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AbstractBackgroundThe feasibility of oral dark contrast media is under exploration in abdominal computed tomography (CT) applications. One of the experimental contrast media in this class is dark borosilicate contrast media (DBCM), which has a CT attenuation lower than that of intra‐abdominal fat.PurposeTo evaluate the performances of DBCM using single‐ and multi‐energy CT imaging on a clinical photon‐counting‐detector CT (PCD‐CT).MethodsFive vials, three with iodinated contrast agent (5, 10, and 20 mg/mL; Omnipaque 350) and two with DBCM (6% and 12%; Nextrast, Inc.), and one solid‐water rod (neutral contrast agent) were inserted into two multi‐energy CT phantoms, and scanned on a clinical PCD‐CT system (NAEOTOM Alpha) at 90, 120, 140, Sn100, and Sn140 kV (Sn: tin filter) in multi‐energy mode. CARE keV IQ level was 180 (CTDIvol: 3.0 and 12.0 mGy for the small and large phantoms, respectively). Low‐energy threshold images were reconstructed with a quantitative kernel (Qr40, iterative reconstruction strength 2) and slice thickness/increment of 2.0/2.0 mm. Virtual monoenergetic images (VMIs) were reconstructed from 40 to 140 keV at 10 keV increments. On all images, average CT numbers for each vial/rod were measured using circular region‐of‐interests and averaged over eight slices. The contrast‐to‐noise ratio (CNR) of iodine (5 mg/mL) against DBCM was calculated and plotted against tube potential and VMI energy level, and compared to the CNR of iodine against water. Similar analyses were performed on iodine maps and VNC images derived from the multi‐energy scan at 120 kV.ResultsWith increasing kV or VMI keV, the negative HU of DBCM decreased only slightly, whereas the positive HU of iodine decreased across all contrast concentrations and phantom sizes. CT numbers for DBCM decreased from −178.5 ± 9.6 to −194.4 ± 6.3 HU (small phantom) and from −181.7 ± 15.7 to −192.1 ± 11.9 HU (large phantom) for DBCM‐12% from 90 to Sn140 kV; on VMIs, the CT numbers for DBCM decreased minimally from −147.1 ± 15.7 to −185.1 ± 9.2 HU (small phantom) and −158.8 ± 28.6 to −188.9 ± 14.7 HU (large phantom) from 40 to 70 keV, but remained stable from 80 to 140 keV. The highest iodine CNR against DBCM in low‐energy threshold images was seen at 90 or Sn140 kV for the small phantom, whereas all CNR values from low‐energy threshold images for the large phantom were comparable. The CNR values of iodine against DBCM computed on VMIs were highest at 40 or 70 keV depending on iodine and DBCM concentrations. The CNR values of iodine against DBCM were consistently higher than iodine to water (up to 460% higher dependent on energy level). Further, the CNR of iodine compared to DBCM is less affected by VMI energy level than the identical comparison between iodine and water: CNR values at 140 keV were reduced by 46.6% (small phantom) or 42.6% (large phantom) compared to 40 keV; CNR values for iodine compared to water were reduced by 86.3% and 83.8% for similar phantom sizes, respectively. Compared to 70 keV VMI, the iodine CNR against DBCM was 13%–79% lower on iodine maps and VNC.ConclusionsWhen evaluated at different tube potentials and VMI energy levels using a clinical PCD‐CT system, DBCM showed consistently higher CNR compared to iodine versus water (a neutral contrast).

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

Background: Predicting technical failure in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can assist with decision making and planning of the procedure. Methods: We analyzed 6,946 CTO PCIs performed between 2016 and June 2022 at 36 international centers in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) and created a score for risk of technical failure. Logistic regression prediction modeling was used to identify independently associated variables with technical failure and model were internally validated with bootstrapping. Results: Mean patient age was 64.0±10 years, 82% were men and technical success was 86%. The following variables were independently associated with technical failure and were included in the final model: age (odds ratio [OR]: 1.08, 95% Confidence Intervals [CI]: [1.00-1.15], p=0.039; age≥ 65 years; 1 point), CTO length (OR: 1.13, 95% CI [1.10, 1.17]; length≥ 20 mm; 1 point), moderate/severe calcification (OR: 1.35, 95% CI [1.17, 1.56]; 1 point), proximal cap ambiguity (OR: 2.25, 95% CI [1.95, 2.59]; 2 points), lack of interventional collaterals (OR: 1.60, 95% CI [1.39, 1.84]; 1 point), and lack of good distal landing zone (OR: 1.51, 95% CI [1.31, 1.75]; 1 point). The resulting score showed acceptable performance on receiver-operating characteristic (ROC) curve, AUC: 0.68 (95% CI [0.67-0.71]). Internal validation with bootstrapping of 1000 samples demonstrated a good agreement with the model, observed AUC: 0.68, (95% bias corrected CI [0.67, 0.70]). PROGRESS-CTO technical failure score and corresponding risk percentage and the percentage of patients in the respective risk group within the PROGRESS-CTO registry are represented in Figure 1. Conclusion: The updated PROGRESS CTO score may be useful for assessing the likelihood of technical failure success in CTO PCI.

Introduction: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is associated with increased risk of periprocedural complications. Estimating the risk of complications facilitates risk-benefit assessment and procedural planning. Methods: We analyzed the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO, NCT02061436) and created a risk score for in-hospital all-cause mortality. Logistic regression prediction modeling was used to identify independently associated variables and the model was internally validated with bootstrapping. Results: Of the 10,480 CTO PCI cases performed between 2012-2022 at 40 US and non-US centers, in-hospital mortality occurred in 47 (0.45%). The final prediction model identified 4 independent predictors of mortality: Age ≥65 years, Odds Ratio [OR]: 2.83 (95% confidence interval [CI], 1.30-6.16), 1-point; Left ventricular ejection fraction ≤45%, OR: 2.13 (95% CI, 1.14-3.98), 1-point; Moderate-severe calcification, OR: 2.45 (95% CI, 1.18-5.08), 1-point; and Antegrade dissection re-entry, OR: 2.81 (95% CI, 1.06-7.43), 1-point; or Retrograde strategy, OR: 3.51 (95% CI, 1.67-7.37), 1-point; with a bootstrap corrected c-statistics of 0.71 (95% confidence interval: 0.63-0.81). The calculated risk percentages for mortality based on the PROGRESS-CTO mortality score ranged from 0.05-2.42% for mortality, and 63% of patients in the PROGRESS-CTO cohort had PROGRESS-CTO mortality score of 1 or 2, corresponding to a mortality risk of 0.1-0.5% (Figure 1). Conclusions: The PROGRESS-CTO in-hospital mortality risk score can facilitate risk-benefit assessment and procedural planning in patients undergoing CTO PCI.

8009 Background: Heavily pretreated patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with standard of care therapy have median overall survival (OS) of ~12 months (mo). In the single-arm, phase 1b/2 CARTITUDE-1 study (NCT03548207), pts received a single infusion of ciltacabtagene autoleucel (cilta-cel), a CAR-T cell therapy targeting BCMA. At the final protocol-specified analysis (27.7-mo median follow-up [MFU]), overall response rate (ORR) was 98%, with 83% stringent complete response (CR); 27-mo rates of progression-free survival (PFS) and OS were 55% and 70%, respectively. Here, we report study closeout results. Methods: Eligible pts received ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD); and had received prior PI, IMiD, and anti-CD38 antibody therapy. Primary endpoint was ORR and safety; secondary endpoints included PFS, OS, and minimal residual disease (MRD) negativity at 10-5. Results: 97 pts received cilta-cel (median age 61 years [y]; median 6 prior LOT; 42% penta-drug refractory; 88% triple-class refractory; 99% refractory to last LOT). As of October 14, 2022, MFU was 33.4 mo (range, 1.5-45.2). Median (m) duration of response was 33.9 mo (95% CI, 25.5–not estimable [NE]). mPFS was 34.9 mo (95% CI, 25.2–NE), with an estimated 47.5% progression free and alive at 36 mo. mOS was not reached (NR), with an estimated 62.9% survival at 36 mo. Of 49 MRD-evaluable pts, 26 had MRD negativity sustained for ≥12 mo, of which 20 had sustained MRD-negative ≥CR. mPFS was NR in these subgroups (Table). 18 pts were MRD negative with ≥CR at 24 mo post infusion. No new safety signals and no new neurotoxicity events were reported since the 27.7-mo MFU. 6 new cases of second primary malignancy were reported, including 2 cases of basal cell carcinoma and 1 case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. 5 additional deaths occurred (progressive disease [PD], n=3; pneumonia and sepsis, n=1 each [both unrelated to cilta-cel]), for a total of 35 (PD, n=17; unrelated to cilta-cel, n=12; related, n=6). Conclusions: Longer mPFS was observed after a single infusion of cilta-cel than any previously reported therapy in heavily pretreated pts with RRMM. Achieving CR and/or sustained MRD negativity was associated with prolonged PFS. Pts continue to be followed for safety and survival in the 15-y CARTINUE long-term study (NCT05201781; MMY4002). Clinical trial information: NCT03548207 . [Table: see text]

Abstract Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harbouring these gain-of-function ANO1 variants had classic features of moyamoya disease, but also had aneurysm, stenosis and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.