Targeted degradation via direct 26S proteasome recruitment.

Engineered destruction of target proteins by recruitment to the cell's degradation machinery has emerged as a promising strategy in drug discovery. The majority of molecules that facilitate targeted degradation do so via a select number of ubiquitin ligases, restricting this therapeutic approach to tissue types that express the requisite ligase. Here, we describe a new strategy of targeted protein degradation through direct substrate recruitment to the 26S proteasome. The proteolytic complex is essential and abundantly expressed in all cells; however, proteasomal ligands remain scarce. We identify potent peptidic macrocycles that bind directly to the 26S proteasome subunit PSMD2, with a 2.5-Å-resolution cryo-electron microscopy complex structure revealing a binding site near the 26S pore. Conjugation of this macrocycle to a potent BRD4 ligand enabled generation of chimeric molecules that effectively degrade BRD4 in cells, thus demonstrating that degradation via direct proteasomal recruitment is a viable strategy for targeted protein degradation.

Imaging after Pancreatic Surgery: Expected Findings and Postoperative Complications.

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.

The Peritoneum: Anatomy, Pathologic Findings, and Patterns of Disease Spread.

Disease spread in the abdomen and pelvis generally occurs in a predictable pattern in relation to anatomic landmarks and fascial planes. Anatomically, the abdominopelvic cavity is subdivided into several smaller spaces or compartments by key ligaments and fascial planes. The abdominal cavity has been traditionally divided into peritoneal, retroperitoneal, and pelvic extraperitoneal spaces. Recently, more clinically relevant classifications have evolved. Many pathologic conditions affect the abdominal cavity, including traumatic, inflammatory, infectious, and neoplastic processes. These abnormalities can extend beyond their sites of origin through various pathways. Identifying the origin of a disease process is the first step in formulating a differential diagnosis and ultimately reaching a final diagnosis. Pathologic conditions differ in terms of pathways of disease spread. For example, simple fluid tracks along fascial planes, respecting anatomic boundaries, while fluid from acute necrotizing pancreatitis can destroy fascial planes, resulting in transfascial spread without regard for anatomic landmarks. Furthermore, neoplastic processes can spread through multiple pathways, with a propensity for spread to noncontiguous sites. When the origin of a disease process is not readily apparent, recognizing the spread pattern can allow the radiologist to work backward and ultimately arrive at the site or source of pathogenesis. As such, a cohesive understanding of the peritoneal anatomy, the typical organ or site of origin for a disease process, and the corresponding pattern of disease spread is critical not only for initial diagnosis but also for establishing a road map for staging, anticipating further disease spread, guiding search patterns and report checklists, determining prognosis, and tailoring appropriate follow-up imaging studies. ©RSNA, 2024 Supplemental material is available for this article.

MRI assessment of rectal cancer response to neoadjuvant therapy: a multireader study.

OBJECTIVES: A watch and wait strategy with the goal of organ preservation is an emerging treatment paradigm for rectal cancer following neoadjuvant treatment. However, the selection of appropriate patients remains a challenge. Most previous efforts to measure the accuracy of MRI in assessing rectal cancer response used a small number of radiologists and did not report variability among them. METHODS: Twelve radiologists from 8 institutions assessed baseline and restaging MRI scans of 39 patients. The participating radiologists were asked to assess MRI features and to categorize the overall response as complete or incomplete. The reference standard was pathological complete response or a sustained clinical response for > 2 years. RESULTS: We measured the accuracy and described the interobserver variability of interpretation of rectal cancer response between radiologists at different medical centers. Overall accuracy was 64%, with a sensitivity of 65% for detecting complete response and specificity of 63% for detecting residual tumor. Interpretation of the overall response was more accurate than the interpretation of any individual feature. Variability of interpretation was dependent on the patient and imaging feature investigated. In general, variability and accuracy were inversely correlated. CONCLUSIONS: MRI-based evaluation of response at restaging is insufficiently accurate and has substantial variability of interpretation. Although some patients' response to neoadjuvant treatment on MRI may be easily recognizable, as seen by high accuracy and low variability, that is not the case for most patients. KEY POINTS: • The overall accuracy of MRI-based response assessment is low and radiologists differed in their interpretation of key imaging features. • Some patients' scans were interpreted with high accuracy and low variability, suggesting that these patients' pattern of response is easier to interpret. • The most accurate assessments were those of the overall response, which took into consideration both T2W and DWI sequences and the assessment of both the primary tumor and the lymph nodes.

Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.

Intracellular lipopolysaccharide from Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic cell death, interleukin-1ß processing, and lethal septic shock. How caspase-11 executes these downstream signalling events is largely unknown. Here we show that gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin-1ß maturation. A forward genetic screen with ethyl-N-nitrosourea-mutagenized mice links Gsdmd to the intracellular lipopolysaccharide response. Macrophages from Gsdmd(-/-) mice generated by gene targeting also exhibit defective pyroptosis and interleukin-1ß secretion induced by cytoplasmic lipopolysaccharide or Gram-negative bacteria. In addition, Gsdmd(-/-) mice are protected from a lethal dose of lipopolysaccharide. Mechanistically, caspase-11 cleaves gasdermin D, and the resulting amino-terminal fragment promotes both pyroptosis and NLRP3-dependent activation of caspase-1 in a cell-intrinsic manner. Our data identify gasdermin D as a critical target of caspase-11 and a key mediator of the host response against Gram-negative bacteria.

Differences between measured and reported volatile organic compound emissions from oil sands facilities in Alberta, Canada.

Large-scale oil production from oil sands deposits in Alberta, Canada has raised concerns about environmental impacts, such as the magnitude of air pollution emissions. This paper reports compound emission rates (E) for 69-89 nonbiogenic volatile organic compounds (VOCs) for each of four surface mining facilities, determined with a top-down approach using aircraft measurements in the summer of 2013. The aggregate emission rate (aE) of the nonbiogenic VOCs ranged from 50 ± 14 to 70 ± 22 t/d depending on the facility. In comparison, equivalent VOC emission rates reported to the Canadian National Pollutant Release Inventory (NPRI) using accepted estimation methods were lower than the aE values by factors of 2.0 ± 0.6, 3.1 ± 1.1, 4.5 ± 1.5, and 4.1 ± 1.6 for the four facilities, indicating underestimation in the reported VOC emissions. For 11 of the combined 93 VOC species reported by all four facilities, the reported emission rate and E were similar; but for the other 82 species, the reported emission rate was lower than E The median ratio of E to that reported for all species by a facility ranged from 4.5 to 375 depending on the facility. Moreover, between 9 and 53 VOCs, for which there are existing reporting requirements to the NPRI, were not included in the facility emission reports. The comparisons between the emission reports and measurement-based emission rates indicate that improvements to VOC emission estimation methods would enhance the accuracy and completeness of emission estimates and their applicability to environmental impact assessments of oil sands developments.

Dual functionality of ß-tryptase protomers as both proteases and cofactors in the active tetramer.

Human ß-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of the allergic inflammatory responses in asthma. During acute hypersensitivity reactions, mast cells degranulate, releasing active tetramer as a complex with proteoglycans. Extensive efforts have focused on developing therapeutic ß-tryptase inhibitors, but its unique activation mechanism is less well-explored. Tryptase is active only after proteolytic removal of the pro-domain followed by tetramer formation via two distinct symmetry-related interfaces. We show that the cleaved I16G mutant cannot tetramerize, likely due to impaired insertion of its N terminus into its "activation pocket," indicating allosteric linkage at multiple sites on each protomer. We engineered cysteines into each of the two distinct interfaces (Y75C for small or I99C for large) to assess the activity of each tetramer and disulfide-locked dimer. Using size-exclusion chromatography and enzymatic assays, we demonstrate that the two large tetramer interfaces regulate enzymatic activity, elucidating the importance of this protein-protein interaction for allosteric regulation. Notably, the I99C large interface dimer is active, even in the absence of heparin. We show that a monomeric ß-tryptase mutant (I99C*/Y75A/Y37bA, where C* is cysteinylated Cys-99) cannot form a dimer or tetramer, yet it is active but only in the presence of heparin. Thus heparin both stabilizes the tetramer and allosterically conditions the active site. We hypothesize that each ß-tryptase protomer in the tetramer has two distinct roles, acting both as a protease and as a cofactor for its neighboring protomer, to allosterically regulate enzymatic activity, providing a rationale for direct correlation of tetramer stability with proteolytic activity.

Iron-Containing Abdominal Pathologies: Exploiting Magnetic Susceptibility Artifact on Dual-Echo Gradient-Echo Magnetic Resonance Imaging.

A multitude of pathologic entities involve abnormal iron deposition in the abdomen. These lesions demonstrate decreased signal on longer magnetic resonance sequences with longer echo time due to T2* effect. Dual-echo gradient-echo sequences demonstrate increased susceptibility artifact with longer echo sequences. In this article, the spectrum of iron-containing abdominal pathologies is illustrated, with their characteristic distributions. Included is a brief discussion of the physics of magnetic resonance imaging of iron-containing lesions.

GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes.

Gasdermin-D (GsdmD) is a critical mediator of innate immune defense because its cleavage by the inflammatory caspases 1, 4, 5, and 11 yields an N-terminal p30 fragment that induces pyroptosis, a death program important for the elimination of intracellular bacteria. Precisely how GsdmD p30 triggers pyroptosis has not been established. Here we show that human GsdmD p30 forms functional pores within membranes. When liberated from the corresponding C-terminal GsdmD p20 fragment in the presence of liposomes, GsdmD p30 localized to the lipid bilayer, whereas p20 remained in the aqueous environment. Within liposomes, p30 existed as higher-order oligomers and formed ring-like structures that were visualized by negative stain electron microscopy. These structures appeared within minutes of GsdmD cleavage and released Ca(2+) from preloaded liposomes. Consistent with GsdmD p30 favoring association with membranes, p30 was only detected in the membrane-containing fraction of immortalized macrophages after caspase-11 activation by lipopolysaccharide. We found that the mouse I105N/human I104N mutation, which has been shown to prevent macrophage pyroptosis, attenuated both cell killing by p30 in a 293T transient overexpression system and membrane permeabilization in vitro, suggesting that the mutants are actually hypomorphs, but must be above certain concentration to exhibit activity. Collectively, our data suggest that GsdmD p30 kills cells by forming pores that compromise the integrity of the cell membrane.

Quantifying the Primary Emissions and Photochemical Formation of Isocyanic Acid Downwind of Oil Sands Operations.

Isocyanic acid (HNCO) is a known toxic species and yet the relative importance of primary and secondary sources to regional HNCO and population exposure remains unclear. Off-road diesel fuel combustion has previously been suggested to be an important regional source of HNCO, which implies that major industrial facilities such as the oil sands (OS), which consume large quantities of diesel fuel, can be sources of HNCO. The OS emissions of nontraditional toxic species such as HNCO have not been assessed. Here, airborne measurements of HNCO were used to estimate primary and secondary HNCO for the oil sands. Approximately 6.2 ± 1.1 kg hr-1 was emitted from off-road diesel activities within oil sands facilities, and an additional 116-186 kg hr-1 formed from the photochemical oxidation of diesel exhaust. Together, the primary and secondary HNCO from OS operations represent a significant anthropogenic HNCO source in Canada. The secondary HNCO downwind of the OS was enhanced by up to a factor of 20 relative to its primary emission, an enhancement factor significantly greater than previously estimated from laboratory studies. Incorporating HNCO emissions and formation into a regional model demonstrated that the HNCO levels in Fort McMurray (∼10-70 km downwind of the OS) are controlled by OS emissions; > 50% of the monthly mean HNCO arose from the OS. While the mean HNCO levels in Fort McMurray are predicted to be below the 1000 pptv level associated with potential negative health impacts, (∼25 pptv in August-September), an order of magnitude increase in concentration is predicted (250-600 pptv) when the town is directly impacted by OS plumes. The results here highlight the importance of obtaining at-source HNCO emission factors and advancing the understanding of secondary HNCO formation mechanisms, to assess and improve HNCO population exposure predictions.

Reducing Variability in Orthogonal Reformatted Image Quality Associated With Axial Long-z-Axis CT Angiography.

OBJECTIVE: The objective of our study was to reduce variation in image quality of orthogonal reformatted images generated from long-z-axis CT angiography (CTA) studies of the upper and lower extremities. SUBJECTS AND METHODS: Upper and lower extremity CTA studies were targeted at a single health care system. A correctly performed CTA examination was defined as one that met the following three criteria: Sagittal and coronal reformats were obtained, a high-resolution matrix greater than 512 × 512 was used, and reformatted images were available in a distance-measurable format. Baseline data were collected from February 1, 2014, through September 30, 2014. Corrective actions were implemented during three consecutive plan-do-check-act (PDCA) cycles from October 1, 2014, through July 31, 2015, that addressed human, technical, and systematic variations. A 3-month maintenance period followed in which no intervention was performed. Longitudinal data were analyzed monthly using a statistical process control chart (p-chart). RESULTS: The total number of long-z-axis extremity CTA studies analyzed was as follows: 351 CTA studies were analyzed at baseline, 94 at the first PDCA cycle, 92 at the second PDCA cycle, 114 at the third PDCA cycle, and 138 during the maintenance period. The monthly rate of correctly performed studies ranged from 7% to 51% (mean, 38% ± 13% [SD]) during the baseline period, 32-59% (mean, 46% ± 14%) during the first PDCA cycle, 40-81% (mean, 61% ± 21%) during the second PDCA cycle, and 80-82% (mean, 81% ± 0.9%) during the third PDCA cycle. The monthly rate improved to 90-91% (mean, 91% ± 0.5%) during the maintenance period. The upper and lower control limits of the p-chart were upshifted after the second and third PDCA cycles. Correcting systematic and technical variations led to the greatest improvements in reformat accuracy. CONCLUSION: Obtaining consistently and correctly reformatted images from long-z-axis CTA studies is achievable using iterative PDCA cycles.

Conformational dynamics control ubiquitin-deubiquitinase interactions and influence in vivo signaling.

Ubiquitin is a highly conserved eukaryotic protein that interacts with a diverse set of partners to act as a cellular signaling hub. Ubiquitin's conformational flexibility has been postulated to underlie its multifaceted recognition. Here we use computational and library-based means to interrogate core mutations that modulate the conformational dynamics of human ubiquitin. These ubiquitin variants exhibit increased affinity for the USP14 deubiquitinase, with concomitantly reduced affinity for other deubiquitinases. Strikingly, the kinetics of conformational motion are dramatically slowed in these variants without a detectable change in either the ground state fold or excited state population. These variants can be ligated into substrate-linked chains in vitro and in vivo but cannot solely support growth in eukaryotic cells. Proteomic analyses reveal nearly identical interaction profiles between WT ubiquitin and the variants but identify a small subset of altered interactions. Taken together, these results show that conformational dynamics are critical for ubiquitin-deubiquitinase interactions and imply that the fine tuning of motion has played a key role in the evolution of ubiquitin as a signaling hub.

Knee MRI: Vascular Pathology.

OBJECTIVE: Patients who undergo knee MRI for presumed musculoskeletal disease can have unexpected vascular findings or pathology in the imaged field. Some vascular processes are limb threatening and affect treatment planning and patient outcome. CONCLUSION: Unexpected vascular findings on knee MRI can range from incidental to symptomatic and can include such processes as variant anatomy, aneurysm, traumatic injury, and neoplasm. The assessment for vascular pathology should be a key component of every radiologist's search pattern when evaluating knee MRI.

Repeatability of diagnostic features and scoring systems for hepatocellular carcinoma by using MR imaging.

PURPOSE: To determine for expert and novice radiologists repeatability of major diagnostic features and scoring systems (ie, Liver Imaging Reporting and Data System [LI-RADS], Organ Procurement and Transplantation Network [OPTN], and American Association for the Study of Liver Diseases [AASLD]) for hepatocellular carcinoma (HCC) by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Institutional review board approval was obtained and patient consent was waived for this HIPAA-compliant, retrospective study. The LI-RADS discussed in this article refers to version 2013.1. Ten blinded readers reviewed 100 liver MR imaging studies that demonstrated observations preliminarily assigned LI-RADS scores of LR1-LR5. Diameter and major HCC features (arterial hyperenhancement, washout appearance, pseudocapsule) were recorded for each observation. LI-RADS, OPTN, and AASLD scores were assigned. Interreader agreement was assessed by using intraclass correlation coefficients and κ statistics. Scoring rates were compared by using McNemar test. RESULTS: Overall interreader agreement was substantial for arterial hyperenhancement (0.67 [95% confidence interval {CI}: 0.65, 0.69]), moderate for washout appearance (0.48 [95%CI: 0.46, 0.50]), moderate for pseudocapsule (0.52 [95% CI: 050, 0.54]), fair for LI-RADS (0.35 [95% CI: 0.34, 0.37]), fair for AASLD (0.39 [95% CI: 0.37, 0.42]), and moderate for OPTN (0.53 [95% CI: 0.51, 0.56]). Agreement for measured diameter was almost perfect (range, 0.95-0.97). There was substantial agreement for most scores consistent with HCC. Experts agreed significantly more than did novices and were significantly more likely than were novices to assign a diagnosis of HCC (P < .001). CONCLUSION: Two of three major features for HCC (washout appearance and pseudocapsule) have only moderate interreader agreement. Experts and novices who assigned scores consistent with HCC had substantial but not perfect agreement. Expert agreement is substantial for OPTN, but moderate for LI-RADS and AASLD. Novices were less consistent and less likely to diagnose HCC than were experts.

Evaluation of low-dose CT angiography with model-based iterative reconstruction after endovascular aneurysm repair of a thoracic or abdominal aortic aneurysm.

OBJECTIVE: The objective of our study was to evaluate image quality and overall adequacy of low-dose CT angiography (CTA) with model-based iterative reconstruction (MBIR) in patients who had undergone endovascular aneurysm repair (EVAR) of a thoracic or abdominal aortic aneurysm. MATERIALS AND METHODS: Thirty patients, all of whom had undergone standard-dose CTA performed previously with adaptive statistical iterative reconstruction (ASIR), underwent low-dose CTA for surveillance after EVAR. Two radiologists randomly evaluated both studies, and quality parameters were assessed. The maximal aneurysm diameter was measured, and the images were evaluated to see whether an endoleak was present. The image noise and contrast-to-noise ratio (CNR) were measured. The volume CT dose index and dose-length product were recorded. RESULTS: The mean image score for low-dose CTA was acceptable to very good in all categories of assessment. There was no significant difference between low-dose CTA and standard-dose CTA in the evaluation of the stent lumen. Subjective assessments of stent configuration, aneurysm outline, aortic branch vessel outline, overall adequacy of vascular imaging, and overall adequacy of solid organ imaging were superior on standard-dose CTA. Interobserver agreement for endoleak detection was higher for low-dose CTA. There was no significant difference in the mean aneurysm diameter between the two readers on low-dose CTA and standard-dose CTA. The effective radiation dose for low-dose CTA was lower than standard-dose CTA during both the arterial (mean, 4.4 vs 16.2 mSv, respectively) and the delayed (2.4 vs 6.7 mSv) phase acquisitions. The measured image noise was lower (14.7 vs 19.3 HU) and CNR was higher (25.6 vs 17.1) on the low-dose CTA studies than on the standard-dose CTA studies. CONCLUSION: Low-dose CTA with MBIR enables up to 73% dose reduction as compared with CTA performed with ASIR while maintaining diagnostic adequacy for CTA surveillance of patients who have undergone EVAR of a thoracic or abdominal aortic aneurysm.

CT angiography in the abdomen: a pictorial review and update.

The development of multidetector CT technology and helical scanning techniques has revolutionized the use of CT for primary diagnostic evaluation of the abdominal vasculature, particularly the arterial system. CT angiography has numerous benefits relative to conventional catheter angiography, and has largely replaced catheter-based techniques in many clinical algorithms. This pictorial review and update will cover important technical principles related to modern CT angiography (including contrast delivery and dose considerations), discuss relevant anatomy and variants, and illustrate numerous arterial conditions related to the abdominal aorta and branch vessels.

MR imaging in the characterization of small renal masses.

OBJECTIVE: The aim of our study was to evaluate the effectiveness of MR imaging for the characterization of small (<2 cm) renal lesions described as indeterminate on prior US or CT. MATERIALS AND METHODS: Sixty-three small renal masses in 51 patients considered indeterminate on prior ultrasound or CT scans were included in the study. A retrospective evaluation of the examinations was performed independently by two body magnetic resonance imaging (MRI) radiologists who were unaware of the final diagnosis. A 3-point confidence scale (1: benign, 2: indeterminate, and 3: malignant) was established to determine the level of suspicion for malignancy. Interobserver agreement was determined with a weighted kappa statistic. The diagnosis was verified by imaging follow-up of at least 24 months (mean 60 months) in 53 lesions and by pathology in 10 lesions. RESULTS: MRI detected all eight malignancies in the series. There were eight malignant lesions and two benign lesions among those with pathologic follow-up. No interval growth or evidence of malignancy in the remaining 53 lesions was found for a minimum of 24 months by repeat imaging. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI for differentiating benign from malignant small renal lesions were 100% (62.9-100%, 95% CI), 94.5% (84.9-98.8%, 95% CI), 72.7% (39.1-93.6%, 95% CI), and 100% (93.1-100%, 95% CI), respectively. The kappa value for interobserver agreement was 0.77 (95% CI 0.59-0.96, p-value <0.001). CONCLUSION: MR imaging is an effective method for characterizing small (<2 cm) renal masses found to be indeterminate by US or CT.

Comparison of acute transient dyspnea after intravenous administration of gadoxetate disodium and gadobenate dimeglumine: effect on arterial phase image quality.

PURPOSE: To determine whether acute transient dyspnea and/or arterial phase image degradation occurs more or less often after intravenous administration of gadoxetate disodium than with intravenous administration of gadobenate dimeglumine. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained for this prospective observational study. One hundred ninety-eight gadolinium-based contrast media administrations (99 with gadoxetate disodium [10 mL, n = 97; 8 mL, n = 1; 16 mL, n = 1] and 99 with gadobenate dimeglumine [0.1 mmol per kilogram of body weight, maximum dose, 20 mL]) for hepatobiliary indications were assessed in 192 patients. Subjective patient complaints were assessed. Objective respiratory motion degradation on T1-weighted precontrast and dynamic postcontrast (arterial, venous, or late dynamic or extracellular) magnetic resonance (MR) imaging datasets were independently assessed in a randomized, blinded fashion by five readers using a five-point scale, with mean scores of 4 or greater indicating severe motion. Comparisons between agents were made by using χ(2) or Fisher exact test, where appropriate. RESULTS: Significantly more patient complaints of acute transient dyspnea occurred after gadoxetate disodium administration than gadobenate dimeglumine (14% [14 of 99] vs 5% [five of 99], P = .05). There were significantly more severely degraded arterial phase data sets for gadoxetate disodium than for gadobenate dimeglumine for both the general population (17% [17 of 99] vs 2% [two of 99], P = .0007) and the subpopulation with cirrhosis (19% [14 of 72] vs 3% [one of 37], P = .02). This effect did not extend to venous (1% [one of 99] vs 2% [two of 99], P > .99 [overall population]) or late dynamic or extracellular (2% [two of 99] vs 0% [zero of 99], P = .5 [overall population]) phases. No patient required treatment for self-limited dyspnea. CONCLUSION: Intravenous gadoxetate disodium can result in acute self-limiting dyspnea that can have a deleterious effect on arterial phase MR image quality and occurs significantly more often than with intravenous gadobenate dimeglumine.

ACR Appropriateness Criteria® Left Lower Quadrant Pain: 2023 Update.

The differential diagnosis for left lower quadrant pain is wide and conditions range from the benign and self-limited to life-threatening surgical emergencies. Along with patient history, physical examination, and laboratory tests, imaging is often critical to limit the differential diagnosis and identify life-threatening abnormalities. This document will discuss the guidelines for the appropriate use of imaging in the initial workup for patients who present with left lower quadrant pain, patients with suspected diverticulitis, and patients with suspected complications from diverticulitis. 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.