Spatial Atlas for Mapping Vascular Microcalcification Using 18F-NaF PET/CT: Application in Hyperphosphatemic Familial Tumoral Calcinosis.

BACKGROUND: Vascular calcification causes significant morbidity and occurs frequently in diseases of calcium/phosphate imbalance. Radiolabeled sodium fluoride positron emission tomography/computed tomography has emerged as a sensitive and specific method for detecting and quantifying active microcalcifications. We developed a novel technique to quantify and map total vasculature microcalcification to a common space, allowing simultaneous assessment of global disease burden and precise tracking of site-specific microcalcifications across time and individuals. METHODS: To develop this technique, 4 patients with hyperphosphatemic familial tumoral calcinosis, a monogenic disorder of FGF23 (fibroblast growth factor-23) deficiency with a high prevalence of vascular calcification, underwent radiolabeled sodium fluoride positron emission tomography/computed tomography imaging. One patient received serial imaging 1 year after treatment with an IL-1 (interleukin-1) antagonist. A radiolabeled sodium fluoride-based microcalcification score, as well as calcification volume, was computed at all perpendicular slices, which were then mapped onto a standardized vascular atlas. Segment-wise mCSmean and mCSmax were computed to compare microcalcification score levels at predefined vascular segments within subjects. RESULTS: Patients with hyperphosphatemic familial tumoral calcinosis had notable peaks in microcalcification score near the aortic bifurcation and distal femoral arteries, compared with a control subject who had uniform distribution of vascular radiolabeled sodium fluoride uptake. This technique also identified microcalcification in a 17-year-old patient, who had no computed tomography-defined calcification. This technique could not only detect a decrease in microcalcification score throughout the patient treated with an IL-1 antagonist but it also identified anatomic areas that had increased responsiveness while there was no change in computed tomography-defined macrocalcification after treatment. CONCLUSIONS: This technique affords the ability to visualize spatial patterns of the active microcalcification process in the peripheral vasculature. Further, this technique affords the ability to track microcalcifications at precise locations not only across time but also across subjects. This technique is readily adaptable to other diseases of vascular calcification and may represent a significant advance in the field of vascular biology.

Ninety-day toxicity and genotoxic effects of synthetically derived fully saturated forms of anacardic acid in mice.

Organically synthesized fully saturated form of Anacardic acid (AA) has previously shown to be effective in the treatment of inflammatory autoimmune disease. In this study, organically synthesized fully saturated form of AA was orally administered to male and female Swiss albino mice for 90 consecutive days at doses of 25, 50 and 100 mg/kg BW (n = 20 per sex/group). Administration of AA was well tolerated at all dose levels. The treated animals did not show a dose-response toxicity in their hematology, liver, or metabolic profile. Minimally significant changes in serum biochemistry and hematology parameters were noted, but these were not considered to be of biological or toxicological importance and were not outside the known accepted ranges. Sporadic differences in organ weights were observed between groups, but all were minimal (<10%) and unlikely to indicate toxicity. The incidence of histopathological lesions was comparable between treated and control groups across all tested organs. Based upon these findings, the no-observed-adverse-effect level was determined to be ≥ 100 mg/kg BW, which was the highest dose tested. There were no genotoxic (mutagenic and clastogenic) effects seen in In-vivo micronucleus test, In-vitro chromosomal aberration test and Bacterial reverse mutation test. These results support, no genotoxicity and no toxicity associated with oral consumption of AA in mice as a dietary supplement for beverages and food.

Differential Efficacy of Storage Temperature and Postharvest Treatment on Shelf Life and Quality of Avocado Fruit (Persea americana Mill.).

Avocado fruit is a rich source of phytonutrients such as vitamins, minerals, carotenoids, carbohydrates, polyphenols and unsaturated fatty acids. However, due to its climacteric nature, fruits are highly susceptible to storage temperature, resulting in poor shelf life and reduced quality. In the present study avocado fruits (Accession CHES-HA-I/I) were stored at different low temperatures (5, 9 and 12 °C with 90-95% relative humidity, RH) to identify optimum low temperature for cold storage. In a further experiment, avocado fruits were treated with 1-methylcyclopropene (1-MCP, 500 ppb) and chitosan (0.5%) to extend the shelf life with better fruit quality. The results showed that storage temperatures had significant effect on physiological, biochemical and antioxidant activities of fruits. Lower physiological loss in weight (PLW), reduced respiration and ethylene production, and higher carbohydrates, protein and fat content were recorded in fruits stored at 9 °C as compared to 12 °C. Similarly, maximum antioxidant properties in terms of free radical scavenging activity (FRSA) and ferric reducing ability of plasma (FRAP) was found in avocado fruits stored at 9 °C. It was also noticed that chilling injury was developed in fruits stored under 5 °C. In addition, exogenous application of 1-MCP significantly reduced respiration and ethylene production rate at 9 °C and extended the shelf life up to 42 days with better fruit quality and more antioxidant activities. However, chitosan treated and control fruits had shelf life up to 28 and 21 days respectively, with minimum nutritional content. From this study it is concluded that a storage temperature of 9 °C and 1-MCP treatment significantly enhanced the shelf life of avocado fruits with better fruit quality as compared to other storage temperatures (5 and 12 °C) and postharvest treatment (chitosan).

Disinfection and Electrostatic Recovery of N95 Respirators by Corona Discharge for Safe Reuse.

With the COVID-19 pandemic surging, the demand for masks is challenging, especially in less-developed areas across the world. Billions of used masks are threatening the environment as a new source of plastic pollution. In this paper, corona discharge (CD) was explored as a safe and reliable method for mask reuse to alleviate the situation. CD can disinfect masks and simultaneously restore electrostatic charges to prevent filtration efficiency deterioration. Electric field, ions, and reactive species generated by CD cause DNA damage and protein denaturation to effectively disinfect N95 respirators. Log reduction of 2-3 against Escherichia coli can be easily reached within 7.5 min. Log reduction of up to 6 can be reached after three cycles of treatment with optimized parameters. CD disinfection is a broad spectrum with log reduction >1 against yeast and >2.5 against spores. N95 respirators can be recharged within 30 s of treatment and the charges can be retained at a higher level than brand-new masks for at least 5 days. The filtration efficiency of masks was maintained at ∼95% after 15 cycles of treatment. CD can provide at least 10 cycles of safe reuse with benefits of high safety, affordability, accessibility, and device scalability/portability.

A physical phantom for amine chemical exchange saturation transfer (CEST) MRI.

OBJECTIVE: To develop a robust amine chemical exchange saturation transfer (CEST) physical phantom, validate the temporal stability, and create a supporting software for automatic image processing and quality assurance. MATERIALS AND METHODS: The phantom was designed as an assembled laser-cut acrylic rack and 18 vials of phantom solutions, prepared with different pHs, glycine concentrations, and gadolinium concentrations. We evaluated glycine concentrations using ultraviolet absorbance for 70 days and measured the pH, relaxation rates, and CEST contrast for 94 days after preparation. We used Spearman's correlation to determine if glycine degraded over time. Linear regression and Bland-Altman analysis were performed between baseline and follow-up measurements of pH and MRI properties. RESULTS: No degradation of glycine was observed (p > 0.05). The pH and MRI measurements stayed stable for 3 months and showed high consistency across time points (R2 = 1.00 for pH, R1, R2, and CEST contrast), which was further validated by the Bland-Altman plots. Examples of automatically generated reports are provided. DISCUSSION: We designed a physical phantom for amine CEST-MRI, which is easy to assemble and transfer, holds 18 different solutions, and has excellent short-term chemical and MRI stability. We believe this robust phantom will facilitate the development of novel sequences and cross-scanners validations.

Risk of pump thrombosis and stroke in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding.

Gastrointestinal (GI) bleeding is a common complication following the placement of continuous-flow left ventricular assist devices (LVADs) in patients with advanced heart failure. Secondary events arising as a result of GI bleeding have not been well-described. Furthermore, attribution of these events to bleeding is complicated by the interruption or de-intensification of antithrombotic therapy, while bleeding is controlled. The purpose of this study was to assess the incidence of pump thrombosis and ischemic stroke in patients with LVADs who experience GI bleeding, while on support. This was a single-center, retrospective, observational cohort study of consecutive patients with LVADs implanted from January 2012 to June 2018. Patients were assigned to comparator groups based on whether they experienced GI bleeding while on LVAD support. The primary endpoint assessed was the composite of pump thrombosis or ischemic stroke. Secondary endpoints assessed included incidence of pump thrombosis or ischemic stroke. A total of 250 patients were included after screening for exclusion criteria, 101 (40.4%) in the GI bleeding group, and 149 (59.6%) in the non-bleeding group. The incidence of pump thrombosis or ischemic stroke was not significantly greater in patients experiencing GI bleeding [23 (22.8%) vs. 21 (14.1%); P = .09]; however, the incidence of ischemic stroke alone was significantly greater [17 (16.8%) vs. 10 (6.7%); P = .01]. We conclude that GI bleeding in LVAD patients may be associated with a greater risk of ischemic stroke.

Tunable adhesion and slip on a bio-mimetic sticky soft surface.

Simultaneous tuning of wettability and adhesion of a surface requires intricate procedures for altering the interfacial structures. Here, we present a simple method for preparing a stable slippery surface, with an intrinsic capability of varying its adhesion characteristics. Cross-linked PDMS, an inherent hydrophobic material commonly used for microfluidic applications, is used to replicate the structures on the surface of a rose petal which acts as a high adhesion solid base and is subsequently oleoplaned with silicone oil. Our results demonstrate that the complex hierarchical rose petal structures can arrest dewetting of the silicone oil on the cross linked PDMS base by anchoring the oil film strongly even under flow. Further, by tuning the extent of submergence of the rose petal structures with silicone oil, we could alter the adhesion characteristics of the surface on demand, while retaining its slippery characteristics for a wide range of the pertinent parameters. We have also demonstrated the possible fabrication of gradient adhesion surfaces. This, in turn, may find a wide variety of applications in water harvesting, droplet maneuverability and no-loss transportation in resource-limited settings.

Large dural-based mass with bony hyperostosis in a 16-year-old male: IgG4-related disease mimicking lymphoplasmacyte-rich meningioma.

BACKGROUND: IgG4-related disease is an autoimmune process that presents with tumefactive lesions characterized by storiform fibrosis, a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, obliterative phlebitis, and often elevated serum IgG4 levels. Central nervous system IgG4-related disease is very rare and usually occurs in the form of hypertrophic pachymeningitis or hypophysitis. Presentation as a large solitary meningioma-like mass with overlying hyperostosis in a young adult has not been reported before. CASE SUMMARY: A 16-year-old male presented with focal seizures for 5 months. Imaging showed a large, extra-axial, and contrast-enhancing mass lesion in the left frontoparietal region with focal calvarial thickening. Histopathology revealed a fibrosclerotic lesion involving dura with a polymorphic infiltrate of plasma cells, mature lymphocytes, histiocytes, and occasional eosinophils. Immunohistochemical workup excluded the possibilities of meningioma, lymphoproliferative neoplasms, and histiocytic lesions. Majority of plasma cells were IgG4+ rendering a diagnosis of IgG4-related disease. Further serological and imaging workup did not reveal any evidence of systemic involvement. His serum IgG4 levels were normal. Considering a gross total resection of the lesion, no further treatment was given and the patient has been asymptomatic since. CONCLUSION: IgG4-related lesions of the CNS are under-recognized and accurate diagnosis, especially in those with isolated CNS disease and normal serum IgG4 levels, necessitates robust histopathological and laboratory workup to exclude mimics. They may occur as large dural masses with hyperostosis and differentiation from lymphoplasmacyte-rich meningiomas, in particular, can be challenging. While steroids are the mainstay of treatment in IgG4-related disease, surgical resection may be curative in solitary lesions presenting with compressive symptoms.

Recurrent Retinoblastoma With Mandibular Metastasis: A Case Report.

Retinoblastoma (RB) is an aggressive intraocular tumor arising from cells of the retina. Infrequently, distant metastasis occurs in advanced stages of the disease. This case report describes the metastasis of the tumor to the mandible, an extremely rare phenomenon. This condition was observed for a recurrent tumor in a patient who initially underwent chemotherapy, making this case report unique and providing new insights into the behavior of this tumor. An overview of the management of a metastatic RB also is discussed.

Adenylate cyclase in Arthrospira platensis responds to light through transcription.

Cyclic 3',5' adenosine monophosphate (cAMP) is a ubiquitous signaling molecule, but its role in higher plants was in doubt due to its very low concentration. In this study we wanted to look at the flux of cAMP in response to light in algae, considered to be the more primitive form of photosynthetic organisms. While it did not fluctuate very much in the tested green algae, in the cyanobacterium Arthrospira platensis its level was closely linked to exposure to light. The expression from cyaC, the major isoform of adenylate cyclase was strongly influenced by exposure of the cells to light. There was about 300 fold enhancement of cyaC transcripts in cells exposed to light compared to the transcripts in cells in the dark. Although post-translational regulation of adenylate cyclase activity has been widely known, our studies suggest that transcriptional control could also be an important aspect of its regulation in A. platensis.

Comparison of Prescribed and Measured Dialysate Sodium: A Quality Improvement Project.

BACKGROUND: There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. STUDY DESIGN: Cross-sectional quality improvement project. SETTING & PARTICIPANTS: 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. QUALITY IMPROVEMENT PLAN: Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. OUTCOMES: Magnitude of differences between prescribed and measured dialysate sodium concentrations. MEASUREMENTS: Dialysate sodium measured pre- and late dialysis. RESULTS: The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. LIMITATIONS: We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. CONCLUSIONS: There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.

Bimodal high-affinity association of Brd4 with murine leukemia virus integrase and mononucleosomes.

The importance of understanding the molecular mechanisms of murine leukemia virus (MLV) integration into host chromatin is highlighted by the development of MLV-based vectors for human gene-therapy. We have recently identified BET proteins (Brd2, 3 and 4) as the main cellular binding partners of MLV integrase (IN) and demonstrated their significance for effective MLV integration at transcription start sites. Here we show that recombinant Brd4, a representative of the three BET proteins, establishes complementary high-affinity interactions with MLV IN and mononucleosomes (MNs). Brd4(1-720) but not its N- or C-terminal fragments effectively stimulate MLV IN strand transfer activities in vitro. Mass spectrometry- and NMR-based approaches have enabled us to map key interacting interfaces between the C-terminal domain of BRD4 and the C-terminal tail of MLV IN. Additionally, the N-terminal fragment of Brd4 binds to both DNA and acetylated histone peptides, allowing it to bind tightly to MNs. Comparative analyses of the distributions of various histone marks along chromatin revealed significant positive correlations between H3- and H4-acetylated histones, BET protein-binding sites and MLV-integration sites. Our findings reveal a bimodal mechanism for BET protein-mediated MLV integration into select chromatin locations.

BET proteins promote efficient murine leukemia virus integration at transcription start sites.

The selection of chromosomal targets for retroviral integration varies markedly, tracking with the genus of the retrovirus, suggestive of targeting by binding to cellular factors. γ-Retroviral murine leukemia virus (MLV) DNA integration into the host genome is favored at transcription start sites, but the underlying mechanism for this preference is unknown. Here, we have identified bromodomain and extraterminal domain (BET) proteins (Brd2, -3, -4) as cellular-binding partners of MLV integrase. We show that purified recombinant Brd4(1-720) binds with high affinity to MLV integrase and stimulates correct concerted integration in vitro. JQ-1, a small molecule that selectively inhibits interactions of BET proteins with modified histone sites impaired MLV but not HIV-1 integration in infected cells. Comparison of the distribution of BET protein-binding sites analyzed using ChIP-Seq data and MLV-integration sites revealed significant positive correlations. Antagonism of BET proteins, via JQ-1 treatment or RNA interference, reduced MLV-integration frequencies at transcription start sites. These findings elucidate the importance of BET proteins for MLV integration efficiency and targeting and provide a route to developing safer MLV-based vectors for human gene therapy.

Cephalometric evaluation of the pharyngeal airway space after orthognathic surgery and distraction osteogenesis of the jaw bones.

OBJECTIVE: Orthognathic surgeries and distraction osteogenesis (DO) of the jaw bones cause a change in the pharyngeal airway space (PAS). The aim of our study was to evaluate the magnitude of changes occurring in the pharyngeal airway after mandibular set-back surgeries and DO of maxilla/mandible. MATERIALS AND METHODS: The study undertaken was a retrospective cephalometric study. Subjects included in our study had undergone mandibular set-back surgery or DO of maxilla/mandible. Lateral cephalograms of the subjects taken pre-operatively (T0), immediate post-operatively (T1) and after a minimum follow-up period of 6 months (T2) were studied. The cephalograms were traced manually and the following parameters were evaluated: Surface area of the PAS, pharyngeal airway width at the level of the base of the tongue, position of the hyoid bone and the tongue. Repeated measure ANOVA test was done to assess the presence of any significant changes in the proposed parameters at T0, T1 and T2. A correlation analysis was made between the mandibular/maxillary movements and the corresponding changes in the PAS. RESULTS: Surgical movements of maxilla and mandible do have an effect on the pharyngeal airway. CONCLUSION: It was clearly evident that the effects of mandibular movements on the PAS and the hyoid bone is more significant than the maxillary movements.

Targeted DeSUMOylation as a therapeutic strategy for multiple sclerosis.

SUMO (small ubiquitin like modifier) conjugated proteins have emerged as an important post translational modifier of cellular function. SUMOylation modulates several cellular processes involved in transcriptional regulation of genes, protein-protein interactions and DNA damage and repair. Since abnormalities in SUMOylation has been observed in neoplastic and neurodegenerative disorders, the SUMO pathway has become an attractive site for targeting of new therapies to regulate SUMOylation and reduce disease burden. Conjugation of SUMO to their respective substrates is orchestrated by an enzymatic cascade involving three main enzymes, E1, activation enzyme, E2, conjugating enzyme and E3, a protein ligase. Each of these enzymes are therefore potential "druggable" sites for future therapeutics. SUMOylation is a well-known mechanism by which the innate immune response is regulated in response to viral infections and in the adaptive immune response to tumor immunity. We have shown that small molecules which inhibit the SUMO activation pathway are also capable of inhibiting autoimmune response. TAK981 which forms adducts with SUMO and anacardic acid which inhibits the E1 enzyme of the SUMO pathway were effective in preventing the development of experimental allergic encephalitis (EAE), a mouse model of multiple sclerosis. Anacardic acid and TAK981 inhibited activation of TH17 cells and reduced clinical and pathological injury in IL-17 mediated myelin oligodendrocyte glycoprotein (MOG) induced EAE. Ginkgolic acid, another known inhibitor of SUMO pathway, was also shown to be effective in reducing the severity of inflammatory arthropathies which is also IL-17 mediated. In addition, the increase in the transcription of myelin genes with TAK981 and anacardic acid improved remyelination in experimental models of demyelination. In the present review paper, we examine the mechanism of action of inhibitors of the SUMO pathway on regulating the immune response and the possibility of the use of these agents as therapeutics for MS.

Comparing Warm and Cold Gutta-Percha Techniques for Root Canal Filling: An In Vitro Study.

Background: Gutta-percha is commonly used in endodontic therapy for obturating root canals after cleaning and shaping procedures. Warm and cold gutta-percha techniques are two common methods employed for obturation, each with its own advantages and limitations. Materials and Methods: Twenty extracted human teeth with single-rooted canals were selected and divided into two groups: warm gutta-percha obturation and cold gutta-percha obturation. In the warm gutta-percha group, gutta-percha was heated to a predetermined temperature using a warm gutta-percha heating device and injected into the root canal using a heated carrier. In the cold gutta-percha group, gutta-percha was applied directly to the root canal without prior heating. Root canal obturation quality was assessed using radiographic imaging to evaluate the presence of voids, completeness of obturation, and adaptation to the canal walls. Micro-computed tomography (micro-CT) analysis was also performed to quantify the volume of obturating material and assess the three-dimensional distribution of gutta-percha within the root canal space. Results: Both warm and cold gutta-percha techniques demonstrated effective obturation of root canals, with comparable outcomes in terms of void formation, completeness of obturation, and adaptation to canal walls. However, micro-CT analysis revealed differences in the volume and distribution of gutta-percha within the root canal space. Warm gutta-percha obturation exhibited more uniform distribution of gutta-percha material and higher volumetric filling compared to cold gutta-percha obturation. Additionally, the warm gutta-percha technique demonstrated superior flowability and adaptation to irregularities within the root canal system. Conclusion: In this in vitro study, warm gutta-percha obturation demonstrated advantages over cold gutta-percha obturation in terms of volumetric filling, distribution within the root canal space, and adaptation to canal irregularities.

Structural and molecular imaging-based characterization of soft tissue and vascular calcification in hyperphosphatemic familial tumoral calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder caused by deficient FGF23 signaling and resultant ectopic calcification. Here, we systematically characterized and quantified macro- and micro-calcification in a HFTC cohort using CT and 18F-sodium fluoride PET/CT (18F-NaF PET/CT). Fourier-transform infrared (FTIR) spectroscopy was performed on 4 phenotypically different calcifications from a patient with HFTC, showing the dominant component to be hydroxyapatite. Eleven patients with HFTC were studied with CT and/or 18F-NaF PET/CT. Qualitative review was done to describe the spectrum of imaging findings on both modalities. CT-based measures of volume (eg, total calcific burden and lesion volume) and density (Hounsfield units) were quantified and compared to PET-based measures of mineralization activity (eg, mean standardized uptake values-SUVs). Microcalcification scores were calculated for the vasculature of 6 patients using 18F-NaF PET/CT and visualized on a standardized vascular atlas. Ectopic calcifications were present in 82% of patients, predominantly near joints and the distal extremities. Considerable heterogeneity was observed in total calcific burden per patient (823.0 ± 670.1 cm3, n = 9) and lesion volume (282.5 ± 414.8 cm3, n = 27). The largest lesions were found at the hips and shoulders. 18F-NaF PET offered the ability to differentiate active vs quiescent calcifications. Calcifications were also noted in multiple anatomic locations, including brain parenchyma (50%). Vascular calcification was seen in the abdominal aorta, carotid, and coronaries in 50%, 73%, and 50%, respectively. 18F-NaF-avid, but CT-negative calcification was seen in a 17-year-old patient, implicating early onset vascular calcification. This first systematic assessment of calcifications in a cohort of patients with HFTC has identified the early onset, prevalence, and extent of calcification. It supports 18F-NaF PET/CT as a clinical tool for distinguishing between active and inactive calcification, informing disease progression, and quantification of ectopic and vascular disease burden.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare disorder in which patients develop sometimes large debilitating calcifications of soft tissues and blood vessels. It is caused by deficient fibroblast growth factor-23 that leads to high phosphate levels, which contributes to the calcifications. The calcifications and manifestations of this disorder have not been well characterized. We determined the mineral composition of the calcifications to be hydroxyapatite. Capitalizing on the fact fluoride can be integrated into hydroxyapatite, we used radiolabeled sodium fluoride PET/CT scans (18F-NaF PET/CT) to characterize and quantify the calcifications in 11 patients. Eighty-two percent of the patients had calcifications, with the largest located at the hips and shoulders. Micro-calcifications were found in the blood vessels of most patients, including children. The technique also enabled us to differentiate between active vs stable calcifications. This first systematic assessment of calcifications in patients with HFTC showed the utility of 18F-NaF PET/CT as a tool to identify and quantify calcifications, as well as distinguish between active and stable calcifications. This approach will inform disease progression and may prove useful for measuring response to treatment.

Unpacking overuse of androgen deprivation therapy for prostate cancer to inform de-implementation strategies.

BACKGROUND: Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse. METHODS: Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation-Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer ("yes"/"probably yes," "probably no"/"no"), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses. RESULTS: Our survey was completed by 84 respondents (13% response rate), with 27% indicating "probably no"/"no" to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity-Social, Motivation-Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse. CONCLUSIONS: Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03579680.

PRO-READ IR: Enhanced PROcedural Information READability for Patient-Centered Care in Interventional Radiology With Large Language Models.

PURPOSE: To evaluate the extent to which Generative Pre-trained Transformer 4 (GPT-4) can educate patients by generating easily understandable information about the most common interventional radiology (IR) procedures. MATERIALS AND METHODS: We reviewed 10 IR procedures and prepared prompts for GPT-4 to provide patient educational instructions about each procedure in layman's terms. The instructions were then evaluated by four clinical physicians and nine nonclinical assessors to determine their clinical appropriateness, understandability, and clarity using a survey. A grade-level readability assessment was performed using validated metrics to evaluate accessibility to a wide patient population. The same procedures were also evaluated from the patient instructions available at radiologyinfo.org and compared with GPT-generated instructions utilizing a paired t test. RESULTS: Evaluation by four clinical physicians shows that nine GPT-generated instructions were fully appropriate, whereas arterial embolization instructions was somewhat appropriate. Evaluation by nine nonclinical assessors shows that paracentesis, dialysis catheter placement, thrombectomy, ultrasound-guided biopsy, and nephrostomy-tube instructions were rated excellent by 57% and good by 43%. The arterial embolization and biliary-drain instructions were rated excellent by 28.6% and good by 71.4%. In contrast, thoracentesis, port placement, and CT-guided biopsy instructions received 43% excellent, 43% good, and 14% fair. The readability assessment across all procedural instructions showed a better Flesch-Kincaid mean grade of GPT-4 instructions compared with radiologyinfo.org (7.8 ± 0.87 versus 9.6 ± 0.83; P = .007) indicating excellent readability at 7th- to 8th-grade level compared with 9th to 10th grade. Additionally there was a lower Gunning Fog mean index (10.4 ± 1.2 versus 12.7 ± 0.93; P = .006), and higher Flesch Reading Ease mean score (69.4 ± 4.8 versus 51.3±3.9; P = .0001) indicating better readability. CONCLUSION: IR procedural instructions generated by GPT-4 can aid in improving health literacy and patient-centered care in IR by generating easily understandable explanations.