Leveraging Radiopharmaceutical Programmatic Collaboration for Management of Pretherapy and On-treatment Urinary Incontinence.

ABSTRACT: Many parenteral radiopharmaceuticals available as anticancer therapy are filtered by the kidneys and excreted in the urine. Here, physician leaders of radiation medicine, nuclear medicine/molecular imaging, and the radiotheranostics programs as well as radiation safety officers, collaborated to develop a decision-making guideline for the administration of therapeutic radiopharmaceuticals in patients with pretherapy or day-of-treatment incontinence. We discussed challenges and opportunities in the screening of patients in urine collection strategies according to grade of urinary incontinence and in subsequent coordination of care. Lutetium-177 ( 177 Lu)-based radiopharmaceutical therapies provided clinical examples of how our procedures were operationalized. Our key management issues of urinary incontinence were cutaneous radiation injury and redness, infection, or pain. In response, we developed clinical practice guidelines for the recognition and management of incontinence-related adverse events. Common adverse events of urinary incontinence were noted in this study. Our how-to guideline for the safe administration of therapeutic radiopharmaceuticals for patients with urinary incontinence warrants further investigation and should continue to be evaluated across all radiopharmaceutical therapy agents.

Evaluation of Patient Transmission Factor Following the Administration of 177Lu-DOTATATE.

ABSTRACT: 177Lu-DOTATATE is a radionuclide therapy that is FDA approved for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Treatment facilities are required to determine the maximum radiation dose from such subjects to the maximally exposed member of the public, ensuring that the total effective dose equivalent (TEDE) does not exceed regulatory limits. If the calculated TEDE meets the regulatory limits, the patient is eligible for release and provided instructions with radiation precautions. This study aims to determine a mean transmission factor to the patient to improve accuracy and individualize the estimation of the TEDE.

A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases.

BACKGROUND: Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need. METHODS: The study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5-10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival. DISCUSSION: Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline. TRIAL REGISTRATION: ClincialTrials.gov Identifier: NCT04616547.

Radiation Exposure Among Orthopaedic Trauma Surgeons: Deconstructing Commonly Held Myths and Misperceptions.

OBJECTIVES: To review and evaluate the validity of common perceptions and practices regarding radiation safety in orthopaedic trauma. DESIGN: Retrospective study. SETTING: Level 1 trauma center. SUBJECTS: N/A. INTERVENTION: The intervention involved personal protective equipment. MAIN OUTCOME MEASUREMENTS: The main outcome measurements included radiation dose estimates. RESULTS: Surgeon radiation exposure estimates performed at the level of the thyroid, chest, and pelvis demonstrate an estimated total annual exposure of 1521 mR, 2452 mR, and 1129 mR, respectively. In all cases, wearing lead provides a significant reduction (90% or better) in the amount of radiation exposure (in both radiation risk and levels of radiation reaching the body) received by the surgeon. Surgeons are inadequately protected from radiation exposure with noncircumferential lead. The commonly accepted notion that there is negligible exposure when standing greater than 6 feet from the radiation source is misleading, particularly when cumulative exposure is considered. Finally, we demonstrated that trauma surgeons specializing in pelvis and acetabular fracture care are at an increased risk of exposure to potentially dangerous levels of radiation, given the amount of radiation required for their caseload. CONCLUSION: Common myths and misperceptions regarding radiation in orthopaedic trauma are unfounded. Proper use of circumferential personal protective equipment is critical in preventing excess radiation exposure.

Phenotypic diversity of patients diagnosed with VACTERL association.

The combination of vertebral, anal, cardiac, tracheo-esophageal, renal and limb anomalies termed VACTERL association, also referred to as VATER, has been used as a clinical descriptor and more recently, a diagnosis of exclusion, for a specific group of phenotypic manifestations that have been observed to co-occur non-randomly. Though the causes remain elusive and poorly understood in most patients, VACTERL association is thought to be due to defects in early embryogenesis and is likely genetically heterogeneous. We present data on 36 patients diagnosed with VACTERL association in addition to describing the phenotypic diversity of each component feature. Unique cases in our cohort include a patient with a 498.59 kb microdeletion in the 16p11.2 region and another with a 215 kb duplication in the 3p25.2 region. Our findings expand upon the current understanding of VACTERL association and guide future research aimed at determining its etiology.

In vivo imaging of the internal nasal valve during different conditions using optical coherence tomography.

OBJECTIVE: Previously, we proposed long-range optical coherence tomography (LR-OCT) to be an effective method for the quantitative evaluation of the nasal valve geometry. Here, the objective was to quantify the reduction in the internal nasal valve angle and cross-sectional area that results in subjective nasal airway obstruction and to evaluate the dynamic behavior of the valve during respiration using LR-OCT. METHODS: For 16 healthy individuals, LR-OCT was performed in each naris during: 1) normal respiration, 2) peak forced inspiration, 3) lateral nasal wall depression (to the onset of obstructive symptoms), and 4) after application of a topical decongestant. The angle and the cross-sectional area of the valve were measured. RESULTS: A reduction of the valve angle from 18.3° to 14.1° (11° in Caucasians and 17° in Asians) and a decrease of the cross-sectional area from 0.65 cm2 to 0.55 cm2 led to subjective nasal obstruction. Forceful breathing did not significantly change the internal nasal valve area in healthy individuals. Application of nasal decongestant resulted in increased values. CONCLUSION: LR-OCT proved to be a fast and readily performed method for the evaluation of the dynamic behavior of the nasal valve. The values of the angle and the cross-sectional area of the valve were reproducible, and changes in size could be accurately delineated. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:E105-E110, 2018.

A Low-Cost Method of Ciliary Beat Frequency Measurement Using iPhone and MATLAB: Rabbit Study.

OBJECTIVES: (1) To determine ciliary beat frequency (CBF) using a consumer-grade cellphone camera and MATLAB and (2) to evaluate the effectiveness and accuracy of the proposed method. STUDY DESIGN: Prospective animal study. SETTING: Academic otolaryngology department research laboratory. METHODS: Five ex vivo tracheal samples were extracted from 3 freshly euthanized (<3 hours postmortem) New Zealand white rabbits and incubated for 30 minutes in buffer at 23°C, buffer at 37°C, or 10% formalin at 23°C. Samples were sectioned transversely and observed under a phase-contrast microscope. Cilia movement was recorded through the eyepiece using an iPhone 6 at 240 frames per second (fps). Through MATLAB programming, the video of the 23°C sample was downsampled to 120, 60, and 30 fps, and Fourier analysis was performed on videos of all frame rates and conditions to determine CBF. CBF of the 23°C sample was also calculated manually frame by frame for verification. RESULTS: Recorded at 240 fps, the CBF at 23°C was 5.03 ± 0.4 Hz, and the CBF at 37°C was 9.08 ± 0.49 Hz (P < .001). The sample with 10% formalin did not display any data beyond DC noise. Compared with 240 fps, the means of other frame rates/methods (120, 60, 30 fps; manual counting) at 23°C all showed no statistical difference (P > .05). CONCLUSION: There is no significant difference between CBF measured via visual inspection and that analyzed by the developed program. Furthermore, all tested acquisition rates are shown to be effective, providing a fast and inexpensive alternative to current CBF measurement protocols.

Modular Component Assembly Approach to Microtia Reconstruction.

BACKGROUND: Current methods of microtia reconstruction include carving an auricular framework from the costal synchondrosis. This requires considerable skill and may create a substantial defect at the donor site. OBJECTIVE: To present a modular component assembly (MCA) approach that minimizes the procedural difficulty with microtia repair and reduces the amount of cartilage to a single rib. DESIGN, SETTING, AND PARTICIPANTS: Ex vivo study and survey. A single porcine rib was sectioned into multiple slices using a cartilage guillotine, cut into components outlined by 3-dimensional printed templates, and assembled into an auricular scaffold. Electromechanical reshaping was used to bend cartilage slices for creation of the helical rim. Chondrocyte viability was confirmed using confocal imaging. Ten surgeons reviewed the scaffold constructed with the MCA approach to evaluate aesthetics, stability, and clinical feasibility. The study was conducted from June 5 to December 18, 2014. MAIN OUTCOMES AND MEASURES: The primary outcome was creation of a modular component assembly method that decreases the total amount of rib needed for scaffold construction, as well as overall scaffold acceptability. The surgeons provided their assessments through a Likert-scale survey, with responses ranging from 1 (disagree with the statement) to 5 (agree with the statement). Thus, a higher score represents that the surgeon agrees that the scaffold is structurally and aesthetically acceptable and feasible. RESULTS: An auricular framework with projection and curvature was fashioned from 1 rib. The 10 surgeons who participated in the survey indicated that the MCA scaffold would meet minimal aesthetic and anatomic acceptability. When embedded under a covering, the region of the helix and antihelix of the scaffold scored significantly higher on the assessment survey than that of an embedded alloplast implant (mean [SD], 4.6 [0.97] vs 3.5 [1.27]; P = .007). Otherwise, no significant difference was found between the embedded MCA and alloplast implants (4.42 [0.48] vs 3.87 [0.41]; P = .13). Cartilage prepared with electromechanical reshaping was viable. CONCLUSIONS AND RELEVANCE: This study demonstrates that 1 rib can be used to create an aesthetic and durable framework for microtia repair. Precise assembly and the ability to obtain thin, uniform slices of cartilage were essential. This cartilage-sparing MCA approach may be an alternative to classic techniques. LEVEL OF EVIDENCE: NA.

Imaging of the internal nasal valve using long-range Fourier domain optical coherence tomography.

OBJECTIVES/HYPOTHESIS: To evaluate for the first time the feasibility and methodology of long-range Fourier domain optical coherence tomography (LR-OCT) imaging of the internal nasal valve (INV) area in healthy individuals. STUDY DESIGN: Prospective individual cohort study. METHODS: For 16 individuals, OCT was performed in each nare. The angle and the cross-sectional area of the INV were measured. OCT images were compared to corresponding digital pictures recorded with a flexible endoscope. RESULTS: INV angle measured by OCT was found to be 18.3° ± 3.1° (mean ± standard deviation). The cross-sectional area was 0.65 ± 0.23 cm(2) . The INV angle measured by endoscopy was 18.8° ± 6.9°. There was no statistically significant difference between endoscopy and OCT concerning the mean INV angle (P = .778), but there was a significant difference in test precision (coefficient of variance 50% vs. 15%; P < .001). CONCLUSIONS: LR-OCT proved to be a fast and easily performed method. OCT could accurately quantify the INV area. The values of the angle and the cross-sectional area of the INV were reproducible and correlated well with the data seen with other methods. Changes in size could be reliably delineated. Endoscopy showed similar values but was significantly less precise. LEVEL OF EVIDENCE: 2b. Laryngoscope, 126:E97-E102, 2016.

Measurement of ciliary beat frequency using Doppler optical coherence tomography.

BACKGROUND: Measuring ciliary beat frequency (CBF) is a technical challenge and difficult to perform in vivo. Doppler optical coherence tomography (D-OCT) is a mesoscopic noncontact imaging modality that provides high-resolution tomographic images and detects micromotion simultaneously in living tissues. In this work we used D-OCT to measure CBF in ex vivo tissue as the first step toward translating this technology to clinical use. METHODS: Fresh ex vivo samples of rabbit tracheal mucosa were imaged using both D-OCT and phase-contrast microscopy (n = 5). The D-OCT system was designed and built to specification in our lab (1310-nm swept source vertical-cavity surface-emitting laser [VCSEL], 6-µm axial resolution). The samples were placed in culture and incubated at 37°C. A fast Fourier transform was performed on the D-OCT signal recorded on the surface of the samples to gauge CBF. High-speed digital video of the epithelium recorded via phase-contrast microscopy was analyzed to confirm the CBF measurements. RESULTS: The D-OCT system detected Doppler signal at the epithelial layer of ex vivo rabbit tracheal samples suggestive of ciliary motion. CBF was measured at 9.36 ± 1.22 Hz using D-OCT and 9.08 ± 0.48 Hz using phase-contrast microscopy. No significant differences were found between the 2 methods (p > 0.05). CONCLUSION: D-OCT allows for the quantitative measurement of CBF without the need to resolve individual cilia. Furthermore, D-OCT technology can be incorporated into endoscopic platforms that allow clinicians to readily measure CBF in the office and provide a direct measurement of mucosal health.