Dealing with Dry Waste Disposal Issues Associated with 177mLu Impurities: A Long-Term Challenge for Nuclear Medicine Departments

Purpose: A strategy for management of radioactive waste associated with 177 Lu-dotatate (Lutathera ® ) treatments was established in our institution based on predicted storage times of 3 to 5 years extrapolated from the results of a 2-year measurement study. The aim of this work was to validate the model used by identifying contaminants and confirming disposal based on the clearance level twice-the-background was within expected time frames. Methods: We conducted a prospective series of measurements of radioactive waste associated with the first 65 treatments administered. Sequential measurements of the first 45 vials used were performed on a dose calibrator to identify contaminants. Exposure rates in contact were monitored with a dose ratemeter on a 6-monthly basis for all types of waste stored: 46 empty vials, 19 vials partially used and 67 biohazard containers. Results: Initial median activity of the first vials used was 118 MBq (4 - 4188 MBq). For each vial, the decay curve of activity obtained was adjusted to a bi-exponential model. The major component, representing 99.7 % of activity, has a half-life of 6.5 ± 0.2 days, corresponding to 177 Lu. The second, representing only 0.3 % of the activity and having a half-life of 156 ± 24 days corresponding to 177m Lu, determines necessary storage times. Partially used vials can be disposed of after 5 years, other waste after 3 years. Compliance with the regulatory clearance level is achieved within expected time frames. Conclusion: Although only present as traces, 177m Lu results in major radioactive waste disposal issues for hospitals. Availability of radiopharmaceuticals without impurities appears to be crucial for an expanding use of targeted radionuclide therapy.

Case Study: The Conservative Management and Rehabilitation of Insertional Patella Tendinopathy in an Elite Footballer

Background and Purpose: Chronic insertional patella tendinopathy is a complex condition to manage within elite athletes. Pain and symptoms increase when spikes or changes in relation to training or game load are experienced. These spikes are often seen in football on return to training or in periods of fixture congestion, presenting a contemporary challenge for the sports medicine team. Study Design: Case Study. Case Description: The presented case summarises the conservative rehabilitation and pain free return to play of a 24 years (yrs) old elite professional footballer with a long-standing history of patella tendinopathy. Symptoms returned post a spike in training load during pre-season, with a diagnosis of a 7.4 mm insertional thickening detected through magnetic resonance imaging. Presented is a summary of the assessment process, 24-week treatment and rehabilitation protocol and subsequent 12-week pre-habilitation plan, routinely completed on return to training and game play. Outcomes: The implemented management strategy led to the successful symptom free return to play of the athlete. Conclusion: The management of this injury was facilitated through subjective and objective assessment markers and imaging obtained to manage the athlete’s symptoms. The authors suggest that medical and conditioning based specialists could apply a rounded loading approach with prescribed isometric and isotonic drills before progression to energy release and pitch-based training to advance the athlete through a safe and controlled return to sport clearance. Level of Evidence: 5.

Nonlinear Dynamics Analysis of a Rolling Bearing

A numerical analysis of the nonlinear bearing model about two degrees of freedom has been presented in this paper. The contact between a ball and ring by Hertz theory is described. Influence of the number of balls, shaft rotation and clearance on the acceleration were investigated in detail. Three numbers of balls from 11 to 16 were analyzed. The clearance level in the range of 0-71μm has been studied. It has been shown that the acceleration responses are different, depending on the vibration direction and are usually higher when the radial internal clearance and the shaft speed are increased. The higher ball number caused that the accelerations decreased in both directions. Moreover, two dynamic indicators that can be used for comparison bearing dynamics have been proposed. These obtained results are useful for understanding the vibration response mechanism from a practical point of view.

Management of hospital radioactive liquid waste: treatment proposal for radioimmunoassay wastes

<abstract> <p>Radioactive liquid wastes are produced at hospitals from diagnostic and therapeutic applications of radionuclides. The most usual management of these wastes is temporary storage at the hospital for radioactivity decay and, then, discharge into sewage if not other pollutants are present in waste, always after authorization of the corresponding institution. In some cases, radioactive wastes have other hazards, such as chemical or biological ones, which can be more dangerous than radiological hazard, and do not allow direct discharge into sewage in spite of decaying activity below the clearance level. Therefore, these wastes have to be treated and condition before discharge in spite of activity decay below discharge limit. This is the case of liquid wastes from radioimmunoassay (RIA), a laboratory technique that allows to determine human substances in very low concentrations (below 10^-12 g/mL), like hormones, using ¹²⁵I as radionuclide. This study summarizes the usual management of radioactive liquid wastes from hospitals, including conventional and recent treatments applied. Furthermore, based on experimental results obtained with real RIA wastes, this work exposes a proposal of treatment with ultrafiltration and reverse osmosis membranes, and determines the most suitable application of this treatment according to radiological and operational considerations.</p> </abstract>

Single Lumen Alternating Micro-Batch Hemodiafiltration (SLAMB-HDF): A Device for Minimally Invasive Renal Replacement Therapy

Blood-based RRT, such as hemodialysis, requires access to the bloodstream and adequate blood flow to enable the requisite clearance. As such, nearly all RRT systems require two lumens, enabling a blood circuit that pulls blood from one lumen or needle and returns it via another lumen or needle. The proposed single lumen alternating micro-batch (SLAMB) technique uses a small single lumen to draw a “micro” batch of blood into a single reservoir. In the reservoir, the “batch” of blood is circulated at a high blood flow rate through a hemofilter or hemodialyzer, enabling efficient small- and middle-molecule clearance. Thereafter, the “purified” blood is returned to the patient and the cycle is repeated. Each batch comprises 20–300 ml of blood, which is adjusted to the vascular access, hemodynamic status, and size of the patient. Up to 15 cycles can be done per hour, allowing this system to achieve a blood clearance level comparable to modern continuous RRT systems. Because the system can function with a small-bore single lumen, this device can work with existing central lines, thus allowing for less invasive vascular access. Because of their size and relative simplicity, SLAMB-based systems are less expensive, smaller, and have improved portability. Lastly, a similar, manual SLAMB-hemofiltration kit, which requires no electricity or battery, can be developed at low cost (<$25) for use in austere medical conditions, thus expanding the availability of RRT for patients with AKI.

P065 CHARACTERIZATION OF EARLY CLINICAL AND PHARMACOKINETIC RESPONSE PROFILES OF VEDOLIZUMAB: AN INTERIM ANALYSIS OF ENTERPRET, A PHASE 4 CLINICAL STUDY

Introduction Vedolizumab (VDZ), a gut-selective antibody that binds specifically to integrin α4β7, is approved for treatment of adults with moderate-to-severe ulcerative colitis (UC). An association between VDZ levels and clinical remission during induction therapy at Week (Wk) 6 was observed in pivotal trial data; the majority of nonresponders at Wk 6 had VDZ levels &lt;40 μg/mL, and those with VDZ clearance &gt;0.14 L/d had reduced efficacy outcomes (Osterman MT, et al. Aliment Pharmacol Ther. 2019). In the ongoing randomized controlled trial (ENTERPRET), we are evaluating whether dose escalation starting at Wk 6 in clinical nonresponders with high VDZ clearance (level &lt;50 μg/mL) at Wk 5 leads to improved outcomes at Wk 30. This is an interim analysis of ENTERPRET in which baseline predictors of response at Wk 6 were investigated. Methods Adults with moderately to severely active UC received VDZ 300 mg IV on Day 1 and Wk 2. At Wk 5, VDZ concentration in serum was measured; clinical response was assessed at Wk 6 based on partial Mayo score (reduction in partial Mayo score ≥2 points and ≥25% from baseline [Day 1] with an accompanying decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding score ≤1 point). Descriptive analysis was used for these interim data, including baseline characteristics in responder and nonresponder groups. Results A total of 117 patients (mean age 41.2 years, 40.2% female) were analyzed; 112 were classified as a responder (n=55) or nonresponder (n=57) based on Wk 6 response. At baseline, mean disease duration was higher in nonresponders than responders (9.5 vs 7.1 years), with 47.4% of nonresponders having disease duration ≥7 years compared with 38.2% of responders. Endoscopic activity score was higher in nonresponders vs responders (49.1% vs 36.4% had severely active disease [Mayo endoscopic subscore=3]). 63.2% of nonresponders had a high stool frequency at baseline (Mayo subscore=3) compared with 49.1% of responders. 63.6% of responders had more severe rectal bleeding scores (Mayo subscore of 2–3) compared with 45.6% of nonresponders. More responders (67.3%) were anti-TNF–naïve at baseline than nonresponders (52.6%). At Wk 6, change in mean (SD) partial Mayo score from baseline was -4.2 (1.65) for responders and -0.2 (0.96) for nonresponders. Wk 5 mean VDZ serum concentrations were numerically lower in nonresponders (31.5 [SD=12.8] vs 40.3 [SD=15.3] μg/mL in responders). There were no unexpected treatment-emergent adverse events in either group. Conclusion Interim data from ENTERPRET show Wk 6 responders had higher VDZ serum concentrations at Wk 5 than nonresponders. Although current results are consistent with the hypothesis that lower response to VDZ at Wk 6 correlates with lower drug exposure, we await the final results of ENTERPRET to better understand the exposure-response relationship of VDZ.

The Effect of Gravity and Rotor Configuration on Dry Friction Whip and Safe Rotor/Stator Clearance

A mathematical model is developed for a real rotor/stator system with high degrees-of-freedoms, multiple disks, flexible bearing supports and couplings. The safe clearance level for coasting up of the rotor is calculated for a general high degree-of-freedom rotor/stator system. The harmful phenomena of dry friction whip, which is generally observable for simple 2 degree-of-freedom Jeffcott rotors in the absence of gravity only, can be proved to exist (in real rotor/stator systems) even in the presence of gravity for a wide range of clearance levels. In case of Jeffcott rotors, by fixing the clearance and increasing the rotor spin frequency, the response of the system follows the pattern: No rub - Forward Annular Rub (FAR) - Partial Forward Whirl (PFW) - Partial Backward Whirl (PBW) - dry whip (WHIP). In case of a real rotor/stator system, at certain frequencies, the system directly jumps to dry whip. The simulated results show a rich variety of system dynamics including FAR, PFW and WHIP in case of vertical rotors where the effect of gravity is neglected. For horizontal rotors, under the effect of gravity, the system response contains multi-harmonics, chaotic responses and multi-period vibrations. Based on these responses, a robust fault diagnosis strategy can be designed to identify the rubbing action in rotating machinery.

Effect of Clearances in Mill Stands on Strip End Motion During Finishing Rolling

The process stability of finishing mill is significantly influenced by the clearance between the chocks and housing in mill stands. The on-site data of a finishing mill had shown that the clearances in the finishing mill stands were clearly associated with the incidence of strip end flip. The aim of this work was to establish a numerical model to analyze the effect of the clearances on the deviation of the centerline of the strip and on the incidence of strip end flip. By adopting conditions from a particular strip, the numerical model not only predicted the strip end shape, but also visualized strip end flip, which would be otherwise invisible. Four different degrees of asymmetry regarding work rolls and backup rolls were postulated. It was found that the degradation of the work rolls’ clearance level was the most significant influence on the centerline deviation of the strip. Strip end flip was most susceptible to the degradation of the horizontal clearance of the work roll. The simultaneous degradation of the work rolls’ and backup rolls’ level of clearance led to larger reactions and enhanced the asymmetric wear on the liners. The superimposed axial clearances at the roll end provided an axial constraint to the work roll, and were able to reverse the trend of centerline deviation. The numerical results provided a guideline for designing a suitable maintenance strategy for clearances.

Effects of Nonuniform Tip Clearance on Fan Performance and Flow Field

Nonuniform tip clearance, caused by the deformation of the casing (casing ovalization), exists in all fans to some extent. However, description of the flow behavior with this kind of nonuniform clearance is seldom given in the open literature. In this paper, both steady and unsteady calculations are performed to study the influence of the nonuniform clearance on fan performance and flow field. The investigation method is based on three dimensional RANS equations, carried out by the ANSYS CFX fluid solver. A new factor τ, which is in the range of 0 to 1, is defined to represent the nonuniformity of the tip clearance. A series of numerical models with different tip clearance nonuniformities τ are investigated. In addition, the original, uniform tip clearance is also performed serving as a reference. The results indicate that the fan performance is mainly affected by two factors: the clearance nonuniformity τ and the average clearance level. There is a clear decreasing trend of the fan performance with increasing nonuniformity and average tip clearance level. The maximum clearance can contribute to the reduction of stall margin. Furthermore, the effects of nonuniform clearance on tip leakage vortex and aerodynamic force are also discussed in detail. The deformation of the casing can affect the pressure fluctuation and thus increase the amplitude of the aerodynamic force.