method reported 14.44 ± 9.51 minutes. The mean SED via the IPAQ was 456.6 ± 156.93 minutes compared to 546.13 ± 104.42 minutes measured by SIP. Equivalence testing demonstrated that the MPA, VPA, and SED methods were not equivalent at the ±10% equivalence zone. A Bland Altman plot was constructed to visualize the MPA data using 95% limits of agreement that are between -121.1 and 200.4. More data points trended below the mean of 39.65, suggesting proportional bias that self-report overestimated activity. CONCLUSIONS: This study provides some support for the use of the IPAQ, but confirms the common observation in self-report instruments with participants tending to overestimate their participation in MPA and underestimate sedentary time. The use of measurement error modeling and calibration methods may be needed to address this error in future studies.

Functional and Prognostic Implications of the Main Pulmonary Artery Diameter to Aorta Diameter Ratio from Chest Computed Tomography in Korean COPD Patients.

BackgroundThe ratio of the diameter of the main pulmonary artery (mPA) to the diameter of the aorta (Ao) on chest computed tomography is associated with diverse clinical conditions. Herein, we determined the functional and prognostic implications of the mPA/Ao ratio in Korean chronic obstructive pulmonary disease (COPD) patients.MethodsThe study population comprised 226 chronic obstructive pulmonary disease patients from the Korean Obstructive Lung Disease cohort who underwent chest computed tomography. We analyzed the relationships between the clinical characteristics, including pulmonary function, echocardiography findings, St. George's Respiratory Questionnaire, 6-minute walking (6MW) distance, and exacerbation with the mPA, Ao, and mPA/Ao ratio.ResultsThe mean age was 65.8 years, and 219 (96.9%) patients were male. The mean FEV1% predicted and FEV1/FVC ratio were 61.2% and 47.3%, respectively. The mean mPA and Ao were 23.7 and 36.4 mm, respectively, and the mPA/Ao ratio was 0.66. The mPA/Ao ratio correlated negatively with the 6MW distance (G = -0.133, P = 0.025) and positively with the right ventricular pressure (G = 0.323, P = 0.001). After adjustment for potential confounders, the mPA/Ao ratio was significantly associated with 6MW distance (β = -107.7, P = 0.017). Moreover, an mPA/Ao ratio >0.8 was a significant predictor of exacerbation at the 1-year (odds ratio 2.12, 95% confidence interval 1.27–3.52) and 3-year follow-ups (odds ratio 2.04, 95% confidence interval 1.42–2.90).ConclusionsThe mPA/Ao ratio is an independent predictor of exercise capacity and an mPA/Ao ratio >0.8 is a significant risk factor of COPD exacerbation.

Comparison of CT-Determined Pulmonary Artery Diameter, Aortic Diameter, and Their Ratio in Healthy and Diverse Clinical Conditions.

BackgroundThe main pulmonary artery diameter (mPA), aortic diameter (Ao), and the mPA/Ao ratio, easily measured using chest computed tomography (CT), provide information that enables the diagnosis and evaluation of cardiopulmonary diseases. Here, we used CT to determine the sex- and age-specific distribution of normal reference values for mPA, Ao, and mPA/Ao ratio in an adult Korean population.MethodsData from non-contrast, ECG-gated, coronary-calcium-scoring CT images of 2,547 individuals who visited the Health Screening Center of the Severance Hospital were analyzed. Healthy individuals (n = 813) included those who do not have hypertension, diabetes, asthma, obstructive lung disease, ischemic heart disease, stroke, smoking, obesity, and abnormal CT findings. Both mPA and Ao were measured at the level of bifurcation of the main pulmonary artery.ResultsThe mean mPA and Ao were 25.9 mm and 30.0 mm in healthy participants, respectively, while the mean mPA/Ao ratio was 0.87. Medical conditions associated with a larger mPA were male, obesity, smoking history, hypertension, and diabetes. A larger mPA/Ao ratio was associated with female, the obese, non-smoker, normotensive, and normal serum level of lipids, while a smaller mPA/Ao ratio was associated with older age. In healthy individuals, the 90th percentile sex-specific mPA, Ao, and mPA/Ao ratio were, 31.3 mm (95% CI 29.9–32.2), 36.8 mm (95% CI 35.7–37.5), and 1.05 (95% CI 0.99–1.07) in males, and 29.6 mm (95% CI 29.1–30.2), 34.5 mm (95% CI 34.1–34.9), and 1.03 (95% CI 1.02–1.06) in females, respectively.ConclusionIn the Korean population, the mean mPA reference values in male and female were 26.5 mm and 25.8 mm, respectively, while the mean mPA/Ao ratio was 0.87. These values were influenced by a variety of underlying medical conditions.