RESUMO
Atropisomerism has been observed in a variety of biaryl compounds and meso-aryl substituted porphyrins. However, in porphyrins, this phenomenon had been shown only with o-substituted 6-membered aromatic groups at the meso-position. We show herein that a 5-membered heteroaromatic (N-mesyl-pyrrol-2-yl) group at the meso-position leads to atropisomerism. In addition, we report a 'one-pot' synthetic route for the synthesis of 'all-pyrrolic' porphyrin (APP) with several N-protection groups (Boc, Cbz, Ms and Ts). Among these groups, we found that only the Ms group gave four individually separable atropisomers of meso-tetra(N-Ms-pyrrol-2-yl) porphyrin. Furthermore, the reductive removal of Cbz- was achieved to obtain meso-tetra(pyrrol-2-yl) porphyrin. Thus, our synthetic procedure provides an easy access to a group of APPs and stable atropisomers, which is expected to expand the application of novel APP-based materials.
RESUMO
Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.
Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Dextranos/química , Humanos , Hipertermia Induzida , Aumento da Imagem , Tamanho da Partícula , Relação Estrutura-Atividade , Nanomedicina TeranósticaRESUMO
Photoacoustic imaging (PAI) is a rapidly evolving field in molecular imaging that enables imaging in the depths of ultrasound and with the sensitivity of optical modalities. PAI bases on the photoexcitation of a chromophore, which converts the absorbed light into thermal energy, causing an acoustic pressure wave that can be captured with ultrasound transducers, in generating an image. For in vivo imaging, chromophores strongly absorbing in the near-infrared range (NIR; > 680 nm) are required. As tetrapyrroles have a long history in biomedical applications, novel tetrapyrroles and inspired mimics have been pursued as potentially suitable contrast agents for PAI. The goal of this review is to summarize the current state of the art in PAI applications using tetrapyrroles and related macrocycles inspired by it, highlighting those compounds exhibiting strong NIR-absorption. Furthermore, we discuss the current developments of other absorbers for in vivo photoacoustic (PA) applications.
Assuntos
Diagnóstico por Imagem/métodos , Técnicas Fotoacústicas , Tetrapirróis , Meios de Contraste , Diagnóstico por Imagem/instrumentação , Indóis/química , Isoindóis , Sondas Moleculares , Estrutura Molecular , Porfirinas/química , Tetrapirróis/químicaRESUMO
PURPOSE: The EPIPHANY index was developed to classify cancer associated pulmonary embolism (PE) into different risk categories using decision tree modeling. In this study, we tried to externally validate this index in a distinct group of patients solely composed of incidental PE (IPE). METHODS: A retrospective study of patients diagnosed with IPE in two Emergency Departments in the USA and South Korea from 2013 to 2014 was performed. The primary outcome was the occurrence of a serious medical complication within 15 days of presentation to ED. Thirty-day complication was the secondary outcome. Cumulative hazard curves for each prognostic category were drawn to show the change in hazards over time. RESULTS: A total of 258 patients with IPE were included (193 from MD Anderson Cancer Center and 65 from Asan Medical Center). Serious complication within 15 days occurred in 23 (8.9%) patients. The risk of overall 15-day and 30-day serious complications increased with each category (low, intermediate, and high risk: 3.4, 8.9, and 23.8%, P = 0.033; 6.9, 9.5, and 33.3%, P = 0.011). Cumulative hazard curves for each prognostic category were drawn and the survival functions factored by prognostic categories were significantly different over 15 days (P = 0.015) and 30 days (P = 0.001). CONCLUSIONS: Our study suggests the EPIPHANY index could be a useful adjunct tool in risk stratification of cancer patients with IPE.
Assuntos
Técnicas de Apoio para a Decisão , Neoplasias/complicações , Embolia Pulmonar/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Árvores de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Prognóstico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/patologia , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
Riboflavin transporters (RFTs) and the riboflavin carrier protein (RCP) are highly upregulated in many tumor cells, tumor stem cells, and tumor neovasculature, which makes them attractive targets for nanomedicines. Addressing cells in different tumor compartments requires drug carriers, which are not only able to accumulate via the EPR effect but also to extravasate, target specific cell populations, and get internalized by cells. Reasoning that antibodies are among the most efficient targeting systems developed by nature, we consider their size (â¼10-15 nm) to be ideal for balancing passive and active tumor targeting. Therefore, small, short-circulating (10 kDa, â¼7 nm, t1/2 â¼ 1 h) and larger, longer-circulating (40 kDa, â¼13 nm, t1/2 â¼ 13 h) riboflavin-targeted branched PEG polymers were synthesized, and their biodistribution and target site accumulation were evaluated in mice bearing angiogenic squamous cell carcinoma (A431) and desmoplastic prostate cancer (PC3) xenografts. The tumor accumulation of the 10 kDa PEG was characterized by rapid intercompartmental exchange and significantly improved upon active targeting with riboflavin (RF). The 40 kDa PEG accumulated in tumors four times more efficiently than the small polymer, but its accumulation did not profit from active RF-targeting. However, RF-targeting enhanced the cellular internalization in both tumor models and for both polymer sizes. Interestingly, the nanocarriers' cell-uptake in tumors was not directly correlated with the extent of accumulation. For example, in both tumor models the small RF-PEG accumulated much less strongly than the large passively targeted PEG but showed significantly higher intracellular amounts 24 h after iv administration. Additionally, the size of the polymer determined its preferential uptake by different tumor cell compartments: the 10 kDa RF-PEGs most efficiently targeted cancer cells, whereas the highest uptake of the 40 kDa RF-PEGs was observed in tumor-associated macrophages. These findings imply that drug carriers with sizes in the range of therapeutic antibodies show balanced properties with respect to passive accumulation, tissue penetration, and active targeting. Besides highlighting the potential of RF-mediated (cancer) cell targeting, we show that strong tumor accumulation does not automatically mean high cellular uptake and that the nanocarriers' size plays a critical role in cell- and compartment-specific drug targeting.
Assuntos
Portadores de Fármacos/química , Polímeros/química , Neoplasias da Próstata/tratamento farmacológico , Riboflavina/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Xenoenxertos , Humanos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Tamanho da Partícula , Polietilenoglicóis/química , Propriedades de Superfície , Distribuição TecidualRESUMO
Lipid peroxidation is a major deleterious effect caused by oxidative stress. It is involved in various diseases such as atherosclerosis, rheumatoid arthritis and neurodegenerative diseases. In order to inhibit lipid peroxidation, antioxidants must efficiently scavenge free radicals and penetrate inside biological membranes. Lipocarbazole has recently been shown to be a powerful antioxidant in solution. Here, we show its powerful capacity as lipid peroxidation inhibitor. Its mechanism of action is rationalized based on molecular dynamics simulations on a biomembrane model, quantum calculations and experimental evaluation. The role of the lipocarbazole side chain is particularly highlighted as a critical chemical feature responsible for its antioxidant activity.
Assuntos
Antioxidantes/química , Carbazóis/química , Ácidos Graxos/química , Lipossomas Unilamelares/química , Antioxidantes/metabolismo , Carbazóis/metabolismo , Ácidos Graxos/metabolismo , Simulação de Dinâmica Molecular , Teoria Quântica , Termodinâmica , Lipossomas Unilamelares/metabolismoRESUMO
Fluorescent chlorophyll catabolites (FCCs) are fleeting intermediates of chlorophyll breakdown, which is seen as an enzyme controlled detoxification process of the chlorophylls in plants. However, some plants accumulate large amounts of persistent FCCs, such as in senescent leaves and in peels of yellow bananas. The photophysical properties of such a persistent FCC (Me-sFCC) were investigated in detail. FCCs absorb in the near UV spectral region and show blue fluorescence (max at 437 nm). The Me-sFCC fluorescence had a quantum yield of 0.21 (lifetime 1.6 ns). Photoexcited Me-sFCC intersystem crosses into the triplet state (quantum yield 0.6) and generates efficiently singlet oxygen (quantum yield 0.59). The efficient generation of singlet oxygen makes fluorescent chlorophyll catabolites phototoxic, but might also be useful as a (stress) signal and for defense of the plant tissue against infection by pathogens.
Assuntos
Clorofila/metabolismo , Fluorescência , Musa/química , Processos Fotoquímicos , Fármacos Fotossensibilizantes/metabolismo , Oxigênio Singlete/química , Clorofila/química , Cor , Musa/metabolismo , Fármacos Fotossensibilizantes/químicaRESUMO
Chlorophyll breakdown is a visual phenomenon of leaf senescence and fruit ripening. It leads to the formation of colorless chlorophyll catabolites, a group of (chlorophyll-derived bilin-type) linear tetrapyrroles. Here, analysis and structure elucidation of the chlorophyll breakdown products in leaves of banana (Musa acuminata) is reported. In senescent leaves of this monocot all chlorophyll catabolites identified were hypermodified fluorescent chlorophyll catabolites (hmFCCs). Surprisingly, nonfluorescent chlorophyll catabolites (NCCs) were not found, the often abundant and apparently typical final chlorophyll breakdown products in senescent leaves. As a rule, FCCs exist only fleetingly, and they isomerize rapidly to NCCs in the senescent plant cell. Amazingly, in the leaves of banana plants, persistent hmFCCs were identified that accounted for about 80 % of the chlorophyll broken down, and yellow leaves of M.â acuminata display a strong blue luminescence. The structures of eight hmFCCs from banana leaves were analyzed by spectroscopic means. The massive accumulation of the hmFCCs in banana leaves, and their functional group characteristics, indicate a chlorophyll breakdown path, the downstream transformations of which are entirely reprogrammed towards the generation of persistent and blue fluorescent FCCs. As expressed earlier in related studies, the present findings call for attention, as to still elusive biological roles of these linear tetrapyrroles.
Assuntos
Clorofila/química , Clorofila/metabolismo , Corantes Fluorescentes/química , Musa/química , Musa/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Tetrapirróis/química , Tetrapirróis/metabolismo , Estrutura MolecularRESUMO
Photoacoustic imaging (PAI) is a non-invasive modality for molecular imaging and is on the way to becoming a routine clinical diagnostic tool. The advantage of PAI over many other currently used modalities is its ability to potentially image in vivo a variety of enzymatic and physiological processes as well as metabolites in real time at high tissue depths. For this purpose, photoacoustic signal generating chromophores, which have the ability to change their signal characteristics upon reaction, to their environments or trapping reactive species, are important. This review article provides an overview of the concepts for activatable small molecule probes for photoacoustic imaging, highlights the requirements for structural and optical properties, and describes their responses to the selective triggers.
Assuntos
Técnicas Fotoacústicas , Corantes , Corantes Fluorescentes/química , Humanos , Imagem Molecular/métodos , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Análise EspectralRESUMO
Cold-chain management is of high importance in preserving perishable products and in retaining quality. A visible marker on packages indicating complete maintenance of the cold chain assures safe consumption of products by end-users and assists in reducing waste. Time-temperature indicators (TTIs) are integrated markers that provide information about exposure of packages to adverse temperature and have been gaining increased attention by consumers. Here we present a methylene-blue-based derivative, N,N,N',N'-tetramethyl-N10 -Boc-phenothiazine-3,7-diamine (BocPTDA), that can be used as a solid-state organic TTI dye, exhibiting an irreversible change from colorless to blue green upon heating. The conversion properties, studied using a silicagel-coated plate, confirmed that BocPTDA undergoes a color change above 20 °C. At temperatures of 4 °C and below, no visible changes are exhibited, making BocPTDA a well-suited marker for monitoring abrupt temperature deviations indicating improper cold-chain management. Thus, application of BocPTDA-based TTI systems on packages could inform consumers about the cold-chain maintenance, assuring quality and safe consumption.
RESUMO
Short-lived reactive intermediates such as reactive oxygen species (ROS) regulate many physiological processes, but overproduction can also lead to severe tissue dysfunction. Thus, there is a high demand for noninvasive detection of reactive molecules, which, however, is challenging. Herein, we report photoacoustic detection of ROS using conjugated BODIPY probes (ROS-BODIPYs). The ROS reaction with conjugated BODIPYs induced a redshift in absorption by â¼100 nm into the near infrared (from â¼700 to â¼800 nm), quenched fluorescence, and generated strong photoacoustic (PA) signals. Thus, the ROS-activated and ROS-nonactivated states of ROS-BODIPYs can be detected in vivo by PA and fluorescence imaging. Interestingly, ROS activation is reversible, in the presence of excess reducing agents, e.g., citric acid, converted back to its original state, suggesting that ROS-BODIPYs can be useful for the detection of over production of ROS but not physiological amounts. This makes the imaging independent of accumulation of the activated probe with the physiological ROS amounts and thus strongly improves applicability and highlights the translational potential of ROS-BODIPYs for detecting overexpression of ROS in vivo by optical and photoacoustic imaging methods.
Assuntos
Técnicas Fotoacústicas , Compostos de Boro , Imagem Óptica , Espécies Reativas de OxigênioRESUMO
Reactive oxygen and nitrogen species (ROS, RNS) are ubiquitous in biology with a variety of physiological and pathological functions. Here we describe a broad spectrum ROS/RNS detecting fluorogenic probe with red fluorescence emission and up to 100-fold gain. Hence these modified probes are useful for in vivo non-invasive quantification of ROS/RNS.
RESUMO
Microbubbles (MB) are used as ultrasound (US) contrast agents and can be efficiently targeted against markers of angiogenesis and inflammation. Due to their gas core, MB locally alter susceptibilities in magnetic resonance imaging (MRI), but unfortunately, the resulting contrast is low and not sufficient to generate powerful molecular MRI probes. Therefore, we investigated whether a potent molecular MR agent can be generated by encapsulating superparamagnetic iron oxide nanoparticles (SPION) in the polymeric shell of poly (n-butylcyanoacrylate) (PBCA) MB and targeted them against αvß3 integrins on the angiogenic vasculature of 4T1 murine breast carcinomas. SPION-MB consist of an air core and a multi-layered polymeric shell enabling efficient entrapment of SPION. The mean size of SPION-MB was 1.61 ± 0.32 µm. Biotin-streptavidin coupling was employed to functionalize the SPION-MB with cyclic RGDfK (Arg-Gly-Asp) and RADfK (Arg-Ala-Asp) peptides. Cells incubated with RGD-SPION-MB showed enhanced transverse relaxation rates compared with SPION-MB and blocking αvß3 integrin receptors with excess free cRGDfK significantly reduced RGD-SPION-MB binding. Due to the fast binding of RGD-SPION-MB in vivo, dynamic susceptibility contrast MRI was employed to track their retention in tumors in real-time. Higher retention of RGD-SPION-MB was observed compared with SPION-MB and RAD-SPION-MB. To corroborate our MRI results, molecular US was performed the following day using the destruction-replenishment method. Both imaging modalities consistently indicated higher retention of RGD-SPION-MB in angiogenic vessels compared with SPION-MB and RAD-SPION-MB. Competitive blocking experiments in mice further confirmed that the binding of RGD-SPION-MB to αvß3 integrin receptors is specific. Overall, this study demonstrates that RGD-SPION-MB can be employed as molecular MR/US contrast agents and are capable of assessing the αvß3 integrin expression in the neovasculature of malignant tumors.
Assuntos
Microbolhas , Neoplasias , Animais , Integrina alfaV , Integrina alfaVbeta3 , Imageamento por Ressonância Magnética , Camundongos , UltrassonografiaRESUMO
OBJECTIVE: Intranasal fentanyl (INF) quickly and noninvasively relieves severe pain, whereas intravenous hydromorphone (IVH) reliably treats severe cancer pain but requires vascular access. The trial evaluated the efficacy of INF relative to IVH for treating cancer patients with severe pain in an emergency department (ED) setting. METHODS: We randomized 82 patients from a comprehensive cancer center ED to receive INF (n = 42) or IVH (n = 40). Eligible patients reported severe pain at randomization (≥7, scale: 0 "none" to 10 "worst pain"). We conducted non-inferiority comparisons (non-inferiority margin = 0.9) of pain change from treatment initiation (T0) to one hour later (T60). T0 pain ratings were unavailable; therefore, we estimated T0 pain by comparing 1) T60 ratings, assuming similar group T0 ratings; 2) pain change, estimating T0 pain = randomization ratings, and 3) pain change, with T0 pain = 10 (IVH group) or T0 pain = randomization rating (INF group). RESULTS: At T60, the upper 90% confidence limit (CL) of the mean log-transformed pain ratings for the INF group exceeded the mean IVH group rating by 0.16 points (>pain). Substituting randomization ratings for T0 pain, the lower 90% CL of mean pain change in the INF group extended 0.32 points below (Assuntos
Analgésicos Opioides/administração & dosagem
, Dor do Câncer/tratamento farmacológico
, Fentanila/administração & dosagem
, Neoplasias/tratamento farmacológico
, Administração Intranasal
, Administração Intravenosa
, Adulto
, Idoso
, Analgésicos Opioides/efeitos adversos
, Dor do Câncer/complicações
, Dor do Câncer/patologia
, Serviço Hospitalar de Emergência
, Feminino
, Fentanila/efeitos adversos
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Neoplasias/complicações
, Neoplasias/patologia
RESUMO
The superoxide (O2â¢-) ion is a highly reactive oxygen species involved in many diseases; hence, its noninvasive detection is desirable to identify the onset of pathological processes. Here, we employed photoacoustic (PA) spectroscopy, which enables imaging at ultrasound resolution with the sensitivity of optical modality, for the first time to detect O2â¢-, using stimuli-responsive contrast agents. meso-(3,5-Di-tert-butyl 4-hydroxyphenyl) porphyrins and oxoporphyrinogens were used as PA contrast agents, which trap the O2â¢- and enable its detection. The trapped O2â¢- increased the PA signal amplitude of chromophores up to 9.6-fold, and induced a red-shift in the PA signal maxima of up to 225 nm. Therefore, these trigger-responsive probes may be highly valuable as smart diagnostic PA probes to investigate pathological events stimulated by O2â¢- species.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas Fotoacústicas , Porfirinogênios/química , Porfirinas/química , Superóxidos/análise , Estrutura MolecularRESUMO
Communication failures during patient handoff can lead to serious errors. A quality improvement team created a standardized handoff tool/process (DE-PASS: Decisive problem requiring admission, Evaluation time, Patient summary, Acute issues/action list, Situation unfinished/awareness, Signed out to) for admitting patients from the emergency department (ED) to the hospitalist inpatient service of a tertiary cancer center. DE-PASS mirrors the institution's ED workflow, stratifies patients as stable/urgent/emergent, and establishes requirements for verbal and email communications between providers. Comparison of preintervention and postintervention results from the 1-month pilot revealed that within a 24-hour period, DE-PASS reduced the number of intensive care unit transfers by 58% ( P = .393), the number of rapid-response team calls by 39% ( P = .637), and time to inpatient order by 31% ( P = .004). ED physicians' and hospitalists' satisfaction with DE-PASS increased. Reduction in intensive care unit transfers was sustained after the pilot ( P = .029). DE-PASS feasibility was evidenced by 100% uptake. By stratifying patients by risk level, DE-PASS reduced admission-to-evaluation times for unstable patients, potentially improving patient safety.
Assuntos
Institutos de Câncer , Serviço Hospitalar de Emergência , Médicos Hospitalares , Hospitalização , Transferência da Responsabilidade pelo Paciente/normas , Idoso , Continuidade da Assistência ao Paciente , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Estudos de Casos Organizacionais , Admissão do PacienteRESUMO
Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL-1. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the 'quinone-fusing' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range.
RESUMO
BACKGROUND: Hospitalization and early anticoagulation therapy remain standard care for patients who present to the emergency department (ED) with pulmonary embolism (PE). For PEs discovered incidentally, however, optimal therapeutic strategies are less clear-and all the more so when the patient has cancer, which is associated with a hypercoagulable state that exacerbates the threat of PE. METHODS: We conducted a retrospective review of a historical cohort of patients with cancer and incidental PE who were referred for assessment to the ED in an institution whose standard of care is outpatient treatment of selected patients and use of low-molecular-weight heparin for anticoagulation. Eligible patients had received a diagnosis of incidental PE upon routine contrast enhanced chest CT for cancer staging. Survival data was collected at 30 days and 90 days from the date of ED presentation and at the end of the study. RESULTS: We identified 193 patients, 135 (70%) of whom were discharged and 58 (30%) of whom were admitted to the hospital. The 30-day survival rate was 92% overall, 99% for the discharged patients and 76% for admitted patients. Almost all (189 patients, 98%) commenced anticoagulation therapy in the ED; 170 (90%) of these received low-molecular-weight heparin. Patients with saddle pulmonary artery incidental PEs were more likely to die within 30 days (43%) than were those with main or lobar (11%), segmental (6%), or subsegmental (5%) incidental PEs. In multivariate analysis, Charlson comorbidity index (age unadjusted), hypoxemia, and incidental PE location (P = 0.004, relative risk 33.5 (95% CI 3.1-357.4, comparing saddle versus subsegmental PE) were significantly associated with 30-day survival. Age, comorbidity, race, cancer stage, tachycardia, hypoxemia, and incidental PE location were significantly associated with hospital admission. CONCLUSIONS: Selected cancer patients presenting to the ED with incidental PE can be treated with low-molecular-weight heparin anticoagulation and safely discharged. Avoidance of unnecessary hospitalization may decrease in-hospital infections and death, reduce healthcare costs, and improve patient quality of life. Because the natural history and optimal management of this condition is not well described, information supporting the creation of straightforward evidence-based practice guidelines for ED teams treating this specialized patient population is needed.
RESUMO
BACKGROUND: Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation. METHODS: We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time. RESULTS: History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations. CONCLUSION: Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017.