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1.
Radiology ; 306(3): e220680, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36066367

RESUMO

Background RSNA consensus guidelines for COVID-19-related chest CT are widely used but, to the knowledge of the authors, their rate of true-positive findings for COVID-19 pneumonia in vaccinated patients has not been assessed. Purpose To assess the rate of true-positive findings of typical appearance for COVID-19 at chest CT by using RSNA guidelines in fully vaccinated patients with polymerase chain reaction (PCR)-confirmed COVID-19 infection compared with unvaccinated patients. Materials and Methods Included were patients with COVID-19 who had typical appearance on chest CT images and one PCR test for COVID-19 with a positive result or two tests with negative results within 7 days of undergoing chest CT between January 2021 and January 2022 at a quaternary academic medical center. True-positive findings were defined as chest CT images interpreted as COVID-19 typical appearance and PCR-confirmed COVID-19 infection within 7 days. Logistic regression models were constructed to quantify the association between PCR results and vaccination status, vaccination status and COVID-19 variants, and vaccination status and number of months. Results Included were 652 patients (median age, 59 years; IQR, 48-72 years; 371 men [57%]) with CT scans classified as typical appearance. Of those patients, 483 (74%) were unvaccinated and 169 (26%) were fully vaccinated. The overall rate of true-positive findings on CT images rated as typical appearance was lower in vaccinated versus unvaccinated patients (70 of 169 [41%; 95% CI: 34, 49] vs 352 of 483 [73%; 95% CI: 69, 77]; odds ratio [OR], 3.8 [95% CI: 2.6, 5.5]; P < .001). Unvaccinated patients were more likely to have true-positive findings on CT images compared with fully vaccinated patients during the peaks of COVID-19 variants Alpha (OR, 16; 95% CI: 6, 42; P < .001) and Delta (OR, 8; 95% CI: 4, 16; P < .001), but no statistical differences were found during the peak of the Omicron variant (OR, 1.7; 95% CI: 0.3, 11; P = .56). Conclusion Fully vaccinated patients with confirmed COVID-19 breakthrough infections had lower rates of true-positive findings of COVID-19 typical appearance at chest CT. © RSNA, 2022 Supplemental material is available for this article.


Assuntos
COVID-19 , Masculino , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos
2.
J Vasc Interv Radiol ; 33(8): 987-992, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35500832

RESUMO

PURPOSE: To identify the variables associated with patient discharge disposition to optimize postprocedural care and discharge planning following lower extremity arterial interventions for peripheral artery disease (PAD). MATERIALS AND METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried using current procedural terminology codes for endovascular infrainguinal interventions for PAD. The main outcome variable of interest was nonhome discharge. Covariates included patient sociodemographic variables, age quartile (upper quartile, ≥77 years), comorbidities (diabetes, renal disease, bleeding disorder, congestive heart failure [CHF], and chronic obstructive pulmonary disease), presence of an open wound before a procedure, type of procedure, operative time, symptom severity, American Society of Anesthesiologists class, and baseline functional status. Univariate analysis and multivariate logistic regression were performed on Stata/SE 15.1. RESULTS: A total of 3,190 patients met the inclusion criteria, of whom 664 (20.8%) had nonhome discharge. Multivariate regression revealed that age (odds ratio [OR], 1.9 for the upper age quartile [>77 years]; 95% confidence interval [CI], 1.46-2.50), operative time (OR, 1.2 per increase in quartile; 95% CI, 1.09-1.30), preoperative wound (OR, 1.5; 95% CI, 1.24-1.90), renal failure (OR, 1.7; 95% CI, 1.30-2.14), CHF (OR, 2.2; 95% CI, 1.51-3.24), symptom severity (OR, 1.7; 95% CI, 1.46-1.98), and independent functional status (OR, 0.74; 95% CI, 0.59-0.92; P = .007) were associated with nonhome discharge. All P values were ≤.001 unless otherwise stated. CONCLUSIONS: Prolonged procedural time, the presence of preprocedural wound and patient comorbidities, symptomatology, and baseline functional status may be used to identify patients who will require a nonhome discharge and early discharge planning.


Assuntos
Alta do Paciente , Doença Arterial Periférica , Idoso , Humanos , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Vasculares
3.
J Vasc Interv Radiol ; 33(6): 695-701, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35311666

RESUMO

PURPOSE: To assess the utility of the radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines (RENAL) nephrometry scoring system at predicting adverse events and outcomes in percutaneous microwave ablation (MWA) of renal tumors. MATERIALS AND METHODS: A retrospective review of 116 patients who underwent MWA from 2004 to 2018 at 2 large university hospitals was conducted. Patient demographics and tumor characteristics were collected. The RENAL nephrometry scores were calculated, and procedure-related adverse events were stratified into minor and major (the Society of Interventional Radiology classification of class C or higher). Technical and oncologic outcomes were based on follow-up magnetic resonance imaging and computed tomography scans after ablation. RESULTS: The mean RENAL score was 6.6 (range, 4-11), and the mean tumor size was 24 mm. Follow-up ranged between 16 and 161 weeks (median, 50 weeks; mean, 65 weeks). Oncologic control was achieved in 96% (n = 111) of patients. The major and minor adverse event rates were 8.6% (n = 10) and 17% (n = 19), respectively. The mean RENAL score for patients with recurrent and/or residual tumor (8.2 ± 2.7) was higher than that for patients without disease recurrence (6.5 ± 3.5, P = .05). However, in a multivariate analysis, the RENAL score was not found to be an independent predictor of oncologic outcomes (odds ratio, 1.548; P = .092). CONCLUSIONS: The RENAL nephrometry score has minimal utility for predicting outcomes and adverse events in MWA of renal tumors. The inconsistent nature of RENAL nephrometry scoring in percutaneous ablation procedures underscores the need for an ablation-specific risk stratification system.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/etiologia , Neoplasias Renais/cirurgia , Micro-Ondas/efeitos adversos , Recidiva Local de Neoplasia/cirurgia , Nefrectomia/efeitos adversos , Estudos Retrospectivos
4.
AJR Am J Roentgenol ; 219(1): 55-65, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35080453

RESUMO

BACKGROUND. Lung-RADS category 3 and 4 nodules account for most screening-detected lung cancers and are considered actionable nodules with management implications. The cancer frequency among such nodules is estimated in the Lung-RADS recommendations and has been investigated primarily by means of retrospectively assigned Lung-RADS classifications. OBJECTIVE. The purpose of this study was to assess the frequency of cancer among lung nodules assigned Lung-RADS category 3 or 4 at lung cancer screening (LCS) in clinical practice and to evaluate factors that affect the cancer frequency within each category. METHODS. This retrospective study was based on review of clinical radiology reports of 9148 consecutive low-dose CT LCS examinations performed for 4798 patients between June 2014 and January 2021 as part of an established LCS program. Unique nodules assigned Lung-RADS category 3 or 4 (4A, 4B, or 4X) that were clinically categorized as benign or malignant in a multidisciplinary conference that considered histologic analysis and follow-up imaging were selected for further analysis. Benign diagnoses based on stability required at least 12 months of follow-up imaging. Indeterminate nodules were excluded. Cancer frequencies were evaluated. RESULTS. Of the 9148 LCS examinations, 857 (9.4%) were assigned Lung-RADS category 3, and 721 (7.9%) were assigned category 4. The final analysis included 1297 unique nodules in 1139 patients (598 men, 541 women; mean age, 66.0 ± 6.3 years). A total of 1108 of 1297 (85.4%) nodules were deemed benign, and 189 of 1297 (14.6%) were deemed malignant. The frequencies of malignancy of category 3, 4A, 4B, and 4X nodules were 3.9%, 15.5%, 36.3%, and 76.8%. A total of 45 of 46 (97.8%) endobronchial nodules (all category 4A) were deemed benign on the basis of resolution. Cancer frequency was 13.1% for solid, 24.4% for part-solid, and 13.5% for ground-glass nodules. CONCLUSION. In the application of Lung-RADS to LCS clinical practice, the frequency of Lung-RADS category 3 and 4 nodules and the cancer frequency in these categories were higher than the prevalence and cancer risk estimated for category 3 and 4 nodules in the Lung-RADS recommendations and those reported in earlier studies in which category assignments were retrospective. Nearly all endobronchial category 4A nodules were benign. CLINICAL IMPACT. Future Lung-RADS iterations should consider the findings of this study from real-world practice to improve the clinical utility of the system.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Idoso , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
5.
J Vasc Interv Radiol ; 32(3): 459-465, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33386206

RESUMO

PURPOSE: To analyze the effect of a patient's renal failure status on acute outcomes after lower extremity endovascular interventions for peripheral artery disease. MATERIALS AND METHODS: A retrospective analysis of the American College of Surgery National Surgical Quality Improvement Program database from 2014 to 2017 was conducted. Patients were included based on current procedural terminology codes. They were divided into renal failure cohorts. Six thousand seven hundred and sixty-five patients were included in the analysis, 11.0% of whom had renal failure. A univariate analysis was performed using chi-squared test or Fischer's exact test as appropriate. Multivariate logistic regression models were constructed, while controlling for relevant patient factors, to identify the effect of renal failure on several outcomes of interest after the intervention. A sensitivity analysis was performed with a propensity score-matched cohort. RESULTS: Patients with renal failure were more likely to have infrapopliteal interventions (38.0% vs 20.9%), critical limb ischemia with tissue loss (73.5% vs 38.9%), diabetes (70.9% vs 52.3%), preoperative wound infection (59.2% vs 30.7%), mortality (5.1% vs 1.3%), prolonged hospital stay (68.5% vs 46.5%), transfusion after the intervention (13.3% vs 9.1%), reoperation (18.3% vs 9.5%), and readmission (24.9% vs 12.6%), compared to patients without renal failure. The multivariate analysis found renal failure to be significant for mortality (odds ratio [OR] = 4.11, 95% confidence interval [CI] = 2.71-6.24), any complication (OR = 2.03, 95% CI = 1.72-2.39), extended length of stay (OR = 1.53, 95% CI = 1.28-1.83), sepsis (OR = 2.37, 95% CI = 1.60-3.51), readmission (OR = 1.89, 95% CI = 1.57-2.29), reoperation (OR = 1.84, 95% CI = 1.48-2.27), major adverse cardiovascular event (OR = 3.50, 95% CI = 2.54-4.84), and major adverse limb event (OR = 1.97, 95% CI = 1.55-2.51). P value was <.001 unless otherwise noted. CONCLUSIONS: Renal failure before the intervention places patients at a significantly elevated risk of morbidity and mortality following endovascular revascularization procedures for peripheral artery disease.


Assuntos
Procedimentos Endovasculares , Rim/fisiopatologia , Doença Arterial Periférica/terapia , Insuficiência Renal/fisiopatologia , Idoso , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/mortalidade , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
6.
AJR Am J Roentgenol ; 217(5): 1093-1102, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33852360

RESUMO

BACKGROUND. Previous studies compared CT findings of COVID-19 pneumonia with those of other infections; however, to our knowledge, no studies to date have included noninfectious organizing pneumonia (OP) for comparison. OBJECTIVE. The objectives of this study were to compare chest CT features of COVID-19, influenza, and OP using a multireader design and to assess the performance of radiologists in distinguishing between these conditions. METHODS. This retrospective study included 150 chest CT examinations in 150 patients (mean [± SD] age, 58 ± 16 years) with a diagnosis of COVID-19, influenza, or non-infectious OP (50 randomly selected abnormal CT examinations per diagnosis). Six thoracic radiologists independently assessed CT examinations for 14 individual CT findings and for Radiological Society of North America (RSNA) COVID-19 category and recorded a favored diagnosis. The CT characteristics of the three diagnoses were compared using random-effects models; the diagnostic performance of the readers was assessed. RESULTS. COVID-19 pneumonia was significantly different (p < .05) from influenza pneumonia for seven of 14 chest CT findings, although it was different (p < .05) from OP for four of 14 findings (central or diffuse distribution was seen in 10% and 7% of COVID-19 cases, respectively, vs 20% and 21% of OP cases, respectively; unilateral distribution was seen in 1% of COVID-19 cases vs 7% of OP cases; non-tree-in-bud nodules was seen in 32% of COVID-19 cases vs 53% of OP cases; tree-in-bud nodules were seen in 6% of COVID-19 cases vs 14% of OP cases). A total of 70% of cases of COVID-19, 33% of influenza cases, and 47% of OP cases had typical findings according to RSNA COVID-19 category assessment (p < .001). The mean percentage of correct favored diagnoses compared with actual diagnoses was 44% for COVID-19, 29% for influenza, and 39% for OP. The mean diagnostic accuracy of favored diagnoses was 70% for COVID-19 pneumonia and 68% for both influenza and OP. CONCLUSION. CT findings of COVID-19 substantially overlap with those of influenza and, to a greater extent, those of OP. The diagnostic accuracy of the radiologists was low in a study sample that contained equal proportions of these three types of pneumonia. CLINICAL IMPACT. Recognized challenges in diagnosing COVID-19 by CT are furthered by the strong overlap observed between the appearances of COVID-19 and OP on CT. This challenge may be particularly evident in clinical settings in which there are substantial proportions of patients with potential causes of OP such as ongoing cancer therapy or autoimmune conditions.


Assuntos
COVID-19/diagnóstico por imagem , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Influenza Humana/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/virologia , Masculino , Massachusetts , Pessoa de Meia-Idade , Variações Dependentes do Observador , Pneumonia Viral/virologia , Radiografia Torácica , Estudos Retrospectivos , SARS-CoV-2
7.
Radiology ; 297(3): E303-E312, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32673191

RESUMO

Background Disease severity on chest radiographs has been associated with higher risk of disease progression and adverse outcomes from coronavirus disease 2019 (COVID-19). Few studies have evaluated COVID-19-related racial and/or ethnic disparities in radiology. Purpose To evaluate whether non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission chest radiographs compared with White or non-Hispanic patients. Materials and Methods This single-institution retrospective cohort study was approved by the institutional review board. Patients hospitalized with confirmed COVID-19 infection between March 17, 2020, and April 10, 2020, were identified by using the electronic medical record (n = 326; mean age, 59 years ±17 [standard deviation]; male-to-female ratio: 188:138). The primary outcome was the severity of lung disease on admission chest radiographs, measured by using the modified Radiographic Assessment of Lung Edema (mRALE) score. The secondary outcome was a composite adverse clinical outcome of intubation, intensive care unit admission, or death. The primary exposure was the racial and/or ethnic category: White or non-Hispanic versus non-White (ie, Hispanic, Black, Asian, or other). Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race and/or ethnicity. Results Non-White patients had significantly higher mRALE scores (median score, 6.1; 95% confidence interval [CI]: 5.4, 6.7) compared with White or non-Hispanic patients (median score, 4.2; 95% CI: 3.6, 4.9) (unadjusted average difference, 1.8; 95% CI: 0.9, 2.8; P < .01). For both White (adjusted hazard ratio, 1.3; 95% CI: 1.2, 1.4; P < .001) and non-White (adjusted hazard ratio, 1.2; 95% CI: 1.1, 1.3; P < .001) patients, increasing mRALE scores were associated with a higher likelihood of experiencing composite adverse outcome with no evidence of interaction (P = .16). Multivariable linear regression analyses demonstrated that non-White patients presented with higher mRALE scores at admission chest radiography compared with White or non-Hispanic patients (adjusted average difference, 1.6; 95% CI: 0.5, 2.7; P < .01). Adjustment for hypothesized mediators revealed that the association between race and/or ethnicity and mRALE scores was mediated by limited English proficiency (P < .01). Conclusion Non-White patients hospitalized with coronavirus disease 2019 infection were more likely to have a higher severity of disease on admission chest radiographs than White or non-Hispanic patients, and increased severity was associated with worse outcomes for all patients. © RSNA, 2020 Online supplemental material is available for this article.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Etnicidade/estatística & dados numéricos , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Grupos Raciais/estatística & dados numéricos , Radiografia Torácica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Radiografia , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto Jovem
8.
Radiology ; 297(1): E207-E215, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32391742

RESUMO

Background Angiotensin-converting enzyme 2, a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates its highest surface expression in the lung, small bowel, and vasculature, suggesting abdominal viscera may be susceptible to injury. Purpose To report abdominal imaging findings in patients with coronavirus disease 2019. Materials and Methods In this retrospective cross-sectional study, patients consecutively admitted to a single quaternary care center from March 27 to April 10, 2020, who tested positive for SARS-CoV-2 were included. Abdominal imaging studies performed in these patients were reviewed, and salient findings were recorded. Medical records were reviewed for clinical data. Univariable analysis and logistic regression were performed. Results A total of 412 patients (average age, 57 years; range, 18 to >90 years; 241 men, 171 women) were evaluated. A total of 224 abdominal imaging studies were performed (radiography, n = 137; US, n = 44; CT, n = 42; MRI, n = 1) in 134 patients (33%). Abdominal imaging was associated with age (odds ratio [OR], 1.03 per year of increase; P = .001) and intensive care unit (ICU) admission (OR, 17.3; P < .001). Bowel-wall abnormalities were seen on 31% of CT images (13 of 42) and were associated with ICU admission (OR, 15.5; P = .01). Bowel findings included pneumatosis or portal venous gas, seen on 20% of CT images obtained in patients in the ICU (four of 20). Surgical correlation (n = 4) revealed unusual yellow discoloration of the bowel (n = 3) and bowel infarction (n = 2). Pathologic findings revealed ischemic enteritis with patchy necrosis and fibrin thrombi in arterioles (n = 2). Right upper quadrant US examinations were mostly performed because of liver laboratory findings (87%, 32 of 37), and 54% (20 of 37) revealed a dilated sludge-filled gallbladder, suggestive of bile stasis. Patients with a cholecystostomy tube placed (n = 4) had negative bacterial cultures. Conclusion Bowel abnormalities and gallbladder bile stasis were common findings on abdominal images of patients with coronavirus disease 2019. Patients who underwent laparotomy often had ischemia, possibly due to small-vessel thrombosis. © RSNA, 2020.


Assuntos
Abdome/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico por imagem , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/virologia , Pneumonia Viral/diagnóstico por imagem , Abdome/patologia , Abdome/cirurgia , Abdome/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Feminino , Gastroenteropatias/patologia , Gastroenteropatias/cirurgia , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
9.
J Vasc Interv Radiol ; 31(2): 294-300, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899108

RESUMO

PURPOSE: To assess safety and efficacy of percutaneous cryoablation for pain palliation of metastases to pleura and chest wall. MATERIALS AND METHODS: This retrospective single-center cohort study included 22 patients (27% female, mean age 63 y ± 11.4) who underwent 25 cryoablation procedures for pain palliation of 39 symptomatic metastases measuring 5.1 cm ± 1.9 (range, 2.0-8.0 cm) in pleura and chest wall between June 2012 and December 2017. Pain intensity was assessed using a numerical scale (0-10 points). Statistical tests t test, χ2, and Wilcoxon signed rank were performed. RESULTS: Patients were followed for a median of 4.1 months (interquartile range [IQR], 2.3-10.1; range, 0.1-36.7 mo) before death or loss to follow-up. Following cryoablation, pain intensity decreased significantly by a median of 4.5 points (IQR, 2.8-6; range, 0-10 points; P = .0002 points, Wilcoxon signed rank). Pain relief of at least 3 points was documented following 18 of 20 procedures. Pain relief occurred within a median of 1 day following cryoablation (IQR, 1-2; range, 1-4 d) and lasted for a median of 5 weeks (IQR, 3-17; range, 1-34 wk). Systemic opioid requirements decreased in 11 of 22 patients (50%) by an average of 56% ± 34. Difference in morphine milligram equivalents was not significant (P = .73, Wilcoxon signed rank). No procedure-related complications occurred despite previous radiation of 7 tumors. Of 25 procedures, 22 (88%) were performed on an outpatient basis. CONCLUSIONS: Percutaneous cryoablation for metastases to pleura and chest wall can safely provide significant pain relief within days following a single session.


Assuntos
Neoplasias Ósseas/cirurgia , Criocirurgia , Manejo da Dor , Dor/prevenção & controle , Cuidados Paliativos , Neoplasias Pleurais/cirurgia , Parede Torácica/cirurgia , Idoso , Analgésicos Opioides/administração & dosagem , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Criocirurgia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/etiologia , Manejo da Dor/efeitos adversos , Medição da Dor , Neoplasias Pleurais/complicações , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/secundário , Estudos Retrospectivos , Parede Torácica/diagnóstico por imagem , Parede Torácica/patologia , Fatores de Tempo , Resultado do Tratamento
14.
Mol Pharm ; 12(12): 4237-46, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26488921

RESUMO

Enhanced glycolysis and poor perfusion in most solid malignant tumors create an acidic extracellular environment, which enhances tumor growth, invasion, and metastasis. Complex molecular systems have been explored for imaging and treating these tumors. Here, we report the development of a small molecule, LS662, that emits near-infrared (NIR) fluorescence upon protonation by the extracellular acidic pH environment of diverse solid tumors. Protonation of LS662 induces selective internalization into tumor cells and retention in the tumor microenvironment. Noninvasive NIR imaging demonstrates selective retention of the pH sensor in diverse tumors, and two-photon microscopy of ex vivo tumors reveals significant retention of LS662 in tumor cells and the acid tumor microenvironment. Passive and active internalization processes combine to enhance NIR fluorescence in tumors over time. The low background fluorescence allows tumors to be detected with high sensitivity, as well as dead or dying cells to be delineated from healthy cells. In addition to demonstrating the feasibility of using small molecule pH sensors to image multiple aggressive solid tumor types via a protonation-induced internalization and retention pathway, the study reveals the potential of using LS662 to monitor treatment response and tumor-targeted drug delivery.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Bibliotecas de Moléculas Pequenas/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos
15.
Adv Healthc Mater ; 13(6): e2301848, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37870153

RESUMO

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.


Assuntos
Criocirurgia , Glicolatos , Neoplasias , Humanos , Adjuvantes Imunológicos , Meios de Contraste
16.
Adv Healthc Mater ; : e2400272, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678431

RESUMO

Image-guided tumor ablative therapies are mainstay cancer treatment options but often require intra-procedural protective tissue displacement to reduce the risk of collateral damage to neighboring organs. Standard of care strategies, such as hydrodissection (fluidic injection), are limited by rapid diffusion of fluid and poor retention time, risking injury to adjacent organs, increasing cancer recurrence rates from incomplete tumor ablations, and limiting patient qualification. Herein, a "gel-dissection" technique is developed, leveraging injectable hydrogels for longer-lasting, shapeable, and transient tissue separation to empower clinicans with improved ablation operation windows and greater control. A rheological model is designed to understand and tune gel-dissection parameters. In swine models, gel-dissection achieves 24 times longer-lasting tissue separation dynamics compared to saline, with 40% less injected volume. Gel-dissection achieves anti-dependent dissection between free-floating organs in the peritoneal cavity and clinically significant thermal protection, with the potential to expand minimally invasive therapeutic techniques, especially across locoregional therapies including radiation, cryoablation, endoscopy, and surgery.

17.
Can J Urol ; 20(4): 6860-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23930614

RESUMO

INTRODUCTION: A small subset of young men die from seminoma. Studying these high risk, clinically atypical seminomas (CASs)-aggressive tumors with visceral metastases and chemotherapy resistance-may provide clues to the nature of drug resistance and the origin of testicular cancers. We explored the possibility that these seminomas are a unique clinical and biologic entity with intrinsic yolk sac tumor (YST) features. MATERIALS AND METHODS: We assayed available archived tissue samples (n = 22) for chemotherapy-resistance markers found in YSTs. Specifically, we analyzed tissues and clinical histories from patients with CASs (those who had visceral metastases and recurrent disease), classical seminomas, and mixed germ-cell tumors containing YST. By using immunohistochemical testing, we evaluated the expression of bone morphogenetic protein 2, alpha fetoprotein, and glutathione S-transferase (pi) [GST (pi)]. RESULTS: GST (pi) expression significantly predicted for overall survival (p = .036). In addition, according to the results of GST (pi) immunohistochemical staining, the CASs appeared to resemble YSTs more than they did classical seminomas (p = 0.043). Less-advanced tumors, both those that expressed GST (pi) and those that were negative for GST (pi), were more amenable to local therapies, and the patients who had those tumors had better clinical outcomes. CONCLUSIONS: Results from this exploratory study suggest that certain CASs that express GST (pi) are more similar to YST than they are to classical seminomas, and that GST (pi) expression may be able to be used as a prognosticator of disease-specific survival. Such CASs thus may have a unique biologic origin that differs from that of classical seminomas. Additional studies are needed to determine the natural history and therapeutic implications of these CASs.


Assuntos
Biomarcadores Tumorais/metabolismo , Tumor do Seio Endodérmico/metabolismo , Seminoma/metabolismo , Neoplasias Testiculares/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/patologia , Glutationa Transferase/metabolismo , Humanos , Imuno-Histoquímica/métodos , Masculino , Prognóstico , Estudos Retrospectivos , Seminoma/diagnóstico , Seminoma/patologia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , alfa-Fetoproteínas/metabolismo
18.
Sci Rep ; 13(1): 13854, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620391

RESUMO

Although ablations are performed with conscious sedation or general anesthesia, microwave ablations can be painful post procedure. Newer analgesic modalities, including regional blocks, have promoted the proliferation of less invasive anesthesia care for ablative procedures. This study evaluates whether bilateral paravertebral blocks reduce the need for additional analgesics in comparison to unilateral blocks in microwave ablations. In this retrospective study, individuals undergoing microwave ablation who underwent unilateral versus bilateral nerve blocks at a single institution from 2017 to 2019 were compared. Categorical variables were analyzed using Pearson's chi-squared tests. Comparisons of means were completed using multiple T-tests corrected using the Holm-Sidak method with α = 0.05. Regression modeling was used to identify factors related to increased MME (milligram morphine equivalent) usage and post-procedure admission rates. A total of 106 patients undergoing 112 liver MWA procedures were included in this analysis, with patients receiving either a bilateral or unilateral block. Pre-procedural characteristics demonstrated no significant differences in age or gender. Bilateral blocks were associated with decreased usage of gabapentin (14% vs. 0%, p = 0.01) and a lower rate of post-procedure admissions (OR 0.23, p = 0.003). Therefore, when using paravertebral blocks, bilateral blocks are superior to unilateral blocks, as demonstrated by decreased rates of hospital admission and reduced use of systemic neuropathic pain medication. Additionally, reducing post-procedural MME may reduce the rate of admission to the hospital.


Assuntos
Neoplasias Hepáticas , Bloqueio Nervoso , Dor Processual , Humanos , Micro-Ondas/efeitos adversos , Estudos Retrospectivos , Hospitais , Neoplasias Hepáticas/cirurgia
19.
Artigo em Inglês | MEDLINE | ID: mdl-38082806

RESUMO

Commercial ultrasound vascular phantoms lack the anatomic diversity required for robust pre-clinical interventional device testing. We fabricated individualized phantoms to test an artificial intelligence enabled ultrasound-guided surgical robotic system (AI-GUIDE) which allows novices to cannulate deep vessels. After segmenting vessels on computed tomography scans, vessel cores, bony anatomy, and a mold tailored to the skin contour were 3D-printed. Vessel cores were coated in silicone, surrounded in tissue-mimicking gel tailored for ultrasound and needle insertion, and dissolved with water. One upper arm and four inguinal phantoms were constructed. Operators used AI-GUIDE to deploy needles into phantom vessels. Two groin phantoms were tested due to imaging artifacts in the other two phantoms. Six operators (medical experience: none, 3; 1-5 years, 2; 5+ years, 1) inserted 27 inguinal needles with 81% (22/27) success in a median of 48 seconds. Seven operators performed 24 arm injections, without tuning the AI for arm anatomy, with 71% (17/24) success. After excluding failures due to motor malfunction and a defective needle, success rate was 100% (22/22) in the groin and 85% (17/20) in the arm. Individualized 3D-printed phantoms permit testing of surgical robotics across a large number of operators and different anatomic sites. AI-GUIDE operators rapidly and reliably inserted a needle into target vessels in the upper arm and groin, even without prior medical training. Virtual device trials in individualized 3-D printed phantoms may improve rigor of results and expedite translation.Clinical Relevance- Individualized phantoms enable rigorous and efficient evaluation of interventional devices and reduce the need for animal and human subject testing.


Assuntos
Inteligência Artificial , Agulhas , Animais , Humanos , Ultrassonografia , Imagens de Fantasmas , Ultrassonografia de Intervenção/métodos
20.
Med ; 4(8): 541-553.e5, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37339635

RESUMO

BACKGROUND: While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. METHODS: We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches. FINDINGS: In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). CONCLUSION: Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models. FUNDING: This work was supported by K. Lisa Yang Center for Bionics at MIT.


Assuntos
Estimulação Elétrica Nervosa Transcutânea , Animais , Suínos , Nervo Isquiático , Ultrassonografia , Regeneração Nervosa/fisiologia
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