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Abstract Background The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer. Methods This retrospective cohort study used data from Surveillance, Epidemiology, and End Results program–Medicare for opioid-naive patients with solid tumor malignancies diagnosed from 2012 through 2017 and a random sample of patients without cancer. We identified 238 470 eligible patients with cancer and further focused on 4 clinical strata: patients without cancer, patients with metastatic cancer, patients with nonmetastatic cancer treated with surgery alone (“surgery alone”), and patients with nonmetastatic cancer treated with surgery plus chemotherapy or radiation therapy (“surgery+”). We identified new, early additional, and long-term additional opioid use and calculated the change in predicted probability of these outcomes from 2012 to 2017. Results New opioid use was higher in patients with cancer (46.4%) than in those without (6.9%) (P < .001). From 2012 to 2017, the predicted probability of new opioid use was more stable in the cancer strata (relative declines: 0.1% surgery alone; 2.4% surgery+; 8.8% metastatic cancer), than in the noncancer stratum (20.0%) (P < .001 for each cancer to noncancer comparison). Early additional use declined among surgery patients (‒14.9% and ‒17.5% for surgery alone and surgery+, respectively) but was stable among patients with metastatic disease (‒2.8%, P = .50). Conclusions Opioid prescribing declined over time at a slower rate in patients with cancer than in patients without cancer. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer.

PURPOSE To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2–positive (HER2+) metastatic biliary tract cancer (mBTC). METHODS SGNTUC-019 (ClinicalTrials.gov identifier: NCT04579380 ) is an open-label phase II basket study evaluating the efficacy and safety of tucatinib and trastuzumab in patients with HER2-altered solid tumors. In the biliary tract cancer cohort, patients had previously treated HER2 overexpressing or amplified (HER2+) tumors (identified with local testing) with no prior HER2-directed therapy. The primary end point was confirmed objective response rate (cORR) per investigator assessment. Patients were treated on a 21-day cycle with tucatinib (300 mg orally twice daily) and trastuzumab (8 mg/kg intravenously followed by 6 mg/kg every 3 weeks). RESULTS Thirty patients were enrolled. As of data cutoff (January 30, 2023), the median duration of follow-up was 10.8 months. The cORR was 46.7% (90% CI, 30.8 to 63.0), with a disease control rate of 76.7% (90% CI, 60.6 to 88.5). The median duration of response and progression-free survival were 6.0 months (90% CI, 5.5 to 6.9) and 5.5 months (90% CI, 3.9 to 8.1), respectively. At data cutoff, 15 patients (50.0%) had died, and the estimated 12-month overall survival rate was 53.6% (90% CI, 36.8 to 67.8). The two most common treatment-emergent adverse events (TEAEs) were pyrexia (43.3%) and diarrhea (40.0%). Grade ≥3 TEAEs were reported in 18 patients (60.0%), with the most common being cholangitis, decreased appetite, and nausea (all 10.0%), which were generally not treatment related. TEAEs led to treatment regimen discontinuation in one patient, and there were no deaths due to TEAEs. CONCLUSION Tucatinib combined with trastuzumab had clinically significant antitumor activity and was well tolerated in patients with previously treated HER2+ mBTC.

Purpose of review Early recurrence of atrial tachyarrhythmia (ERAT) during blanking period (BP) is not uncommon after catheter ablation of AF. Current guidelines and consensus statements recommend conservative treatment of ERAT. This review summarized recent studies, underlying mechanism and clinical managements of ERAT, and proposed a reconsideration of the definition and clinical significance of BP. Recent findings Recent studies have shown that the entity of ERAT in the very early phase of BP (i.e., first 4 weeks of the 3-month period) is different from those ERATs occurring late which is strongly associated with the late recurrence of atrial tachyarrhythmia. The optimal BP duration suggested by clinical observation ranges from 21 to 58 days. Using antiarrhythmic drugs and early electrical cardioversion are the effective management for ERAT, whereas re-ablation is a reasonable strategy although remains controversial. Summary The definition of BP with a shorter duration, that is, 1 month instead of 3 months post AF ablation, is supported by the observations of latest clinical studies. Recurrent atrial tachyarrhythmia beyond the 1-month time frame is associated with higher risk of late recurrence and may warrant repeat ablation. A revisit to the guideline recommendation on management of ERAT is needed to change clinical practice.

ABSTRACT Cytomegalovirus (CMV) is a significant cause of morbidity and mortality among immunocompromised hosts, including transplant recipients. Antiviral prophylaxis or treatment is used to reduce the incidence of CMV disease in this patient population; however, there is concern about increasing antiviral resistance. Detection of antiviral resistance in CMV was traditionally accomplished using Sanger sequencing of UL54 and UL97 genes, in which specific mutations may result in reduced antiviral activity. In this study, a novel next-generation sequencing (NGS) method was developed and validated to detect mutations in UL54 / UL97 associated with antiviral resistance. Plasma samples ( n = 27) submitted for antiviral resistance testing by Sanger sequencing were also analyzed using the NGS method. When compared to Sanger sequencing, the NGS assay demonstrated 100% (27/27) overall agreement for determining antiviral resistance/susceptibility and 88% (22/25) agreement at the level of resistance-associated mutations. The limit of detection of the NGS method was determined to be 500 IU/mL, and the lower threshold for detecting mutations associated with resistance was established at 15%. The NGS assay represents a novel laboratory tool that assists healthcare providers in treating patients who are infected with CMV harboring resistance-associated mutations and who may benefit from tailored antiviral therapy.

AbstractBackgroundPeripheral arterial disease (PAD) is a chronic occlusive disease that restricts blood flow in the lower limbs, causing partial or complete blockages of the blood flow. While digital subtraction angiography (DSA) has traditionally been the preferred method for assessing blood flow in the lower limbs, advancements in wide beam Computed Tomography (CT), allowing successive acquisition at high frame rate, might enable hemodynamic measurements.PurposeTo quantify the arterial blood flow in stenotic below‐the‐knee (BTK) arteries. To this end, we propose a novel method for contrast bolus tracking and assessment of quantitative hemodynamic parameters in stenotic arteries using 4D‐CT.MethodsFifty patients with suspected PAD underwent 4D‐CT angiography in addition to the clinical run‐off computed tomography angiography (CTA). From these dynamic acquisitions, the BTK arteries were segmented and the region of maximum blood flow was extracted. Time attenuation curves (TAC) were estimated using 2D spatio‐temporal B‐spline regression, enforcing both spatial and temporal smoothness. From these curves, quantitative hemodynamic parameters, describing the shape of the propagating contrast bolus were automatically extracted. We evaluated the robustness of the proposed TAC fitting method with respect to interphase delay and imaging noise and compared it to commonly used approaches. Finally, to illustrate the potential value of 4D‐CT, we assessed the correlation between the obtained hemodynamic parameters and the presence of PAD.Results280 out of 292 arteries were successfully segmented, with failures mainly due to a delayed contrast arrival. The proposed method led to physiologically plausible hemodynamic parameters and was significantly more robust compared to 1D temporal regression. A significant correlation between the presence of proximal stenoses and several hemodynamic parameters was found.ConclusionsThe proposed method based on spatio‐temporal bolus tracking was shown to lead to stable and physiologically plausible estimation of quantitative hemodynamic parameters, even in the case of stenotic arteries. These parameters may provide valuable information in the evaluation of PAD and contribute to its diagnosis.

SAGE-Journals-Accessible-Video-Player 10.1089/ve.2023.0025.M1 sj-vid-1-vde-10.1089_ve.2023.0025

Abstract Photon counting detector (PCD) CT represents the newest advance in CT technology, with improved radiation dose efficiency, increased spatial resolution, inherent spectral imaging capabilities, and the ability to eliminate electronic noise. Its design fundamentally differs from conventional energy integrating detector CT because photons are directly converted to electrical signal in a single step. Rather than converting X-rays to visible light and having an output signal that is a summation of energies, PCD directly counts each photon and records its individual energy information. The current commercially available PCD-CT utilizes a dual-source CT geometry, which allows 66 ms cardiac temporal resolution and high-pitch (up to 3.2) scanning. This can greatly benefit pediatric patients by facilitating high quality fast scanning to allow sedation-free imaging. The energy-resolving nature of the utilized PCDs allows “always-on” dual-energy imaging capabilities, such as the creation of virtual monoenergetic, virtual non-contrast, virtual non-calcium, and other material-specific images. These features may be combined with high-resolution imaging, made possible by the decreased size of individual detector elements and the absence of interelement septa. This work reviews the foundational concepts associated with PCD-CT and presents examples to highlight the benefits of PCD-CT in the pediatric population.

Background: Although pitch count and rest guidelines have been promoted for youth and adolescent baseball players for nearly 2 decades, compliance with guidelines remains poorly understood. Purpose/Hypothesis: The purpose of this study was to determine the frequency of compliance with Major League Baseball (MLB) Pitch Smart guidelines as well as the association between compliance and range of motion (ROM), strength, velocity, injury, and pitcher utilization. It was hypothesized that pitchers in violation of current recommendations would have increased strength, velocity, and injury. Study Design: Case-control study; Level of evidence, 3. Methods: This was a prospective, multicenter study of 115 high school pitchers throughout the United States. Pitchers were surveyed about their compliance with current off-season, rest-related guidelines, and history of injury. During the preseason, pitchers underwent standardized physical examinations, and pitch velocity was measured. Pitch counts were collected during the baseball season that followed. Dynamometer strength testing of shoulder forward flexion, and external rotation as well as grip strength was recorded. We compared pitchers who were compliant with recommendations with those who were noncompliant using Student t and Mann-Whitney U tests. Results: Based on preseason data, 84% of pitchers had violated current Pitch Smart guidelines. During the season, 14% had at least 1 violation of the Pitch Smart guidelines. Across both the preseason survey and in-season pitch counts, 89% of players had at least 1 violation of the Pitch Smart guidelines. While there were no significant differences in ROM or strength, the noncompliant group had higher maximum pitch velocity than the compliant group (74 ± 8 vs 69 ± 5 mph [119 ± 13 vs 111 ± 8 kph], respectively; P = .009). Players’ self-reported velocity differed significantly from the direct measurement, for both peak velocity (80 ± 6 vs 73 ± 8 mph [129 ± 9 vs 117 ± 13 kph], respectively; P < .001) and mean velocity (73 ± 8 vs 53 ± 27 mph [117 ± 13 vs 85 ± 43 kph], respectively; P < .001). Conclusion: Most high school pitchers were not fully compliant with current Pitch Smart guidelines, and they tended to overestimate their peak velocity by 7 mph (11 kph). Pitchers who threw with greater velocity were at higher risk for violating Pitch Smart recommendations.