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Purpose: To evaluate the prognostic significance of different descriptive parameters in head-and-neck cancer patients undergoing pretreatment [F-18] fluoro-D-glucose-positron emission tomography (FDG-PET) imaging. Patients and Methods: Head-and-neck cancer patients who underwent FDG-PET before a course of curative intent radiotherapy were retrospectively analyzed. FDG-PET imaging parameters included maximum (SUV(max)), and mean (SUV(mean)) standard uptake values, and total lesion glycolysis (TLG). Tumors and lymph nodes were defined on co-registered axial computed tomography (CT) slices. SUV(max) and SUV(mean) were measured within these anatomic regions. The relationships between pretreatment SUV(max), SUV(mean), and TLG for the primary site and lymph nodes were assessed using a univariate analysis for disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Kaplan-Meier survival curves were generated and compared via the log-rank method. SUV data were analyzed as continuous variables. Results: A total of 88 patients was assessed. Two-year OS, LRC, DMFS, and DFS for the entire cohort were 85%, 78%, 81%, and 70%, respectively. Median SUV(max) for the primary tumor and lymph nodes was 15.4 and 12.2, respectively. Median SUV(mean) for the primary tumor and lymph nodes was 7 and 5.2, respectively. Median TLG was 770. Increasing pretreatment SUV(mean) of the primary tumor was associated with decreased disease-free survival (p = 0.01). Neither SUV(max) in the primary tumor or lymph nodes nor TLG was prognostic for any of the clinical endpoints. Patients with pretreatment tumor SUV(mean) that exceeded the median value (7) of the cohort demonstrated inferior 2-year DFS relative to patients with SUV(mean) ≤ the median value of the cohort, 58% vs. 82%, respectively, p = 0.03. Conclusion: Increasing SUV(mean) in the primary tumor was associated with inferior DFS. Although not routinely reported, pretreatment SUV(mean) may be a useful prognostic FDG-PET parameter and should be further evaluated prospectively. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic significance of different descriptive parameters in head-and-neck cancer patients undergoing pretreatment [F-18] fluoro-D-glucose-positron emission tomography (FDG-PET) imaging. Patients and Methods: Head-and-neck cancer patients who underwent FDG-PET before a course of curative intent radiotherapy were retrospectively analyzed. FDG-PET imaging parameters included maximum (SUVmax), and mean (SUVmean) standard uptake values, and total lesion glycolysis (TLG). Tumors and lymph nodes were defined on co-registered axial computed tomography (CT) slices. SUVmax and SUVmean were measured within these anatomic regions. The relationships between pretreatment SUVmax, SUVmean, and TLG for the primary site and lymph nodes were assessed using a univariate analysis for disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Kaplan-Meier survival curves were generated and compared via the log‒rank method. SUV data were analyzed as continuous variables. Results: A total of 88 patients was assessed. Two-year OS, LRC, DMFS, and DFS for the entire cohort were 85%, 78%, 81%, and 70%, respectively. Median SUVmax for the primary tumor and lymph nodes was 15.4 and 12.2, respectively. Median SUVmean for the primary tumor and lymph nodes was 7 and 5.2, respectively. Median TLG was 770. Increasing pretreatment SUVmean of the primary tumor was associated with decreased disease-free survival (p = 0.01). Neither SUVmax in the primary tumor or lymph nodes nor TLG was prognostic for any of the clinical endpoints. Patients with pretreatment tumor SUVmean that exceeded the median value (7) of the cohort demonstrated inferior 2-year DFS relative to patients with SUVmean ≤ the median value of the cohort, 58% vs. 82%, respectively, p = 0.03. Conclusion: Increasing SUVmean in the primary tumor was associated with inferior DFS. Although not routinely reported, pretreatment SUVmean may be a useful prognostic FDG-PET parameter and should be further evaluated prospectively. [ABSTRACT FROM AUTHOR]

Purpose: Calculation of the precontrast longitudinal relaxation times (T10) is an integral part of the Tofts-based pharmacokinetic (PK) analysis of dynamic contrast enhanced–magnetic resonance images. The purpose of this study was to investigate the interpatient and over time variability of T10 in head and neck primary tumors and involved nodes and to determine the median T10 for primary and nodes (T10p,n). The authors also looked at the implication of using voxel-based T10 values versus region of interest (ROI)-based T10 on the calculated values for vascular permeability (Ktrans) and extracellular volume fraction (ve). Methods: Twenty head and neck cancer patients receiving concurrent chemoradiation and molecularly targeted agents on a prospective trial comprised the study population. Voxel-based T10’s were generated using a gradient echo sequence on a 1.5 T MR scanner using the variable flip angle method with two flip angles [J. A. Brookes et al., “Measurement of spin-lattice relaxation times with FLASH for dynamic MRI of the breast,” Br. J. Radiol. 69, 206–214 (1996)]. The voxel-based T10, Ktrans, and ve were calculated using iCAD’s® (Nashua, NH) software. The mean T10’s in muscle and fat ROIs were calculated (T10m,f). To assess reliability of ROI drawing, T10p,n values from ROIs delineated by 2 users (A and B) were calculated as the average of the T10’s for 14 patients. For a subset of three patients, the T10 variability from baseline to end of treatment was also investigated. The Ktrans and ve from primary and node ROIs were calculated using voxel-based T10 values and T10p,n and differences reported. Results: The calculated T10 values for fat and muscle are within the range of values reported in literature for 1.5 T, i.e., T10m=0.958 s and T10f=0.303 s. The average over 14 patients of the T10’s based on drawings by users A and B were T10pA=0.804 s, T10nA=0.760 s, T10pB=0.849 s, and T10nB=0.810 s. The absolute percentage difference between Ktrans and ve calculated with voxel-based T10 versus T10p,n ranged from 6% to 81% and from 2% to 24%, respectively. Conclusions: There is a certain amount of variability in the median T10 values between patients, but the differences are not significant. There were also no statistically significant differences between the T10 values for primary and nodes at baseline and the subsequent time points (p=0.94 Friedman test). Voxel-based T10 calculations are essential when quantitative Tofts-based PK analysis in heterogeneous tumors is needed. In the absence of T10 mapping capability, when a relative, qualitative analysis is deemed sufficient, a value of T10p,n=0.800 s can be used as an estimate for T10 for both the primary tumor and the affected nodes in head and neck cancers at all the time points considered. [ABSTRACT FROM AUTHOR]

Competing Interests: Disclosures Dr Turagam has served as a consultant for Biosense Webster and Boston Scientific. Dr Nair has served as a consultant for Boston Scientific and Johnson & Johnson. Dr Doshi has served as a consultant for Boston Scientific and Abbott Vascular. Dr Valderrabano has served as a consultant for Biosense Webster and Abbott. Dr Natale has served as a consultant for Abbott, Biosense Webster, and Boston Scientific. Dr Halperin has served as a consultant for Abbott and Bayer HealthCare. Dr Mansour has received consulting fees from Biosense Webster and Boston Scientific. Dr Reddy has served as an unpaid consultant for Boston Scientific, Biosense Webster, and Abbott. Dr Reddy has served as a consultant to Boston Scientific and Abbott; and unrelated to this manuscript, he has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, Append Medical, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, Cardiofocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EP Frontiers, Farapulse-Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Laminar Medical, LuxMed, Medlumics, Neutrace, Nuvera-Biosense Webster, Oracle Health, Pulse Biosciences, Restore Medical, Sirona Medical, SoundCath; and unrelated to this work, has served as a consultant for Adagio Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, Philips; and has equity in Atraverse, DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Purpose: To identify the effects of Rho Kinase (ROCK) inhibitor medications on human orbital adipogenesis, fibroblast proliferation, and fibrosis., Methods: Orbital adipose tissue was obtained from patients with Graves' ophthalmopathy (GO) as well as controls (non-GO or normal) after informed consent was done. These tissue samples were cultured and adipogenesis was initiated. Levels of Rho Kinase as well as cellular mediators of orbital inflammation and fibrosis. The same cultures and measurements were then repeated with the use of a ROCK inhibitor (KD025-ROCK2) to assess for changes in adipogenesis as well as markers associated with inflammation and fibrosis., Results: Rho Kinase levels in GO tissue were more highly expressed than in controls. These levels were suppressed with the use of the ROCK inhibitor KD025. There was a dose-dependent reduction in differentiation of orbital adipocytes with the use of KD025. KD025 reduced the levels of fibrosis-related gene expression. Finally, there was a significant reduction of transforming growth factor beta mediated phosphorylation signaling pathways in the KD025-treated GO tissue., Conclusion: This study shows that the ROCK inhibitor, KD025, helps to reduce the expression of ROCK in GO tissue along with reducing orbital adipocyte differentiation as well as cell mediators involved in fibrosis that occurs in GO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: Strokes after left atrial appendage closure (LAAC) prophylaxis are generally less severe than those after warfarin prophylaxis-thought to be secondary to more hemorrhagic strokes with warfarin. Hemorrhagic strokes are similarly infrequent with direct oral anticoagulant (DOAC) prophylaxis, so the primary subtype after either LAAC or DOAC prophylaxis is ischemic stroke (IS)., Objectives: The purpose of this study was to compare the severity of IS using the modified Rankin Scale in atrial fibrillation patients receiving prophylaxis with DOACs vs LAAC., Methods: A retrospective analysis was performed of consecutive patients undergoing LAAC at 8 centers who developed an IS (IS LAAC ) compared with contemporaneous consecutive patients who developed IS during treatment with DOACs (IS DOAC ). The primary outcome was disabling/fatal stroke (modified Rankin Scale 3-5) at discharge and 3 months later., Results: Compared with IS DOAC patients (n = 322), IS LAAC patients (n = 125) were older (age 77.2 ± 13.4 years vs 73.1 ± 11.9 years; P = 0.002), with higher HAS-BLED scores (3.0 vs 2.0; P = 0.004) and more frequent prior bleeding events (54.4% vs 23.6%; P < 0.001), but similar CHA 2 DS 2 -VASc scores (5.0 vs 5.0; P = 0.28). Strokes were less frequently disabling/fatal with IS LAAC than IS DOAC at both hospital discharge (38.3% vs 70.3%; P < 0.001) and 3 months later (33.3% vs 56.2%; P < 0.001). Differences in stroke severity persisted after propensity score matching. By multivariate regression analysis, IS LAAC was independently associated with fewer disabling/fatal strokes at discharge (OR: 0.22; 95% CI: 0.13-0.39; P < 0.001) and 3 months (OR: 0.25; 95% CI: 0.12-0.50; P < 0.001), and fewer deaths at 3 months (OR: 0.28; 95% CI: 0.12-0.64; P < 0.001)., Conclusions: Ischemic strokes in patients with atrial fibrillation are less often disabling or fatal with LAAC than DOAC prophylaxis., Competing Interests: Funding Support and Author Disclosures Dr Turagam has served as a consultant for Biosense Webster and Sanofi. Dr Nair has served as a consultant for and receives honoraria for speaking engagements from Boston Scientific, Johnson and Johnson, and Medtronic. Dr Doshi has served as a consultant to Boston Scientific, Biosense Webster, and Abbott Vascular. Dr Valderrabano has received scientific research support from and served as a consultant to Circa; has received research support from and served as a consultant to Biosense Webster; and has served as a consultant to Abbott. Dr Dukkipati has received payment for Farapulse acquisition from Boston Scientific; and has equity in Manual Surgical Sciences. Dr Natale has served as a consultant for Abbott, Baylis, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. Dr Reddy has served as an unpaid consultant to Boston Scientific; unrelated to this paper, he has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, and Valcare; unrelated to this work, has served as a consultant for Abbott, AtriAN, Biosense Webster, BioTel Heart, Biotronik, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore and Associates, Impulse Dynamics, Medtronic, Novartis, Philips, and Pulse Biosciences; and has equity in DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Thebaine is an alkaloid in poppy seeds that is neurotoxic to animals. Data on its clinical effects and toxicokinetics in people are minimal. In 2022, poppy seeds high in thebaine entered the Australian food market, and people consuming tea made from these poppy seeds developed poisoning., Methods: Three patients who drank poppy seed tea and developed neuromuscular toxicity consented for thebaine to be quantitated in serial blood samples. Blood samples were analyzed by liquid chromatography with high-resolution mass spectrometry., Results: Case 1: A man in his 60s presented with drowsiness, vomiting, malaise and myoclonus. He developed metabolic acidosis with hyperlactataemia, acute kidney injury requiring haemodialysis, convulsions, rhabdomyolysis, and was in the hospital for 18 days. The admission thebaine blood concentration was 2.1 mg/L, and the apparent elimination half-life was 14.8 h. Case 2: A man in his 30s presented with myoclonus, rigidity, vomiting, and dizziness. He developed metabolic acidosis with hyperlactataemia, acute kidney injury, and myalgias. The admission thebaine blood concentration was 4.1 mg/L, and the apparent elimination half-life was 11.6 h. Case 3: A man in his 30s presented with myoclonus, rigidity, clonus, diaphoresis, and abdominal pain. The admission thebaine blood concentration was 2.2 mg/L, and the apparent elimination half-life was 8.3 h., Discussion: Neuromuscular toxicity, metabolic acidosis with hyperlactataemia, acute kidney injury, and gastrointestinal symptoms were prominent clinical features in these patients after drinking poppy seed tea. Effects persisted for days, and all survived, despite thebaine concentrations far exceeding those in published forensic reports, although human data are sparse. Compared to rats, the thebaine apparent elimination half-life is much longer in humans who develop symptoms at lower concentrations., Conclusions: Despite relatively high thebaine blood concentrations and moderate to severe poisoning, outcomes were favourable with early presentations. It is possible that acute kidney injury prolongs the apparent elimination half-life of thebaine.

Purpose: To review the demographics, clinical features, and response of orbital squamous cell carcinoma treated with cemiplimab., Methods: This is a retrospective multi-institutional series. Patient characteristics, drug dosing, duration, and response to treatment were evaluated., Results: The study cohort consisted of 11 patients from 5 institutions. All patients received a regimen of 350 mg q 3 weeks and an average of 11.2 cycles (SD 5.8). No patient experienced significant side effects requiring treatment or cessation of cemiplimab. Complete response was achieved in 9 patients (82%) treated with cemiplimab., Conclusions: Immune checkpoint inhibitors, such as cemiplimab provide a globe-sparing option for the treatment of orbital squamous cell carcinoma. It is important to consider these agents especially when orbital exenteration is the alternative., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Optical microscopy images and confocal data for Aerosol Jet Printed (AJP) lines over a 16 hour print duration is provide in this dataset ("Mapping Drift in Morphology and Electrical Performance in Aerosol Jet Printing" [1]). Lines were uninterruptedly printed by AJP on a glass substrate using silver nanoparticle ink over a 16-hour time frame. The ink used for this experiment was a 0.6:0.3:0.2 mL mixture of Clariant Prelect TPS 50 G2 silver nanoparticle ink, ethylene glycol, and deionized water, respectively. Deposition was achieved with an Optomec AJ 300-UP Aerosol Jet TM Deposition System using a Sprint Series Ultrasonic Atomizer MAX, aerodynamic filtering, and a nozzle having an orifice diameter of 150 µm. The typical focus ratio of 1.75 within standard range was used. The optical microscopic images of 350 µm AJP printed lines at 80 different time points were then selectively collected. Keyence VK-X200 with 150x magnification was used, which provided 50 µm to 267 pixel resolution image with more than 1000 cross-sections at each time point. Filtering of the pixels with outlying heights was performed with a multi-file analyzer. The dataset was primarily collected to understand system-level, temporal drifts in print morphology, which would further allow to predict electrical performance in time domain. Additional purposes for the dataset include: 1) benchmark dataset for morphology and print performance between AJP systems and print settings, 2) test data for new image filtering, segmentation, and classification algorithms and 3) baseline training data for real-time, in situ classification of operational time windows for AJP feedback control., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article.

Two automated treatment planning techniques were evaluated for multiple brain metastases using a single isocenter. One technique is knowledge-based planning (KBP) using a stereotactic radiosurgery (SRS) model in Eclipse treatment planning system (TPS); and the other is the Multiple Brain Mets (MBM) SRS technique in Brainlab Elements TPS. Eighteen plans each with 3-10 lesions were used for the study. Plan evaluation metrics included the planning target volume (PTV) coverage, conformity index (CI), total monitor units (MUs), plan optimization time, brain V 12 Gy , V 8 Gy , and V 5 Gy . Both the KBP and MBM planning techniques produced comparable plans to the manually generated clinical plans in terms of PTV coverage and CI. For irregularly shaped lesions, the KBP plans provided more conformal dose distribution to the PTV than the MBM plans. The KBP plans took significantly longer time to plan but have fewer MUs than the MBM plans. The MBM plans spared normal brain tissues better than the KBP plans in terms of V 5 Gy ., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2022 Old City Publishing, Inc.)

Background: Residual peri-device leakage (PDL) is frequent after left atrial appendage occlusion (LAAO). Little is known about management strategies, procedural aspects and outcomes of interventional PDL closure., Aims: The aim of this study was to assess the safety and feasibility of PDL closure after LAAO., Methods: Fifteen centres contributed data on baseline characteristics, in-hospital and follow-up outcomes of patients who underwent PDL closure after LAAO. Outcomes of interest included acute success and complication rates and long-term efficacy of the procedure., Results: A total of 95 patients were included and a cumulative number of 104 leaks were closed. The majority of PDLs were detected within 90 days (range 41-231). Detachable coils were the most frequent approach (42.3%), followed by the use of the AMPLATZER Vascular Plug II (29.8%) and the AMPLATZER Duct Occluder II (17.3%). Technical success was 100% with 94.2% of devices placed successfully within the first attempt. There were no major complications requiring surgical or transcatheter interventions. During follow-up (96 days [range 49-526]), persistent leaks were found in 18 patients (18.9%), yielding a functional success rate of 82.7%, although PDLs were significantly reduced in size (pre-leak sizemax: 6.1±3.6 mm vs post-leak sizemax: 2.5±1.3 mm, p<0.001). None of the patients had a leak >5 mm. Major adverse events during follow-up occurred in 5 patients (2 ischaemic strokes, 2 intracranial haemorrhages, and 1 major gastrointestinal bleeding)., Conclusions: Several interventional techniques have become available to achieve PDL closure. They are associated with high technical and functional success and low complication rates.

Purpose of Review: Our understanding of the fundamental cellular and molecular factors leading to atrial fibrillation (AF) remains stagnant despite significant advancement in ablation and device technologies. Diagnosis and prevention strategies fall behind that of treatment, but expanding knowledge in AF genetics holds the potential to drive progress. We aim to review how an understanding of the genetic contributions to AF can guide an approach to individualized risk stratification and novel avenues in drug discovery., Recent Findings: Rare familial forms of AF identified monogenic contributions to the development of AF. Genome-wide association studies (GWAS) further identified single-nucleotide polymorphisms (SNPs) suggesting polygenic and multiplex nature of this common disease. Polygenic risk scores accounting for the multitude of associated SNPs that each confer mildly elevated risk have been developed to translate genetic information into clinical practice, though shortcomings remain. Additionally, novel laboratory methods have been empowered by recent genetic findings to enhance drug discovery efforts. AF is increasingly recognized as a disease with a significant genetic component. With expanding sequencing technologies and accessibility, polygenic risk scores can help identify high risk individuals. Advancement in digital health tools, artificial intelligence and machine learning based on standard electrocardiograms, and genomic driven drug discovery may be integrated to deliver a sophisticated level of precision medicine in this modern era of emphasis on prevention. Randomized, prospective studies to demonstrate clinical benefits of these available tools are needed to validate this approach., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma., Patients and Methods: Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550-4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy., Results: Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%-83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4 + T-cell subsets., Conclusions: Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted., (©2020 American Association for Cancer Research.)

Purpose: Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18 F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes., Methods and Materials: Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18 F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs)., Results: From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUV max (normalized to blood pool SUV mean ) <6.7 or SUV max (normalized to blood pool SUV mean ) ≥6.7 with intratreatment SUV 40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively., Conclusions: PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and study aims  A reliable outcome measure is needed for bowel preparation quality during capsule endoscopy. Currently, no scales are adequately validated. Our objective was to update an existing small bowel preparation score, create a standardized training module, then determine its inter-rater and intra-rater reliability. Patients and methods  Modification to produce standardized scoring of an existing small bowel preparation score was performed followed by development of a training module and validation to create the new Korea-Canada (KODA) score. Twenty readers from a range of backgrounds, including capsule endoscopists, gastroenterology fellows, residents, medical students, and nurses rated bowel cleanliness in 25 capsule videos consisting of 1,233 images, in duplicate 4 weeks apart, after completing the training module. Sequential images selected in 5-minute intervals during small bowel transit were rated on a scale between 0-3 based on the amount of visualized mucosa and the degree of obstruction. Reliability was assessed using estimates of intraclass correlation coefficients (ICCs). Results  Intraclass correlation coefficients for inter-rater (ICC 0.81, 95 % CI 0.70-0.87) and intra-rater (ICC 0.92, 95 % CI 0.87-0.94) reliability were almost perfect among the 20 readers. Inter-rater reliability ranged between 0.72 (95 % CI 0.57-0.81) and 0.89 (95 % CI 0.79-0.93) for nurses and residents, respectively. Intra-rater reliability was greater than 0.90 for all groups except for nurses, which was still almost perfect (ICC 0.86, 95 % CI 0.79-0.90). Conclusions  Almost perfect inter-rater and intra-rater reliability was observed for the KODA score. This simple score could be used for future clinical trials after completion of the training module., Competing Interests: Competing interests Michael Sai Lai Sey – Received arms-length research grant from Pharmascience Inc. and educational grants from Cook Medical, Medtronic, and Olympus. All other authors declare that they have no conflict of interest.

Background Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in cardiac transplant recipients. Progression of intimal thickening noted during routine surveillance intracoronary imaging is associated with the development of CAV. However, mechanisms of CAV development are poorly understood and targets for therapy modification remain elusive. We investigated the association of neovessels (INs) within the intima, noted by optical coherence tomography (OCT) during routine CAV surveillance imaging, with intimal thickening and co-incident CAV. Methods Coronary angiography and OCT images of 45 consecutive cardiac transplant recipients undergoing surveillance coronary imaging were reviewed. The presence of INs, defined as dark, tubular or rotund intimal structures, measuring 50-200 µm in diameter, noted in at least three OCT frames, was quantified. CAV diagnosis was determined by utilizing the International Society of Heart and Lung Transplant classification system. Demographic and clinical data was obtained by chart review. Significant associations between the presence of INs and CAV, intimal thickening, and demographic features were evaluated. Results INs were observed in 22/45 evaluated patients (49%), while angiographic CAV was observed in 24/45 patients, with a significant association noted between the presence of INs and CAV ( p < 0.001). INs were also associated with increasing intimal thickness ( p < 0.001), co-morbid hypertension ( p = 0.010), and increasing transplant age ( p = 0.002) on multivariate analysis. Conclusion INs are prevalent in cardiac transplant recipients and are significantly associated with CAV, increased intimal thickness, increasing transplant age, and co-morbid hypertension. Further investigation is warranted regarding the temporal relationship of IN development and the onset of CAV, as well as the mechanisms of IN development in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Chahal et al.)

Objective: The purpose of this study was to define baseline variability of apparent diffusion coefficient (ADC) on diffusion-weighted MR imaging (DWI) in patients with head and neck squamous cell carcinoma (HNSCC) and to compare it with early treatment-induced ADC change., Subjects and Methods: Patients with American Joint Committee on Cancer stages III and IV HNSCC were imaged with two baseline DWI examinations 1 week apart and a third DWI examination during the 2nd week of curative-intent chemoradiation therapy. Mean ADC was measured in the primary tumor and largest lymph node for each patient on the three DWI scans. Mean baseline percentage differences (%∆ADC) were compared with intratreatment change. The repeatability coefficient for baseline %∆ADC was calculated and compared with intratreatment %∆ADC. Repeatability was also assessed with Bland-Altman plots and the intraclass correlation coefficient (ICC)., Results: Sixteen patients underwent double baseline imaging, with 14 also undergoing intratreatment imaging. Baseline nodal disease ADC could be measured in 16 patients, but ADC in primary tumors could only be measured in five patients. The nodal mean (SD) baseline %∆ADC was 8% (± 7%), which was significantly different compared with intratreatment changes of 32% (± 31%) (p = 0.01). Baseline ICC was 0.86 for nodal disease and 0.99 for primary tumor (excellent correlation). The calculated repeatability coefficient for baseline nodal ADC was 15%. No patients had decreases in intratreatment ADC of more than 15%., Conclusion: Baseline ADC variability for HNSCC is less than intratreatment ADC change for nodal disease. Assessment of response should consider intrinsic baseline variability.

Radiotherapy plays an integral role in the management of most patients with cancers of the head and neck. Better understanding of radiobiology and radiation physics has allowed radiation oncologists to enhance the tumoricidal effects of radiation and reduce the severity of normal tissue toxicities. This article reviews the biologic foundation of head and neck radiotherapy, the physical principles and technological innovations that enable delivery of highly conformal radiation, the acute and late complications of radiation-based treatments, and the clinical evidence supporting contemporary practice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: To evaluate how well the tumor, node, metastasis (TNM) 6 and TNM 7 staging systems predict rates of local/regional recurrence (LRR) after surgery alone for non-small cell lung cancer., Methods: All patients who underwent surgery for non-small cell lung cancer at Duke between 1995 and 2005 were reviewed. Those undergoing sublobar resections, with positive margins or involvement of the chest wall, or those who received any chemotherapy or radiation therapy (RT) were excluded. Disease recurrence at the surgical margin, or within ipsilateral hilar and/or mediastinal lymph nodes, was considered as a LRR. Stage was assigned based on both TNM 6 and TNM 7. Rates of LRR were estimated using the Kaplan-Meier method. A Cox regression analysis evaluated the hazard ratio of LRR by stage within TNM 6 and TNM 7., Results: A total of 709 patients were eligible for the analysis. Median follow-up was 32 months. For all patients, the 5-year actuarial risk of LRR was 23%. Conversion from TNM 6 to TNM 7 resulted in 21% stage migration (upstaging in 13%; downstaging in 8%). Five-year rates of LRR for stages IA, IB, IIA, IIB, and IIIA disease using TNM 6 were 16%, 26%, 43%, 35%, and 40%, respectively. Using TNM 7, corresponding rates were 16%, 23%, 37%, 39%, and 30%, respectively. The hazard ratios for LRR were statistically different for IA and IB in both TNM 6 and 7 but were also different for IB and IIA in TNM 7., Conclusions: LRR risk increases monotonically for stages IA to IIB in the new TNM 7 system. This information might be valuable when designing future studies of postoperative RT.