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Scapular notching is a radiographic finding associated with the use of a reverse shoulder prosthesis. The morphological characteristics of the glenoid neck have been scarcely explored as a relevant factor in relation to scapular notching. The objective of this study is to measure the length of the glenoid neck in a three-dimensional CT reconstruction of a healthy population and to simulate the scapular notching free range of motion for the "long neck" and for the "short neck" groups.CT scans of 214 shoulders were reviewed, excluding incomplete, poor quality, or altered studies. 100 CT scans were finally processed. The mean age was 51.7 years (SD 19.4; range, 15-84 years), with 49 female and 51 male patients. For each of the scapulae, four morphometric measurements were obtained: anterior glenoid neck (AGN), middle glenoid neck (MGN), posterior glenoid neck (PGN) and alternative posterior glenoid neck (aPGN). Using 3D software, we simulated a reverse shoulder prosthesis, and the scapular notching free range of motion was registered. Differences between measurements were evaluated with an unpaired t-test using StataIC16®. P-values0.05 were considered significant. The intraobserver and interobserver correlation was evaluated with the intraclass correlation coefficient.The AGN measured 7.43 ± 2.52 mm (range, 1.72-13.3 mm); MGN measured 8.05 mm ± 1.93 (range, 2.92-13.2 mm); PGN measured 7.26 ± 2.6 mm (range, 2-13.4 mm); and aPGN measured 8.97 ± 2.3 mm (range, 4.08-15.4 mm). The scapular notching free range of motion for the "long neck" group was 74.98° ± 7.35 (range, 55-83°) and for the "short neck" group, it was 62.93° ± 6.84 (range, 45-70°) (p = 0.0004).Measurement of posterior glenoid neck length exhibits excellent reliability and reproducibility, as well as being associated to the scapular notching free range of motion.Basic, retrospective, CT images research.

Background The rotator cuff surgery (RCS) incidence is rising rapidly in North America, Europe, Asia, and Australia. Despite this, multiple factors limit patients’ access to surgery. In Latin America, barriers to orthopedic surgery have been largely ignored. The purpose of this study was to calculate the rate of RCS in Chile between 2008 and 2018, investigating possible associated factors to access such as age, sex, and the health insurance. Methods An ecological study was carried out with nationwide data obtained from the Database of Hospital Discharges of the Department of Statistics. All Chilean inhabitants aged 25 years or more were included. We used the ICD-10 codes M751, M754, and S460. The annual incidence rate of surgeries and the incidence rate for the period studied per 100,000 inhabitants were calculated. Data were analyzed stratified by age, sex, year of study, and the health insurance. Negative binomial regression was used to compare rates. Statistical analyzes were performed with Stata v.14 software. Results 39,366 RCSs were performed, with a total rate for the period of 32.36 per 100,000 inhabitants. The annual rate of surgeries from 2008 to 2018 increased from 24.55 to 49.11 per 100,000/year. When adjusting for year, an annual increase in surgery rates of 8.19% (95% CI 6.7–9.6) and 101% growth between 2008 and 2018 (95% CI 90–109%, p < 0.001) was observed. When comparing the global rates according to the health insurance, the public system corresponds to 21.3 per 100,000 and the private system to 72 per 100,000, the latter being 3.4-times higher (95% CI 2.7–4.4; p < 0.001). Conclusion RCS rates are increasing in Chile concordantly with previous reports of other western countries. The most important factor associated with RCS rate found was the patients’ health insurance, with higher rates observed for the private sector.

Introducción: La fractura diafisaria de húmero es frecuente y, en la actualidad, se privilegia el tratamiento quirúrgico. La consolidación en mala rotación puede causar un deterioro de la función y artrosis a largo plazo. Con las técnicas mínimamente invasivas, es difícil manejar la rotación intraoperatoria al no tener una visión directa de la reducción fracturaria. Objetivo: Describir criterios radiográficos para la reducción rotatoria en las fracturas diafisarias de húmero. Materiales y Métodos: Estudio retrospectivo de radiografías de húmero comparando criterios radiográficos del húmero distal entre radiografías con rotación interna (sin retroversión proximal) y rotación externa (con retroversión fisiológica). Criterios estudiados: sobreproyección del epicóndilo lateral por sobre el capitellum >50%, esclerosis del borde inferior de la fosa olecraneana, esclerosis del borde lateral de la fosa olecraneanay asimetría de la fosa olecraneana. Resultados: El 97% de las 200 radiografías estudiadas cumplió con los criterios de inclusión y exclusión. Sobreproyección del epicóndilo por sobre el capitellum: 83,3% de los casos; esclerosis del borde inferior de la fosa olecraneana: 30%, esclerosis del borde lateral de la fosa olecraneana: 86,6% y asimetría: 80% de ellas. Todos los criterios con significancia estadística (p

Growth Promoters (GP) have been used for decades in animal production, although some countries restrict or forbid their use. With the increasing population worldwide, the demand for animal protein ...

In the present day, consumers are increasingly concerned about the relationship between diet and health, which has led to an increase in demand for healthier products. However, developing these types of products, while preserving their sensory quality is very challenging. In this sense, the use of sensory science plays an important role in the development of healthier processed meat products. Thus, this communication highlights recent advances in the use of sensory science as a tool to assist the development of healthier processed meat products. The opinion article was structured in 4 parts: (1) different sensory methodologies for sensory profiling of healthier processed meat products; (2) main strategies to improve the sensory quality of healthier processed meat products; (3) sensory attributes negatively affected by the reformulation process and (4) conclusions and future perspectives. According to the literature, obtaining healthier processed meat products implies a drastic reformulation process that causes negative changes in sensory attributes. Based on this, the use of sensory science can be an essential tool for the development of healthier processed meat products with greater chances of success in the market.

Parsonage-Turner syndrome (PTS), also known as idiopathic brachial plexopathy or neuralgic amyotrophy, was first described by Julius Dreschfeld in 1887. PTS is characterized by a single or multiple mononeuropathies at the level of the brachial plexus (not exclusive), acute and self-limited, associated with motor deficit and muscle atrophy. The exact pathophysiology is still unknown. Of the many proposed causes, an infectious or immune-mediated process seems to be the most supported. Viral illness is the most common associated risk factor (25% to 55%). Currently, there are only three case reports in the literature on the relation of COVID-19 with PTS. The COVID- 19 neurological involvement has been described mainly at the central nervous system, with Guillain-Barre syndrome being the most frequent at the peripheral nervous system. In the context of a coronavirus pandemic, we should suspect this disease in patients with neuropathic pain in the shoulder region within the possible differential diagnoses. This publication is about a case of PTS in association with COVID-19 and a review of scientific literature available.

Purpose Although peer review in radiation oncology (RO) has been recommended to improve quality of care, an analysis of modifications resulting from an RO multidisciplinary presimulation standardized review process has yet to be empirically demonstrated. Methods and Materials A standardized simulation directive was used for patients undergoing simulation for external beam radiation therapy at a single tertiary care institution. The simulation directives were presented, and all aspects were reviewed by representatives from key RO disciplines. Modifications to the original directives were prospectively captured in a quality improvement registry. Association between key variables and the incidence of modifications were performed using Fisher exact test and t test. Results A registry of 500 consecutive simulations for patients undergoing radiation therapy was reviewed. A median of 105 simulations occurred per month. All simulation directives were entered by a physician a median of 3 days before simulation (range, 1-76 days). The treatment intent was curative for 269 patients (53.8%), palliative for 203 patients (40.6%), and benign for 3 patients (0.6%). Twenty-five (5%) patients did not have a treatment intent selected. Based on RO multidisciplinary review, 105 directives (21%) were modified from the original intent, with 29 (5.8%) requiring more than 1 modification. A total of 149 modifications were made and categorized as changes to patient positioning and immobilization (n = 100, 20%), treatment site and care path (n = 34, 6.8%), simulation coordination activities (n = 6, 1.2%), and treatment technique and planning instructions (n = 9, 1.8%). A higher proportion of modifications occurred at the time of multidisciplinary review in patients receiving more complex treatments (intensity modulated radiation therapy/stereotactic radiosurgery/stereotactic body radiation therapy [IMRT/SRS/SBRT] vs 3-dimensional radiation therapy [3DCRT] radiation therapy, 25% vs 16%, P Conclusions Given the complexity of radiation therapy simulation, standardization of directives with prospective RO multidisciplinary presimulation peer review is critical to optimizing department processes and reducing errors. Approximately 1 in 5 patients benefits from this peer review process, especially patients treated with IMRT/SRS/SBRT.

Today, patient management generally requires a multidisciplinary approach. However, due to the growing knowledge base and increasing complexity of Medicine, clinical practice has become even more specialised. Radiation oncology is not immune to this trend towards subspecialisation, which is particularly evident in ablative radiotherapy techniques that require high dose fractions, such as stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). The aim of the present report is to establish the position of the Spanish Society of Radiation Oncology (SEOR), in collaboration with the Spanish Society of Medical Physics (SEFM), with regard to the roles and responsibilities of healthcare professionals involved in performing SRS and SBRT. The need for this white paper is motivated due to the recent changes in Spanish Legislation (Royal Decree [RD] 601/2019, October 18, 2019) governing the use and optimization of radiotherapy and radiological protection for medical exposure to ionizing radiation (article 11, points 4 and 5) [1 ], which states: “In radiotherapy treatment units, the specialist in Radiation Oncology will be responsible for determining the correct treatment indication, selecting target volumes, determining the clinical radiation parameters for each volume, directing and supervising treatment, preparing the final clinical report, reporting treatment outcomes, and monitoring the patient’s clinical course.” Consequently, the SEOR and SEFM have jointly prepared the present document to establish the roles and responsibilities for the specialists—radiation oncologists (RO), medical physicists (MP), and related staff —involved in treatments with ionizing radiation. We believe that it is important to clearly establish the responsibilities of each professional group and to clearly establish the professional competencies at each stage of the radiotherapy process.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

β-cell death is regarded as a major event driving loss of insulin secretion and hyperglycemia in both type 1 and type 2 diabetes mellitus. In this review, we explore past, present, and potential future advances in our understanding of the mechanisms that promote β-cell death in diabetes, with a focus on the primary literature. We first review discoveries of insulin insufficiency, β-cell loss, and β-cell death in human diabetes. We discuss findings in humans and mouse models of diabetes related to autoimmune-associated β-cell loss and the roles of autoreactive T cells, B cells, and the β cell itself in this process. We review discoveries of the molecular mechanisms that underlie β-cell death-inducing stimuli, including proinflammatory cytokines, islet amyloid formation, ER stress, oxidative stress, glucotoxicity, and lipotoxicity. Finally, we explore recent perspectives on β-cell death in diabetes, including: (1) the role of the β cell in its own demise, (2) methods and terminology for identifying diverse mechanisms of β-cell death, and (3) whether non-canonical forms of β-cell death, such as regulated necrosis, contribute to islet inflammation and β-cell loss in diabetes. We believe new perspectives on the mechanisms of β-cell death in diabetes will provide a better understanding of this pathological process and may lead to new therapeutic strategies to protect β cells in the setting of diabetes.

Pro-social behavior is crucial to the sustainable governance of common-pool resources such as fisheries. Here, we investigate how key socioeconomic characteristics influence fishers’ pro-social and bargaining behavior in three types of experimental economic games (public goods, trust, and trade) conducted in fishing associations in Chile. Our games revealed high levels of cooperation in the public goods game, a high degree of trust, and that sellers rather than buyers had more bargaining power, yet these results were strongly influenced by participants’ socioeconomic characteristics. Specifically, gender, having a secondary income source, age, and being the main income provider for the household all had a relationship to multiple game outcomes. Our results highlight that engagement in pro-social behaviors such as trust and cooperation can be influenced by people’s socioeconomic context.

Introduction: Triple negative breast cancers (TNBC, which lack estrogen receptor (ER), progesterone receptor and HER2), occur three times more frequently in premenopausal women and metastasize expeditiously to brain and lungs. Clinical and experimental evidence shows that estrogen, the main premenopausal ovarian hormone, promotes metastases of TNBC, through their action on the tumor microenvironment. We have shown that 17-β-Estradiol (E2) promotes experimental brain metastases (BM) of TNBC cells by inducing estrogen-receptor positive (ER+) astrocytes in the brain niche to secrete growth factors that promote cancer cell migration, invasion and growth. Given that 53% of pre-menopausal women with TNBC develops BM and 80% die within a year, it is now critical to define whether blocking estrogen signaling could have therapeutic value to prevent or delay progression of BM. Results: To assess whether E2-depletion could prevent brain metastatic colonization, brain trophic sublines of human TNBC (231BR), murine TNBC (4T1BR5), a non-selected TN cell line syngeneic to C57BL mice (E0771-GFP-luc) were intracardially (ic) injected two-days post-endocrine initiation, in ovariectomized (OVX) female mice treated with a) E2 (levels equivalent to those found in pre-menopausal women), b) placebo (OVX), or c) the aromatase-inhibitor (AI) letrozole (OVX + Letrozole) to block brain and peripheral E2-synthesis. BM were quantified histologically, via MRI or ex-vivo imaging of brains at euthanasia. E2-treated mice injected with E0771-GFP-luc cells showed an average of 6.6± 3.5 metastatic clusters per mice, compared to 3.6 ± 3.2 and 1.8 ± 1.8 in OVX mice alone or OVX + letrozole treated mice (a 3.6 fold increase, P=0.0013, E2 vs OVX + Let). Imaging of excised brains showed comparable results, with a mean total photon flux of 5.1 × 106 ± 5.3 × 106 in E2 vs 1.1 × 106 ± 1.5 × 106 in OVX + letrozole (P=0.0056). Similar preventive effects of E2-depletion were found in 4T1BR5 and 231BR-cell injected mice, using histological quantification and MRI as endpoints. To assess whether E2-depletion therapies could decrease brain metastatic progression in a therapeutic model mimicking the clinical setting, E0771-GFP-luc cells were injected in OVX-mice that had been supplemented with E2 and metastasis allowed to develop for 6 days. Mice were then randomized to a) E2, b) E2-withdrawal (E2WD) or c) E2WD+ letrozole, and then all mice were irradiated (whole brain irradiation, single-dose, 15 Gy) to mimic current standard of care for BMs. All mice were euthanized 10 days later, when E2-treated mice showed signs of CNS impairment. Mice that received E2WD+letrozole showed the lowest BM burden compared to mice that remained in E2-treatments, as assessed by histological quantification (0.7 ± 1.2 vs 6.5 ± 5.3 metastatic clusters, respectively, P=0.0132) and ex-vivo brain imaging (mean total-photon flux 3.4 × 105 ± 4.1 × 105 in E2WD + let vs 3.1 × 106 ± 1.4 × 106 in E2, P=0.037). Brain metastasis in TNBC often occur in women who also present with systemic metastatic disease, and E0771-GFP-luc cells can colonize multiple organs following ic injection. Thus, non-brain metastatic burden (systemic metastasis) was measured by in vivo imaging before euthanasia in this cohort. Unlike brain metastasis, E2WD or E2WD+letrozole showed no statistically significant effect on systemic metastatic burden (mean total flux 1.41 × 106 ± 0.9 × 106 in E2, vs 0.54 × 106 ± 2.6 × 106 in E2WD vs 0.79 × 106 ± 1.0 × 106 in E2WD+let, P=0.416), supporting the notion that brain-specific rather than systemic mechanisms drive progression of brain metastasis in response to E2. Conclusions: These studies have important clinical implications as they provide pre-clinical evidence that ovarian suppression in combination with AIs can prevent and delay progression of established brain metastasis in younger women with TNBC. Citation Format: Diana M. Cittelly, Maria J. Contreras-Zarate, Ricaurte A. Marquez-Ortiz, Nicole Day, Bebhinn Nagle, Ryan Ormond, Virginia F. Borges, Peter Kabos. Estrogen-depletion therapies prevent and delay progression of brain metastasis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-03.

Introduction: Brain metastases (BM) occurs in ~40% of breast cancer patients with Her2+ tumors, which are typically treated with the Her-2 targeting drugs ado-trastuzumab emtansine (T-DM1) and trastuzumab. Radiotherapy (RTx), including stereotactic radiosurgery (SRS), is often utilized to treat BM. A subset of BM patients treated with SRS develops brain edema and radionecrosis (ERN), causing neurological deterioration, functional loss, and rarely death. We have reported an increased rate of ERN in patients treated with T-DM1 and SRS (39.1%), compared to those receiving SRS alone (4.5%). Thus, defining the mechanisms underlying ERN alone or in combination with T-DM1, is critical to reduce life-threatening side effects. While brain edema associated with BM and RTx is often attributed to blood-brain-barrier (BBB) disruption (vasogenic edema), recent studies now identify cytotoxic edema (osmotic cell expansion) as the initial andreversible step in a sequence of changes that leads to ionic edema, vasogenic edema, and ultimately brain swelling and necrosis. Here, we test the hypothesis that RTx alone and in combination with T-DM1 induces cytotoxic edema in astrocytes via upregulation of the water channel Aquaporin 4 (AQP4) and that blockage of cytotoxic edema will decrease ERN. Results: A cohort of BM from Her2+ patients treated with T-DM1/SRS showed enlarged reactive astrocytes expressing high levels of AQP4. To assess the role of astrocytic swelling in ERN, human astrocytes (THV) were treated with increasing doses of RTx and astrocytic cell size was measured 24 h later. A single 8 Gy RTx-dose increased cell size by 4.5 times compared to non-treated astrocytes (1248 ± 760.8 µm2 vs 5685 ± 4475 µm2, P Citation Format: María J Contreras-Zárate, Steven Lai, Priscilla Stumpf, Christine Fisher, Ryan Ormond, Sana D Karam, Peter Kabos, Diana M Cittelly. Mechanisms of radiation-induced brain edema alone and in combination with T-DM1 in Her2+ brain metastases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-20.

Hepatic encephalopathy (EH) is a common complication among patients with liver cirrhosis associated with a high mortality rate. The costs attributed to the management of patients with cirrhosis are especially high due to complications such as EH, since it increases the days of hospitalization. Currently for the treatment of EH, there are different drugs of which the standout lactulose, L-ornithine, L-aspartate (LOLA) and certain antibiotics, especially rifaximin-α (RFX). Although many of them have been shown to be as effective as the others, in order to that it is important to have information that allows us to discern about each other. Furthermore, that can help to individualize the patient's treatment and choose the best options in different scenarios. Therefore, the objective of this study was to analyze the evidence on the advantages and disadvantages of individual use or in combination of the 3 main treatments of EH, specifically its effectiveness in different grades of EH, its impact on quality of life, prophylaxis and costs reduction. Resumen: La encefalopatía hepática (EH) es una complicación frecuente en pacientes con cirrosis hepática y se asocia a una alta tasa de mortalidad. Los costos atribuidos al manejo de pacientes con cirrosis son especialmente elevados debido a complicaciones como la EH puesto que prolongan los días de estancia hospitalaria. Actualmente para el tratamiento de la EH, existen diferentes fármacos de los cuales los principales son la lactulosa, L-ornitina, L-aspartato (LOLA) y ciertos antibióticos, especialmente la rifaximina-α (RFX). Aunque muchos de ellos han demostrado ser efectivos en mayor o menor medida, es importante contar con información que permite discernir sobre uno y otro con el objetivo de individualizar el tratamiento al paciente y elegir la mejor opción en diferentes escenarios. Por lo anterior el objetivo de este estudio fue analizar la evidencia sobre las ventajas y desventajas del uso individual o en combinación de los 3 principales tratamientos de la EH, específicamente su eficacia en los diferentes grados, su impacto en la calidad de vida, profilaxis y reducción de costos. Palabras clave: Encefalopatía hepática, Cirrosis hepática, Rifaximina, Lactulosa, L-ornitina, L-aspartato, Calidad de vida, Keywords: Hepatic encephalopathy, Cirrhosis of the liver, Rifaximin, Lactulose, L-ornithine, L-aspartate, Quality of life

Background and Purpose To quantify the indication for adaptive, gated breath-hold (BH) MR-guided radiotherapy (MRgRTBH) versus BH or free-breathing (FB) CT-based image-guided radiotherapy (CT-IGRT) for the ablative treatment of adrenal malignancies. Materials and Methods Twenty adrenal patients underwent adaptive IMRT MRgRTBH to a median dose of 50 Gy/5 fractions. Each patient was replanned for VMAT CT-IGRTBH and CT-IGRTFB on a c-arm linac. Only CT-IGRTFB used an ITV, summed from GTVs of all phases of the 4DCT respiratory evaluation. All used the same 5 mm GTV/ITV to PTV expansion. Metrics evaluated included: target volume and coverage, conformality, mean ipsilateral kidney and 0.5 cc gastrointestinal organ-at-risk (OAR) doses (D0.5cc). Adaptive dose for MRgRTBH and predicted dose (i.e., initial plan re-calculated on anatomy of the day) was performed for CT-IGRTBH and MRgRTBH to assess frequency of OAR violations and coverage reductions for each fraction. Results The more common VMAT CT-IGRTFB, with its significantly larger target volumes, proved inferior to MRgRTBH in mean PTV and ITV/GTV coverage, as well as small bowel D0.5cc. Conversely, VMAT CT-IGRTBH delivered a dosimetrically superior initial plan in terms of statistically significant (p≤0.02) improvements in target coverage, conformality and D0.5cc to the large bowel, duodenum and mean ipsilateral kidney compared to IMRT MRgRTBH. However, non-adaptive CT-IGRTBH had a 71.8% frequency of predicted indications for adaptation and was 2.8 times more likely to experience a coverage reduction in PTV D95% than predicted for MRgRTBH. Conclusion Breath-hold VMAT radiotherapy provides superior target coverage and conformality over MRgRTBH, but the ability of MRgRTBH to safely provide ablative doses to adrenal lesions near mobile luminal OAR through adaptation and direct, real-time motion tracking is unmatched.

Necroptosis is an inflammatory and immunogenic form of lytic cell death that can occur downstream of TNFα signaling. Receptor interacting protein kinase 3 (RIPK3) mediates TNFα-induced necroptosis when caspase activity is repressed, but this pathway has not been examined in insulin-producing β-cells. As TNFα contributes to β-cell death in the setting of diabetes and since we found RIPK3 is expressed in INS-1 β-cells and mouse islets, we hypothesized that β-cells are susceptible to necroptosis. To test this hypothesis, INS-1 cells were treated with TNFα (40 ng/ml) in the absence or presence of a synthetic pan-caspase inhibitor (zVAD, 50 μM) for 24 h, cell death was monitored in real-time, and caspase activity was determined. TNFα increased INS-1 cell death (1.63 ± 0.13 vs. 2.44 ± 0.13 fold, n=7, p Disclosure C. J. Contreras: None. L. Lin: None. M. F. Hogan: None. A. Oberst: None. S. E. Kahn: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. A. T. Templin: None. Funding U.S. Department of Veterans Affairs (IK2BX004659, I01BX001060)

Purpose/Objective(s) The primary objective of this study is to evaluate the utility and value of an institutional, multi-disciplinary peer review process prior to radiotherapy simulation. Materials/Methods Over a period of 3 months and through an iterative process, a standardized simulation requisition directive (SSRD) was developed, piloted, modified, and subsequently implemented for all patients treated with external beam radiotherapy at a single tertiary care institution from January to December 2020. The SSRDs were reviewed at a daily multi-disciplinary peer review conference (“morning huddle”); modifications in the simulation process consequential to the review were prospectively recorded in a quality database. Descriptive statistics were used to identify characteristics associated with modifications. Independent sample t test and Chi-square test were used to compare continuous and categorical variables. Results A total of 1500 consecutive SSRDs were prospectively reviewed and met inclusion criteria for this study. The median time between the physician SSRD order and date of simulation was 4 days (Range: 0-97 days), and the majority of patients were treated with curative intent (n = 872, 58%). A total of 369 modifications on 269 (17.9%) simulation directives were recorded and parsed into 17 categories. The most common modifications resulted from omission of pregnancy testing orders (n = 92, 24.9%), immobilization device changes (n = 88, 23.8%), changes in the radiotherapy care path (n = 56, 15.1%), and arm positioning (n = 43, 11.6%). Modifications were less likely to occur if the directives were entered within 1 week of simulation (15.6% vs. 21.7%, P = 0.0028). Significant differences were also observed across tumor sites (P = 0.0091) with the highest modification rates observed for stomach, esophagus, and pelvis sites (40%, 30%, and 26.9% modified, respectively). A significant change in department workflow and clinic visits occurred in March 2020 as a result of COVID-19, with transition to virtual platforms. An increased rate of simulation directive modifications was also observed for patients simulated after these changes were implemented (April – December 2020 19.3% vs. Jan – March 2020 13.5%, P = 0.013). No differences in modification rates were observed by modality, i.e., photon or proton therapy (P = 0.20). Overall, with this prospective peer review process, only 14 patients (0.9%) needed re-simulation during the entire study period. Conclusion Prospective peer review prior to simulation in radiotherapy identifies actionable change in approximately 18% of procedures, and results in an extremely low, 1 week before from simulation and gastrointestinal and pelvic sites were at higher risk of requiring modifications during peer review. As departmental processes transition to virtual meeting platforms, more thorough attention is needed to identify patients at higher risk of simulation modifications.

Purpose/objective(s) Randomized data show an overall survival (OS) benefit of stereotactic ablative body radiation therapy (SABR) in addition to chemotherapy (CT) in selected patients with oligometastasis (OM). While ablative dose can be safely delivered to some lesions, others in proximity to some organs at risk (OARs) such as bowel may be treated with non-ablative dose to limit toxicity. Stereotactic magnetic resonance image-guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting OARs, which may improve long-term disease control. Materials/methods The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Patients with Results 101 patients with 114 OM lesions were treated on a 0.35T-MR Linac at 2 institutions between 2018-2020. Median age was 62 years (range 23-89), and 99% were ECOG 0-1 performance status. The primary tumor was definitively managed in 34.7%, most commonly in the lung (30.7%), colon/rectum (22.8%), cervix/uterus/ovary (13.9%), or breast (5.9%). About 50% received CT for OM prior to SMART. SMART was delivered to 1 (87.7%) or 2 (10.5%) lesions, mostly involving abdominal/pelvic lymph nodes (40.4%), liver (17.5%), lung (17.5%), or adrenal gland (11.4%). All were treated without fiducial markers and with real-time tissue tracking and automated beam gating, typically in breath hold. The median prescribed RT dose was 45 Gy (range 24-60Gy) in a median 5 fractions (range 3-15). The median biologically effective dose (BED10) was 100 Gy10 (range 41.4-180). The median PTV was 14.5 cm3 (range 1.5-567.8). Median follow-up was 10 months (range 3-25) from SMART. One-year LC, FFDP, PFS, and OS were 88%, 38.2%, 36.1%, and 90.6%, respectively. Median PFS and OS were 9 months and not reached, respectively. No acute/late grade 3+ toxicities were recorded. Conclusion To our knowledge, this represents the largest analysis of SMART for OM. A median prescribed BED10 of 100 Gy10 resulted in excellent early LC and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. These outcomes are noteworthy given the predominance of OM, especially LNs, treated with dose escalation in proximity to gastrointestinal OARs; such lesions are notably underrepresented in SABR OM trials. Prospective evaluation of dose-escalated SMART for OM is warranted.

PURPOSE/OBJECTIVE(S) Although early larynx cancers require treatment of only the vocal cord(s), radiation for early larynx cancer historically consisted of opposed lateral portals that included the entire larynx. Treatment techniques have advanced to 3D conformal and intensity modulated radiotherapy (IMRT), but the treatment target has remained the entire larynx. One concern preventing volume reduction in these patients is periodic swallowing that occurs during treatment delivery due to normal patient physiology. Such intrafraction swallowing can displace the treatment target up to 2 cm and could lead to tumor underdosing. Treatment with real-time target tracking could greatly mitigate this concern. Herein, we describe our initial experience using MR-guided radiotherapy (MRgRT) to visualize and understand the impact of intrafraction larynx motion. MATERIALS/METHODS Three patients with cT1-2 laryngeal cancer were treated using an MRgRT Linac. Treatment volume included the entire larynx to evaluate feasibility of setup, immobilization, patient tracking, and treatment planning. A commercial MR-compatible head-and-heck immobilization system was developed and utilized, consisting of an indexable baseplate with integrated MR receiver coils affixed to a head cradle, with an open-face thermoplastic mask and head-mold cushion. Treatment plans were inversely planned utilizing 5 anterior IMRT fields to eliminate entrance dose to posterior organs at risk (OARs). The tracking structure consisted of patients' intrinsic larynx muscles delineated by a head and neck radiation oncologist on a 35cm x 35cm x 0.70cm sagittal MR plane. Patients were instructed not to swallow during setup imaging and during treatment. Continuous real-time tracking was performed at 4 frames per second with automatic beam hold if > 5% of the area of the tracking structure exceeded the 3mm isotropic boundary limit. RESULTS Images were taken during patient treatment, and movement of the intrinsic muscles of the larynx was apparent in all patients due to periodic deglutition. At the time of analysis, 63 fractions have been delivered. The average total in-room time for the three patients in the study was 27:22 minutes (range 18:00 - 45:00 minutes), while the average beam-on time was 8:44 minutes (range 4:00 - 30:00 minutes). CONCLUSION MR real-time visualization of the patient's intrinsic laryngeal muscles during MRgRT provides a method of gating treatment during patient swallowing. Robust intrafraction target tracking appears to enable higher confidence in reducing the treatment volume for early larynx cancers such that improvements in preservation of voice quality and deglutition capabilities are possible without sacrificing local control. A clinical trial is planned to examine such volume reduction and its effect on patient quality of life and function.

A 37-year-old woman presented to the emergency room with a 1-week history of abdominal pain. On examination, she had pain in the right upper quadrant that worsened after meals and was febrile with a temperature of 38.3°. Laboratory studies demonstrated leukocytosis (white blood cell count of over 13,000), elevated inflammatory markers, and normal liver function tests. An ultrasound confirmed acute cholecystitis and pericholecystic fluid. Per hospital protocol, COVID-19 PCR was performed despite no respiratory symptoms. The PCR detected SARS-CoV-2. The risk-benefit was analyzed and the patient was taken to the operating room for an open cholecystectomy. The gallbladder was found with severe inflammation. A cholecystectomy was performed with a fundus-cystic technique. During the procedure, a choledochal duct injury was identified, and an intraoperative cholangiogram was requested, showing lesion Strasberg-E1. The hepatobiliary surgeon was requested who evaluated the case and decided to perform an early biliodigestive derivation (hepaticojejunal anastomosis). After the procedure, the patient developed respiratory acidosis and hemodynamic instability and was classified as having COVID-19 with severe illness. The patient was intubated for 6 days, then extubated and kept on high flow oxygen and nasal cannula as respiratory parameters improved. Eighteen days after admission, she was discharged to go home. Results: During the subsequent follow-up visit, a postoperative day 30 there were no operative or medical complications. A Cholangioresonance was requested, on day 90 postoperative, which showed functional hepaticojejunal anastomosis. [Formula presented] Conclusion: As described in the literature, up to 50 percent of patients with perioperative COVID-19 infection develop pulmonary complications. This patient presented metabolic and respiratory deterioration, requiring mechanical ventilation for 6 days. The case presented a surgical challenge due to the type of injury and the infectious control precautions required to operate on SARS-CoV-2 positive patients. Complex medical management was also required. Careful multidisciplinary management results in positive patient outcomes when dealing with complicated surgical cases.

To describe the clinical characteristics and sociodemographic factors associated with COVID-19 among pregnant women in a maternal and children's hospital in Lima, Peru.Quantitative observational study. The population under study consisted of pregnant women who attended an emergency room and had a COVID-19 test. These women were assessed for age, gestational age, place of origin, occupation, education, marital status, number of children, previous body mass index, gestational body mass index, tetanus vaccination, prenatal controls, and hemoglobin. After bivariate analysis, a generalized linear regression model was applied.We included 200 women aged between 18 and 34 years (84.5%) with a median gestational age of 36 weeks. More than half were from Lima (52.5%), most were housewives (79%), had high school education (71.9%), and had a cohabiting marital status (60%). The COVID-19 test positivity was 31.5% by rapid tests. Pregestational body mass index assessment showed that 36.7% of normal weight, 38,1% of overweight, and 30.3% of obese pregnant women had COVID-19 infection. 39.7% of patients with hemoglobin levels greater than or equal to 11 g/dL, 21.2% of patients with values between 10 and 10.9 g/dL, and 20% of patients with values between 7 and 9.9 g/dL had COVID-19 infection. The prevalence ratio (with a 95% confidence interval) found that cohabitation was associated with a lower risk of having COVID-19 infection in pregnant women (prevalence ratio: 0.41, p0.001).Cohabiting pregnant women had a lower risk of COVID-19 infection compared with other marital statuses. Further research is needed to evaluate COVID-19 associated factors in pregnant women and possible sociodemographic or economic factors behind cohabiting marital status association among this population.Describir las características clínicas y factores sociodemográficos asociados a COVID-19 en gestantes de un hospital materno infantil de Lima, Perú.Estudio cuantitativo observacional. La población estuvo compuesta por gestantes atendidas en la unidad de emergencia, con la prueba para el diagnóstico de COVID-19. A las madres se les valoró edad, edad gestacional, lugar de procedencia, ocupación, nivel de estudios, estado civil, número de hijos, índice de masa corporal previa, índice de masa corporal de la gestación, vacuna antitetánica, controles prenatales, y hemoglobina. Después de un análisis bivariado se aplicó un modelo de regresión lineal generalizado.Incluimos a 200 mujeres, con edades de 18 a 34 años (84,5%). Más de la mitad procedía de Lima (52,5%), 79% tenía como ocupación el ser ama de casa, 71,9% alcanzó estudios secundarios y 60% registró estado civil de conviviente. La incidencia de COVID-19 fue de 31,5% mediante pruebas rápidas. La mediana de edad gestacional al momento de la evaluación para COVID-19 fue de 36 semanas. El índice de masa corporal pregestacional, comparado entre las gestantes con COVID-19 y las que no lo tuvieron, fue normal en 36,7 y 63,3%. Se detectó sobrepeso en 38,1 y 61,9% de las pacientes, obesidad en 30,3 y 69,7%, respectivamente. Los niveles de hemoglobina superiores o iguales a 11 gramos por decilitro se reportaron en 39,7 y 60,3% en cada grupo; hemoglobina entre 10 y 10,9 gramos por decilitro, en 21,2 y 78,8%; y hemoglobina entre 7 y 9,9 gramos por decilitro, en 20 y 80%, respectivamente. La razón de prevalencia con un intervalo de confianza al 95%, identificó al estado civil conviviente asociado a menor riesgo de tener COVID-19 en gestantes (razón de prevalencia: 0,41, valor p0,001).Las gestantes cuyo estado civil fue de conviviente presentaron menor riesgo de experimentar COVID-19. Es necesario seguir estudiando los factores que se asocian a la presencia de COVID-19 en gestantes, así como posibles factores sociodemográficos o económicos detrás del estado civil conviviente.

Purpose: The survival of women with brain metastases (BM) from breast cancer remains very poor, with over 80% dying within a year of their diagnosis. Here, we define the function of IL13Rα2 in outgrowth of breast cancer brain metastases (BCBM) in vitro and in vivo, and postulate IL13Rα2 as a suitable therapeutic target for BM. Experimental Design: We performed IHC staining of IL13Rα2 in BCBM to define its prognostic value. Using inducible shRNAs in TNBC and HER2+ breast–brain metastatic models, we assessed IL13Rα2 function in vitro and in vivo. We performed RNAseq and functional studies to define the molecular mechanisms underlying IL13Rα2 function in BCBM. Results: High IL13Rα2 expression in BCBM predicted worse survival after BM diagnoses. IL13Rα2 was essential for cancer-cell survival, promoting proliferation while repressing invasion. IL13Rα2 KD resulted in FAK downregulation, repression of cell cycle and proliferation mediators, and upregulation of Ephrin B1 signaling. Ephrin-B1 (i) promoted invasion of BC cells in vitro, (ii) marked micrometastasis and invasive fronts in BCBM, and (iii) predicted shorter disease-free survival and BM-free survival (BMFS) in breast primary tumors known to metastasize to the brain. In experimental metastases models, which bypass early tumor invasion, downregulation of IL13Rα2 before or after tumor seeding and brain intravasation decreased BMs, suggesting that IL13Rα2 and the promotion of a proliferative phenotype is critical to BM progression. Conclusions: Non-genomic phenotypic adaptations at metastatic sites are critical to BM progression and patients' prognosis. This study opens the road to use IL13Rα2 targeting as a therapeutic strategy for BM.

Background Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. Materials and methods This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. Results Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. Conclusions This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies., Highlights • The number of new cancer patients decreased 20.8% • Assistance protocols were adapted • Inclusion in clinical trials decreased by 12.9%

Background Strategies for the reformulation of meat products respond to consumers’ demand for healthier food alternatives. The reduction of salt or sodium and animal fat, and the substitution of synthetic antioxidants by natural ones have been a subject of study for Brazilian researchers for many years, but the industrial application of new technological alternatives presents the challenge of adapting to regulations related to the processing of meat products. Scope and approach Reports by Brazilian researchers from 2011 to 2019 were collected from the Scopus database and their abstracts were submitted to a textual analysis to visualize the trend of studies over these years. The relationship between the approaches/ingredients proposed in the studies and the Brazilian regulation was discussed. Key findings and conclusions Numerous alternatives for natural antioxidants and salt and animal fat substitutes have been proposed, but Brazilian regulation is restrictive with respect to the use of natural antioxidants and the most studied salt substitute in meat products. However, studies using alternatives more compatible with Brazilian regulations have been proposed. For industrial application purposes, some flavorings and spices may have antioxidant activity and act as natural antioxidants, delaying the lipid oxidation of meat products; the sodium content can be reduced using several morphologies or sizes of salt particles; and the incorporation of oils rich in polyunsaturated fatty acids, embedded in oleogels and microparticles using encapsulating proteins, seem to be a viable alternative for reducing animal fat in meat products.

Background Orthotopic heart transplant (OHT) is indicated for end-stage heart failure due to cardiac sarcoidosis (CS). However, utilization of OHT for CS has been controversial due to concern for involvement of other organs by sarcoidosis affecting long term outcomes. Purpose Our objective was to study the trends in OHT in patients with CS in the United States using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) from 1999 to 2014. Methods Using NIS data, we identified patients older than 18 years with cardiac sarcoidosis using codes ICD 9-CM codes of 135 and 425.8. Among these patients, we identified those who underwent cardiac transplantation using ICD 9-CM procedure codes 37.5 and 33.6. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results A weighted total of 24231 hospitalizations for CS was extracted from 1999 to 2014 of which 248 (1.02%) CS patients underwent OHT. The trends in cardiac transplant for CS is as shown in Figure 1. The mean age of CS patients undergoing OHT was 51.7±1.1 years and 60.4% (n=150) were males. 114 (45.9%) were Caucasians and 27.8% (n=25) were African-American. 100% of the transplants were performed at medium (n=5) or large sized (n=243) teaching hospitals and 97.9% of cardiac transplants were also done at teaching hospitals. Heart transplants were mostly done in the South (36.3%) followed by Midwest (26.2%), West (25%) and Northeast (12.5%). Private insurance was the major payor source which covered 149 (60.1%) patients followed by Medicare covering 65 (26.2%) patients. A total of 10 (3.9%) cardiac sarcoidosis patients died during the same hospitalization for cardiac transplantation. Following OHT, 84.2% (n=209) were discharged home and 11.6% (n=29) to short term hospitalization. The mean cost of hospitalization for OHT in CS when adjusted for inflation was 535144±56060 dollars while the average length of stay for heart transplant for CS was 46.2±6.6 days. Conclusions Cardiac transplant trends in CS have not changed from 1999 to 2014 despite recent studies showing improved outcomes and are associated with substantial cost of hospitalization and length of stay. Majority of cardiac transplant was done in Caucasians despite cardiac sarcoidosis being more common in African-Americans. Funding Acknowledgement Type of funding source: None

Background Orthotopic heart transplant (OHT) is indicated in 1–8% of patients with myocarditis. However, national trends in the utilization of transplantation and outcomes in myocarditis across the United States are not well established. Purpose Our objective was to study the trends and baseline characteristic of myocarditis patients undergoing heart transplant in the United States using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) from 1999 to 2014. Methods Using NIS data, we identified patients older than 18 years with myocarditis using codes ICD9 codes of 422.0 and 422.9. Among these patients, we identified those who underwent cardiac transplantation using ICD9 procedure codes 37.5 and 33.6. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results We identified a total of 62,264 hospitalizations for myocarditis from 1999–2014. 430 (0.69%) myocarditis patients underwent OHT which consisted of 0.82% of all 29990 cardiac transplants identified in the same period. The trends in OHT for myocarditis is as shown in Figure 1. The mean age was 32.9±2.4 years and 51.1% (n=219) were females. 235 (54.6%) were Caucasians and 60 (13.9%) were Hispanic. Majority of the transplants were performed at medium (16%) and large sized hospitals (80.4%). Cardiac transplants were mainly done at teaching hospitals (98.9%). Further, with regards to the geographical distribution of transplant procedure, most were done in the West (37.2%) followed by South (25.3%), Northeast (21.4%) and Mid-west (16%) of the United States. Private insurance was the major payor source which covered 245 (58%) patients followed by Medicaid covering 112 (26%) patients. A total of 26 (6%) myocarditis patients died during the same hospitalization for OHT. In terms of discharge following OHT in myocarditis 85.8% (n=369) were discharged home and 8.1% (n=35) to short term hospitalization. The average length of stay for OHT for myocarditis was 64.3±6.3 days. Also, the mean cost of hospitalization for heart transplant in myocarditis when adjusted for inflation was 789,566±93,108 dollars. In-patient mortality following OHT was not significantly different in large sized hospital compared to small and medium sized hospitals (7.6% vs 5.7%, p=0.54). However, the cost of hospitalization was significantly lesser in small and medium sized hospitals (588,363±154,349 vs 826,864±106,110 dollars, p Conclusions Only a small percentage of OHT is done for myocarditis with high proportion done in female when compared to OHT for other etiologies. Further studies need to be done to compare long term outcomes of heart transplant in myocarditis. Funding Acknowledgement Type of funding source: None

Background Takotsubo cardiomyopathy (TC) is a reversible stress-induced myocardial dysfunction with increased sympathetic activity caused by excessive release of catecholamines playing a central role in its pathophysiology. The occurrence of TC in transplanted hearts is rare given the complete denervation done during transplantation. However, it has been demonstrated that 40% of transplant recipients undergo sympathetic re-innervation. There have only been case reports describing TC in post-transplant recipients. Purpose To evaluate the incidence, baseline characteristics and outcomes of TC occurring in heart transplant recipients using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) in United States from 2009 to 2014. Methods Using NIS data, we identified patients who underwent cardiac transplantation using ICD9 procedure codes 37.5 and 33.6. Among these patients, we identified those admitted to the hospital with diagnosis of TC based on ICD-9-CM code 429.83. We presented categorical data as percentages and continuous data as mean or median as appropriate. Results We identified 257 hospitalizations for TC in heart transplant recipient patients. There was an approximately 9-fold increase in admissions from 11 in 2009 to 95 in 2014. Among patients with TC, the mean age was 65.3±1.8 years and majority were female (76.6%). A majority of patients were Caucasians (63%) followed by smaller proportion of African-Americans (13.2%). In-patient mortality in patients admitted with TC following heart transplant was 11.3% (n=29). During the hospitalization, 4.8% of patients had cardiogenic shock and 2.8% required mechanical circulatory support. The average length of stay for patients with TC was 16.6±3.3 days. The mean cost of hospitalization for these patients when adjusted for inflation were 237248±55709 dollars. Conclusion TC can still occur in substantially in heart transplant recipients and should be considered one of the differential diagnosis in transplant patients presenting to the hospital. Funding Acknowledgement Type of funding source: None

Background Breast cancer and cardiovascular disease (CVD) share common risk factors, and breast cancer therapies are well known to cause cardiotoxicity. Prior studies highlighted the higher burden coronary artery disease and the importance to further assess its consequences on breast cancer patients. Purpose We sought to evaluate the revascularization rate and in-hospital short-term outcomes of breast cancer patients following acute coronary syndrome (ACS) compared to the general female population. Methods We reviewed the Nationwide Inpatient Sample from 2010 to 2014 to identify female patients with principal diagnosis of ACS (ST-elevation and non ST-elevation myocardial infarction, and unstable angina). Two subgroups were identified, women with a history of breast cancer and women without, and were propensity matched. Multivariate regression analyses were performed to evaluate the impact of breast cancer on primary outcome (in-hospital mortality) and secondary outcomes: occurrence of shock, acute kidney injury (AKI), mechanical ventilation (MV), and length of stay (LOS). We also compared the rate of cardiac procedures. Statistical significance of odd ratios (OR) is defined with p-value Results We identified a total of 245,563 female patients with primary diagnosis of ACS, among them 10,625 (4.3%) had a history of breast cancer. The comorbidity of breast cancer was associated with statistically significant lower rates of mortality (OR 0.83, CI 0.74–0.94), shock (OR 0.87, CI 0.77–0.99), AKI (OR 0.90, CI 0.82–0.98), MV (OR 0.81, CI 0.71–0.92) and relative 5.4% decrease in LOS (CI: −7.8%, −3.0%). The cardiac procedural rates were similar for left heart catheterization (OR 0.96, CI 0.90–1.02), for percutaneous coronary intervention (OR 0.95, CI 0.89–1.02) and for CABG (OR 0.88, CI 0.78–1.00) compared to control group. Conclusion Breast cancer patients received a comparable catheterization and revascularization procedure rate and exhibited a statistically significant lower morbidity and mortality rates during hospitalization after an ACS event compared to the general female population. Funding Acknowledgement Type of funding source: None

Background Orthotopic heart transplantation is the most effective long-term therapy for end-stage heart disease. Denervation of transplanted heart with the loss of autonomic modulation, vasculopathy, utilization of immunosuppressant drugs, and risk of allograft rejection may result in change in the prevalence of arrhythmias in transplanted hearts. Purpose To describe the trends, distribution and the clinical impact of arrhythmias in transplanted hearts in a large nationwide population. Methods We queried the National Inpatient Sample with administrative codes. Cardiac transplant patients were identified using procedure ICD-9-CM codes 37.5 and 33.6. Common arrhythmias were extracted using appropriate validated ICD-9-CM codes. Statistical Analysis System (SAS) version 9.4 was used for analysis of data. Results There was a total of 30,020 hospitalizations of heart transplant recipients between 1999 and 2014 in the United States and 16342 (54.4%) of these had arrhythmias. The prevalence of total arrhythmias increased from 53.6% (n=1,158) in 1999 to 67.3% (n=1,575) in 2014. The most common arrhythmia was atrial fibrillation (26.83%) followed by ventricular tachycardia (22.86%) and the prevalence of individual arrhythmias is as shown in Figure 1. Cardiogenic shock was higher in transplanted hearts with arrhythmias when compared with patients without arrhythmias (25.96% vs 18.18%; p The total hospital cost when adjusted for inflation was significantly higher in the arrhythmic patients, with an average cost of about $570,415±9,590 vs $439,707±8362 in patients without arrhythmias (p Conclusion A significant proportion of patients with heart transplant have cardiac arrhythmias and are associated with worse in-hospital outcomes of cardiogenic shock, increased length of stay, and cost of hospitalization. However, they are not associated with worse inpatient mortality. Funding Acknowledgement Type of funding source: None

Currently, consumers’ interest in healthy products has attracted the attention of academia and the meat industry, which has focused mainly on incorporating ingredients with healthier properties. In this context, the aim of this study was to investigate the social representation of original burgers and burgers with mushroom addition considering different sexes and body mass indexes (BMIs) of individuals. Thus, 209 Brazilians answered a word association task followed by a word classification based on their importance and valence for original burgers and burgers with the addition of mushrooms. To obtain the structure of social representation, the words were positioned into four distinct zones based on their frequency of elicitation and importance. Also, the polarity index was used to give a connotation to the words. Three groups of consumers were identified. The first group (consumers with class-1 obesity of both sexes) associated the original burger with positive categories (cheese, juicy, seasoned, food, tasty, joy, salad and delicious). The second one (female consumers with pre-obesity and class-1 obesity) associated the burger with the addition of mushrooms with the elements price, different, vegetarian, flavor, gourmet and healthy. Finally, the third group (men and women for both stimuli and with a wide range of BMI) characterized burgers with sensory attributes, feelings and moments of consumption. In conclusion, the social representation of the original burger and the burger with the addition of mushrooms differed among consumers, suggesting that the main associations can be the main motivations for the consumption of a certain product.

Background Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. Methods This is a multicentre phase II study randomizing 90 patients with T1–4 N0–2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. Discussion This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. Trial registration Clinicaltrials.gov identifier: NCT03997643. Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Background: Shoulder pain syndrome (SPS) is frequent and management in primary care is precarious, with a high rate of referral without adequate treatment, overloading rehabilitation and orthopedic services. Aim: To assess the effectiveness of a self-administered rehabilitation program in adults with shoulder pain syndrome in primary care. Patients and Methods: A randomized, single-blind clinical trial (evaluators) with an experimental group (self-administered rehabilitation) and a control group (standard physical therapy) was carried out in 271 adult patients aged 18 or older with unilateral shoulder pain lasting more than six weeks and less than three months. The primary outcome was the recovery perceived by the patient. Constant score for function, quality of life using SF-36, simple shoulder test (SST) and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were also calculated at six, 12 and 24 weeks of follow-up. Results: The self-administered rehabilitation program showed an adjusted effectiveness of 51% at the end of treatment compared to 54% of the standard physical therapy (p > 0.05). No differences in the evolution of the other scores assessed were observed between groups. Conclusions: A self-administered rehabilitation program for painful shoulder was non-inferior than usual physical therapy.

PURPOSE/OBJECTIVE(S) Proton therapy plans for head and neck cancer patients receiving ipsilateral neck radiotherapy have limited angle options given desired avoidance of contralateral tissue and other at-risk organs. This may lead to dose enhancement at the mucosal surfaces at the end of range. Herein, we study the relationship between potential areas of mucosal toxicity and biological dose (BD). MATERIALS/METHODS The patient cohort comprised of 5 patients with oropharyngeal carcinoma treated between 2019 and 2020 with adjuvant proton therapy to doses of 60-66 Gy in 30-33 fractions to the tumor bed with/without ipsilateral neck treatment after radical resection. Monte-Carlo based linear energy transfer (LET), relative biological effectiveness (RBE), and BD distributions of clinical plans were generated using the research version of a commercial treatment planning system. BD and RBE were calculated using the McNamara (MCN) model, which includes dependencies with dose-weighted LET (LETd), alpha/beta ratio, and physical dose (PD). α/β = 3.1 Gy and a reference dose of 2 Gy per fraction, were used to perform RBE computations. 10 mm rings around the mucosal targets were used to quantify biological dose enhancement outside the target structure. Mean and max RBE, LETd Volume Histograms, as well as D2cc and near-maximum (D1%) values in comparison to conventional PD × 1.1 were analyzed. RESULTS As summarized in Table 1, the rings showed an increase of 8-10 % when comparing D2cc numbers between conventional PD × 1.1 and BD. The RBE predicted by the McNamara model showed an average of 1.207 and a maximum (RBE1%) of 1.358 for this group of patients. LETd2cc and LETd1% had average values of 5.998 and 6.413 keV/µm, respectively. CONCLUSION BD enhancement was observed at the periphery of mucosal targets in these patients. An additional study is needed to evaluate the correlation of this dose enhancement with clinical/radiologic outcomes. In the future, use of additional beam angles and/or incorporating LET in treatment planning may mitigate this effect.

PURPOSE/OBJECTIVE(S) To quantitatively compare plan quality between mid-inspiration breath-hold (BH) MR-guided radiotherapy (MRgRTBH) and free-breathing (FB) CT-based intensity modulated radiotherapy (CT-IGRTFB) for the ablative treatment of adrenal malignancies. We hypothesized that MRgRTBH would provide improved target coverage and lower organ-at-risk (OAR) doses due to smaller target volumes compared to CT-IGRTFB. MATERIALS/METHODS Twenty adrenal metastasis patients were treated on a 0.35T MR-Linac with real-time sagittal tracking at four frames per second for gated BH delivery. All patients underwent IMRT planning to a median prescription dose of 50 Gy (range: 40-50 Gy) in 5 fractions. For MRgRTBH, the CTV was delineated on the primary 3D TRUFI scan with no internal target volume (ITV). Each patient was retrospectively replanned using a 3-arc, VMAT CT-IGRTFB treatment on a c-arm Linac (HD MLC). 4DCT respiratory evaluation was performed during MRgRTBH simulation. The average intensity projection CT was used to determine the ITV for the CT-IGRTFB plan. All plans used a 5 mm ITV to PTV margin. Target volume metrics used were: target coverage (TC) (PTV V100%/PTV vol), PTV D95%/Rx, PTV D90%/Rx, PTV D80%/Rx, homogeneity index (HI) (PTV D2%/ D98%), high dose conformity (PITV), low dose conformity (D2cm), and gradient (R50%). Additional dose metrics were evaluated for mean ipsilateral kidney and 0.5 cc gastrointestinal (GI) OARs. RESULTS The Wilcoxon signed-rank test showed a statistically significant increase (P 0.05). There were significant reductions (P 0.05) and significant GI OAR sparing (P < 0.05) resulted from the smaller target volumes and reduced OAR-to-PTV proximity. MRgRTBH was shown to be dosimetrically superior for OAR sparing to the small bowel, the large bowel and the duodenum (P < 0.05). Adaptive MRgRTBH was used for all patients, but only initial treatment doses were considered in quantifying the impact of gated BH versus ITV for this study.

PURPOSE/OBJECTIVE(S) Emerging data suggest that ablative stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for inoperable pancreas cancer (PCa) achieves favorable local control (LC) and overall survival (OS) compared to non-ablative dose. In the current SMART workflow, each adaptive fraction is reoptimized without accounting for previously delivered dose. Cumulative target volume (TV) dose from all SMART fractions has not previously been evaluated with respect to clinical outcomes. MATERIALS/METHODS We evaluated 44 inoperable PCa patients who were prescribed 50 Gy in 5 daily fractions on a 0.35T-MR LINAC. 33 patients (75%) were treated with elective nodal irradiation, typically including the celiac axis and superior mesenteric artery. PTV margin was 3 mm. On-table adaptive replanning was performed to primarily satisfy gastrointestinal (GI) organ at risk (OAR) constraints, and secondarily maximize TV coverage. Cumulative dose for all fractions was summed onto a TRUFI MR fractional scan (i.e., fraction 5). A rigid transformation was performed for fractions 1 to 4 scans onto the fraction 5 frame of reference (FOR) based on alignment of gross disease. Each fractional dose was transformed onto fraction 5 FOR and summed cumulatively for all 5 fractions. Locoregional failure (LRF) was delineated on follow-up imaging by a diagnostic radiologist with PCa expertise. Cumulative TV dose metrics (D80, D90, mean, max) were evaluated with respect to LRF. Diagnostic scans were rigidly registered to the fraction 5 FOR based on recurrence region to investigate recurrence characteristics and target dose metrics. A Spearman correlation was used to investigate LRF and (1) ENI vs. no ENI, (2) TV coverage metrics, (3) planning TV (PTV) volume. RESULTS The median PTV volume for all patients, with ENI, and without ENI was 125.9 cc (range: 20.6-356.8), 137.3 cc (range: 72.8-356.8, and 55.4 (range: 20.6-280.15), respectively. LRF occurred in 12 patients (27.3%); the median LRF volume was 10.9 cc (range: 1.1-145.5cc). The median Dice similarity coefficient taken to characterize LRF overlap with PTV was 0.05 (range: 0-0.45). Moderate negative correlation coefficients were noted between recurrence to ENI [-0.59 (P < 0.001)], recurrence to PTV volume [-0.41 (P < 0.001)] and recurrence to max PTV dose [-0.47 (P < 0.001)]. No correlation was observed for cumulative D80, D90, mean dose to recurrence. CONCLUSION To our knowledge, this is the first analysis of cumulative TV dose from 5-fraction SMART for PCa. While use of ENI is controversial, moderate and statistically significant correlations were noted between LRF and ENI, in addition to PTV volume and maximum dose. Additional investigation is warranted to better understand whether specific dose thresholds exist for gross disease and electively treated volumes with respect to long-term LC and OS.

PURPOSE/OBJECTIVE(S) Salivary glands are exquisitely sensitive to radiotherapy. Patients treated with radiotherapy to the head and neck region commonly develop salivary gland volume loss and associated xerostomia. Salivary volume loss is associated with salivary function loss, making it a useful surrogate indicator of xerostomia. Previous studies have correlated the degree of salivary gland volume loss with mean radiation doses in patients undergoing photon head and neck radiation. However, change in salivary gland volume relative to radiation dose has not been evaluated in patients undergoing proton therapy. Currently, a constant value of 1.1 is used to relate physical dose (PD) to biological dose (BD) for proton therapy. However, specific tissues may respond differently and thus require a different PD to BD conversion. Herein, we evaluate changes in salivary gland volumes relative to radiation dose in head and neck cancer patients receiving proton therapy to examine the validity of current PD to BD conversions for head and neck salivary glands. MATERIALS/METHODS Dosimetric data and pre-radiation parotid gland and submandibular gland (SMG) volumes were collected for 20 head and neck cancer patients that received proton therapy at our institution between 2018-2020. Pre-radiation volumes of the SMGs and parotids were collected from treatment planning scans. Post-treatment salivary gland volumes were contoured on 3-month post-treatment diagnostic scans. Mean doses to the glands were gathered from dose-volume histograms generated from treatment plans. Linear logistical regression was performed to measure the effect of dose on volume change. RESULTS Volume changes of 27 parotids and 38 SMGs were evaluated. Mean doses were 10.0 Gy (standard deviation (SD) 13.2) and 25.2 Gy (SD 25.0) for parotids and SMGs, respectively. Mean dose was < 1 Gy, < 30 Gy, and < 50 Gy in 59.3%, 92.6%, and 100% of parotids compared to 39.5%, 55.3%, and 81.6% of SMGs, respectively. Mean ratios of gland volumes at 3 months post-treatment relative to pre-treatment were 0.962 (SD 0.210) and 1.106 (SD 0.273) for parotids and SMGs, respectively. Effect of mean dose on gland volume change was not statistically significant for either parotids or SMGs. CONCLUSION The greater relative size reduction in parotids versus SMGs was consistent with previous photon data. The mean increase in SMG volume could represent post-treatment functional compensation in preserved glands, but this requires additional investigation. Also, determination of the effect of proton dose on salivary gland volume change requires further analysis. Currently, no conclusions can be drawn whether salivary glands are equally or differentially sensitive to proton therapy relative to photon therapy.

PURPOSE/OBJECTIVE(S) Historically, pencil beam algorithms (PBA), have been used for intensity-modulated proton therapy (IMPT) dose calculation. Recently, improvements in calculation speeds and a desire to generate more accurate plans have led to wider adoption of Monte Carlo (MC) algorithms for IMPT. Our goal was to ascertain the impact of both PBA and MC calculation algorithms on the skin dose in breast cancer treated with IMPT by means of measurements. MATERIALS/METHODS Twenty-one comprehensive chest wall patients were included in this study with treatment planning performed using a treatment planning system. All IMPT plans were generated with 1 or 2 en-face fields. Single- and multiple-field-optimization were used in 19 and 2 patients, respectively. The prescription doses were 50.4 Gy for 15 and 45 Gy for 6 patients, all at 1.8 Gy/fraction. The skin OAR was defined as a 3 mm thick rind anterior to the chest wall target volume. For 12 patients, the skin dose was optimized with the objectives of V95%

Purpose/Objective(s) Post-radiation xerostomia is an important toxicity of head and neck radiotherapy, contributing to decreased quality of life and other adverse effects. Submandibular gland (SMG) transfer prior to radiation previously demonstrated a statistically significant benefit in xerostomia reduction in the 2/3 dimensional treatment era. In the procedure, the SMG is transposed anteriorly to the submental space. In patients receiving radiation to the level II but not level IB neck, this displacement removes the SMG from the treatment portal, thereby preserving gland function. Herein we evaluate the dosimetric implications of SMG transfer on intensity modulated radiotherapy (IMRT) treatment plans. Materials/Methods We conducted a retrospective review of oropharynx cancer patients who underwent SMG transfer surgery followed by curative IMRT at our institution. Pre-surgery computed tomography (CT) scans had previously been fused with the planning CT. Separate scans were fused to the planning CT for 5 patients who had not had previous fusions. Pre-surgery SMG glands were contoured. Dose to the pre-surgery SMG was assessed on the treated clinical plan (TCP). A new plan (NP) was then generated, optimizing based on the pre-surgery SMG. Dosimetry attempted to meet all standard institutional constraints and match the salivary gland mean doses of the TCPs. Mean salivary gland, oral cavity, and larynx doses were collected. We evaluated the differences in plan outcomes using t-tests. Results 18 patients with median age 61.5 years (range 25-74) underwent SMG transfer between 2019 and 2021 (94.4% male and 94.4% received concurrent cisplatin). Mean SMG dose and mean total parotid and SMG gland (TPSG) dose post-transfer was 27.5 Gy and 26.1 Gy (standard deviation (SD) 6.9 and 3.3), respectively; pre-transfer SMG and TPSG mean dose was 40.4 Gy and 27.8 Gy (SD 9.4 and 3.5) and 29.6 Gy and 26.4 Gy (SD 7.7 and 3.9) in TCPs and NPs, respectively. Differences between pre- and post-transfer SMG and TPSG doses in TCPs were statistically significant, as were differences between pre-transfer SMG and TPSG doses in TCPs versus NPs (all P 0.1). Mean oral cavity and larynx doses were 32.9 Gy and 31.4 Gy (SD 6.8 and 9.9) and 33.5 Gy and 30.8 Gy (SD 7.5 and 9.6) in TCPs and NPs, respectively (all P > 0.1). Conclusion SMG mean dose was lower by ∼2 Gy in TCPs relative to the non-transferred SMG mean dose in reoptimized NPs, although this difference did not reach statistical significance. Inverse planning likely decreases the benefit of SMG transfer to reduce the risk of xerostomia. More investigation is needed to evaluate if patient subsets would benefit more than others based on tumor location (tongue base versus tonsil) and treatment modality (proton versus photon).

282 Background: The COVID-19 pandemic resulted in the use of telemedicine for evaluation and management visits in radiation oncology departments to decrease in-person interactions. The primary objective of this study is to evaluate the utility of telemedicine for patient consultation and its effect on radiotherapy simulation and treatment processes. Methods: A standardized simulation requisition directive was used for all consults (telemedicine and in-person) undergoing simulation for external beam radiation therapy at a single tertiary care institution from January to December 2020. These directives were reviewed at daily multi-disciplinary peer review meetings; modifications occurring as a result of this review were prospectively recorded in a departmental quality database. Descriptive statistics were used to identify characteristics associated with consultation type. Mann Whitney and Chi-square tests were used to compare continuous and categorical variables. Results: 1500 consecutive patients were reviewed in this prospective peer review process; 444 (29.6%) had telemedicine visits preceding simulation and 1056 (70.4%) had in-person consults. The median time between physician simulation order and date of simulation was 5 days (IQR: 2-11 days) for telemedicine visits and 4 days (IQR: 1-8 days) for in-person consults ( p

Modern society is facing serious problems with the transportation systems given the increase in traffic jams, accidents, fatalities and CO2 emissions. Thus, improving the safety and efficiency of transportation systems is imperative. Developing a sustainable transportation system requires a better usage of the existing infrastructure, the adoption of emerging technologies (e.g. embedded devices, sensors and short-range radio transmitters) and the development of applications capable of operating in wireless and spontaneous networks. In this paper, the authors give readers a global vision of the challenges and issues related to the development of applications for vehicular ad-hoc networks (VANET). It also presents a classification of applications and an overview of the top-level application domain. In addition, it investigates the importance of information in vehicular networks and analyses the requirements for different types of vehicular applications placing them in a table which summarized the findings. Finally, the communication schemes that underpin the operation of VANET applications as well as the security threats they are exposed to are studied.