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OBJECTIVE: To compare the indications, surgical techniques and outcomes for revision orbital decompression surgery for thyroid eye disease in open, endoscopic, and combined open and endoscopic approaches. METHODS: A retrospective review of all revision orbital decompression procedures for thyroid eye disease from a single large academic institution over a 17-year period (01/01/2004-01/01/2021) was performed. Patient demographics, as well as indications and types of surgery were reviewed. Outcome measures included changes in proptosis, intraocular pressure, visual acuity and diplopia. RESULTS: Thirty procedures were performed on 21 patients. There was a median of 9.4 months between primary orbital decompression and revision decompression surgery. There were 6 bilateral procedures, and 2 of these patients underwent additional revision surgeries due to decreased visual acuity with concern for persistent orbital apex compression or sight-threatening ocular surface exposure in the setting of proptosis. Twenty-five procedures were performed as open surgeries with 5 endoscopic/combined cases. Combined Ophthalmology/Otolaryngology surgery via combined open/endoscopic approaches was favoured for persistent orbital apex disease. Visual acuity remained preserved in all patients. The overall median reduction in proptosis was 2 mm and intraocular pressure change was 1 mmHg regardless of surgical approach. The overall rate of new onset diplopia after surgery was 15%. These patients had open approaches. All endoscopic/combined approach patients had pre-existing diplopia. There were no statistically significant differences between the open and endoscopic/combined groups in regard to change in visual acuity, reduction in proptosis or intraocular pressure. CONCLUSION: Revision orbital decompression is an uncommon procedure indicated for those patients with progressive symptoms despite previous surgery and intensive medical management. Both endoscopic and non-endoscopic techniques offer favourable outcomes with respect to visual acuity, decrease in intraocular pressure, and improvement in proptosis and overall lead to a low incidence of new onset diplopia. LEVEL OF EVIDENCE: Level IV.
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Descompressão Cirúrgica/métodos , Endoscopia/métodos , Oftalmopatia de Graves/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Reoperação/métodos , Idoso , Diplopia/etiologia , Exoftalmia/etiologia , Feminino , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
The fusion of immersive virtual reality, kinematic movement tracking, and EEG offers a powerful test bed for naturalistic neuroscience research. Here, we combined these elements to investigate the neuro-behavioral mechanisms underlying precision visual-motor control as 20 participants completed a three-visit, visual-motor, coincidence-anticipation task, modeled after Olympic Trap Shooting and performed in immersive and interactive virtual reality. Analyses of the kinematic metrics demonstrated learning of more efficient movements with significantly faster hand RTs, earlier trigger response times, and higher spatial precision, leading to an average of 13% improvement in shot scores across the visits. As revealed through spectral and time-locked analyses of the EEG beta band (13-30 Hz), power measured prior to target launch and visual-evoked potential amplitudes measured immediately after the target launch correlated with subsequent reactive kinematic performance in the shooting task. Moreover, both launch-locked and shot/feedback-locked visual-evoked potentials became earlier and more negative with practice, pointing to neural mechanisms that may contribute to the development of visual-motor proficiency. Collectively, these findings illustrate EEG and kinematic biomarkers of precision motor control and changes in the neurophysiological substrates that may underlie motor learning.
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Realidade Virtual , Biomarcadores , Humanos , Aprendizagem , Desempenho Psicomotor , Tempo de ReaçãoRESUMO
Flattening filter free (FFF) linear accelerators produce a fluence distribution that is forward peaked. Various dosimetric benefits, such as increased dose rate, reduced leakage and out of field dose has led to the growth of FFF technology in the clinic. The literature has suggested the idea of vendors offering dedicated FFF units where the flattening filter (FF) is removed completely and manipulating the beam to deliver conventional flat radiotherapy treatments. This work aims to develop an effective way to deliver modulated flat beam treatments, rather than utilizing a physical FF. This novel optimization model is an extension of the direct leaf trajectory optimization (DLTO) previously developed for volumetric modulated radiation therapy (VMAT) and is capable of accounting for all machine and multileaf collimator (MLC) dynamic delivery constraints, using a combination of linear constraints and a convex objective function. Furthermore, the tongue and groove (T&G) effect was also incorporated directly into our model without introducing nonlinearity to the constraints, nor nonconvexity to the objective function. The overall beam flatness, machine deliverability, and treatment time efficiency were assessed. Regular square fields, including field sizes of 10 × 10 cm2 to 40 × 40 cm2 were analyzed, as well as three clinical fields, and three arbitrary contours with "concave" features. Quantitative flatness was measured for all modulated FFF fields, and the results were comparable or better than their open FF counterparts, with the majority having a quantitative flatness of less than 3.0%. The modulated FFF beams, due to the included efficiency constraint, were able to achieve acceptable delivery time compared to their open FF counterpart. The results indicated that the dose uniformity and flatness for the modulated FFF beams optimized with the DLTO model can successfully match the uniformity and flatness of their conventional FF counterparts, and may even provide further benefit by taking advantage of the unique FFF beam characteristics.
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Modelos Estatísticos , Neoplasias/radioterapia , Aceleradores de Partículas/instrumentação , Fótons , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador/normas , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodosRESUMO
BACKGROUND AND PURPOSE: Patients with ischemic stroke of cardioembolic origin are at risk of visceral (renal or splenic) infarction. We hypothesized that serum troponin level at time of ischemic stroke would be associated with presence of visceral infarction. METHODS: Data were abstracted from a single center prospective stroke database over 18 months and included all patients with ischemic stroke who underwent contrast-enhanced computerized tomography (CT) of the abdomen and pelvis for clinical purposes within 1 year of stroke. The primary predictor was troponin concentration ≥.1ng/mL. The primary outcome was visceral infarct (renal and/or splenic) on CT abdomen and pelvis. Univariate and multivariable logistic regression models were used to estimate the odds ratio and 95% confidence intervals (OR, 95% CI) for the association of troponin with visceral infarction. RESULTS: Of 1233 patients with ischemic stroke, 259 patients had a qualifying visceral CT. Serum troponin level on admission was measured in 237 of 259 patients (93.3%) and 41 of 237 (17.3%) had positive troponin. There were 25 patients with visceral infarcts: 16 renal, 7 splenic, and 2 both. In univariate models, patients with a positive troponin level (versus negative) were more likely to have visceral infarcts (39.1% [9/23] versus 15.0% [32/214], P = .008) and this association persisted in multivariable models (adjusted OR 3.83; 95% CI 1.42-10.31, P = .006). CONCLUSIONS: In ischemic stroke patients, elevated serum troponin levels may help identify patients with visceral infarcts. This suggests that troponin in the acute stroke setting is a biomarker of embolic risk. Larger studies with systematic visceral imaging are needed to confirm our findings.
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Isquemia Encefálica/sangue , Infarto/sangue , Rim/irrigação sanguínea , Infarto do Baço/sangue , Acidente Vascular Cerebral/sangue , Troponina I/sangue , Idoso , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Bases de Dados Factuais , Feminino , Humanos , Infarto/diagnóstico por imagem , Infarto/etiologia , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Baço/diagnóstico por imagem , Infarto do Baço/etiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios X , Regulação para CimaRESUMO
Quantitative disease progression models for neurodegenerative disorders are gaining recognition as important tools for drug development and evaluation. In Parkinson's disease (PD), several models have described longitudinal changes in the Unified Parkinson's Disease Rating Scale (UPDRS), one of the most utilized outcome measures for PD trials assessing disease progression. We conducted a literature review to examine the methods and applications of quantitative disease progression modeling for PD using a combination of key words including "Parkinson disease," "progression," and "model." For this review, we focused on models of PD progression quantifying changes in the total UPDRS scores against time. Four different models reporting equations and parameters have been published using linear and nonlinear functions. The reasons for constructing disease progression models of PD thus far have been to quantify disease trajectories of PD patients in active and inactive treatment arms of clinical trials, to quantify and discern symptomatic and disease-modifying treatment effects, and to demonstrate how model-based methods may be used to design clinical trials. The historical lack of efficiency of PD clinical trials begs for model-based simulations in planning for studies that result in more informative conclusions, particularly around disease modification. © 2016 International Parkinson and Movement Disorder Society.
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Progressão da Doença , Modelos Teóricos , Doença de Parkinson , HumanosRESUMO
PRIMARY OBJECTIVE: To evaluate the evidence on saliva management options in those people who have a tracheostomy in situ following an acquired brain injury and to ascertain whether any of these treatments may facilitate tracheostomy decannulation. METHODS: The search was conducted on Medline, Embase, Cinahl and Central databases since 1990 and the evidence has been critiqued and summarized. Saliva management options were identified and analysed to see whether they had evidence or clinical support for the population. MAIN OUTCOMES AND RESULTS: There is a paucity of evidence in this area and clinical decision-making requires evidence from other populations. Saliva management issues in this population are most likely to be related to dysphagia. Treatment options include behavioural/compensatory therapies which should be tried in all cases, with adjunct pharmaceutical therapies or surgical options to reduce saliva volume as clinically appropriate. CONCLUSION AND FUTURE DIRECTIONS: This group of people is complex and requires a multi-disciplinary team to guide decision-making. High quality control studies looking at the effectiveness of dysphagia therapy and guidelines regarding botulinum toxin injections are recommended.
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Lesões Encefálicas/terapia , Saliva/metabolismo , Traqueostomia/métodos , Traqueostomia/reabilitação , Bases de Dados Factuais , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/terapia , HumanosRESUMO
The phosphatidylinositide 3-kinase (PI3K) pathway is activated and correlated with drug resistance in multiple myeloma (MM). In the present study we investigated the role of PI3KCA (PI3K-α) in the progression and drug resistance in MM. We showed that the gene expression of PI3KCA isoform was higher in MM compared to normal subjects. BYL719, a novel and specific PI3KCA inhibitor inhibited the survival of primary MM cells and cell lines but not normal peripheral blood mononuclear cells. BYL719 induced the apoptosis of MM cells and inhibited their cell cycle by causing G1 arrest. BYL719 inhibited PI3K signalling, decreased proliferation and cells cycle signalling, and induced apoptosis signalling in MM cells. Finally, BYL719 synergized with bortezomib and carfilzomib, and overcame drug resistance induced by bone marrow stroma. These results were confirmed using in silico simulation of MM cell lines, BYL719 and bortezomib, and showed similar trends in survival, proliferation, apoptosis, cell signalling and synergy with drugs. In conclusion, PI3KCA plays a major role in proliferation and drug resistance of MM cells, the effects of which were inhibited with BYL719. These results provide a preclinical basis for a future clinical trial of BYL719 in MM as a single agent or in combination with other drugs.
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Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Células Estromais/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Sinergismo Farmacológico , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Mieloma Múltiplo/patologia , Inibidores de Proteassoma/farmacologiaRESUMO
BACKGROUND: Epi proColon® is a new blood-based colorectal cancer (CRC) screening test designed to determine the methylation status of a promoter region of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe the analytical and clinical performance of the test. METHODS: Analytical performance at 4 testing laboratories included determination of limit of detection, precision, and reproducibility of the SEPT9 test. Clinical performance was evaluated in a prospective study by use of samples (n = 1544) from subjects enrolled in the PRESEPT clinical trial. Results were analyzed by comparison with colonoscopy, the reference standard. RESULTS: The limit of detection for methylated SEPT9 DNA was 7.8 pg/mL (95% CI 6-11 pg/mL) corresponding to <2 genome copies of methylated SEPT9 per milliliter of plasma. In the prospective clinical trial, sensitivity for all stages of CRC was 68% (95% CI 53%-80%) and for stage I-III CRC, 64% (48%-77%). Adjusted specificity, on the basis of negative colonoscopy findings, was 80.0% (78%-82%). SIGNIFICANCE: The Epi proColon test is a simple, real-time PCR-based assay for the detection of methylated SEPT9 DNA in blood that may provide a noninvasive CRC screening alternative for people noncompliant with current CRC screening guidelines.
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Neoplasias do Colo/diagnóstico , Metilação de DNA , Detecção Precoce de Câncer/métodos , Reação em Cadeia da Polimerase , Septinas/sangue , Idoso , Detecção Precoce de Câncer/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Two major factors that determine the efficiency of programs designed to mitigate greenhouse gases by encouraging voluntary changes in U.S. agricultural land management are the effect of land use changes on producers' profitability and the net sequestration those changes create. In this work, we investigate how the interaction of these factors produces spatial heterogeneity in the cost-efficiency of voluntary programs incentivizing tillage reduction and cover-cropping practices. We map county-level predicted rates of adoption for each practice with the greenhouse gas mitigation or carbon sequestration benefits expected from their use. Then, we use these bivariate maps to describe how the cost efficiency of agricultural mitigation efforts is likely to vary spatially in the United States. RESULTS: Our results suggest the combination of high adoption rates and large reductions in net emissions make reduced tillage programs most cost efficient in the Chesapeake Bay watershed or the Upper Mississippi and Lower Missouri sub-basins of the Mississippi River. For programs aiming to reduce net emissions by incentivizing cover-cropping, we expect cost-efficiency to be greatest in the areas near the main stem of the Mississippi River within its Middle and Lower sections. CONCLUSIONS: Many voluntary agricultural conservation programs offer the same incentives across the United States. Yet spatial variation in profitability and efficacy of conservation practices suggest that these uniform approaches are not cost-effective. Spatial targeting of voluntary agricultural conservation programs has the potential to increase the cost-efficiency of these programs due to regional heterogeneity in the profitability and greenhouse gas mitigation benefits of agricultural land management practices across the continental United States. We illustrate how predicted rates of adoption and greenhouse gas sequestration might be used to target regions where efforts to incentivize cover-cropping and reductions in tillage are most likely to be cost -effective.
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Introduction: MRI-guided radiotherapy (MRgRT) allows for direct motion management and real-time radiation treatment plan adaptation. We report our institutional experience using low strength 0.35T MRgRT for thoracic malignancies, and evaluate changes in treatment duty cycle between first and final MRgRT fractions. Methods: All patients with intrathoracic tumors treated with MRgRT were included. The primary reason for MRgRT (adjacent organ at risk [OAR] vs. motion management [MM] vs. other) was recorded. Tumor location was classified as central (within 2cm of tracheobronchial tree) vs. non-central, and further classified by the Expanded HILUS grouping. Gross tumor volume (GTV) motion, planning target volume expansions, dose/fractionation, treatment plan time, and total delivery time were extracted from the treatment planning system. Treatment plan time was defined as the time for beam delivery, including multileaf collimator (MLC) motion, and gantry rotation. Treatment delivery time was defined as the time from beam on to completion of treatment, including treatment plan time and patient respiratory breath holds. Duty cycle was calculated as treatment plan time/treatment delivery time. Duty cycles were compared between first and final fraction using a two-sample t-test. Results: Twenty-seven patients with thoracic tumors (16 non-small cell lung cancer and 11 thoracic metastases) were treated with MRgRT between 12/2021 and 06/2023. Fifteen patients received MRgRT due to OAR and 11 patients received MRgRT for motion management. 11 patients had central tumors and all were treated with MRgRT due to OAR risk. The median dose/fractionation was 50 Gy/5 fractions. For patients treated due to OAR (n=15), 80% had at least 1 adapted fraction during their course of radiotherapy. There was no plan adaptation for patients treated due to motion management (n=11). Mean GTV motion was significantly higher for patients treated due to motion management compared to OAR (16.1mm vs. 6.5mm, p=0.011). Mean duty cycle for fraction 1 was 54.2% compared to 62.1% with final fraction (p=0.004). Mean fraction 1 duty cycle was higher for patients treated due to OAR compared to patients treated for MM (61% vs. 45.0%, p=0.012). Discussion: Duty cycle improved from first fraction to final fraction possibly due to patient familiarity with treatment. Duty cycle was improved for patients treated due to OAR risk, likely due to more central location and thus decreased target motion.
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BACKGROUND: Persistent hydrocephalus requiring a ventriculoperitoneal shunt (VPS) can complicate the management of aneurysmal subarachnoid hemorrhage (aSAH). Identification of high-risk patients may guide external ventricular drain management. OBJECTIVE: To identify early radiographic predictors for persistent hydrocephalus requiring VPS placement. METHODS: In a 2-center retrospective study, we compared radiographic features on admission noncontrast head computed tomography scans of patients with aSAH requiring a VPS to those who did not, at 2 referral academic centers from 2016 through 2021. We quantified blood clot thickness in the basal cisterns including interpeduncular, ambient, crural, prepontine, interhemispheric cisterns, and bilateral Sylvian fissures. We then created the cisternal score (CISCO) using features that were significantly different between groups. RESULTS: We included 229 survivors (mean age 55.6 years [SD 13.1]; 63% female) of whom 50 (22%) required VPS. CISCO was greater in patients who required a VPS than those who did not (median 4, IQR 3-6 vs 2, IQR 1-4; P < .001). Higher CISCO was associated with higher odds of developing persistent hydrocephalus with VPS requirement (odds ratio 1.6 per point increase, 95% CI 1.34-1.9; P < .001), independent of age, Hunt and Hess grades, and modified GRAEB scores. CISCO had higher accuracy in predicting VPS requirement (area under the curve 0.75, 95% CI 0.68-0.82) compared with other predictors present on admission. CONCLUSION: Cisternal blood clot quantification on admission noncontrast head computed tomography scan is feasible and can be used in predicting persistent hydrocephalus with VPS requirement in patients with aSAH. Future prospective studies are recommended to further validate this tool.
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Hidrocefalia , Hemorragia Subaracnóidea , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Hemorragia Subaracnóidea/complicações , Derivação Ventriculoperitoneal/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgiaRESUMO
BACKGROUND: Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients. METHODS: We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD). RESULTS: The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome. CONCLUSION: Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Anti-Hipertensivos , Infarto Cerebral , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. METHODS: We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0-3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. RESULTS: We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586-0.755) compared with each component alone. CONCLUSIONS: WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.
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Biomarcadores/sangue , Contagem de Leucócitos , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicações , Adulto , Idoso , Isquemia Encefálica/etiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. METHODS: We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naïve. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. RESULTS: Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06-0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18-0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. CONCLUSION: Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.
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Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor/tratamento farmacológico , Hemorragia Subaracnóidea/psicologia , Sobreviventes , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Dor/psicologia , Fatores de Risco , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/terapiaRESUMO
PURPOSE: Despite being the standard metric in patient-specific quality assurance (QA) for intensity-modulated radiotherapy (IMRT), gamma analysis has two shortcomings: (a) it lacks sensitivity to small but clinically relevant errors (b) it does not provide efficient means to classify the error sources. The purpose of this work is to propose a dual neural network method to achieve simultaneous error detection and classification in patient-specific IMRT QA. METHODS: For a pair of dose distributions, we extracted the dose difference histogram (DDH) for the low dose gradient region and two signed distance-to-agreement (sDTA) maps (one in x direction and one in y direction) for the high dose gradient region. An artificial neural network (ANN) and a convolutional neural network (CNN) were designed to analyze the DDH and the two sDTA maps, respectively. The ANN was trained to detect and classify six classes of dosimetric errors: incorrect multileaf collimator (MLC) transmission (±1%) and four types of monitor unit (MU) scaling errors (±1% and ±2%). The CNN was trained to detect and classify seven classes of spatial errors: incorrect effective source size, 1 mm MLC leaf bank overtravel or undertravel, 2 mm single MLC leaf overtravel or undertravel, and device misalignment errors (1 mm in x- or y direction). An in-house planar dose calculation software was used to simulate measurements with errors and noise introduced. Both networks were trained and validated with 13 IMRT plans (totaling 88 fields). A fivefold cross-validation technique was used to evaluate their accuracy. RESULTS: Distinct features were found in the DDH and the sDTA maps. The ANN perfectly identified all four types of MU scaling errors and the specific accuracies for the classes of no error, MLC transmission increase, MLC transmission decrease were 98.9%, 96.6%, and 94.3%, respectively. For the CNN, the largest confusion occurred between the 1-mm-MLC bank overtravel class and the 1-mm-device alignment error in x-direction class, which brought the specific accuracies down to 90.9% and 92.0%, respectively. The specific accuracy for the 2-mm-single MLC leaf undertravel class was 93.2% as it misclassified 5.7% of the class as being error free (false negative). Otherwise, the specific accuracy was above 95%. The overall accuracies across the fivefold were 98.3 ± 0.7% and 95.6% ± 1.5% for the ANN and the CNN, respectively. CONCLUSIONS: Both the DDH and the sDTA maps are suitable features for error classification in IMRT QA. The proposed dual neural network method achieved simultaneous error detection and classification with excellent accuracy. It could be used in complement with the gamma analysis to potentially shift the IMRT QA paradigm from passive pass/fail analysis to active error detection and root cause identification.
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Radioterapia de Intensidade Modulada , Raios gama , Humanos , Redes Neurais de Computação , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
The continuous delivery of volumetric modulated arc therapy (VMAT) plans is usually approximated by discrete apertures at evenly-spaced gantry angles for dose calculation purposes. This approximation can potentially lead to large dose calculation errors if the gantry angle spacings are large and/or there are large changes in the MLC apertures from one control point (CP) to the next. In this work, we developed a sliding-window (SW) method to improve VMAT dose calculation accuracy. For any 2 adjacent VMAT CPs ni and niâ¯+â¯1, the dose distribution was approximated by a 2-CP SW IMRT beam with the starting MLC positions at CP ni and ending MLC positions at CP niâ¯+â¯1, with the gantry angle fixed in the middle of the 2 VMAT CPs. Therefore, a VMAT beam with N CPs was approximated by a SW plan with N-1 SW beams. To validate the method, VMAT plans were generated for 10 patients in Pinnacle using 4° gantry spacing. Each plan was converted to a SW plan and dose was recalculated. Another VMAT plan, with 1° gantry spacing, was created by interpolating the original VMAT beam. The original plans were delivered on an Elekta Versa HD and measured with ArcCHECK. For both the isodose distribution and DVH, there were significant differences between the original VMAT plan and either the SW or the interpolated plan. However, they were indistinguishable between the SW and the interpolated plans. When compared with measurement, the average passing rates of the original VMAT plans were 87.3 ± 2.8% and 93.1 ± 1.0% for the 5 HN and 5 spine SBRT cases, respectively. On the other hand, the passing rates for both the VMAT1 and SW plans were above 95% for all the 10 cases studied. The dose calculation times of the original VMAT plans and the SW plans were very similar. We conclude that the proposed SW approach improves VMAT dose calculation accuracy without increase in dose calculation time.
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Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Neoplasias da Coluna Vertebral/radioterapia , Humanos , Radiometria , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. METHODS: We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. RESULTS: Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) CONCLUSIONS: Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.
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Isquemia Encefálica/sangue , Acidente Vascular Cerebral/sangue , alfa 1-Antitripsina/sangue , Idoso , Artérias , Aterosclerose/complicações , Calcinose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de RiscoRESUMO
Various dosimetric benefits such as increased dose rate, and reduced leakage and out of field dose have led to the growth of flattening-filter-free (FFF) technology in the clinic. In this study, we concentrate on investigating the feasibility of using FFF beams to deliver conventional flat beams, since completely getting rid of the flattening-filter module from the gantry head can not only simplify the gantry design but also decrease the workload on machine maintenance and quality assurance. Two intensity modulated radiotherapy techniques, step-and-shoot (S&S) and sliding window (SW), were used to generate flat beam profiles for 6 regular-shaped beams and 3 clinical beams while operating in FFF mode. The inverse plans were generated based on uniform dose optimization. Degree of flatness, MU efficiency, and beam delivery time for both methods were assessed. S&S technique is able to achieve a degree of flatness less than 2.5% for most field configurations. While SW technique was able to generate relatively flat beams for field sizes less than 18 × 18 cm2. For all field configurations, S&S beams resulted in a longer delivery time compared to reference flat beams and SW beams. For field sizes less than 18 × 18 cm2, SW modulated FFF beams resulted in a faster delivery time compared to reference flat beams. The ability to deliver conventional flat beams is not absent when operating in FFF mode. Utilizing beam modulation, FFF mode can achieve reasonable flat profiles and comparable efficiency to conventional flat beams. The ability to deliver most clinical treatments from the same treatment unit will allow for less quality assurance as well as maintenance, and completely eliminate the need for the flattening filter on modern linacs.
Assuntos
Fótons/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Estudos de Viabilidade , Humanos , RadiometriaRESUMO
With an increased use of color dye in textile industries and elevated fabrics output, more scientific studies and technology developments are needed to effectively treat wastewater containing dyes. However, better understanding of the interactions between dyes and suspended solids is a necessity to advance such developments. In this study the interactions between rhodamine 6G (R6G), a cationic dye, and different types of clays minerals, commonly found in the wastewater sludge, were elucidated. The uptake of R6G on the clay minerals was attributed to cation exchange on the external surfaces of non-swelling clays, and at both external and interlayer spaces for swelling clays. In the interlayer of montmorillonite, the R6G molecules form monolayer and bilayer configurations under low and high uptake levels. The significant amounts of R6G uptake indicate that clay minerals are good sorbents for the removal of cationic dyes from water. And the R6G could be readily removed in wastewater treatment by adding small amount of clays and flocculated the clays out.