Illicit Fentanyl Exposure Among Victims of Violence Treated at a Trauma Center.

INTRODUCTION: Opioid overdoses and violent injury are leading causes of death in the United States, yet testing for novel opioids like fentanyl remains uncommon. The purpose of this investigation is to characterize a population of victims of violence who test positive for illicit fentanyl. METHODS: Retrospective cohort study of patients treated at a level-one trauma center between January 31, 2019 and February 21, 2020. Data were extracted from the electronic medical record. Subjects were included if they had an encounter diagnosis for a violent or intentional injury, using the International Classification of Diseases, v10 (X92-Y09). We excluded patients who received licit fentanyl as a part of their care before testing. Those who tested positive for fentanyl exposure on our standard hospital urine drug screen were considered to have been exposed to illicit fentanyl. Those testing negative for fentanyl were considered controls. RESULTS: Of the 1132 patients treated for intentional injuries during the study period, 366 were included in the study (32.3%). Of these, 133 (36.3%) subjects were exposed to illicit fentanyl prehospital. There were no demographic differences between cases and controls. Cases had a lower GCS voice score on arrival (median = 4, interquartile range [IQR] = 4-5 versus median = 5, IQR = 4-5, P = 0.02), higher rates of ventilator usage (32.3% versus 21.5%, P = 0.02), and more intensive care unit admissions (27.1% versus 12.0%, P = 0.005). More than half of cases tested negative for opiates (78/133, 58.6%). Cases had more trauma center encounters (26.3% had ≥2 visits versus 15.5%). CONCLUSIONS: Exposure to illicit fentanyl was common among victims of violence in this single-center study. These patients are at increased risk of being admitted to intensive care units and repeated trauma center visits, suggesting fentanyl testing may help identify those who could benefit from violence prevention and substance abuse treatment.

Deep learning-based prediction of deliverable adaptive plans for MR-guided adaptive radiotherapy: A feasibility study.

Purpose: Fast and automated plan generation is desirable in radiation therapy (RT), in particular, for MR-guided online adaptive RT (MRgOART) or real-time (intrafractional) adaptive RT (MRgRART), to reduce replanning time. The purpose of this study is to investigate the feasibility of using deep learning to quickly predict deliverable adaptive plans based on a target dose distribution for MRgOART/MRgRART. Methods: A conditional generative adversarial network (cGAN) was trained to predict the MLC leaf sequence corresponding to a target dose distribution based on reference plan created prior to MRgOART using a 1.5T MR-Linac. The training dataset included 50 ground truth dose distributions and corresponding beam parameters (aperture shapes and weights) created during MRgOART for 10 pancreatic cancer patients (each with five fractions). The model input was the dose distribution from each individual beam and the output was the predicted corresponding field segments with specific shape and weight. Patient-based leave-one-out-cross-validation was employed and for each model trained, four (44 training beams) out of five fractionated plans of the left-out patient were set aside for testing purposes. We deliberately kept a single fractionated plan in the training dataset so that the model could learn to replan the patient based on a prior plan. The model performance was evaluated by calculating the gamma passing rate of the ground truth dose vs. the dose from the predicted adaptive plan and calculating max and mean dose metrics. Results: The average gamma passing rate (95%, 3mm/3%) among 10 test cases was 88%. In general, we observed 95% of the prescription dose to PTV achieved with an average 7.6% increase of max and mean dose, respectively, to OARs for predicted replans. Complete adaptive plans were predicted in ≤20 s using a GTX 1660TI GPU. Conclusion: We have proposed and demonstrated a deep learning method to generate adaptive plans automatically and rapidly for MRgOART. With further developments using large datasets and the inclusion of patient contours, the method may be implemented to accelerate MRgOART process or even to facilitate MRgRART.

20-year mortality after discharge in a cohort of 1,099 former trauma inpatients with and without substance use disorders.

INTRODUCTION: Psychoactive substance use disorders (SUDs) are common in trauma patients and substance use has become a leading cause of death in the United States. The purpose of this study is to examine the impact of a lifetime SUD and SUD characteristics (substance used, current SUD versus in remission from dependence, etc.) on the long-term survival of trauma patients. METHODS: Cohort study of consecutive adult trauma inpatients who were discharged alive from a level-one trauma center (1994-1996). The presence of lifetime SUD was determined at the time of admission by the Structured Clinical Interview for the Diagnostic and Statistical Manual III-R. Mortality follow-up through the end of 2017 was obtained by linking patients to a national database of death certificates. Cox proportional hazards analysis was used to determine the association of lifetime SUD and death after adjusting for age and tobacco use. RESULTS: 1,220 patients were approached, 1,118 consented to participate, and 1,099 had personal identifiers for matching. 789 (71.8%) of subjects were men, 596 (54.2%) had lifetime SUDs, and 325 (29.6%) died. Injury was the most common cause of death (24.6%, 80/325), with poisonings (40.0%, 32/80) being the most common injury-related cause of death. Compared to those without a lifetime SUD, lifetime SUD was associated with increased all-cause mortality (adjusted hazard ratio [HRadj]=1.83; 95% CI, 1.4 to 2.4), injury death (HRadj=2.47; 95% CI: 1.4 to 4.2), and fatal opioid overdose (HRadj=12.96; 95% CI, 1.7 to 100.4)(p ≤ 0.01 for all HRadj). CONCLUSIONS: The presence of a lifetime SUD was associated with early death, particularly from reinjury, in trauma patients. It is important to address a patient's SUD during admission to decrease their chances of dying after discharge, especially due to injury-related causes.

250 MHz Rapid Scan Cross Loop Resonator.

A 25 mm diameter 250 MHz crossed-loop resonator was designed for rapid scan electron paramagnetic resonance imaging. It has a saddle coil for the driven resonator and a fine wire, loop gap resonator for the sample resonator. There is good separation of E and B fields and high isolation between the two resonators, permitting a wide range of sample types to be measured. Applications to imaging of nitroxide, trityl, and LiPc samples illustrate the utility of the resonator. Using this resonator and a trityl sample the signal-to-noise of a rapid scan absorption spectrum is about 20 times higher than for a first-derivative CW spectrum.

Background correction in rapid scan EPR spectroscopy.

In rapid scan EPR the rapidly-changing magnetic field induces a background signal that may be larger than the EPR signal. A method has been developed to correct for that background signal by acquiring two sets of data, denoted as scan 1 and scan 2. In scan 2 the external field B0 is reversed and the data acquisition trigger is offset by one half cycle of the scan field relative to the settings used in scan 1. For data acquired with a cross-loop resonator subtraction of scan 2 from scan 1 cancels the background and enhances the EPR signal. Experiments were performed at an EPR frequency of about 258 MHz, which is in the range that is commonly used for in vivo imaging. Samples include nitroxide radicals, a trityl radical, a dinitroxide, and a nitroxide in the presence of a magnetic field gradient. This method has the advantage that no assumption is made about the shape of the background signal, and it provides an approach to automating the background correction.

Definitive Wound Closure Techniques in Fournier's Gangrene.

Necrotizing soft tissue infection of the perineum, or Fournier's gangrene (FG), is a morbid and mortal diagnosis. Despite the severity of FG, the optimal definitive wound closure strategy is unknown, as are long-term wound outcomes. A retrospective review was performed over a 3-year period at a single trauma center. Patients were managed according to our institutional approach focusing on primary wound closure and secondary intention healing in residual wounds. Overall 168 patients were included. Complete primary wound closure was accomplished in 39.9 per cent of patients. Patients undergoing primary wound closure were primarily male (89.6 vs 64.4%, P < 0.001), had lower mean sequential organ failure assessment (SOFA) scores (1.70 ± 2.30 vs 2.98 ± 3.36, P = 0.004), more often had perineum-limited FG (67.2 vs 42.6%, P = 0.003), and required fewer debridements (2.40 vs 2.79, P = 0.02). On logistic regression, predictors of primary closure included gender (odds ratio 4.643, 95% confidence interval 1.885-11.437, P = 0.001) and SOFA score (odds ratio 0.834, 95% confidence interval 0.727-0.957, P = 0.01). Wound healing rates increased over time, to an 82.1 per cent wound healing rate without further intervention at greater than six months of follow-up. Wounds healed with secondary intention ranged from 70 to 9520 cm3 and primary closure ranged from 126 to 6912 cm3, whereas wounds requiring skin grafts ranged from 405 to 16,170 cm3. Complete primary wound closure is often achievable in FG patients. Using this standardized approach to FG wound management, even large wounds and wounds undergoing secondary intention healing will often close with long-term wound care and do not require flap creation or early skin grafting.

Tabletop 700 MHz electron paramagnetic resonance imaging spectrometer.

Low frequency electron paramagnetic resonance imaging is a powerful tool to non-invasively measure the physiological status of tumors. Here, we report on the design and functionality of a rapid scan and pulse table-top imaging spectrometer based around an arbitrary waveform generator and 25mm cross-loop resonator operating at 700 MHz. Two and four-dimensional rapid scan spectral-spatial images are presented. This table-top imager is a prototype for future pre-clinical imagers.

An X-Band Crossed-Loop EPR Resonator.

A copper X-band (9.22 GHz) cross loop resonator has been constructed for use with 4 mm sample tubes. The Q for the two resonators are 380 and 350, respectively. The resonator efficiency is about 1 G per square root of watt. Operation has been demonstrated with measurement of T1 by saturation recovery for samples of coal and an immobilized nitroxide radical.

Triarylmethyl Radical OX063d24 Oximetry: Electron Spin Relaxation at 250 MHz and RF Frequency Dependence of Relaxation and Signal-to-Noise.

The triarylmethyl radical OX063d24 is currently used for pulsed electron paramagnetic resonance oximetry at 250 MHz. Both 1/T 1 and 1/T 2 increase with increasing oxygen concentration. The dependence of 1/T 1 on probe concentration is smaller than for 1/T 2. To inform the selection of the optimum frequency for in vivo oximetry 1/T 1, 1/T 2 and signal-to-noise were measured as a function of frequency between 400 and 1000 MHz on a variable-frequency spectrometer with an adjustable-frequency cross-loop resonator. 1/T 1 and 1/T 2 decrease with increasing frequency and signal-to-noise increases with increasing frequency, which are all favourable for imaging at higher frequencies. However, depth of penetration of the radio frequency (RF) into an animal decreases with increasing frequency. Assuming that the RF loss in the animal to be studied determines the resonator Q, our results indicate that the optimum frequency for in vivo imaging will be determined by the desired depth of penetration in the tissue.

Rapid-scan EPR imaging.

In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250MHz.

Triarylmethyl Radical: EPR Signal to Noise at Frequencies between 250 MHz and 1.5 GHz and Dependence of Relaxation on Radical and Salt Concentration and on Frequency.

In vivo oximetry by pulsed electron paramagnetic resonance is based on measurements of changes in electron spin relaxation rates of probe molecules, such as the triarylmethyl radicals. A series of experiments was performed at frequencies between 250 MHz and 1.5 GHz to assist in the selection of an optimum frequency for oximetry. Electron spin relaxation rates for the triarylmethyl radical OX063 as a function of radical concentration, salt concentration, and resonance frequency were measured by electron spin echo 2-pulse decay and 3-pulse inversion recovery in the frequency range of 250 MHz-1.5 GHz. At constant OX063 concentration, 1/T1 decreases with increasing frequency because the tumbling dependent processes that dominate relaxation at 250 MHz are less effective at higher frequency. 1/T2 also decreases with increasing frequency because 1/T1 is a significant contribution to 1/T2 for trityl radicals in fluid solution. 1/T2-1/T1, the incomplete motional averaging contribution to 1/T2, increases with increasing frequency. At constant frequency, relaxation rates increase with increasing radical concentration due to contributions from collisions that are more effective for 1/T2 than 1/T1. The collisional contribution to relaxation increases as the concentration of counter-ions in solution increases, which is attributed to interactions of cations with the negatively charged radicals that decrease repulsion between trityl radicals. The Signal-to-Noise ratio (S/N) of field-swept echo-detected spectra of OX063 were measured in the frequency range of 400 MHz-1 GHz. S/N values, normalized by √Q, increase as frequency increases. Adding salt to the radical solution decreased S/N because salt lowers the resonator Q. Changing the temperature from 19 to 37 °C caused little change in S/N at 700 MHz. Both slower relaxation rates and higher S/N at higher frequencies are advantageous for oximetry. The potential disadvantage of higher frequencies is the decreased depth of penetration into tissue.

Resonators for In Vivo Imaging: Practical Experience.

Resonators for preclinical electron paramagnetic resonance imaging have been designed primarily for rodents and rabbits and have internal diameters between 16 and 51 mm. Lumped circuit resonators include loop-gap, Alderman-Grant, and saddle coil topologies and surface coils. Bimodal resonators are useful for isolating the detected signal from incident power and reducing dead time in pulse experiments. Resonators for continuous wave, rapid scan, and pulse experiments are described. Experience at the University of Chicago and University of Denver in design of resonators for in vivo imaging is summarized.

Systematic review and meta-analysis of randomised controlled trials on the effects of potassium supplements on serum potassium and creatinine.

OBJECTIVES: High potassium intake could prevent stroke, but supplementation is considered hazardous. We assessed the effect of oral potassium supplementation on serum or plasma potassium levels and renal function. SETTING: We updated a systematic review of the effects of potassium supplementation in randomised clinical trials carried out worldwide, published in 2013, extending it to July 2015. We followed the PRISMA guidelines. PARTICIPANTS: Any individual taking part in a potassium supplementation randomised clinical trial. Studies included met the following criteria: randomised clinical trials, potassium supplement given and circulating potassium levels reported. INTERVENTION: Oral potassium supplementation. PRIMARY OUTCOME MEASURES: Serum or plasma potassium and serum or plasma creatinine. RESULTS: A total of 20 trials (21 independent groups) were included (1216 participants from 12 different countries). All but 2 were controlled (placebo n=16, control n=2). Of these trials, 15 were crossover, 4 had a parallel group and 1 was sequential. The duration of supplementation varied from 2 to 24 weeks and the amount of potassium given from 22 to 140 mmol/day. In the pooled analysis, potassium supplementation caused a small but significant increase in circulating potassium levels (weighted mean difference (WMD) 0.14 mmol/L, 95% CI 0.09 to 0.19, p<1×10(-5)), not associated with dose or duration of treatment. The average increase in urinary potassium excretion was 45.75 mmol/24 hours, 95% CI 38.81 to 53.69, p<1×10(-5). Potassium supplementation did not cause any change in circulating creatinine levels (WMD 0.30 µmol/L, 95% CI -1.19 to 1.78, p=0.70). CONCLUSIONS: In short-term studies of relatively healthy persons, a moderate oral potassium supplement resulted in a small increase in circulating potassium levels and no change in renal function.

Evaluation of multi-echo ICA denoising for task based fMRI studies: Block designs, rapid event-related designs, and cardiac-gated fMRI.

Multi-echo fMRI, particularly the multi-echo independent component analysis (ME-ICA) algorithm, has previously proven useful for increasing the sensitivity and reducing false positives for functional MRI (fMRI) based resting state connectivity studies. Less is known about its efficacy for task-based fMRI, especially at the single subject level. This work, which focuses exclusively on individual subject results, compares ME-ICA to single-echo fMRI and a voxel-wise T2(⁎) weighted combination of multi-echo data for task-based fMRI under the following scenarios: cardiac-gated block designs, constant repetition time (TR) block designs, and constant TR rapid event-related designs. Performance is evaluated primarily in terms of sensitivity (i.e., activation extent, activation magnitude, percent detected trials and effect size estimates) using five different tasks expected to evoke neuronal activity in a distributed set of regions. The ME-ICA algorithm significantly outperformed all other evaluated processing alternatives in all scenarios. Largest improvements were observed for the cardiac-gated dataset, where ME-ICA was able to reliably detect and remove non-neural T1 signal fluctuations caused by non-constant repetition times. Although ME-ICA also outperformed the other options in terms of percent detection of individual trials for rapid event-related experiments, only 46% of all events were detected after ME-ICA; suggesting additional improvements in sensitivity are required to reliably detect individual short event occurrences. We conclude the manuscript with a detailed evaluation of ME-ICA outcomes and a discussion of how the ME-ICA algorithm could be further improved. Overall, our results suggest that ME-ICA constitutes a versatile, powerful approach for advanced denoising of task-based fMRI, not just resting-state data.

The effect of acute pre-workout supplementation on power and strength performance.

BACKGROUND: Consumption of pre-workout dietary supplements by both recreational and competitive athletes has increased dramatically in recent years. The purpose of this study was to determine the acute effects of a caffeine-containing pre-workout dietary supplement on various measures of performance including anaerobic power, upper and lower body power, and upper body strength in recreationally trained males. METHODS: Thirteen males (mean ± SD age = 24 ± 6 yrs; height = 180.3 ± 5 cm; body mass = 83.4 ± 9 kg) participated in this investigation in which they reported to the laboratory on four separate occasions, each separated by one week. Each subject underwent an initial familiarization session on week one followed by baseline (BA) performance testing on week two. Performance testing included a medicine ball put (MBP) to determine upper body explosive power, vertical jump test (VJ) to determine lower body explosive power, one-rep maximum bench press (1-RM) for determining upper body strength, and a Wingate Anaerobic Power Test (WAnT) to determine measures of anaerobic power. On week three, subjects were randomly assigned to ingest either a pre-workout supplement (SUP) or a placebo (PL) and again complete the performance testing protocol. Subjects were provided with the crossover treatment on the fourth and final week. Performance testing commenced 20-minute following ingestion of both treatments, which was similar to previous investigations. RESULTS: Significant differences in anaerobic peak power relative to the WAnT were observed following ingestion of the SUP (782 ± 191 W) in comparison to the PL (722 ± 208 W; p = 0.003; effect size = 0.30) and BA (723 ± 205 W; p = 0.011; effect size = 0.28). Significant differences were also observed for anaerobic mean power following ingestion of the SUP (569 ± 133 W) in comparison to the PL (535 ± 149 W; p = 0.006; effect size = 0.24) and BA (538 ± 148 W; p = 0.020; effect size = 0.22). No significant differences between trials were observed for upper body power, lower body power, or upper body strength. CONCLUSIONS: Ingestion of the pre-workout dietary supplement led to significant improvements in anaerobic peak and mean power values in comparison to the placebo and baseline treatments. No improvements were observed in upper and lower body power or upper body strength. Taken prior to exercise, a caffeine-containing pre-workout dietary supplement may improve anaerobic power performance.

The effects of a fat loss supplement on resting metabolic rate and hemodynamic variables in resistance trained males: a randomized, double-blind, placebo-controlled, cross-over trial.

BACKGROUND: While it is known that dietary supplements containing a combination of thermogenic ingredients can increase resting metabolic rate (RMR), the magnitude can vary based on the active ingredient and/or combination of active ingredients. The purpose of this study was to examine the effects of a commercially available thermogenic fat loss supplement on RMR and hemodynamic variables in healthy, resistance trained males. METHODS: Ten resistance-trained male participants (29 ± 9 years; 178 ± 4 cm; 85.7 ± 11 kg, and BMI = 26.8 ± 3.7) volunteered to participate in this randomized, double-blind, placebo controlled cross-over study. Participants underwent two testing sessions separated by at least 24 h. On their first visit, participants arrived to the laboratory after an overnight fast and a 24-h avoidance of exercise, and underwent a baseline RMR, HR, and BP assessment. Next, each participant ingested a thermogenic fat loss supplement (TFLS) or a placebo (PLA) and repeated the RMR, HR, and BP assessments at 60, 120, and 180 min post-ingestion. During the second visit the alternative supplement was ingested and the assessments were repeated in the exact same manner. Data were analyzed via a 2-factor [2x4] within-subjects repeated measures analysis of variance (ANOVA). Post-hoc tests were analyzed via paired samples t-tests. The criterion for significance was set at p ≤ 0.05. RESULTS: A significant main effect for time relative to raw RMR data (p = 0.014) was observed. Post-hoc analysis revealed that the TFLS significantly increased RMR at 60-min, 120-min, and 180-min post ingestion (p < 0.05) as compared to baseline RMR values. No significant changes in RMR were observed for the PLA treatment (p > 0.05). Specifically, RMR was increased by 7.8 % (from 1,906 to 2,057 kcal), 6.9 % (from 1,906 to 2,037 kcal), and 9.1 % (from 1,906 to 2,081 kcal) in the TFLS, while the PLA treatment increased RMR by 3.3 % (from 1,919 to 1,981 kcal), 3.1 % (from 1,919 to 1,978 kcal), and 2.1 % (from 1,919 to 1,959 kcal) above baseline at 60, 120, and 180-min post ingestion, respectively. Additionally, the TFLS significantly elevated RMR at the 3-h time point as compared to the PLA treatment (2,081 vs 1,959 kcal, p = 0.034). A main effect for groups was observed for systolic blood pressure, and a significant interaction and main effect for time were observed for diastolic blood pressure. It should be noted that although changes in diastolic blood pressure were significant, all values stayed within normal clinical ranges (<80 mmHg). CONCLUSIONS: The TFLS led to significant elevations in RMR as compared to baseline. These elevations came with no adverse effect relative to resting heart rate, but a slight increase in blood pressure values. Taken on a daily basis, this TFLS may increase an individual's overall energy expenditure, however; future studies should investigate if this leads to a reduction in fat mass loss over time.

The effects of a single-dose thermogenic supplement on resting metabolic rate and hemodynamic variables in healthy females--a randomized, double-blind, placebo-controlled, cross-over trial.

BACKGROUND: Recent investigations have identified that commercially available dietary supplements, containing a combination of thermogenic ingredients, can increase resting metabolic rate (RMR). Thermogenic dietary supplements can have a positive influence on RMR, but the magnitude can vary based on the active ingredient and/or combination of active ingredients. Additionally, further safety evaluation is needed on multi-ingredient supplements that contain caffeine, due to its potential effect on heart rate (HR) and blood pressure (BP). The purpose of this study was to examine the effects of a commercially available dietary supplement on RMR and hemodynamic variables in healthy females. METHODS: 13 female participants (26.1 ± 11.3 years; 163.4 ± 9.1 cm; 63.7 ± 8.0 kg, and 24 ± 5 BMI) volunteered to participate in this investigation. Participants underwent two testing sessions separated by approximately 7 days. On their first visit, participants arrived to the laboratory after an overnight fast and underwent a baseline RMR, HR, and BP assessment. Next, each participant ingested a thermogenic dietary supplement or placebo and repeated the RMR, HR, and BP assessments at 60, 120, and 180-minutes post-ingestion. Approximately 1-week later, the alternative supplement was ingested and the assessments were repeated in the exact same manner. Data were analyzed via a 2-factor [2x4] within-subjects repeated measures analysis of variance (ANOVA). Post-hoc tests were analyzed via paired samples t-tests. RESULTS: Repeated measures ANOVA revealed a significant effect for time relative to raw RMR data. Post-hoc analysis revealed that the dietary supplement treatment significantly increased RMR at 60-minutes, 120-minutes, and 180-minutes post ingestion (p < 0.05) as compared to baseline RMR values. No changes in RMR were observed for the placebo treatment (p > 0.05). Heart rate was not significantly affected at any time point with either supplement; however, main effects of treatment and time were observed for both systolic and diastolic blood pressure (p < 0.05). CONCLUSIONS: The thermogenic dietary supplement treatment experienced greater elevations in RMR as compared to baseline. Due to the slight elevations in blood pressure, caution should be taken for those with increased risk for hypertension or pre-hypertension. Taken on a daily basis, thermogenic dietary supplementation may increase overall energy expenditure, potentially leading to reductions in fat mass over time.

Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation.

Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12-week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%-90%). Four patients relapsed, but no on-treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child-Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12-week RBV-free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635-643 2016 AASLD.

UHF EPR spectrometer operating at frequencies between 400 MHz and 1 GHz.

A spectrometer was designed and constructed to facilitate measurements of T1, T2, spin echo signal-to-noise, and resonator quality factor, Q, between about 400 and 1000 MHz. Pulse patterns are generated at 250 MHz and mixed with the output from a second source to perform excitation and detection. A cross-loop resonator was constructed in which the same sample could be measured in the same resonator over the full range of frequencies. An air-core, 4-coil, water-cooled electromagnet with a large experimental volume was built.

Imaging disulfide dinitroxides at 250 MHz to monitor thiol redox status.

Measurement of thiol-disulfide redox status is crucial for characterization of tumor physiology. The electron paramagnetic resonance (EPR) spectra of disulfide-linked dinitroxides are readily distinguished from those of the corresponding monoradicals that are formed by cleavage of the disulfide linkage by free thiols. EPR spectra can thus be used to monitor the rate of cleavage and the thiol redox status. EPR spectra of (1)H,(14)N- and (2)H,(15)N-disulfide dinitroxides and the corresponding monoradicals resulting from cleavage by glutathione have been characterized at 250 MHz, 1.04 GHz, and 9 GHz and imaged by rapid-scan EPR at 250 MHz.