Cough-induced laryngeal oedema requiring ventilator.

This case report describes laryngeal oedema occurring in a 35-year-old woman with chronic bowel-associated dermatosis-arthritis syndrome, and stenosis of the left main bronchus. The oedema was attributed to persistent cough exacerbated by delayed treatment and intubation-related irritation. Evaluations ruled out inflammatory, autoimmune, and malignant causes. Literature lacks on specific descriptions of cough-induced laryngeal oedema, emphasizing the need for a multidisciplinary approach and early intervention in complex cases to prevent severe hospitalizations in patients with known serious conditions and symptom exacerbation.

Crystal Nucleation in Supercooled Atomic Liquids.

The liquid-to-solid phase transition is a complex process that is difficult to investigate experimentally with sufficient spatial and temporal resolution. A key aspect of the transition is the formation of a critical seed of the crystalline phase in a supercooled liquid, that is, a liquid in a metastable state below the melting temperature. This stochastic process is commonly described within the framework of classical nucleation theory, but accurate tests of the theory in atomic and molecular liquids are challenging. Here, we employ femtosecond x-ray diffraction from microscopic liquid jets to study crystal nucleation in supercooled liquids of the rare gases argon and krypton. Our results provide stringent limits to the validity of classical nucleation theory in atomic liquids, and offer the long-sought possibility of testing nonclassical extensions of the theory.

Development of a probabilistic risk model for pharmaceuticals in the environment under population and wastewater treatment scenarios.

Preparing for future environmental pressures requires projections of how relevant risks will change over time. Current regulatory models of environmental risk assessment (ERA) of pollutants such as pharmaceuticals could be improved by considering the influence of global change factors (e.g., population growth) and by presenting uncertainty more transparently. In this article, we present the development of a prototype object-oriented Bayesian network (BN) for the prediction of environmental risk for six high-priority pharmaceuticals across 36 scenarios: current and three future population scenarios, combined with infrastructure scenarios, in three Norwegian counties. We compare the risk, characterized by probability distributions of risk quotients (RQs), across scenarios and pharmaceuticals. Our results suggest that RQs would be greatest in rural counties, due to the lower development of current wastewater treatment facilities, but that these areas consequently have the most potential for risk mitigation. This pattern intensifies under higher population growth scenarios. With this prototype, we developed a hierarchical probabilistic model and demonstrated its potential in forecasting the environmental risk of chemical stressors under plausible demographic and management scenarios, contributing to the further development of BNs for ERA. Integr Environ Assess Manag 2024;00:1-21. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Real-time swelling-collapse kinetics of nanogels driven by XFEL pulses.

Stimuli-responsive polymers are an important class of materials with many applications in nanotechnology and drug delivery. The most prominent one is poly-N-isopropylacrylamide (PNIPAm). The characterization of the kinetics of its change after a temperature jump is still a lively research topic, especially at nanometer-length scales where it is not possible to rely on conventional microscopic techniques. Here, we measured in real time the collapse of a PNIPAm shell on silica nanoparticles with megahertz x-ray photon correlation spectroscopy at the European XFEL. We characterize the changes of the particles diffusion constant as a function of time and consequently local temperature on sub-microsecond timescales. We developed a phenomenological model to describe the observed data and extract the characteristic times associated to the swelling and collapse processes. Different from previous studies tracking the turbidity of PNIPAm dispersions and using laser heating, we find collapse times below microsecond timescales and two to three orders of magnitude slower swelling times.

X-ray beam diagnostics at the MID instrument of the European X-ray Free-Electron Laser Facility.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

Supporting self-regulated-learning in colonoscopy training-A comparison cohort trial.

Aim: This study aimed to demonstrate that using a self-regulated learning (SRL) approach can improve colonoscopy performance skills. Background: Colonoscopy is the gold standard for detecting colorectal cancer and removing its precursors: polyps. Acquiring proficiency in colonoscopy is challenging, requiring completion of several hundred procedures. SRL seems to be beneficial to help trainees acquire competencies in regulating their future learning processes and enhance the outcomes of current learning situations. SRL is a learner-centred approach that refers to a trainee's ability to understand and control their learning environment, including cognitions, motivations and emotions. The key abilities include self- and situational awareness, task analysis, and strategic planning. This study is the first to use an SRL approach for workplace-based colonoscopy training. Methods: In this comparison cohort trial, participants used two SRL supports: a self-review of videotaped performance, and an online learning platform with procedural and conceptual knowledge about colonoscopy. In the control cohort, participants performed patient-based colonoscopy as usual in their departments. Improvement was monitored via three video-based ratings (study start, end of the study period, and follow-up) using the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT). Outcomes were analysed using two-way analysis of variance with repeated measurements. Results: This study recruited 21 participants (12, intervention cohort; nine, control cohort); 58 videos were recorded. The intraclass correlation coefficient was 0.88 (95% CI 0.61-0.98; p < 0.001). The global rating scale (GRS) and checklist (CL) in GiECAT were analysed separately. No statistically significant main effects of cohort (GRS: F(1,16) = 2.84, p = 0.11; CL: F(1,16) = 1.06, p = 0.32), test (GRS: F(2,32) = 2.56, p = 0.09; CL: F(2,32) = 0.76, p = 0.48), or interactions between cohort and test were observed (GRS: F(2,32) = 1.16, p = 0.33; CL: F(2,32) = 1.01, p = 0.37). Conclusions: SRL in patient-based colonoscopy is feasible; however, no clear effect on performance scores was observed.

Experiment data: Human-in-the-loop decision support in process control rooms.

These datasets contain measures from multi-modal data sources. They include objective and subjective measures commonly used to determine cognitive states of workload, situational awareness, stress, and fatigue using data collection tools such as NASA-TLX, SART, eye tracking, EEG, Health Monitoring Watch, a survey to assess training, and a think-aloud situational awareness assessment following the SPAM methodology. Also, data from a simulation formaldehyde production plant based on the interaction of the participants in a controlled control room experimental setting is included. The interaction with the plant is based on a human-in-the-loop alarm handling and process control task flow, which includes Monitoring, Alarm Handling, Recovery planning, and intervention (Troubleshooting, Control and Evaluation). Data was collected from 92 participants, split into four groups while they underwent the described task flow. Each participant tested three scenarios lasting 15-18 min with a -10-min survey completion and break period in between using different combinations of decision support tools. The decision support tools tested and varied for each group include alarm prioritisation vs. none, paper-based vs. Digitised screen-based procedures, and an AI recommendation system. This is relevant to compare current practices in the industry and the impact on operators' performance and safety. It is also applicable to validate proposed solutions for the industry. A statistical analysis was performed on the dataset to compare the outcomes of the different groups. Decision-makers can use these datasets for control room design and optimisation, process safety engineers, system engineers, human factors engineers, all in process industries, and researchers in similar or close domains.

Jetting bubbles observed by x-ray holography at a free-electron laser: internal structure and the effect of non-axisymmetric boundary conditions.

In this work, we study the jetting dynamics of individual cavitation bubbles using x-ray holographic imaging and high-speed optical shadowgraphy. The bubbles are induced by a focused infrared laser pulse in water near the surface of a flat, circular glass plate, and later probed with ultrashort x-ray pulses produced by an x-ray free-electron laser (XFEL). The holographic imaging can reveal essential information of the bubble interior that would otherwise not be accessible in the optical regime due to obscuration or diffraction. The influence of asymmetric boundary conditions on the jet's characteristics is analysed for cases where the axial symmetry is perturbed and curved liquid filaments can form inside the cavity. The x-ray images demonstrate that when oblique jets impact the rigid boundary, they produce a non-axisymmetric splash which grows from a moving stagnation point. Additionally, the images reveal the formation of complex gas/liquid structures inside the jetting bubbles that are invisible to standard optical microscopy. The experimental results are analysed with the assistance of full three-dimensional numerical simulations of the Navier-Stokes equations in their compressible formulation, which allow a deeper understanding of the distinctive features observed in the x-ray holographic images. In particular, the effects of varying the dimensionless stand-off distances measured from the initial bubble location to the surface of the solid plate and also to its nearest edge are addressed using both experiments and simulations. A relation between the jet tilting angle and the dimensionless bubble position asymmetry is derived. The present study provides new insights into bubble jetting and demonstrates the potential of x-ray holography for future investigations in this field. Supplementary Information: The online version contains supplementary material available at 10.1007/s00348-023-03759-9.

Incorporating climate projections in the environmental risk assessment of pesticides in aquatic ecosystems.

Global climate change will significantly impact the biodiversity of freshwater ecosystems, both directly and indirectly via the exacerbation of impacts from other stressors. Pesticides form a prime example of chemical stressors that are expected to synergize with climate change. Aquatic exposures to pesticides might change in magnitude due to increased runoff from agricultural fields, and in composition, as application patterns will change due to changes in pest pressures and crop types. Any prospective chemical risk assessment that aims to capture the influence of climate change should properly and comprehensively account for the variabilities and uncertainties that are inherent to projections of future climate. This is only feasible if they probabilistically propagate extensive ensembles of climate model projections. However, current prospective risk assessments typically make use of process-based models of chemical fate that do not typically allow for such high-throughput applications. Here, we describe a Bayesian network model that does. It incorporates a two-step univariate regression model based on a 30-day antecedent precipitation index, circumventing the need for computationally laborious mechanistic models. We show its feasibility and application potential in a case study with two pesticides in a Norwegian stream: the fungicide trifloxystrobin and herbicide clopyralid. Our analysis showed that variations in pesticide application rates as well as precipitation intensity lead to variations in in-stream exposures. When relating to aquatic risks, the influence of these processes is reduced and distributions of risk are dominated by effect-related parameters. Predicted risks for clopyralid were negligible, but the probability of unacceptable future environmental risks due to exposure to trifloxystrobin (i.e., a risk quotient >1) was 8%-12%. This percentage further increased to 30%-35% when a more conservative precautionary factor of 100 instead of 30 was used. Integr Environ Assess Manag 2024;20:384-400. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Laser speckle contrast imaging for intraoperative assessment of intestinal microcirculation in normo- and hypovolemic circulation in a porcine model.

INTRODUCTION: Healing is essential for successful colorectal surgery. Optimal microcirculation is needed to ensure this; however, this is only subjectively assessed by the surgeon. Laser Speckle Contrast Imaging (LSCI) is an objective non-contact, image-based method to quantify microcirculation in bowel ends. This study aimed to evaluate the application of LSCI in an open surgery porcine model, determine differences between normal and impaired microcirculation, and test the LSCI applicability to repeated measurements. METHOD: A midline laparotomy was made in ten healthy female pigs to expose the colon and small intestine. Subsequently, baseline measurements were conducted. A local arteria supplying the colonic or small intestine mesentery was clamped for 5 min. and LSCI measures were made again. After an hour's rest, LSCI measurements were done in two unaffected areas on the colon and the small intestine, and baseline values were recorded. Hypotension was induced with rapid bleeding and LSCI measurements were done. After the mean arterial blood pressure (MAP) dropped to 50-60 mmHg, norepinephrine infusion was started. At a stable MAP of 85-100 mmHg, LSCI measurements were repeated at 0 min. and 30 min. during continuous norepinephrine infusion. RESULTS: Cross-clamping caused LSCI levels to drop equally in both the colon and small intestine by 60% in the entire the clamped zone. Compared to baseline, the microcirculation measured by LSCI in the unclamped adjacent transition zone was diminished by 33% and 40%, colon and small intestines, respectively. During hypotension due to bleeding, LSCI decreased as expected. When MAP was stabilized by norepinephrine infusion, LSCI values dropped further: compared to baseline, measurements decreased with 24% and 20% in colon and small intestines, respectively. CONCLUSION: LSCI can be used as a quantitative, real-time, non-contact method to detect changes in the microcirculation during open intestinal surgery with large changes in microcirculation due to e.g., hypovolemic and norepinephrine infusion. It is simple to use and in contrast to the existing intraoperative microcirculation assessment techniques, LSCI stands out primarily for its elimination of the requirement for a dye. As our study has shown, this feature allows us to perform time-independent measurements and repeat them indefinitely in nearby regions without compromising the effectiveness of the method.

Unveiling polyamorphism and polyamorphic interconversions in pharmaceuticals: the peculiar case of hydrochlorothiazide.

Polyamorphism has been a controversial and highly debated solid-state phenomenon in both material and pharmaceutical communities. Although some evidence of this fascinating phenomenon has been reported for several inorganic systems, and more recently also for a few organic compounds, the occurrence of polyamorphism is poorly understood and the molecular-level organization of polyamorphic forms is still unknown. Here we have investigated the occurrence of polyamorphism and polyamorphic interconversions in hydrochlorothiazide (HCT), using both experimental and computational methods. Three distinct HCT polyamorphs, presenting distinct physical and thermal stabilities as well as distinct relaxation properties, were systematically prepared using spray-drying (SD), quench-cooling (QC) and ball milling (BM) methods. HCT polyamorph II (obtained by QC) was found to be more physically stable than polyamorphs I and III (obtained by SD and BM, respectively). Furthermore, polyamorphs I and III could be converted into polyamorph II after QC, while polyamorph II did not convert to any other polyamorph after SD or BM. Molecular dynamics simulations show that HCT dihedral angle distributions are significantly different for polyamorphs I and II, which is postulated as a possible explanation for their different physicochemical properties.

Technical assessment in minimally invasive complete mesocolic excision: Is the complete mesocolic excision competency assessment tool valid and reliable?

AIM: The complete mesocolic excision competency assessment tool (CMECAT) is a novel tool designed to assess technical skills in minimally invasive complete mesocolic excision (CME) surgery. The aim of this study was to assess construct validity and reliability of CMECAT in a clinical context. METHOD: Colorectal surgeons were asked to submit video recorded laparoscopic CME resections for independent assessment of their technical abilities. The videos were grouped by surgeons' training level, and four established CME experts were recruited as CMECAT assessors. Extended reliability analysis (G-theory) was applied to describe assessor agreement. RESULTS: A total of 19 videos and 72 assessments were included in the analysis. Overall, technical skills assessed by CMECAT improved with increased training level: the experts scored significantly better than the untrained surgeons (3.3 vs. 2.5 points; p < 0.01). On right-sided resections, significantly higher scores were reported with increased training level for all categories and sections, while for left-sided resections, the variance across groups was smaller and significantly higher scores were only reported for oncological safety describing items. Overall, assessor agreement was high (G-coefficient: 0.81). CONCLUSION: This study confirms that CMECAT can be applied to video recorded CME cases for technical skill assessment. Further, it can reliably assess technical performance in right sided CME surgery, where construct validity has now been established. More videos are required to evaluate its validity on left colonic CME. In the future, we hope CMECAT can improve feedback during CME training, serve as a tool in certification processes and contribute to distinguishing CME from conventional surgery in future research.

Resonant X-ray excitation of the nuclear clock isomer 45Sc.

Resonant oscillators with stable frequencies and large quality factors help us to keep track of time with high precision. Examples range from quartz crystal oscillators in wristwatches to atomic oscillators in atomic clocks, which are, at present, our most precise time measurement devices1. The search for more stable and convenient reference oscillators is continuing2-6. Nuclear oscillators are better than atomic oscillators because of their naturally higher quality factors and higher resilience against external perturbations7-9. One of the most promising cases is an ultra-narrow nuclear resonance transition in 45Sc between the ground state and the 12.4-keV isomeric state with a long lifetime of 0.47 s (ref. 10). The scientific potential of 45Sc was realized long ago, but applications require 45Sc resonant excitation, which in turn requires accelerator-driven, high-brightness X-ray sources11 that have become available only recently. Here we report on resonant X-ray excitation of the 45Sc isomeric state by irradiation of Sc-metal foil with 12.4-keV photon pulses from a state-of-the-art X-ray free-electron laser and subsequent detection of nuclear decay products. Simultaneously, the transition energy was determined as [Formula: see text] with an uncertainty that is two orders of magnitude smaller than the previously known values. These advancements enable the application of this isomer in extreme metrology, nuclear clock technology, ultra-high-precision spectroscopy and similar applications.

Development and validation of a simulation-based assessment tool in colonoscopy.

BACKGROUND: Colonoscopy is difficult to learn. Virtual reality simulation training is helpful, but how and when novices should progress to patient-based training has yet to be established. To date, there is no assessment tool for credentialing novice endoscopists prior to clinical practice. The aim of this study was to develop such an assessment tool based on metrics provided by the simulator. The metrics used for the assessment tool should be able to discriminate between novices, intermediates, and experts and include essential checklist items for patient safety. METHODS: The validation process was conducted based on the Standards for Educational and Psychological Testing. An expert panel decided upon three essential checklist items for patient safety based on Lawshe's method: perforation, hazardous tension to the bowel wall, and cecal intubation. A power calculation was performed. In this study, the Simbionix GI Mentor II simulator was used. Metrics with discriminatory ability were identified with variance analysis and combined to form an aggregate score. Based on this score and the essential items, pass/fail standards were set and reliability was tested. RESULTS: Twenty-four participants (eight novices, eight intermediates, and eight expert endoscopists) performed two simulated colonoscopies. Four metrics with discriminatory ability were identified. The aggregate score ranged from 4.2 to 51.2 points. Novices had a mean score of 10.00 (SD 5.13), intermediates 24.63 (SD 7.91), and experts 30.72 (SD 11.98). The difference in score between novices and the other two groups was statistically significant (p<0.01). Although expert endoscopists had a higher score, the difference was not statistically significant (p=0.40). Reliability was good (Cronbach's alpha=0.86). A pass/fail score was defined at 17.1 points with correct completion of three essential checklist items, resulting in three experts and three intermediates failing and one novice passing the assessment. CONCLUSION: We established a valid and reliable assessment tool with a pass/fail standard on the simulator. We suggest using the assessment after simulation-based training before commencing work-based learning.

Risk assessment and antibody responses to SARS-CoV-2 in healthcare workers.

Background: Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings. Methods: From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021. Results: We identified a prevalence of 10.5% (95% confidence interval, CI: 8.8-12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5-17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5-35.1) and occupational exposure (OR 2.2; 95% CI: 1.4-3.2). Conclusion: We found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.

The structure of magnesium stearate trihydrate determined from a micrometre-sized single crystal using a microfocused synchrotron X-ray beam.

Crystalline magnesium stearate has been extensively used as an additive in pharmaceutical and other industries for decades. However, the lack of suitably large crystals has hindered the determination of the crystal structure and thereby a more fundamental understanding of the structure-functionality relationship. Presented here is the structure of magnesium stearate trihydrate as determined from X-ray diffraction data of a micrometre-sized single crystal measured at a fourth-generation synchrotron facility. Despite the small size of the single crystals and the weak diffraction, it was possible to determine the positions of the non-hydrogen atoms reliably. Periodic dispersion-corrected density functional theory calculations were used to obtain the positions of the hydrogen atoms playing an important role in the overall organization of the structure via a hydrogen-bond network.

Quality of life and symptom burden after rectal cancer surgery: a randomised controlled trial comparing patient-led versus standard follow-up.

PURPOSE: After curatively intended rectal cancer (RC) surgery, new follow-up strategies are warranted, seeking more individualised care and targeting health-related quality of life (HRQoL) and functional outcomes. The FURCA trial aimed to investigate the effect of patient-led follow-up on HRQoL and symptom burden 3 years after surgery. METHODS: RC patients from four Danish centres were randomised 1:1 to intervention (patient-led follow-up with patient education and self-referral to a specialist nurse) or control (standard follow-up with five routine doctor visits). Patients in both groups had a computed tomography (CT) at 1 and 3 years. The primary outcome (HRQoL) was assessed by the Functional Assessment of Cancer Therapy - colorectal (FACT-C) score (Ward et al. in Qual Life Res. 8(3):181-95, 18). Secondary outcomes were functional measures, patient involvement and satisfaction and cancer recurrence at 3 years. RESULTS: From Feb 2016 to Aug 2018, 336 patients were included of whom 248 completed 3 years of follow-up. Between-group differences were found neither for the primary endpoint, nor for functional outcomes. The recurrence rate did not differ between the groups. Patient involvement and satisfaction were higher in the intervention group with statistical significance in almost half of the items. CONCLUSIONS: We found no effect on HRQoL and symptom burden from patient-led follow-up, although it may improve patient-perceived involvement and satisfaction. IMPLICATIONS FOR CANCER SURVIVORS: The findings in this study suggest that patient-led follow-up is a more tailored approach to meet cancer survivors' needs and might improve their ability to cope with survivorship. GOV IDENTIFIER: R97-A6511-14-S23.

Imaging via Correlation of X-Ray Fluorescence Photons.

We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecond-duration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters. Since fluorescence can dominate coherent scattering, this may enable imaging uncrystallised macromolecules.

Evaluation of Surgeon-Performed Ultrasonography With or Without Contrast Enhancement vs Scintigraphy in Patients With Primary Hyperparathyroidism.

Importance: Scintigraphy and ultrasonography are common imaging modalities for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism. When comparing the 2 modalities, the benefits of ultrasonography in terms of convenience, patient comfort, duration, cost, and lack of radiation should be taken into account. Objective: To investigate whether surgeon-performed ultrasonography, with or without contrast-enhanced ultrasonography (CEUS), is noninferior to scintigraphy for localizing pathological parathyroid glands in patients with primary hyperparathyroidism. Design, Setting, and Participants: Prospective, paired, noninferiority cohort study performed at a high-volume tertiary referral center for parathyroidectomy with blinded examiners and a 6-month follow-up. Participants were adults (age ≥18 years) referred for parathyroidectomy due to primary hyperparathyroidism. Of 207 eligible patients, 35 were excluded, leaving 172 enrolled in the study. Inclusion lasted from September 2019 until February 2021. Follow-up ended in December 2021. Exposures: 99mTechnetium-pertechnetate/99mtechnetium-sestamibi subtraction scintigraphy with 99mtechnetium-sestamibi single-photon emission computed tomography/computed tomography, followed by surgeon-performed ultrasonography and CEUS. Main Outcomes and Measures: The sensitivity of each imaging modality in localizing pathological parathyroid glands, calculated on a per-quadrant and a per-patient basis, respectively. The a priori noninferiority margin was a lower 95% confidence limit for the difference in sensitivity not falling below -10%. Results: Out of 172 participants, 139 (80.8%) were women, the median (range) age was 65 (24-87) years, and the median (IQR) follow-up was 200.5 (181-280.25) days. Quadrant sensitivity (95% CI) was 70.9% (63.2%-78.5%) for ultrasonography, 68.4% (60.4%-76.5%) for ultrasonography plus CEUS, and 67.0% (60.0%-74.0%) for scintigraphy. The sensitivity difference (95% CI) compared with scintigraphy was 3.9% (-4.1% to 11.8%) for ultrasonography and 1.5% (-6.4% to 9.3%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Per-patient sensitivity was 81.4% (74.8%-86.9%) for ultrasonography and 79.1% (72.2%-84.9%) for both scintigraphy and ultrasonography plus CEUS. The sensitivity difference compared with scintigraphy was 2.3% (-6.8% to 11.4%) for ultrasonography and 0.0% (-9.1% to 9.1%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Conclusions and Relevance: In this cohort study, conventional ultrasonography by an experienced parathyroid surgeon-sonographer was noninferior to scintigraphy and may constitute a valid first-line imaging modality in patients with primary hyperparathyroidism, even without the addition of CEUS. Further imaging should be reserved for cases that are equivocal or nonlocalizing on ultrasonography.