Citations

Abstract Background Upadacitinib (UPA), an oral, reversible JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, or tyrosine kinase 2 (TYK2), demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). This analysis evaluated the efficacy of UPA on early symptomatic improvement for the first 14 days, using pooled data from U-ACHIEVE Induction and U-ACCOMPLISH. Methods U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and centrally reviewed endoscopy subscore of 2 to 3. A total of 998 patients were randomized to receive UPA 45mg once daily (QD) (n=658) or PBO (n=328) for 8 weeks (wks) in a 2:1 ratio. First dose of study drug was administered on Day 0. Improvement in symptoms including stool frequency subscore (SFS), rectal bleeding subscore (RBS), abdominal pain, and bowel urgency were analysed from daily symptom diary data. Multivariate regression analysis was used to determine if early changes in UC symptoms could be used to evaluate a potential correlation with patients’ likelihood of achieving clinical response or clinical remission per Adapted Mayo score at the end of induction. Results Baseline characteristics were similar between both treatment groups. Patients treated with UPA 45 mg QD experienced significant improvement in daily symptoms, with significantly more subjects achieving SFS≤1 (p<0.001), RBS of 0 (p<0.05), and SFS of 0 (p<0.05) as early as day 1 and maintained through day 14 (Figure 1). A significantly higher percentage of patients who received UPA 45 mg QD compared to PBO, achieved abdominal pain=0 and the absence of bowel urgency within 3 days of beginning treatment through day 14 (p<0.05). Multivariate analysis revealed that patients who achieved day 7 SFS≤1 (OR 2.42, 95% CI, 1.53–3.82) were more likely to attain clinical response (Table). Patients who attained day 7 SFS≤1 (OR 2.53, 95% CI 1.59–4.00) or day 7 bowel urgency absent (OR 2.40, 95% CI 1.52–3.79) were more likely to achieve clinical remission at week 8. Conclusion UPA 45 mg QD significantly improved UC symptoms as early as day 1, providing patients with rapid symptom relief. Patients who achieved early symptom improvement were more likely to attain clinical remission or clinical response at week 8. [Clinicaltrials.gov, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026)]

AbstractModern fluoroscopes used for image guidance have become quite complex. Adding to this complexity are the many regulatory and accreditation requirements that must be fulfilled during acceptance testing of a new unit. Further, some of these acceptance tests have pass/fail criteria, whereas others do not, making acceptance testing a subjective and time‐consuming task. The AAPM Task Group 272 Report spells out the details of tests that are required and gives visibility to some of the tests that while not yet required are recommended as good practice. The organization of the report begins with the most complicated fluoroscopes used in interventional radiology or cardiology and continues with general fluoroscopy and mobile C‐arms. Finally, the appendices of the report provide useful information, an example report form and topics that needed their own section due to the level of detail.

AbstractPurposeTo demonstrate the feasibility of simultaneous dual‐contrast imaging in a large animal using a newly developed dual‐source energy‐integrating detector (EID)‐based multi‐energy computed tomography (MECT) system.MethodsTwo imaging tasks that may have potential clinical applications were investigated: head/neck (HN) CT angiography (CTA)/CT venography (CTV) with iodine and gadolinium, and small bowel imaging with iodine and bismuth in domestic swine. Dual‐source X‐ray beam configurations of 70 kV + Au120/Sn120 kV and 70 kV + Au140/Sn140 kV were used for the HN‐CTA/CTV and small bowel imaging studies, respectively. A test bolus scan was performed for each study. The regions of interest (ROIs) in the carotid artery and jugular vein for HN‐CTA/CTV imaging and abdominal aorta for small bowel imaging were used to determine the time‐attenuation curves, based on which the timing for contrast injection and the CT scan was determined. In the HN‐CTA/CTV study, an MECT scan was performed at the time point corresponding to the optimal arterial enhancement by iodine and the optimal venous enhancement by gadolinium. In the small bowel imaging study, an MECT scan was performed at the optimal time point to simultaneously capture the mesenteric arterial enhancement of iodine and the enteric enhancement of bismuth. Image‐based material decomposition was performed to decompose different materials for each study. To quantitatively characterize contrast material separation and misclassification, two ROIs on left common carotid artery and left internal jugular vein in HN‐CTA/CTV imaging and three ROIs on superior mesenteric artery, ileal lumen, and collapsed ileum (ileal wall) in small bowel imaging were placed to measure the mean concentration values and the standard deviations.ResultsIn the HN‐CTA/CTV study, common carotid arteries containing iodine and internal/external jugular veins containing gadolinium were clearly delineated from each other. Fine vessels such as cephalic veins and branches of external jugular veins were noticeable but clear visualization was hindered by image noise in gadolinium‐specific (CTV) images, as reviewed by a neuroradiologist. In the small bowel imaging study, the mesenteric arteries and collapsed bowel wall containing iodine and the small bowel loops containing bismuth were clearly distinctive from each other in the iodine‐ and bismuth‐specific images after material decomposition, as reviewed by an abdominal radiologist. Quantitative analyses showed that the misclassifications between the two contrast materials were less than 1.7 and 0.1 mg/ml for CTA/CTV and small bowel imaging studies, respectively.ConclusionsFeasibility of simultaneous CTA/CTV imaging in head and neck with iodine and gadolinium and simultaneous imaging of arterial and enteric phases of small bowel with iodine and bismuth, using a dual‐source EID‐MECT system, was demonstrated in a swine study. Compared to iodine and gadolinium in CTA/CTV, better delineation and classification of iodine and bismuth in small bowel imaging were achieved mainly due to wider separation between the corresponding two K‐edge energies.

PURPOSECurrent tools in predicting survival outcomes for patients with colon cancer predominantly rely on clinical and pathologic characteristics, but increasing evidence suggests that diet and lifestyle habits are associated with patient outcomes and should be considered to enhance model accuracy.METHODSUsing an adjuvant chemotherapy trial for stage III colon cancer (CALGB 89803), we developed prediction models of disease-free survival (DFS) and overall survival by additionally incorporating self-reported nine diet and lifestyle factors. Both models were assessed by multivariable Cox proportional hazards regression and externally validated using another trial for stage III colon cancer (CALGB/SWOG 80702), and visual nomograms of prediction models were constructed accordingly. We also proposed three hypothetical scenarios for patients with (1) good-risk, (2) average-risk, and (3) poor-risk clinical and pathologic features, and estimated their predictive survival by considering clinical and pathologic features with or without adding self-reported diet and lifestyle factors.RESULTSAmong 1,024 patients (median age 60.0 years, 43.8% female), we observed 394 DFS events and 311 deaths after median follow-up of 7.3 years. Adding self-reported diet and lifestyle factors to clinical and pathologic characteristics meaningfully improved performance of prediction models (c-index from 0.64 [95% CI, 0.62 to 0.67] to 0.69 [95% CI, 0.67 to 0.72] for DFS, and from 0.67 [95% CI, 0.64 to 0.70] to 0.71 [95% CI, 0.69 to 0.75] for overall survival). External validation also indicated good performance of discrimination and calibration. Adding most self-reported favorable diet and lifestyle exposures to multivariate modeling improved 5-year DFS of all patients and by 6.3% for good-risk, 21.4% for average-risk, and 42.6% for poor-risk clinical and pathologic features.CONCLUSIONDiet and lifestyle factors further inform current recurrence and survival prediction models for patients with stage III colon cancer.