Wilcoxon Matched-pairs Signed-rank Test Research Articles

A Bayesian estimation method for cerebral blood flow measurement by area-detector CT perfusion imaging.

Bayesian estimation with advanced noise reduction (BEANR) in CT perfusion (CTP) could deliver more reliable cerebral blood flow (CBF) measurements than the commonly used reformulated singular value decomposition (rSVD). We compared the efficacy of CBF measurement by CTP using BEANR and rSVD, evaluating both relative to N-isopropyl-p-[(123) I]- iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT) as a reference standard, in patients with cerebrovascular disease. Thirty-one patients with suspected cerebrovascular disease underwent both CTP on a 320 detector-row CT system and SPECT. We applied rSVD and BEANR in the ischemic and contralateral regions to create CBF maps and calculate CBF ratios from the ischemic side to the healthy contralateral side (CBF index). The analysis involved comparing the CBF index between CTP methods and SPECT using Pearson's correlation and limits of agreement determined with Bland-Altman analyses, before comparing the mean difference in the CBF index between each CTP method and SPECT using the Wilcoxon matched pairs signed-rank test. The CBF indices of BEANR and 123I-IMP SPECT were significantly and positively correlated (r = 0.55, p < 0.0001), but there was no significant correlation between the rSVD method and SPECT (r = 0.15, p > 0.05). BEANR produced smaller limits of agreement for CBF than rSVD. The mean difference in the CBF index between BEANR and SPECT differed significantly from that between rSVD and SPECT (p < 0.001). BEANR has a better potential utility for CBF measurement in CTP than rSVD compared to SPECT in patients with cerebrovascular disease.

Assessing the Impact of Changes to USMLE Step 1 Grading on Evaluation of Neurosurgery Residency Applicants in the United States: A Program Director Survey

Neurosurgery (NS) is among the most selective specialties in the United States. As the United States Medical Licensing Examination (USMLE) Step 1 transitions to a binary pass/fail score, residency programs face unclear challenges in screening and evaluating applicants. The aim of this study is to provide insights into the perceived impact of changes to the USMLE Step 1 grading in the applicant selection process. We created a survey using questions regarding NS program demographics, the perceived predictive abilities of Step 1 and Step 2 clinical knowledge (CK), and several factors that programs consider when assessing applicants. We queried program directors (PDs), program coordinators (PCs), and assistant PDs at 117 NS residency programs. Respondents were asked to rank these factors in order of importance for selection at their respective training program. We used descriptive statistics and a Wilcoxon matched-pairs signed-rank test to evaluate the effects of these changes using STATA17. A total of 35 (30%) residency programs responded with 26 (74%) completing the factor ranking questions. 86% (95% confidence interval, 71.5%-94.3%) disagreed that the changes will better prepare students clinically. USMLE Step 2 CK scores, class rank, and away rotations saw significant increases in priority in the absence of a graded Step 1, whereas letters of recommendation and surrogates for research productivity saw notable, but not significant, changes after adjusting for multiple testing. Reporting binary Step 1 grades marks a significant shift in assessing applicants for NS residency by emphasizing Step 2 CK, class rank, and research productivity.

Respiratory Sinus Arrhythmia is Mainly Driven by Central Feedforward Mechanisms in Healthy Humans.

Heart rate variability (HRV) has prognostic and diagnostic potential, however, the mechanisms behind respiratory sinus arrhythmia (RSA), a main short-term HRV, are still not well understood. We investigated if the central feedforward mechanism or pulmonary stretch reflex contributed most to RSA in healthy humans. Ventilatory support reduces the centrally mediated respiratory effort but remains the inspiratory stretch of the pulmonary receptors. We aimed to quantify the difference in RSA between spontaneous breathing and ventilatory support. Nineteen healthy, young subjects underwent spontaneous breathing and non-invasive intermittent positive pressure ventilation (NIV) while we recorded heart rate (HR, from ECG), mean arterial pressure (MAP) and stroke volume (SV) estimated from the non-invasive finger arterial pressure curve, end-tidal CO2 (capnograph), and respiratory frequency (RF) with a stretch band. Variability was quantified by an integral between 0.15–0.4 Hz calculated from the power spectra. Median and 95% confidence intervals (95%CI) were calculated as Hodges–Lehmann’s one-sample estimator. Statistical difference was calculated by the Wilcoxon matched-pairs signed-rank test. RF and end-tidal CO2 were unchanged by NIV. NIV reduced HR by 2 bpm, while MAP and SV were unchanged in comparison to spontaneous breathing. Variability in both HR and SV was reduced by 60% and 75%, respectively, during NIV as compared to spontaneous breathing, but their interrelationship with respiration was maintained. NIV reduced RSA through a less central respiratory drive, and pulmonary stretch reflex contributed little to RSA. RSA is mainly driven by a central feedforward mechanism in healthy humans. Peripheral reflexes may contribute as modifiers of RSA.

Functional Medicine Approach to Patient Care Improves Sleep, Fatigue, and Quality of Life in Patients With Inflammatory Bowel Disease.

A Functional Medicine program was developed at an inflammatory bowel disease (IBD) center with the goal of integrating strategies to address modifiable lifestyle factors and to complete a 6-week elimination diet under the direction of a trained Functional Medicine dietitian and Functional Medicine providers. From January 2019 to November 2019, patients with controlled, but persistent, symptoms from IBD were offered enrollment. Each of the 5 visits incorporated an educational session focused on nutrition followed by a session focusing on modifiable lifestyle factors. The patients were placed on a supervised 6-week elimination diet. At each visit, patients completed the SIBDQ (Short Inflammatory Bowel Disease Questionnaire), FSS (Fatigue Severity Scale), PSQI (The Pittsburgh Sleep Quality Index), and MSQ (Medical Symptoms Questionnaire). Statistical analysis was performed using the Wilcoxon matched pairs signed-rank test. Nineteen patients enrolled (2 men: 1 ulcerative colitis [UC], 1 Crohn's disease [CD]; 17 women: 3 UC, 14 CD). 15 patients completed all modules. There was improvement in all patient-reported outcomes (PROs) (FSS, P < .001; PSQI, P < .001; SIBDQ, P < .001; MSQ, P < .001). Every patient who completed the last session demonstrated weight loss. The psychoemotional roots to immune disease states, particularly IBD, are complicated and often not addressed in traditional care. We are just beginning to understand the impact of nutrition, sleep, stress, movement, and relationships on IBD. In this cohort, utilizing Functional Medicine as an adjunct to traditional care resulted in improvement in all PROs.

Cardiac Effort to Compare Clinic and Remote 6-Minute Walk Testing in Pulmonary Arterial Hypertension

BackgroundThe SARS-CoV-2 pandemic has limited objective physiologic assessments. A standardized remote alternative is not currently available. “Cardiac effort” (CE), that is, the total number of heart beats divided by the 6-min walk test (6MWT) distance (beats/m), has improved reproducibility in the 6MWT and correlated with right ventricular function in pulmonary arterial hypertension.Research QuestionCan a chest-based accelerometer estimate 6MWT distance remotely? Is remote cardiac effort more reproducible than 6MWT distance when compared with clinic assessment?Study Design and MethodsThis was a single-center, prospective observational study, with institutional review board approval, completed between October 2020 and April 2021. Group 1 subjects with pulmonary arterial hypertension, receiving stable therapy for > 90 days, completed four to six total 6MWTs during a 2-week period to assess reproducibility. The first and last 6MWTs were performed in the clinic; two to four remote 6MWTs were completed at each participant’s discretion. Masks were not worn. BioStamp nPoint sensors (MC10) were worn on the chest to measure heart rate and accelerometry. Two blinded readers counted laps, using accelerometry data obtained on the clinic or user-defined course. Averages of clinic variables and remote variables were used for Wilcoxon matched-pairs signed rank tests, Bland-Altman plots, or Spearman correlation coefficients.ResultsEstimated 6MWT distance, using the MC10, correlated strongly with directly measured 6MWT distance (r = 0.99; P < .0001; in 20 subjects). Remote 6MWT distances were shorter than clinic 6MWT distances: 405 m (330-464 m) vs 389 m (312-430 m) (P = .002). There was no difference between in-clinic and remote CE: 1.75 beats/m (1.48-2.20 beats/m) vs 1.86 beats/m (1.57-2.14 beats/m) (P = .14).InterpretationRemote 6MWT was feasible on a user-defined course; 6MWT distance was shorter than clinic distance. CE calculated by chest heart rate and accelerometer-estimated distance provides a reproducible remote assessment of exercise tolerance, comparable to the clinic-measured value.

Abstract 1289: Systemic immune response of prostate cancer patients to alpha-emitting radiotherapy

Abstract Targeted alpha therapy (TAT) is a type of radiotherapy (RT) that uses alpha-emitting radionuclides. These radionuclides have a natural affinity for areas of bone metastases (i.e., radium-223, Ra-223) or can label specific tumour targets (i.e., prostate-specific membrane antigen). Conventional photon irradiation (i.e., external beam) can activate or suppress immune responses. The resulting immune response is dictated by the release of soluble markers such as cytokines (i.e., IL-6) and damage associated molecular patterns, DAMPs (calreticulin). Less is known about the immune response induced by alpha-emitters. With increased interest in using TAT for cancer patients, it is important to gain a more in depth knowledge regarding the immune response of alpha emitters. Aim: Explore the systemic immune response of prostate cancer (PCa) patients to alpha-emitting RT by studying circulating cytokines, checkpoint molecules, matrix metalloproteinases (MMPs) and DAMPs. Methods: The cohort comprised of 43 patients with metastatic castration-resistant PCa treated with up to six four-weekly injections of the alpha emitter, Ra-223. We measured longitudinal changes in 61 plasma markers using the Luminex assay. The plasma markers included cytokines, checkpoint molecules and DAMPs. Results: Ra-223 induced longitudinal changes in 14 plasma markers over the course of treatment (T2-T6) compared with pre-treatment levels (T1). Most of the observed RT-induced changes occurred after four injections of Ra-223 (T5), where 9 of the 14 plasma markers changed significantly. The table summarises T5 findings (presented as mean concentration, pg/ml; statistical analysis using Wilcoxon matched-pairs signed rank test). Conclusion: Our data demonstrates that alpha-emitting RT induces systemic immune responses that can be measured in the plasma of patients. Given the diverse role of these markers, further study is needed to explore the biological implications of these systemic changes on patient outcome. Changes in plasma markers in patients treated with Ra-223 T1 T5 P value IL-8 6.7±0.9 9.7±1.3 0.0009 IL-2R 293.5±42.9 364.5±69.7 0.0247 IP-10 18.4±2.3 21.8±2.5 0.0243 RANTES 2668.8±173.4 2944.7±164.6 0.0455 BTLA 549.9±153.5 527.7±265.2 0.0319 CD137 49.6±8.9 39.1±13.5 0.0099 Calreticulin 7868±3514.9 9238.4±808.5 0.0386 RAGE 63.9±4.7 52.3±5.1 0.0014 MMP1 66.1±7.5 84.9±12.6 0.0245 Citation Format: Sapna Lunj, Hitesh Mistry, YeePei Song, Kamlesh Patel, Hannah Nightingale, Tim Smith, Peter Hoskin, Catharine West, Ananya Choudhury. Systemic immune response of prostate cancer patients to alpha-emitting radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1289.

Sofosbuvir-based direct-acting antivirals and changes in cholesterol and low density lipoprotein-cholesterol

Worsened lipid profiles were observed in chronic hepatitis C (CHC) patients during direct-acting antivirals (DAAs) treatment, among which combination drugs confounded the effect of individual ingredient on lipid. Tenofovir alafenamide (TAF) also worsened lipid profiles in HIV patients. Structural similarity between sofosbuvir (SOF) and TAF prompted us to investigate rapid increase in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in CHC patients treated with SOF-based DAAs. A retrospective study was performed to analyze 487 CHC patients receiving DAAs with SVR12. Relative risks on elevating TC and LDL-C were analyzed by logistic regression to determine SOF-based over non-SOF-based regimens. TC or LDL-C levels at baseline, week-4 and SVR12 were compared by Wilcoxon matched-pairs signed rank test. Week 4 or SVR12 to baseline ratios of serum TC or LDL-C between regimens were compared by Mann–Whitney's test. 487 patients were treated with Harvoni (SOF-based, 206 patients), Epclusa (SOF-based, 124 patients), Maviret (non-SOF-based, 122 patients), or Zepatier (non-SOF-based, 35 patients). At week 4 during drug treatment, Harvoni, Epclusa, and Maviret induced statistically significant elevation of TC and LDL-C, but Zepatier did not. SOF-based regimens had 2.72-fold higher relative risk (RR) causing 10% elevation of TC (95% CI 1.84–4.02, p < 0.001) and 2.04-fold higher RR causing 10% elevation of LDL-C (95% CI 1.39–3.01, p < 0.001) than non-SOF-based DAAs. SOF-based DAAs were associated with significantly larger amplitude of increases in TC and LDL-C than non-SOF-based DAAs during the initial 4 weeks of treatment, but the increases were not sustained to SVR12.

Relationship between IL-1β and IL-8 serum concentrations in patients with metastatic melanoma taking checkpoint inhibitors.

e21510 Background: Melanoma is a disease that is most often treated with immune checkpoint inhibitors (ICI). The principle mechanism of ICI is based on the activation of the antitumor immune response. This therapy is not effective in all patients, which may be due to the immunosuppressive effect of tumor microenvironment (TME). IL-1β is one of the most important participants in the TME, however, it is difficult to determine it in blood serum, in contrast to IL-8, the synthesis of which is induced by IL-1β. The study aims to determine the relationship between IL-1β and IL-8 in patients with metastatic (mts) melanoma and to reveal their diagnostic significance. Methods: The study involved 28 patients (pts) with mts melanoma taking ICI. The level of IL-1β and IL-8 in blood serum was determined using the ELISA method. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using Fisher, Mann-Whitney, ROC, Wilcoxon matched-pairs signed rank test, Spearman statistical analysis. Results: IL-1β was detected in 35.5% (11/31) of patients before therapy, while an elevated level was recorded in only one patient. IL-8 was found in all patients, an elevated level before therapy was observed in 64.5% (20/31) of cases, after 2-3 months - in 35.5% (11/31). During ICI therapy, a statistically significant decrease in the concentration of IL-1β (p = 0.0498) and IL-8 (p = 0.0002) were observed. In the presence of IL-1β, the level of IL-8 was statistically higher (139.6±65.26 pg/ml), p = 0.024, while a mean positive correlation was found between IL-1β and IL-8 concentrations (R = 0.6469, p = 0.035). According to ROC analysis (Area = 0.76), with an increase in the concentration of IL-8 more than 42.31 pg/ml with a diagnostic sensitivity of 66.67% and a specificity of 90.00%, it can be assumed that the level of IL-1β will be detected in the patient (p = 0.025). Conclusions: According to the study, with an IL-8 concentration of more than 42.31 pg/ml in patients with mts melanoma, the presence of IL-1β in the blood serum can be expected. At the same time, the level of IL-8 correlated with the level of IL-1β. It can be assumed that high level of IL-8 may indicate the overexpression IL-1β in TME and it`s high activity, which may be associated with the possible risk of low ICI efficacy.

Comparison of Estimated Late Toxicities between IMPT and IMRT Based on Multivariable NTCP Models for High-Risk Prostate Cancers Treated with Pelvic Nodal Radiation.

PurposeTo compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen.Materials and MethodsTwelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance.ResultsProton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT.ConclusionProton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.

The Effect of Mandibular Angulation on Preoperative Assessment of Dental Implant Insertion at Premolar Region: CBCT Study.

Backgrounds This study investigated the effect of mandibular angulation on the perioperative evaluation of the implant placement at the premolar region on panoramic reconstructed images using cone beam computed tomography (CBCT). Methods A total of six dried anonymous human mandibles was included. Two implants were inserted in the left and right first premolar region. CBCT scans were obtained from each mandible at the standard position, +20° extension, and -20° flexion. The distance of the implant from the anterior loop of the inferior alveolar nerve and mental foramen was measured. Mean absolute error (MAE) of the distance of the implant from both anatomical landmarks was measured. The Wilcoxon matched-pair signed-rank test was used for the comparison of the measurements. All data were analyzed with the Stata program (version 15.1). Results No statistically significant differences were found between the distance of the implant from the mental foramen and the anterior loop of the inferior alveolar nerve up to 20° extension and flexion at both sides of the mandible. (All p > 0.1) However, a variable range of MAE (SD) in the distance of the implant from different anatomical landmarks was found (0.9 ± 0.7 to 3.3 ± 2.1). Conclusions We found no statistical difference in measurements of the distance of the implant from two anatomical landmarks at different head positions up to 20° extension and flexion. However, clinically, variable range in the distance of the implant from anatomical landmarks should be considered. Our findings could alert dentists of the possibility of error up to 20° extension and flexion on the perioperative evaluation of dental implant placement.

Effectiveness and Utility of Virtual Reality Infection Control Simulation for Children With COVID-19: Quasi-Experimental Study.

BackgroundIt is essential that nurses quickly learn the proper methods for preventing and controlling nosocomial infection and managing intensive care patients during the COVID-19 pandemic, including the donning and doffing of personal protective equipment (PPE). Virtual reality (VR) simulation offers the advantage of learning in a safe environment with a sense of realism similar to that of an actual clinical setting and has been reported to enhance self-efficacy in infection control, safety performance, and learning satisfaction among students.ObjectiveThis study aims to develop a virtual reality infection control simulation (VRICS) program regarding donning and doffing of PPE and respiratory care for pediatric patients admitted to an isolation unit for COVID-19 and to identify the effects of the program on PPE knowledge, infection control performance, and self-efficacy for nursing students. Additionally, the realism of the VRICS program and the students’ level of satisfaction with the program were assessed.MethodsThis was a quasi-experimental study based on a controlled pretest-posttest design. Third- and fourth-year nursing students were divided into an experimental group (n=25) who participated in a VRICS program and a control group (n=25) with no participation. Data were collected from November 13 to December 10, 2021, and analyzed using descriptive statistics and the t test, paired t test, Mann-Whitney U test, and Wilcoxon matched-pair signed-rank test. The VRICS program consisted of a prebriefing, including direct practice of donning and doffing PPE, VR simulation, and debriefing. The VR simulation comprised 3 sessions: donning and inspection of PPE in the dressing room before entering the negative-pressure isolation unit; assessing for suction care, nasopharyngeal suctioning, and checking of COVID-19 patients in the negative-pressure isolation unit; and doffing PPE in the dressing room. The total execution time for the program was 180 min.ResultsCompared with the control group, the experimental group showed significantly greater improvements in PPE knowledge (z=–3.28, P<.001), infection control performance (t48=4.89, P<.001), and self-efficacy (t36.2=4.93, P<.001). The experimental group’s mean scores for realistic immersion and learner satisfaction were 4.49 (SD 0.50) points and 4.75 (SD 0.38) points (on a 5-point Likert scale), respectively.ConclusionsThe VR simulation training program involving pediatric COVID-19 patients combined skills training effectively and enhanced theoretical knowledge, respiratory care skills, and infectious disease preparedness. Thus, it could be applied to training nurses to respond more effectively to public health situations involving infectious diseases, including the COVID-19 pandemic.

Two-dimensional Versus Three-dimensional Registration for Image Fusion Technology

Image fusion technology allows for reduced operative time and radiation exposure during complex endovascular aortic operations. There are two approaches to register the preoperative computed tomography (CT) scan to the patient; either using two x-ray images (2D) or using a cone beam CT (three-dimensional [3D]). The goal of this study was to compare the accuracy of initial mask alignment as well as the duration of mask creation for 2D versus 3D registration. We performed a retrospective analysis of patients who underwent endovascular aortic aneurysm repair at our institution. Offline, we used VesselNavigator technology (Philips Healthcare, Best, the Netherlands) to re-register the patient's preoperative CT scan to the images stored from the procedure. We used an anterior-posterior image and a lateral image to register for the 2D approach and used a cone beam CT scan for the 3D registration. We then used the patient's initial aortogram to measure the distance from the aortogram to the mask for both 2D and 3D registration. We chose the inferior angle between bilateral renal arteries and aorta as the fiducial markers. Furthermore we measured the time for the two registration processes. We then used the Wilcoxon matched-pairs signed-rank test to compare the two populations. A total of 27 patients were evaluated, 12 patients underwent endovascular aneurysm repair, 9 fenestrated endovascular aneurysm repair, and 6 had a physician-modified endograft; 7 patients had a prior endovascular aneurysm repair. The median (Q1, Q3) difference between the aortogram and the virtual mask for 3D registration was 8 (4, 11) and for 2D was 14 (9, 23) (P < .001). Twenty-two patients had a more accurate registration with 3D image fusion. The 2D fusion on average was faster by 88 seconds (P < .001) where time to register was 107 seconds for 2D and 193 seconds for 3D registration. A 3D registration yields higher, unadjusted accuracy over the 2D registration, both in mean distances between aortogram and mask as well as frequency. This superior accuracy, is at the expense of a marginally longer registration time. Despite this added effort, we believe the 3D registration to be the preferred approach.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Impact of Bayesian penalized likelihood reconstruction on quantitative and qualitative aspects for pulmonary nodule detection in digital 2-[18F]FDG-PET/CT

To evaluate the impact of block sequential regularized expectation maximization (BSREM) reconstruction on quantitative and qualitative aspects of 2-[18F]FDG-avid pulmonary nodules compared to conventional ordered subset expectation maximization (OSEM) reconstruction method. Ninety-one patients with 144 2-[18F]FDG-avid pulmonary nodules (all ≤ 20 mm) undergoing PET/CT for oncological (re-)staging were retrospectively included. Quantitative parameters in BSREM and OSEM (including point spread function modelling) were measured, including maximum standardized uptake value (SUVmax). Nodule conspicuity in BSREM and OSEM images was evaluated by two readers. Wilcoxon matched pairs signed-rank test was used to compare quantitative and qualitative parameters in BSREM and OSEM. Pulmonary nodule SUVmax was significantly higher in BSREM images compared to OSEM images [BSREM 5.4 (1.2–20.7), OSEM 3.6 (0.7–17.4); p = 0.0001]. In a size-based analysis, the relative increase in SUVmax was more pronounced in smaller nodules (≤ 7 mm) as compared to larger nodules (8–10 mm, or > 10 mm). Lesion conspicuity was higher in BSREM than in OSEM (p < 0.0001). BSREM reconstruction results in a significant increase in SUVmax and a significantly improved conspicuity of small 2-[18F]FDG-avid pulmonary nodules compared to OSEM reconstruction. Digital 2-[18F]FDG-PET/CT reading may be enhanced with BSREM as small lesion conspicuity is improved.

Physiological Effects of Wearing N95 Respirator on Medical Staff During Prolong Work Hours in Covid-19 Departments.

The objective of the current study was to determine gas exchange abnormalities and physiological changes among healthcare workers during a 4-hour emergency department (ED) shift while wearing the N95 respirator. Single-center prospective observational study. Comparisons of paired measurements were performed using a non-parametric Wilcoxon matched-pairs signed-rank test. Results: Forty-one subjects were included. Prolonged N95 respirator use was associated with a significant decline in plasma pH (7.35 mmHg vs 7.34 mmHg, P = 0.02), PvO 2 (23.2 mmHg vs 18.6 mmHg, P < 0.001) and a concurrent increase in EtCO 2 (32.5 mmHg vs 38.5 mmHg, P < 0.0001). PvCO 2 and bicarbonate levels did not differ. No significant change was observed for heart rate or oxygen saturation. Using an N95 respirator for prolonged periods by healthcare professionals may provoke changes in gas exchange. The clinical significance of these changes remains to be determined.

MO247: Exogen ATP has a Suppressive Effect on CD4+-T-Cells In Aav-Patients And Healthy Controls

Abstract BACKGROUND AND AIMS Anti-neutrophil-cytoplasmatic-antibody-associated vasculitis (AAV) is a life-threatening autoimmune disease. It is a necrotizing vasculitis of small- and medium-sized vessels. T-cells play a pivotal role in pathogenesis and mediating damage in the vessels. Exogen ATP (adenosine triphosphate) is normally in a low nanomolar range. Under inflammatory conditions, various cells can release ATP to the extracellular department. In this case, ATP is a DAMP (damage-associated molecular pattern), but its effect on disease mechanisms in AAV is not well understood. It is the aim of the study to determine the effect of exogenous ATP on T-cells in healthy controls and AAV-patients. METHOD A total of 22 AAV-patients in remission and 13 healthy controls were recruited. Peripheral blood mononuclear cells (PBMC) were isolated and then labeled with a tracking dye. The PBMC were cultured for 3 days with different concentrations of ATP in presence or absence of anti-CD3/CD28 stimulation. After 3 days, the cells were restimulated with PMA/Ionomycin and Brefeldin A for 4 hours. Cytokine production and cell proliferation were assessed by flow cytometry. Baseline was defined as T-cell proliferation in absence of exogenous ATP. The fold change was calculated by: $\frac{{{\rm{T}} - {\rm{cell\ proliferation\ with\ ATP}}}}{{{\rm{T}} - {\rm{cell\ proliferation\ without\ ATP}}}}$ . The P-value for paired values was calculated by the Wilcoxon matched-pairs signed rank test. The P-value for unpaired groups was calculated by the Mann Whitney U-test. RESULTS The mean T-cell proliferation of CD4+-T-cells for healthy controls was significantly different comparing 0 µM ATP and 500 µM ATP (mean proliferated fraction, 0 µM ATP versus 500 µM ATP: 40.48% versu 22.58%, P = .0002). In presence of ATP, a suppression of T-cell proliferation was found in patients and healthy controls (patients versus healthy controls, fold change T-cell proliferation from baseline with 50 µM ATP: 0.81 ± 0.03 versus 0.79 ± 0.03, P = .60; 125 µM ATP: 0.75 ± 0.03 versus 0.70 ± 0.04, P = .38; 250 µM ATP: 0.68 ± 0.03 versus 0.59 ± 0.05, P = .17; 500 µM ATP: 0.53 ± 0.03 versus 0.54 ± 0.05, P = .77); the higher the concentration of ATP, the stronger the suppression of proliferation. IFNγ+-CD4+-T-cells of healthy controls were also suppressed by exogenous ATP (0 µM ATP versus 500 µM ATP, CD4+ T-cells: %IFNγ+: 19.94% versus 10.59%, P = .0002). INFγ production by CD4+-T-cells was reduced after addition of ATP in both patients and healthy controls (patients versus healthy controls, fold change CD4+-IFNγ+ -T-cells from baseline with 50 µM ATP: 0.69 ± 0.04 versus 0.64 ± 0.04, P = 0.45; 125 µM ATP: 0.62 ± 0.04 versus 0.58 ± 0.04, P = .63; 250 µM ATP: 0.62 ± 0.04 versus 0.49 ± 0.04, P = .11; 500 µM ATP: 0.59 ± 0.05 versus 0.51 ± 0.05, P = .56). CONCLUSION Exogenous ATP induced suppression of T-cells in healthy controls and might be important for the maintenance of immunotolerance. DAMP-mediated inhibitory mechanisms were functional in AAV-patients in remission.

MO161: Comparison of Therapeutic Plasma Exchange with Centrifugation and Filter Technique with a Focus on Efficacy, Safety, Platelet Loss and Patients' Comfort

Abstract BACKGROUND AND AIMS Therapeutic plasma exchange (TPE) is an established therapy in the treatment of various immunologic kidney and neurological diseases. Humoral factors as antibodies, complement factors, cytokines and immune complexes, which all are assumed to play a role in demyelinating or inflammatory disorders as multiple sclerosis, can be eliminated. TPE has been implemented into therapeutic guidelines of a broad spectrum of neurological diseases [1–3]. Centrifugal (cTPE) and membrane-based (mTPE) are the methods of choice for TPE. Head to head studies comparing both methods are scarce and patients’ comfort has not yet been investigated [4–7]. Our aim was to compare cTPE (Spectra Optia™, TerumoBCT) with mTPE (multiFiltrate™, Fresenius Medical Care) with a focus not only on safety and efficacy parameters but also on patients’ comfort with the present monocentric, prospective and randomized crossover study. This is, to the best of our knowledge, the first study addressing patients’ comfort comparing both systems. METHODS The study was conducted as an open-label prospective trial with a cross-over design comparing cTPE using the Spectra Optia™ (Terumo BCT, Lakewood, CO, USA), and mTPE using the multiFiltrate™ with the plasmafilter plasmaFluxP2dry™ (Fresenius Medical Care, Bad Homburg, Germany). The first two treatments were performed within the study for each patient: one with the Spectra Optia and one with the multiFiltrate. Duration of set-up and priming of the devices, total procedure time, blood flow, total plasma volume exchanged, volume of the removal bag, volume of the anticoagulant and the type of vascular access were documented. Laboratory parameters such as IgG, IgA, IgM, fibrinogen, white blood cell, red blood count and thrombocytes were documented before and after treatment. Data from the first two treatments were documented. The differences of the parameters were compared using the Wilcoxon matched-pairs signed-rank or Mann-Whitney (U) test. RESULTS A total of 26 patients (17 women /9 mem) were included in the study and 52 treatments were documented. A median of 3000 mL of plasma was treated; the median duration of the procedure was 117 min (cTPE) versus 154 min (mTPE) (P = .03). Despite removal of fibrinogen (P = .04), no significant differences were found for the removal IgG (P = .09), IgM (P = .18) and IgA (P = .57). Both methods were equally effective. Erythrocyte loss was higher with mTPE (P = .003), platelet loss tended to be higher with mTPE, but without reaching a level of significance (P = .22; Table 1). The results of the patient questionnaire are shown in Figure 1. CONCLUSION Both procedures can be performed safely with comparable results regarding parameters of quality as fibrinogen, IgG, IgM and IgA with a trend to better elimination with cTPE. Comparing the duration of the procedure, cTPE was significantly superior to mTPE. An advantage regarding cell loss (RBC) was seen for cTPE, platelet loss tended to be higher with mTPA, but without statistical significance. Finally, as a result of shorter duration, patients’ comfort was significantly higher with cTPE.

MO552: Self-Administered Exercise and Bone Mineral Density in Patients With Chronic Kidney Disease: A Substudy of Renexc—A Randomized Controlled Trial

Abstract BACKGROUND AND AIMS The aim of the study was to evaluate the effects of 12 months self-administered exercise training on bone mineral density (BMD) in non-dialysis-dependent patients with chronic kidney disease stages 3–5. METHOD In this single-centre, randomized controlled trial, 151 patients were allotted 60 minutes of endurance training in combination with 90 minutes of either balance or strength training. The exercise was prescribed and monitored by a physiotherapist and performed at home or a gym. Total body-, hip- and lumbar BMD (g/m2), T-score and Z-score were measured at baseline (T0) and after 12 months (T12) using dual-energy X-ray absorptiometry (DEXA). A total of 112 patients completed the study. Of these, five patients were excluded from analysis because they missed either the T0 or T12 DEXA evaluation. To evaluate between-group changes after the study period delta BMD, delta T-score and delta Z-score values (T12 value–T0 value) were calculated. These results were also used to define progressors and non-progressors. Statistical analyses were performed using SPSS for Windows 24. Statistical significance was assessed using Student's t-test, paired-sample t-test, Mann–Whitney or Wilcoxon matched-pairs signed-rank tests depending on normality of data distribution. The two-tailed chi-squared test was used to compare categorical variables. Values are given as mean ± SD or median (min-max). A P-value &amp;lt; 0.05 was accepted as the level of significance. RESULTS A total of 107 patients [69 men, 38 women; age 66 ± 13.5 years, measured glomerular filtration rate (GFR) 22 ± 8 mL/min/1.73 m2] were analysed. There were 50 patients (34 men, 16 women) in the strength group and 57 (35 men, 22 women) in the balance group. After 12 months of training the whole group showed a statistically significant decrease in hip BMD [0.886 (0.479–1.922) T0 versus 0.873 (0.521–2.045) T12, P = 0.002], hip T score [−1.177 ± 1.419 T0 versus − 1.4 (−4.0 to 6.6) T12, P = 0.049] and total body BMD (1.156 ± 0.508 T0 versus 1.149 ± 0.164 T12, P = 0.032). When data were analysed separately within each group, the strength group showed a decrease in total body BMD (1.152 ± 0.151 T0 versus 1.141 ± 0.153 T12, P = 0.001). Changes in total body T-score and Z-score did not reach the level of significance (T-score − 0.392 ± 1.56 T0 versus − 0.484 ± 1.56 T12, P = 0.138; Z-score 0.07 ± 1.19 T0 versus − 0.012 ± 1.21 T12, P = 0.052). The balance group showed a statistically significant increase after 12 months training in total body T-score (−0.312 ± 1.659 T0 and − 0.196 ± 1.707 T12, P = 0.035) and total body Z-score [0.05 ± 1.626 T0 and 0.4 (−5.1 to 6.8) T12, P = 0.003] but not in total body BMD [1.16 ± 0.151 T0 versus 1.123 (0.668 to 1.818) T12, P = 0.135]. Delta total body T-score was negative in the strength group [−0.10 (−1.0 to 2.1) and unchanged in the balance group 0.00 (−0.60 to 1.00), showing a significant between-group difference (P = 0.005)]. Delta total body Z-score was negative in the strength group (−0.092 ± 0.430) and positive in the balance group (0.1158 ± 0.403) showing a significant between-group difference (P = 0.001). Moreover, the proportion of progressors was higher in the strength group as shown by the delta total body T-score (60%) strength versus (40%) balance group (P = 0.006) and delta total body Z-score (61%) and (40%) respectively (P = 0.029). CONCLUSION Balance—in combination with endurance training seemed to be superior to strength—in combination with endurance training in preserving and even improving bone health. The 12 months of balance training resulted in an increase in total body T-score and Z-score, respectively. The strength group showed a decrease in total body BMD after 12 months of training. Moreover, when comparing the delta values there were significant between-group effects with the balance group showing an unchanged T-score in comparison with the strength group's decreased T-score and a positive Z score in comparison with the strength group's negative value. Finally, a greater proportion of participants in the strength group were classified as progressors with a deterioration of bone health.

Low-dose morphine reduces tolerance to central hypovolemia in healthy adults without affecting muscle sympathetic outflow.

Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Low-dose (i.e., an analgesic dose) morphine is recommended for use in the prehospital (i.e., field) setting. Morphine administration reduces hemorrhagic tolerance in rodents. However, it is unknown whether morphine impairs autonomic cardiovascular regulation and consequently reduces hemorrhagic tolerance in humans. Thus, the purpose of this study was to test the hypothesis that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thirty adults (15 women/15 men; 29 ± 6 yr; 26 ± 4 kg·m-2, means ± SD) completed this randomized, crossover, double-blinded, placebo-controlled trial. One minute after intravenous administration of morphine (5 mg) or placebo (saline), we used a presyncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (mmHg·min), which was compared between trials using a Wilcoxon matched-pairs signed-rank test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat blood pressure (photoplethysmography) during the LBNP test using mixed-effects analyses [time (LBNP stage) × trial]. Median LBNP tolerance was lower during morphine trials (placebo: 692 [473-997] vs. morphine: 385 [251-728] mmHg·min, P < 0.001, CI: -394 to -128). Systolic blood pressure was 8 mmHg lower during moderate central hypovolemia during morphine trials (post hoc P = 0.02; time: P < 0.001, trial: P = 0.13, interaction: P = 0.006). MSNA burst frequency responses were not different between trials (time: P < 0.001, trial: P = 0.80, interaction: P = 0.51). These data demonstrate that low-dose morphine reduces hemorrhagic tolerance in conscious humans. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.NEW & NOTEWORTHY In this randomized, crossover, placebo-controlled trial, we found that tolerance to simulated hemorrhage was lower after low-dose morphine administration. Such reductions in hemorrhagic tolerance were observed without differences in MSNA burst frequency responses between morphine and placebo trials. These data, the first to be obtained in conscious humans, demonstrate that low-dose morphine reduces hemorrhagic tolerance. Thus, morphine is not an ideal analgesic for a hemorrhaging individual in the prehospital setting.

Acceptability of a Game-Based Intervention to Prevent Adolescent Prescription Opioid Misuse.

Objective: This study assessed the initial acceptability of SafeUse, a game-based opioid misuse prevention intervention for delivery via smartphone among adolescents. Evidence-based educational and refusal skills training materials were adapted, and game design elements were applied to clinically and scientifically informed scenarios in which opioids are typically introduced to adolescents using standard product development methods to create the SafeUse prototype. Materials and Methods: In a mixed-methods study, 14 adolescents were assessed on their knowledge and perceptions of opioids before and following 5-7 days of access to SafeUse. Participants provided feedback in focus groups on the acceptability, relevance, and understandability of SafeUse and made suggestions for its improvement. Feedback was coded and summarized as to playability, acceptability, appropriateness, content development, and knowledge transfer. Pre- and post-access quantitative data were analyzed using Wilcoxon matched pairs signed-rank tests. Results: Overall, participants liked SafeUse, its characters, graphics, and approach, finding it more appealing than lectures/reading materials and appropriate for school settings. They moderately to extremely "liked the game," "would like to play more game modules," "liked playing through the decisions," thought the game was realistic/relevant and fun, and they learned new information about opioids. Participants reported increased confidence to refuse opioids and decreased likelihood of accepting opioids from someone they know. Knowledge about opioids increased (P < 0.006), and adolescent perception that prescription drugs are safer than illegal drugs decreased (P < 0.003) after playing SafeUse. Conclusion: Findings suggest that SafeUse is acceptable and likely educational to adolescents and worthy of further development and research.

Desensitization Therapy Among Highly Sensitized LVAD Patients

<h3>Purpose</h3> Among patients listed for heart transplantation (HT), human leukocyte antigen (HLA) sensitization is a major risk factor for prolonged wait-list time, wait-list mortality, and delisting. Desensitization therapies (Dx) like immunoglobulins (Ig), plasmapheresis and direct immunomodulators (IM)s such as B-cell depletion therapies (BCDT) or proteosome inhibitors (PI) have been used to reduce levels of sensitization. Specifically, for left ventricular assist device (LVAD) patients, however, Dx may pose unique problems: plasmapheresis removes coagulation factors and can increase bleeding risk, and IMs may worsen the risk of LVAD associated infections. We sought to assess safety and efficacy of Dx among LVAD patients. <h3>Methods</h3> LVAD patients undergoing Dx including plasmapheresis, Ig, Rituximab (BCDT) or Bortezomib (PI) were analyzed. Data on major coagulopathic and infectious complications while on LVAD support, changes in HLA antibodies and rates of HT were collected. Wilcoxon matched-pairs signed-ranks test was performed to compare changes in HLA antibody profiles following Dx. <h3>Results</h3> Between March 2016 and June 2021, 14 waitlisted LVAD patients underwent Dx [age: 52 years (inter-quartile range (IQR): 44, 60), 78% female, 43% Black, 64% HeartWare and 36% HeartMate III]. DTs were initiated 282 days (IQR: 129, 429) post LVAD implantation, with the majority receiving plasmapheresis (86%), Ig (86%) and bortezomib (93%). Two patients developed de-novo LVAD infections, and 2 suffered neurological events (1 hemorrhagic stroke and 1 transient ischemic event); no episodes of de-novo mucosal bleeding or hemolysis were noted. Eleven (78.6%) patients underwent HT, 2 remain waitlisted and 1 was delisted (myocardial recovery). Figure shows changes in antibody profiles with Dx. <h3>Conclusion</h3> In our cohort of highly sensitized LVAD patients, Dx were largely safe, significantly reduced class I panel reactive antibodies, and resulted in successful HT for most patients; future large scale trial data is necessary to validate our findings.