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Abstract Background For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16–26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. Trial registration ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

The clinical syndrome of intracranial hypotension refers to the symptoms caused by cerebrospinal fluid hypovolemia and is primarily characterized by postural headaches, but can be associated with a multitude of other neurological symptoms. Imaging plays a critical role in helping to establish a diagnosis of intracranial hypotension, localize the source of cerebrospinal fluid leak, and assist in directing targeted treatments. Using the best available evidence, this document provides diagnostic imaging recommendations for the workup of intracranial hypotension across various clinical presentations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]

Ectopic parathyroid glands are not rare. They are usually located between the mandible and mediastinum, and usually localized with standard imaging modalities (99mTc-sestamibi subtraction scintigraphy and 4D-CT). We report the case of a 67-year-old woman with severe hypercalcemia due to symptomatic primary hyperparathyroidism whose preoperative 99mTc-sestamibi and 4D-CT scans were non-localizing. During 4-gland exploration, one hypercellular parathyroid was excised, two normocellular parathyroids were biopsied, and bilateral low internal jugular vein sampling showed similar parathyroid hormone (PTH) levels. Despite treatment with zolendronic acid and cinacalcet, symptomatic PHPT persisted. A99mTc-sestamibi study using a modified anterior and posterior whole-body scintigraphy protocol with SPECT/CT revealed mild focal uptake in the right para-tracheal area, correlating with a mass on SPECT/CT. Sestamibi uptake was visually more conspicuous on posterior projection whole-body image. Thoracoscopic resection of this mass revealed a parathyroid gland (2.6 × 1.5 × 0.7 cm) composed almost entirely of chief cells. The lack of identifiable oxyphil content could explain the lack of or limited radiotracer uptake. The modified protocol differed from standard parathyroid imaging in the timing of radiotracer administration, timing of image capture, and types of images obtained could account for the eventual visualization of the ectopic tissue, and may be considered in challenging cases of suspected ectopic parathyroid gland.

Interband cascade light-emitting diodes (ICLEDs) offer attractive advantages for infrared applications, which would greatly expand if high-quality growth on silicon substrates could be achieved. This work describes the formation of threading dislocations in ICLEDs grown monolithically on GaSb-on-Silicon wafers. The epitaxial growth is done in two stages: the GaSb-on-Silicon buffer is grown first, followed by the ICLED growth. The buffer growth involves the nucleation of a 10-nm-thick AlSb buffer layer on the silicon surface, followed by the GaSb growth. The AlSb nucleation layer promotes the formation of 90° and 60° interfacial misfit dislocations, resulting in a highly planar morphology for subsequent GaSb growth that is almost 100% relaxed. The resulting GaSb buffer for growth of the ICLED has a threading dislocation density of ∼107/cm2 after ∼3 μm of growth. The fabricated LEDs showed variations in device performance, with some devices demonstrating comparable light–current–voltage curves to those for devices grown on GaSb substrates, while other devices showed somewhat reduced relative performance. Cross-sectional transmission electron microscopy observations of the inferior diodes indicated that the multiplication of threading dislocations in the active region had most likely caused the increased leakage current and lower output power. Enhanced defect filter layers on the GaSb/Si substrates should provide more consistent diode performance and a viable future growth approach for antimonide-based ICLEDs and other infrared devices. [ABSTRACT FROM AUTHOR]

Abstract Background 18 F‐Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. Methods This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. Results Forty‐five (PET+) ITNs were identified: 31 Afirma‐tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma “suspicious” non‐resected ITNs and assuming all Afirma “benign” ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC‐tested ITNs, the BCR was higher in ITNs demonstrating low/very low‐risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring

The aim of the study was to assess the quality and reproducibility of reducing the injected [18F] sodium fluoride ([18F]NaF) dose while maintaining diagnostic imaging quality in bone imaging in a preclinical skeletal model using digital photon counting PET (dPET) detector technology. Beagles (n = 9) were administered three different [18F]NaF doses: 111 MBq (n = 5), 20 MBq (n = 5), and 1.9 MBq (n = 9). Imaging started ≃45 min post-injection for ≃30 min total acquisition time. Images were reconstructed using Time-of-Flight, ultra-high definition (voxel size of 1 × 1 × 1 mm3), with 3 iterations and 3 subsets. Point spread function was modeled and Gaussian filtering was applied. Skeleton qualitative and quantitative molecular image assessment was performed. The overall diagnostic quality of all images scored excellent (61%) and acceptable (39%) by all the reviewers. [18F]NaF SUVmean showed no statistically significant differences among the three doses in any of the region of interest assessed. This study demonstrated that a 60-fold [18F]NaF dose reduction was not significantly different from the highest dose, and it had not significant effect on overall image quality and quantitative accuracy. In the future, ultra-low dose [18F]NaF dPET/CT imaging may significantly decrease PET radiation exposure to preclinical subjects and personnel.

Chronic hand and wrist pain is a common presenting complaint. The intricate anatomy results in a variety of pain generators—multiple bones, articular cartilage, intrinsic ligaments, triangular fibrocartilage complex, joint capsules and synovium, tendons and tendon sheaths, muscles, and nerves—in a compact space. The need for imaging and the choice of the appropriate imaging modality are best determined by the patient's presentation, physical examination, and the clinician's working differential diagnosis. Radiography is usually appropriate as the initial imaging study in the evaluation of chronic hand or wrist pain. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation. [ABSTRACT FROM AUTHOR]

Guided by theories of socialization and just policy theory, we explore how students allocate blame when sexual assault prevention programming hypothetically varies, net of the effects of evaluators' traits. Using a survey instrument containing a series of vignettes, we ask whether university students' (N = 254) perceptions of responsibility attributed to victims, perpetrators, bystanders, and university administrators varies by hypothetical program trainee and also by the hypothetical implementation of any program versus no program. Findings indicate that students allocate more blame to bystanders and perpetrators when hypothetical programming includes bystander training but that programs that train victims are not associated with increased victim blaming. Administrators are blamed less when bystander intervention is included in programming. However, compared to when no training is hypothetically implemented, students allocate more blame to victims and bystanders when any programming is present and less to administrators. Among respondent-level controls, victim blaming is consistently predicted by evaluators' rape myth acceptance. Implications for future work, theoretical development, and policy are discussed. [ABSTRACT FROM AUTHOR]

Background: Totally endoscopic ear surgery is a novel method of conducting otological surgery. Hierarchical task analysis and the systematic human error reduction and prediction approach ('SHERPA') are valuable tools that can effectively deconstruct the technical and non-technical skills required to successfully complete a surgical procedure. Methods: Twenty-five endoscopic tragal cartilage tympanoplasties were observed, to identify the tasks and subtasks required for completion of totally endoscopic tragal cartilage tympanoplasty. The systematic human error reduction and prediction approach was used to identify the potential risks and methods, to reduce or remediate these risks. Results: A hierarchical task analysis was performed, identifying 8 tasks and 50 subtasks for a safe approach to completing totally endoscopic tragal cartilage tympanoplasty. A risk score for each subtask was calculated to produce a systematic human error reduction and prediction approach and to highlight potential errors. Conclusion: This hierarchical task analysis allowed for quick reference to a correct method of endoscopic tympanoplasty. The systematic human error reduction and prediction approach was employed to reduce the risks associated with undergoing endoscopic tympanoplasty, to improve patient safety. [ABSTRACT FROM AUTHOR]

Worldwide, about 600,000 head and neck squamous cell carcinoma (HNSCC) are detected annually, many of which involve high risk human papilloma virus (HPV). Surgery is the primary and desired first treatment option. Following surgery, the existence of cancer cells at the surgical margin is strongly associated with eventual recurrence of cancer and a poor outcome. Despite improved surgical methods (robotics, microsurgery, endoscopic/laparoscopic, and external imaging), surgeons rely only on their vision and touch to locate tumors during surgery. Diagnostic imaging systems like computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and positron-emission tomography (PET) are too large, slow and costly to use efficiently during most surgeries and, ultrasound imaging, while fast and portable, is not cancer specific. This purpose of this article is to review the fundamental technologies that will radically advance Precision Otolaryngology practices to the benefit of patients with HNSCC. In particular, this article will address the potential for tumor-targeting peptides to enable more precise diagnostic imaging while simultaneously advancing new therapeutic paradigms for next generation image-guided surgery, tumor-specific chemotherapeutic delivery and tumor-selective targeted radiotherapy (i.e., theranostic). Keywords: Squamous cell carcinoma, Peptide, Optical surgical navigation, Diagnostic imaging, Theranostic

Objective: Cancer affects the head and neck region frequently and leads to significant morbidity and mortality. Oncolytic viral therapy has the potential to make a big impact in cancers that affect the head and neck. We intend to review the current state of oncolytic viruses in the treatment of cancers that affect the head and neck region. Method: Data sources are from National clinical trials database, literature, and current research. Results: There are many past and active trials for oncolytic viruses that show promise for treating cancers of the head and neck. The first oncolytic virus was approved by the FDA October 2015 (T-VEC, Amgen) for the treatment of melanoma. Active translational research continues for this and many other oncolytic viruses. Conclusion: The evolving field of oncolytic viruses is impacting the treatment of head and neck cancer and further trials and agents are moving forward in the coming years. Keywords: Head and neck squamous cell carcinoma, Oncolytic viruses, Clinical trials, Novel therapeutics

Sentinel lymph node biopsy has become a well-established and commonplace practice in many oncologic disease sites as a means to stage the regional lymphatics, avoid unnecessary surgery and decrease patient morbidity. In the head and neck, its role is well established for cutaneous melanoma with proven fidelity and survival benefit. Its role in use for other sites such as oral cavity carcinoma continues to develop with promising results from several recent trials. Although not widely adopted, the potential benefits of sentinel lymph node biopsy in the management of oral cavity carcinoma are apparent. Refinements in technology and protocols including development of novel radiopharmaceutical tracers, routine incorporation of detailed anatomic imaging, increasing surgeon experience and development of new intraoperative identification aids will likely lead to improvements in the use and accuracy of this technique. Keywords: Oral cavity cancer, Sentinel lymph node, Head and neck cancer, Squamous cell carcinoma, Lymphoscintigraphy

We review the history, development, design principles, experimental operating characteristics, and specialized architectures of interband cascade lasers for the mid-wave infrared spectral region. We discuss the present understanding of the mechanisms limiting the ICL performance and provide a perspective on the potential for future improvements. Such device properties as the threshold current and power densities, continuous-wave output power, and wall-plug efficiency are compared with those of the quantum cascade laser. Newer device classes such as ICL frequency combs, interband cascade vertical-cavity surface-emitting lasers, interband cascade LEDs, interband cascade detectors, and integrated ICLs are reviewed for the first time.