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PURPOSE: A subpopulation of women with ductal carcinoma in situ (DCIS) remains at risk for in-breast recurrence (IBR) following breast-conserving surgery (BCS) and radiation therapy (RT). The NSABP B-43 trial evaluated the role of concurrent RT and trastuzumab in patients with HER2-positive DCIS but did not reach the prespecified endpoint. We hypothesized that a 7-gene biosignature (DCISionRT) with its Residual Risk subtype (RRt) could identify 2 groups of HER2(3+) patients with significantly different IBR risks after BCS plus RT. PATIENTS AND METHODS: All patients with HER2(3+) DCIS (n = 178) treated with BCS plus RT were selected from a combined multinational patient cohort. Treatment decisions were neither randomized nor strictly rules-based. Biosignature testing was performed on all patients and stratified with previously defined groups: (1) Combined Low Risk group (DS ≤ 2.8) and Elevated Risk group (DS > 2.8) without RRt or (2) Residual Risk subtype. Kaplan-Meier analysis was used to compute IBR curves. RESULTS: Sixty-three percent of HER2(3+) patients (113/178) were classified into the Residual Risk subtype. These patients had significantly higher 10-year rates of IBR compared to the nonresidual risk group (16.2% vs. 1.6%, P = .01). The Residual Risk subtype had more nuclear grade 3 disease (87% vs. 63%, P < .001), but age, size, and grade were not associated with IBR rate (P = NS) on univariate and multivariable analysis. Only the Residual Risk group was associated with IBR (P = .05) in multivariate analysis. CONCLUSION: The 7-gene biosignature with RRt identified a subset of HER2(3+) patients with greater IBR rates following BCS and RT beyond traditional clinical and pathologic features. Consideration of therapies to reduce these elevated IBR rates should be evaluated, including the incorporation of HER2-targeted therapy.
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BACKGROUND/OBJECTIVES: To determine the impact of stereotactic radiosurgery on outcomes of metastatic breast cancer with intracranial metastases. METHODS: We systematically searched the PubMed and EMBASE databases for studies published between 1 January 1990 and 1 August 2024. Primary research articles evaluating the outcomes of stereotactic radiosurgery on intracranial metastases from breast cancer were included. Adverse events were defined as leptomeningeal disease, radiation necrosis, seizure, and headache. The pooled estimate was calculated using the DerSimonian and Laird approach. RESULTS: Sixteen studies encompassing 1228 patients met the inclusion criteria. Our analysis revealed a median survival duration of 13.1 ± 3.8 months and a pooled 1-year overall survival rate of 53.1% after SRS treatment. There was a 29% local recurrence rate at 1 year and a 35% overall distant recurrence rate. In addition, our analysis found a relatively low rate of acute adverse events at 15.5%. CONCLUSIONS: SRS demonstrates promising efficacy and safety in managing intracranial metastases from breast cancer, with a favorable toxicity profile.
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As outcomes for low-risk breast cancer continue to improve, research and clinical paradigms are increasingly focused on appropriate deintensification with the goal of improving the therapeutic ratio of breast cancer treatment. These deintensification approaches span across disciplines including breast surgery, radiation therapy, and systemic therapy. With regard to breast surgery, studies have continued to push deintensification when it comes to surgical margins with breast conservation, reducing re-excision rates, whereas deintensification of axillary surgery has reduced the rates of axillary lymph node dissection and increasingly the need for any axillary surgery, including sentinel lymph node biopsy for low-risk patients. With regard to radiation therapy, studies have allowed for a drastic reduction in treatment duration, whereas approaches that reduce the target of treatment have led to a change from from treatment daily for 5-7 weeks to many low-risk patients completing treatment in just five treatments. With regard to systemic therapy, use of genomic assays and tumor biology has led to reduced utilization of cytotoxic chemotherapy, with studies also allowing for dose reduction of endocrine therapy for patients with ductal carcinoma in situ. Moving forward, greater focus should be placed on interdisciplinary deintensification approaches such as the consideration of radiation therapy alone as compared with endocrine therapy alone for low-risk breast cancers.
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/terapia , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/terapia , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/radioterapia , FemeninoRESUMEN
Background/Objectives: This study aims to identify the most accurate regression model for predicting total corneal astigmatism (TCA) from anterior corneal astigmatism (ACA) and to fine-tune the best model's architecture to further optimize predictive accuracy. Methods: A retrospective review of 19,468 eyes screened for refractive surgery was conducted using electronic medical records. Corneal topography data were acquired using the Pentacam HR. Various types (7) and subtypes (21) of regression learners were tested, with a deep neural network (DNN) emerging as the most suitable. The DNN was further refined, experimenting with 23 different architectures. Model performance was evaluated using root mean squared error (RMSE), R2, average residual error, and circular error. The final model only used age, ACA magnitude, and ACA axis to predict TCA magnitude and axis. Results were compared to predictions from one of the leading TCA prediction formulas. Results: Our model achieved higher performance for TCA magnitude prediction (R2 = 0.9740, RMSE = 0.0963 D, and average residual error = 0.0733 D) compared to the leading formula (R2 = 0.8590, RMSE = 0.2257 D, and average residual error = 0.1928 D). Axis prediction error also improved by an average of 8.1° (average axis prediction error = 4.74° versus 12.8°). The deep learning approach consistently demonstrated smaller errors and tighter clustering around actual values compared to the traditional formula. Conclusion: Deep learning techniques significantly outperformed traditional methods for TCA prediction accuracy using the Pentacam HR. This approach may lead to more precise TCA calculations and better IOL selection, potentially enhancing surgical outcomes.
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RATIONAL: Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial "field" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases). METHODS: Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot. RESULTS: (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs. CONCLUSIONS: These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis.
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Bronquios , Proliferación Celular , Neoplasias Pulmonares , Transducción de Señal , Fumar , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Transducción de Señal/fisiología , Masculino , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Proliferación Celular/fisiología , Fumar/efectos adversos , Fumar/metabolismo , Anciano , Bronquios/metabolismo , Bronquios/patología , Células Cultivadas , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genéticaRESUMEN
Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Radioterapia Adyuvante/métodos , Carcinoma Intraductal no Infiltrante/radioterapia , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/patología , Mastectomía Segmentaria , Estadificación de Neoplasias , Medición de RiesgoRESUMEN
PURPOSE: Persons experiencing homelessness (PEHs) represent a medically underserved population with a disproportionately high rate of late-stage cancer diagnoses and cancer mortality. During mobile onsite mammography and breast health education events, we studied PEH's barriers to and uptake of cancer screenings. METHODS: This study used patient surveys and review of the electronic health record. The main outcome measures included mammogram and diagnostic imaging (as needed) results. A questionnaire assessed patient's views and barriers related to social determinants of health. The study included women accessing community organization resources who were 40 years or older or who met criteria for screening mammography. RESULTS: Forty-six individuals completed mammograms and 41 individuals participated in the survey, for a response rate of 89%. Thirty-five participants (85%) held health insurance provided by a Medicaid managed plan. Thirty-six participants (87%) received a negative mammogram result, and five participants (12%) required follow-up for abnormal results. Of these five, two participants completed diagnostic follow-up with negative results, and three did not complete diagnostic follow-up. In addition to barriers related to housing insecurity, five patients (12%) reported transportation barriers. A majority (n = 28, 68%) disagreed or strongly disagreed with the statement, "I'm afraid the mammogram will be painful." A majority (n = 31, 76%) disagreed or strongly disagreed with the statement, "I'm busy and do not have time." Nearly all participants (n = 37, 90%) responded yes to the statement, "I believe in preventative care screenings." Eight participants (20%) completed at least one additional cancer screening. CONCLUSION: By creating enduring programs offering screening, navigation, and education, academic-community partnerships may begin to address the increased cancer mortality among PEHs by improving screening adherence.
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BACKGROUND: The PREVENT randomized control trial monitored progression to chronic breast cancer-related lymphedema (cBCRL) following intervention for subclinical breast cancer-related lymphedema (sBCRL) assessed by bioimpedance spectroscopy (BIS) versus tape-measure (TM). This multi-institutional trial demonstrated a 92% risk reduction of developing cBCRL. This secondary analysis reviews the timing of sBCRL and cBCRL following breast cancer (BC) treatment. PATIENTS AND METHODS: Women at risk of cBCRL (n = 919) were screened regularly up to 36 months after BC treatment using either BIS or TM. Following diagnosis of sBCRL, patients underwent a 4-week compression sleeve intervention. The time in months from BC treatment to detection was reviewed at 3-month intervals. RESULTS: In total 209 patients developed sBCRL (BIS: n = 89, TM: n = 120) and were eligible for intervention. 30 progressed to cBCRL postintervention (BIS: 7, TM: 23). More than half of patients had measurements consistent with sBCRL within 9 months of BC treatment. Patients continued to have initial detections of sBCRL, regardless of screening method, with rates remaining consistent in years two and three (p > 0.242) post surgery. Additionally, 39 patients progressed to cBCRL without developing sBCRL or receiving intervention across the 3-year period. CONCLUSIONS: The timing of sBCRL detection demonstrates that patients continue to be at risk years after treatment and may continue to progress to cBCRL years after surgery. Early detection of sBCRL allows for early intervention decreasing the likelihood of progression to cBCRL. Patients should continue to be monitored for a minimum of 3 years following completion of cancer treatment. Specifically, careful targeted monitoring over the initial 9-month period is important.
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Neoplasias de la Mama , Espectroscopía Dieléctrica , Humanos , Femenino , Estudios Prospectivos , Espectroscopía Dieléctrica/métodos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/cirugía , Persona de Mediana Edad , Estudios de Seguimiento , Linfedema del Cáncer de Mama/diagnóstico , Linfedema del Cáncer de Mama/etiología , Linfedema del Cáncer de Mama/terapia , Factores de Tiempo , Pronóstico , Anciano , Adulto , Progresión de la EnfermedadRESUMEN
BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) offers a safe and minimally invasive alternative for percutaneous cholecystostomy (PCC) in acute cholecystitis patients with high-surgical risk. Additionally, EUS-GBD serves as a rescue biliary drainage in malignant distal biliary obstruction. Despite its widespread application, data within the Indian context remains sparse. This study aims to report the outcomes of EUS-GBD through the first multi-center study from India. METHODS: We retrospectively analyzed patients undergoing EUS-GBD at six tertiary care centers of India from March 2022 to November 2023. EUS-GBD was performed by free hand or over-the-guidewire technique with lumen-apposing metal stent (LAMS) or large caliber metal stent (LCMS). The primary outcome was technical success (defined as successful deployment of stent between gallbladder and stomach/duodenal lumen). The secondary outcomes were clinical success (defined as resolution of symptoms of acute cholecystitis and more than > 50% reduction in bilirubin level within two weeks in distal biliary obstruction), adverse event rate, 30-day mortality rate and 90-day reintervention rate. RESULTS: Total 29 patients (mean age 65.86 ± 12.91, 11 female) underwent EUS-GBD. The indication for EUS-GBD were acute cholecystitis (79.31%) and rescue biliary drainage for malignant distal biliary obstruction (20.69%). LAMS was deployed in 92.86%, predominantly by free-hand technique (78.57%). Technical and clinical success rates were 96.55% and 82.75%, respectively. Adverse events occurred in 27.59% patients, with severe adverse events (bile leak and bleeding) being uncommon (10%). Both 30-day mortality rate and 90-day reintervention rate were 13.79% in patients. Cholecysto-duodenal fistula facilitated cholecystoscopic intervention and stone removal in one patient and transgastric EUS-GBD did not hamper bilio-enteric anastomosis during Whipple surgery in two patients. CONCLUSION: EUS-GBD is a safe and effective technique for managing acute cholecystitis in high-risk patients and for biliary drainage in cases with malignant distal biliary obstruction.
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BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Mastectomía Segmentaria , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/radioterapia , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Persona de Mediana Edad , Radioterapia Adyuvante , Pronóstico , Estudios Prospectivos , Anciano , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Toma de Decisiones Clínicas , Adulto , Toma de Decisiones , Biomarcadores de TumorRESUMEN
Importance: The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White, with Hispanic ethnicity. Despite the Affordable Care Act mandating Office of Management and Budget-based collecting and reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity. Objective: To quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials. Evidence Review: In this systematic review, PubMed and Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in each clinical trial publication by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov. Findings: Among 1202 publications evaluated, 364 met inclusion criteria: 16 JAMA, 241 Journal of Clinical Oncology, 19 Lancet, and 88 New England Journal of Medicine. Publications included 268â¯209 patients (171â¯132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included American Indian or Alaska Native in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), Native Hawaiian or Other Pacific Islander in 28 (8%), and White in 254 (70%). Median RQ varied across race (P < .001 BC), with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients. Sensitivity analyses showed similar findings on subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for American Indian or Alaska Native (14% vs 45%; P < .001 per McNemar χ2 test with continuity correction [MC]) and Native Hawaiian or Other Pacific Islander (8% vs 43%; P < .001 MC). Conclusions and Relevance: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act-concordant race and ethnicity federal reporting requirements.
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Grupos Raciales , Humanos , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto , Etnicidad/estadística & datos numéricos , Neoplasias/etnología , Neoplasias/terapia , Grupos Raciales/estadística & datos numéricos , Estados Unidos , Asiático , Indio Americano o Nativo de Alaska , Negro o Afroamericano , Nativos de Hawái y Otras Islas del Pacífico , Blanco , Hispánicos o LatinosRESUMEN
OBJECTIVES: Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm. METHODS: This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy. RESULTS: A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57 mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10 cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups. CONCLUSIONS: Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.
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Fraccionamiento de la Dosis de Radiación , Sarcoma , Humanos , Teorema de Bayes , Cuidados Preoperatorios , Sarcoma/radioterapia , Sarcoma/cirugía , Sarcoma/patologíaRESUMEN
Simulation is a technique used in healthcare to replicate clinical scenarios and improve patient safety, efficacy, and efficiency. Simulation-based medical education facilitates training and assessment in healthcare without increasing risk to patients, supported by ample evidence from surgical/procedural specialties. Simulation in radiation oncology has been leveraged to an extent, with successful examples of both screen-based and hands-on simulators that have improved confidence and performance in trainees. In the current era, evidence substantiates a significant deficit in brachytherapy procedure education, with radiation oncology residents reporting low confidence in this procedural skill, largely attributable to insufficient caseloads at some centers. Simulation-based medical education can facilitate structured training and competency-based assessment in brachytherapy skills. This review discusses existing advances and future directions in brachytherapy simulation, using examples from simulation in surgical specialties.
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Braquiterapia , Competencia Clínica , Internado y Residencia , Oncología por Radiación , Entrenamiento Simulado , Humanos , Oncología por Radiación/educaciónRESUMEN
Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh-EVs). Using our customizable antibody-purification assay, EV-CATCHER, we initially determined that exh-EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh-EVs harbour lung-specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh-EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV-CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti-CCSP/SFTPC EV-CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh-EV subpopulations from EBC allows non-invasive sampling of EVs produced by lung tissues.
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Pruebas Respiratorias , Vesículas Extracelulares , Pulmón , MicroARNs , Humanos , MicroARNs/metabolismo , MicroARNs/genética , Vesículas Extracelulares/metabolismo , Pulmón/metabolismo , Pruebas Respiratorias/métodos , Femenino , Masculino , Espiración , Persona de Mediana Edad , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Biomarcadores/metabolismo , AdultoRESUMEN
AIM: Same day discharge (SDD) for colorectal surgery shows increasing promise in the era of enhanced recovery after surgery protocols and minimally invasive surgery. It has become increasingly relevant due to the constraints posed by the COVID-19 pandemic. The aim of this study was to compare SDD and postoperative day 1 (POD1) discharge to understand the clinical outcomes and financial impact on factors such as cost, charge, revenue, contribution margin and readmission. METHOD: A retrospective review of colectomies was performed at a single institution over a 2-year period (n = 143). Two populations were identified: SDD (n = 51) and POD1 (n = 92). Patients were selected by International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) and Diagnosis Related Grouper (DRG) codes. RESULTS: There was a statistically significant difference favouring SDD in total hospital cost (p < 0.0001), average direct costs (p < 0.0001) and average charges (p < 0.0016). SDD average hospital costs were $8699 (values in USD throughout) compared with $11 652 for POD 1 (p < 0.0001), and average SDD hospital charges were $85 506 compared with $97 008 for POD1 (p < 0.0016). The net revenue for SDD was $22 319 while for POD1 it was $26 173 (p = 0.14). Upon comparison of contribution margins (SDD $13 620 vs. POD1 $14 522), the difference was not statistically significant (p = 0.73). There were no identified statistically significant differences in operating room time, robotic console time, readmission rates or surgical complications. CONCLUSIONS: Amidst the pandemic-related constraints, we found that SDD was associated with lower hospital costs and comparable contribution margins compared with POD1. Additionally, the study was unable to identify any significant difference between operating time, readmissions, and surgical complications when performing SDD.