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1.
Cell ; 171(2): 481-494.e15, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28985567

RESUMO

Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease.


Assuntos
Sistemas CRISPR-Cas , Perfilação da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Células Cultivadas , Exoma , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Rituximab/administração & dosagem
2.
Radiographics ; 44(3): e230057, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38329900

RESUMO

Editor's Note.-RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics. These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Diagnóstico por Imagem
3.
Artigo em Inglês | MEDLINE | ID: mdl-38649529

RESUMO

INTRODUCTION: Research in various areas indicates that expert judgment can be highly inconsistent. However, expert judgment is indispensable in many contexts. In medical education, experts often function as examiners in rater-based assessments. Here, disagreement between examiners can have far-reaching consequences. The literature suggests that inconsistencies in ratings depend on the level of performance a to-be-evaluated candidate shows. This possibility has not been addressed deliberately and with appropriate statistical methods. By adopting the theoretical lens of ecological rationality, we evaluate if easily implementable strategies can enhance decision making in real-world assessment contexts. METHODS: We address two objectives. First, we investigate the dependence of rater-consistency on performance levels. We recorded videos of mock-exams and had examiners (N=10) evaluate four students' performances and compare inconsistencies in performance ratings between examiner-pairs using a bootstrapping procedure. Our second objective is to provide an approach that aids decision making by implementing simple heuristics. RESULTS: We found that discrepancies were largely a function of the level of performance the candidates showed. Lower performances were rated more inconsistently than excellent performances. Furthermore, our analyses indicated that the use of simple heuristics might improve decisions in examiner pairs. DISCUSSION: Inconsistencies in performance judgments continue to be a matter of concern, and we provide empirical evidence for them to be related to candidate performance. We discuss implications for research and the advantages of adopting the perspective of ecological rationality. We point to directions both for further research and for development of assessment practices.

4.
J Asthma ; 60(2): 277-287, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35195484

RESUMO

OBJECTIVE: To characterize adolescents' practical knowledge of asthma self-management and experiences during acute asthma episodes, and compare practical knowledge between minority and non-minority groups. METHODS: We conducted a secondary analysis using a qualitative descriptive design of textual data collected from 126 adolescents that participated in a randomized controlled trial of an asthma self-management program. Directed content analysis was conducted using four constructs of asthma self-management including symptom prevention, symptom monitoring, acute symptom management, and symptom communication. RESULTS: Most of the adolescents knew how to prevent exercised-induced bronchoconstriction, but had limited understanding about how to assess and monitor the severity of acute symptoms, appropriately use bronchodilators, seek timely medical help, and communicate acute symptoms to caregivers or healthcare providers during a slow-onset and rapid-onset asthma attack. More minority participants monitored asthma using peak expiratory flow than non-minority participants, who often relied on symptom-based monitoring. Minority adolescents more frequently mentioned bronchodilator use to manage asthma attacks, while non-minority adolescents often reported use of complementary and alternative approaches. Minority youth mentioned accessing healthcare services for acute episodes more often than their non-minority counterparts. Minority participants mentioned communicating acute symptoms to their providers, or family members less frequently than non-minority youth. CONCLUSIONS: Adolescents have insufficient practical knowledge about ways to prevent and manage acute asthma. Periodic assessment of learning needs related to asthma attacks should be considered a routine part of clinical visits for adolescents to provide targeted information support to address their identified needs.


Assuntos
Asma , Autogestão , Estado Asmático , Humanos , Adolescente , Asma/tratamento farmacológico , Estado Asmático/tratamento farmacológico , Família , Grupos Minoritários , Broncodilatadores/uso terapêutico
5.
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
6.
Surg Endosc ; 36(1): 778-786, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33528667

RESUMO

BACKGROUND: Laryngopharyngeal reflux (LPR) symptoms are often present in patients with Gastroesophageal reflux disease (GERD). Whereas antireflux surgery (ARS) provides predictably excellent results in patients with typical GERD, those with atypical symptoms have variable outcomes. The goal of this study was to characterize the response of LPR symptoms to antireflux surgery. METHODS: Patients who underwent ARS between January 2009 and May 2020 were prospectively identified from a single institutional database. Patient-reported information on LPR symptoms was collected at standardized time points (preoperative and 2 weeks, 8 weeks, and 1 year postoperatively) using a validated Reflux Symptom Index (RSI) questionnaire. Patients were grouped by preoperative RSI score: ≤ 13 (normal) and > 13 (abnormal). Baseline characteristics were compared between groups using chi-square test or t-test. A mixed effects model was used to evaluate improvement in RSI scores. RESULTS: One hundred and seventy-six patients fulfilled inclusion criteria (mean age 57.8 years, 70% female, mean BMI 29.4). Patients with a preoperative RSI ≤ 13 (n = 61) and RSI > 13 (n = 115) were similar in age, BMI, primary reason for evaluation, DeMeester score, presence of esophagitis, and hiatal hernia (p > 0.05). The RSI > 13 group had more female patients (80 vs 52%, p = < 0.001), higher mean GERD-HRQL score, lower rates of PPI use, and normal esophageal motility. The RSI of all patients improved from a mean preoperative value of 19.2 to 7.8 (2 weeks), 6.1 (8 weeks), and 10.9 (1 year). Those with the highest preoperative scores (RSI > 30) had the best response to ARS. When analyzing individual symptoms, the most likely to improve included heartburn, hoarseness, and choking. CONCLUSIONS: In our study population, patients with LPR symptoms achieved a rapid and durable response to antireflux surgery. Those with higher preoperative RSI scores experienced the greatest improvement. Our data suggest that antireflux surgery is a viable treatment option for this patient population.


Assuntos
Esofagite Péptica , Hérnia Hiatal , Refluxo Laringofaríngeo , Feminino , Fundoplicatura/métodos , Hérnia Hiatal/cirurgia , Humanos , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/etiologia , Refluxo Laringofaríngeo/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
BMC Health Serv Res ; 22(1): 394, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35337315

RESUMO

BACKGROUND: Case-mix based prospective payment of homecare is being implemented in several countries to work towards more efficient and client-centred homecare. However, existing models can only explain a limited part of variance in homecare use, due to their reliance on health- and function-related client data. It is unclear which predictors could improve predictive power of existing case-mix models. The aim of this study was therefore to identify relevant predictors of homecare use by utilizing the expertise of district nurses and health insurers. METHODS: We conducted a two-round Delphi-study according to the RAND/UCLA Appropriateness Method. In the first round, participants assessed the relevance of eleven client characteristics that are commonly included in existing case-mix models for predicting homecare use, using a 9-Point Likert scale. Furthermore, participants were also allowed to suggest missing characteristics that they considered relevant. These items were grouped and a selection of the most relevant items was made. In the second round, after an expert panel meeting, participants re-assessed relevance of pre-existing characteristics that were assessed uncertain and of eleven suggested client characteristics. In both rounds, median and inter-quartile ranges were calculated to determine relevance. RESULTS: Twenty-two participants (16 district nurses and 6 insurers) suggested 53 unique client characteristics (grouped from 142 characteristics initially). In the second round, relevance of the client characteristics was assessed by 12 nurses and 5 health insurers. Of a total of 22 characteristics, 10 client characteristics were assessed as being relevant and 12 as uncertain. None was found irrelevant for predicting homecare use. Most of the client characteristics from the category 'Daily functioning' were assessed as uncertain. Client characteristics in other categories - i.e. 'Physical health status', 'Mental health status and behaviour', 'Health literacy', 'Social environment and network', and 'Other' - were more frequently considered relevant. CONCLUSION: According to district nurses and health insurers, homecare use could be predicted better by including other more holistic predictors in case-mix classification, such as on mental functioning and social network. The challenge remains, however, to operationalize the new characteristics and keep stakeholders on board when developing and implementing case-mix classification for homecare prospective payment.


Assuntos
Serviços de Assistência Domiciliar , Humanos
8.
J Genet Couns ; 31(3): 689-697, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34826361

RESUMO

Individuals with sickle cell disease (SCD) and individuals with sickle cell trait (SCT) have different health trajectories, but it is unknown whether sociodemographic and clinical characteristics are associated with their likelihood to be a parent. The purpose of this study was to examine the sociodemographic and clinical characteristics associated with perceived likelihood-to-parent among a cohort of young adults with SCD or SCT in the USA. The participants were 234 young adults (82 males, 152 females) who had either SCD (n = 138) or SCT (n = 96). The average age was 25.9 years (SD = 4.9), and most participants (87%) were single. Study participants completed the likelihood-to-parent item (0-4 scale) included in the valid and reliable Sickle Cell Reproductive Health Knowledge Parenting Intent and Behavior Questionnaire (SCKnowIQ). The mean likelihood-to-parent score was M = 2.3 (SD = 1.1) and 41% indicated that they were 'very' or 'extremely' likely to be a parent. Bivariate analysis showed that likelihood-to-parent was associated with the participant's sickle cell genotype (p = .03), age (p = .003), educational level (p = .04), income (p = .01), employment (p = .04), number of children (p < .001), health insurance (p = .02), and influenced by others (p < .001). In multiple regression analysis, participants reported higher likelihood-to-parent scores if they had at most 2 children (p = .03), higher income (p = .03), had no insurance (p = .01), and reported higher levels of being influenced by others (p = .001). Additional research is needed to confirm these findings in larger representative samples with more young adult males and to understand the likelihood to become parents over time by implementing longitudinal studies in the SCD and SCT populations. Such research is needed to guide appropriate education and genetic counseling for reproductive decision-making among young adults with SCD or SCT.


Assuntos
Anemia Falciforme , Traço Falciforme , Adulto , Anemia Falciforme/genética , Criança , Feminino , Aconselhamento Genético , Humanos , Masculino , Pais , Saúde Reprodutiva , Traço Falciforme/genética , Adulto Jovem
9.
Fam Community Health ; 45(4): 215-217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35985021

RESUMO

As the United States grapples with social injustices, greater attention is being placed on the historical lack of equity practices among health and social service organizations that serve marginalized and predominantly racially minoritized communities. We describe strategies health and social service organizations that partner with community-led organizations must take to ensure actionable equitable changes. The opportunity and promise are upon us to resolve health inequities and promote equity-oriented practices, policies, systems, and social-environmental changes.


Assuntos
Populações Vulneráveis , Humanos , Estados Unidos
10.
Comput Inform Nurs ; 40(9): 633-640, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35930415

RESUMO

Our study purpose was to evaluate the variation and accuracy of tailored parenting plans individually generated as a supplement to reproductive health education on the genetic inheritance of sickle cell disease or sickle cell trait. We present a secondary data analysis of experimental group data from a randomized controlled trial. Participants completed the valid and reliable Internet-based Sickle Cell Reproductive Health Knowledge Parenting Intent Questionnaire. We created a computerized algorithm that used participants' responses to generate tailored parenting plans based on their parenting preferences and partner's sickle cell status. Thirty-one different parenting plans were generated to meet the variety in the participants' preferences. The most frequently generated plan was for participants with sickle cell disease who had a partner with hemoglobin AA, who wanted to be a parent, was not likely to be pregnant, and wanted their child to be sickle cell disease free. More than half of the participants required alteration in their reproductive behavior to achieve their parenting goals. Findings provide insight into the variety and accuracy of computer algorithm-generated parenting plans, which could further guide refinement of the algorithm to produce patient-centered, tailored parenting plans supplemental to Internet-based genetic inheritance education.


Assuntos
Anemia Falciforme , Traço Falciforme , Anemia Falciforme/genética , Anemia Falciforme/terapia , Criança , Educação em Saúde , Humanos , Poder Familiar , Traço Falciforme/genética , Inquéritos e Questionários , Adulto Jovem
14.
Radiology ; 301(2): 443-454, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34427460

RESUMO

Background Isoattenuating and hyperattenuating thymic cysts at CT are often misinterpreted as lymphadenopathy or thymic epithelial neoplasms. Purpose To evaluate the longitudinal change in thymic cyst appearance at CT and MRI. Materials and Methods All chest MRI studies showing thymic cysts between July 2008 and December 2019, identified from a retrospective search of a quality assurance database, were included in this study if initial CT depicted a thymic lesion, the patient was referred for follow-up MRI for characterization, and the baseline (ie, index) MRI indicated a cystic lesion. Follow-up CT scans and/or MRI scans were identified through July 2020. Thymic cyst characteristics, such as size, location, and morphologic features, as well as CT and MRI characteristics, were recorded. Change in size, attenuation, and T1-weighted MRI signal was assessed longitudinally. Descriptive statistics of longitudinal change were tabulated. Results A total of 244 chest MRI studies in 140 patients with 142 unique cysts and 392 CT examinations (636 total examinations and 645 thymic cysts-nine examinations with two cysts each) were evaluated. The median follow-up duration was 2.2 years. Thirty-three patients with 34 unique cysts (34 of 142 cysts [24%]) underwent imaging follow-up for more than 5 years. Thymic cysts followed up for more than 5 years were most commonly saccular (189 of 274 cysts [69% axially]) and retrosternal (14 of 34 cysts [41%]). Craniocaudal dimension was larger than transverse and anteroposterior dimensions in 223 of 274 cysts (81%). Mean thymic cyst attenuation was 25 HU (range, 15-100 HU). Five of 31 cysts (16%) exhibited wall calcification. The median cyst wall thickness was 2.0 mm (range, 0.9-3.0 mm). Most thymic cysts changed in volume (31 of 34 cysts [91%]), CT attenuation (15 of 35 cysts [43%]), and T1-weighted MRI signal (12 of 18 cysts [67%]) over time. None developed mural irregularity, nodularity, or septations. Conclusion Unilocular thymic cysts, defined at index MRI, never developed irregular wall thickening, mural nodularity, or septations that would raise concern for malignant transformation. However, these cysts showed mural calcification and change in size, CT attenuation, and MRI signal over more than 5 years of follow-up. © RSNA, 2021 Online supplemental material is available for this article.


Assuntos
Imageamento por Ressonância Magnética/métodos , Cisto Mediastínico/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Radiology ; 301(3): 712-720, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34546133

RESUMO

Background To address disparities in lung cancer screening (LCS) that may exclude large numbers of high-risk African American smokers, revised U.S. Preventive Services Task Force (USPSTF) recommendations lowered LCS eligibility thresholds. However, there are limited recent data about the impact of newly revised guidelines on disparities in LCS eligibility. Purpose To evaluate the impact of revised USPSTF guidelines on racial and ethnic disparities in LCS eligibility. Materials and Methods Cross-sectional survey data from 20 states were retrospectively evaluated from the 2019 Behavioral Risk Factor Surveillance System survey (median response rate, 49.4%). Respondents without a history of lung cancer aged 55-79 years (ie, under the previous guidelines) or aged 50-79 years (ie, under the revised guidelines) were included. Multivariable logistic regression analyses were performed to evaluate the association between race and ethnicity and LCS eligibility. All analyses were performed accounting for complex survey design features (ie, weighting, stratification, and clustering). Results Under previous guidelines, 11% of 67 567 weighted survey respondents were eligible for LCS (White [12%], Hispanic [4%], African American [7%], American Indian [17%], Asian or Pacific Islander [4%], and other [12%]). Under revised USPSTF guidelines, 14% of 77 689 weighted survey respondents were eligible for LCS (White [15%], Hispanic [5%], African American [9%], American Indian [21%), Asian or Pacific Islander [5%], and other [18%]). Compared with White respondents, African American respondents (adjusted odds ratio [OR] = 0.36; 95% CI: 0.27, 0.47; P < .001) and Hispanic respondents (adjusted OR = 0.15; 95% CI: 0.09, 0.24; P < .001) were less likely to be eligible for LCS under previous guidelines. African American respondents (adjusted OR = 0.39; 95% CI: 0.32, 0.47; P < .001) and Hispanic respondents (adjusted OR = 0.15; 95% CI: 0.10, 0.23; P < .001) were less likely to be eligible under the revised guidelines. The Wald test showed no evidence of differences in the degree to which racial and ethnic minority groups were less likely to be eligible for LCS when comparing previous versus revised USPSTF guidelines (P = .76). Conclusion The revised U.S. Preventive Services Task Force guidelines (version 2.0) may perpetuate lung cancer disparities, as racial and ethnic minority groups are still less likely to be eligible for lung cancer screening. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jacobs and Springfield in this issue.


Assuntos
Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico por imagem , Grupos Raciais/estatística & dados numéricos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos
16.
Eur J Nucl Med Mol Imaging ; 48(6): 1976-1986, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33415433

RESUMO

PURPOSE: To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in primary abdominal malignancies. METHODS: This retrospective IRB-approved study included [18F]-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated. RESULTS: A total of 505 nodules (mean 4 mm, range 1-23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients' management. CONCLUSIONS: Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.


Assuntos
Neoplasias Abdominais , Neoplasias Pulmonares , Neoplasias Abdominais/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
17.
Hematol Oncol ; 39(3): 284-292, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33480087

RESUMO

We investigated the intratumoral source of PD-L1 expression and the infiltration of tumor-associated macrophages (TAMs) in large B-cell lymphomas (LBCLs) with or without MYC-translocation, as well as possible correlations to BCL2-and BCL6-translocations and cell of origin (COO). One-hundred and twenty-six patient samples were studied in a cohort enriched for MYC-translocated tumors with 34 samples carrying this translocation. Demonstration of intratumoral distribution and cellular source of PD-L1 was enabled by immunohistochemical (IHC) dual staining specifically highlighting PD-L1 expression in lymphoma B-cells with antibodies against PD-L1 and PAX5. Additional IHC with antibodies against CD68 and CD163 identified TAMs. We found that CD68-positive TAMs were the main source of PD-L1 protein expression in contrast to lymphoma B cells which rarely expressed PD-L1. Semiquantitative IHC demonstrated a significant correlation between CD68 and PD-L1 protein expression. Unsupervised hierarchical analysis of PD-L1, CD68, and CD163 IHC data subsequently demonstrated three potential clusters defined by expression of the three biomarkers. Cluster A consisted of patient samples with significantly lower expression of PD-L1, CD68, and CD163, but also significantly higher prevalence of BCL2-translocation and MYC-BCL2-double-hit (DH) compared to the other two clusters. In cluster C we found a significant accumulation of BCL6 translocated tumors. This cluster in contrast had the highest protein expression of PD-L1, CD68, and CD163. Cluster B tumors had an intermediate expression of the three biomarkers, but no accumulation of the specific genetic translocations. Our data, which were based on morphological analysis, immunophenotyping and genotyping by fluorescence in situ hybridization were in line with new concepts of LBCL taxonomy integrating genetic, phenotypical, and immunological characteristics with identification of new subgroups where MYC translocation and MYC-BCL2 DH may identify a noninflamed subtype. These findings may furthermore hold significant predictive value especially regarding immune checkpoint blockade therapy, but further molecular characterization should be done to substantiate this hypothesis.


Assuntos
Linfócitos B , Antígeno B7-H1 , Regulação Leucêmica da Expressão Gênica , Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-myc , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/metabolismo , Linfócitos B/patologia , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia
18.
J Surg Res ; 264: 408-417, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33848840

RESUMO

BACKGROUND: Inguinal hernia repair is the most commonly performed elective operation in the United States, with over 800,000 cases annually. While clinical outcomes comparing laparoscopic versus open techniques have been well documented, there is little data comparing costs associated with these techniques. This study evaluates the cost of healthcare resources during the 90-d postoperative period following inguinal hernia repair. METHODS: We analyzed data from the Truven Health MarketScan Research Databases. Adult patients with an ICD-9 or CPT code for inguinal hernia repair from 2012 to 2014 were included. Patients with continuous enrollment for 6 mo prior to surgery and 6 mo after surgery were analyzed. Related healthcare service costs (readmission and/or ER visit and/or outpatient visit) were calculated by clinical classification software and generalized linear modeling was used to compare healthcare utilization between groups. RESULTS: 124,582 cases were identified (open = 84,535; lap = 40,047). Index surgery cost was 41% higher in laparoscopic cases. The cost for readmission was close to $25,000 and similar between both groups, but the laparoscopic group were 12% less likely to be readmitted for surgical complications within 90-d when compared to the open group. Cost of bilateral laparoscopic repair is less than that of serial unilateral open repairs. CONCLUSION: Laparoscopic inguinal hernia repair carries a higher index surgery cost than open repair. However, open repair has an increased rate of readmission. To maximize value, efforts should be directed at minimizing readmissions and improving identification of bilateral hernias at the time of initial presentation.


Assuntos
Efeitos Psicossociais da Doença , Hérnia Inguinal/cirurgia , Herniorrafia/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Pós-Operatórias/economia , Adulto , Idoso , Análise Custo-Benefício/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/economia , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Hérnia Inguinal/economia , Herniorrafia/efeitos adversos , Herniorrafia/economia , Humanos , Laparoscopia/economia , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/economia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Estudos Retrospectivos , Estados Unidos/epidemiologia
19.
AJR Am J Roentgenol ; 216(2): 318-329, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32755209

RESUMO

BACKGROUND. Lung cancer (LC) associated with cystic airspaces is an uncommon presentation that is underrecognized on imaging. Additionally, understanding of its underlying pathology and risk factors is limited, which can contribute to delays in diagnosis. OBJECTIVE. The purpose of this analysis was to systematically review, analyze, and synthesize the medical literature to determine the imaging features of LC associated with cystic airspaces. EVIDENCE ACQUISITION. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included published research reporting the clinical, pathologic, and imaging features of LC associated with cystic airspaces. We then performed a pooled analysis of continuous and categoric data with respect to patient clinical characteristics, tumor pathologic features, underlying driver mutation, CT features, and evolution of these features over time. EVIDENCE SYNTHESIS. The analysis included eight original observational studies with a combined total of 341 patients with LC associated with cystic airspaces (weighted mean age, 61.8 years; range, 30-87 years; 135 women and 206 men). Most patients were current or previous smokers (127/192 [66.1%]). The most common histologic finding was adenocarcinoma (289/328 [88.1%]) followed by squamous cell carcinoma (30/328 [9.1%]). The most common driver mutations were EGFR (46/122 [37.7%]) and KRAS (21/122 [17.2%]). The cysts in LC associated with cystic airspaces commonly had nonuniform (104/114 [91.2%]) and thick (83/222 [37.4%]) walls, irregular margins (53/142 [37.3%]), and were unilocular (173/272 [63.6%]). Most cysts had a nodular component (210/328 [64.0%]). Over time, most cysts showed development or enlargement of the nodular component (61/89 [68.5%]), approximately half showed wall thickening (43/89 [48.3%]), and a minority evolved into completely solid lesions (11/89 [12.4%]). The size of the cystic component increased in 36 of 89 patients (40.4%), decreased in 28 (31.5%), and remained stable in 24 (27.0%). CONCLUSION. LC associated with cystic airspaces occurs most commonly as adeno-carcinoma and is seen in both smokers and nonsmokers. The cysts associated with LC show wall thickening and mural nodularity, which may evolve over time. LC associated with cystic airspaces can be indolent, and long-term surveillance with imaging should be considered if cysts are not resected. CLINICAL IMPACT. Familiarity with the imaging features and temporal evolution of LC associated with cystic airspaces can minimize delays in LC diagnosis. Future management guidelines should include protocols for follow-up and management of cystic lung lesions identified during diagnostic and LC screening CT.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Humanos , Neoplasias Pulmonares/complicações
20.
AJR Am J Roentgenol ; 217(5): 1083-1092, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33377416

RESUMO

BACKGROUND. Incidental findings are frequently encountered during lung cancer screening (LCS). Limited data describe the prevalence of suspected acute infectious and inflammatory lung processes on LCS and how they should be managed. OBJECTIVE. The purpose of this study was to determine the prevalence, radiologic reporting and management, and outcome of suspected infectious and inflammatory lung processes identified incidentally during LCS and to propose a management algorithm. METHODS. This retrospective study included 6314 low-dose CT (LDCT) examinations performed between June 2014 and April 2019 in 3800 patients as part of an established LCS program. Radiology reports were reviewed, and patients with potentially infectious or inflammatory lung abnormalities were identified and analyzed for descriptors of imaging findings, Lung-RADS designation, recommendations, and clinical outcomes. Using the descriptors, outcomes, and a greater than 2% threshold risk of malignancy, a follow-up algorithm was developed to decrease additional imaging without affecting cancer detection. RESULTS. A total of 331/3800 (8.7%) patients (178 men, 153 women; mean age [range], 66 [53-87] years) undergoing LCS had lung findings that were attributed to infection or inflammation. These abnormalities were reported as potentially significant findings using the S modifier in 149/331 (45.0%) and as the dominant nodule used to determine the Lung-RADS category in 96/331 (29.0%). Abnormalities were multiple or multifocal in 260/331 (78.5%). Common descriptors were ground-glass (155/331; 46.8%), tree-in-bud (56/331; 16.9%), consolidation (41/331; 12.4%), and clustered (67/331; 20.2%) opacities. A follow-up chest CT outside of screening was performed within 12 months or less in 264/331 (79.8%) and within 6 months or less in 186/331 (56.2%). A total of 260/331 (78.5%) opacities resolved on follow-up imaging. Two malignancies (2/331; 0.6%) were associated with these abnormalities and both had consolidations. Theoretic adoption of a proposed management algorithm for suspected infectious and inflammatory findings reduced unnecessary follow-up imaging by 82.6% without missing a single malignancy. CONCLUSION. Presumed acute infectious or inflammatory lung abnormalities are frequently encountered in the setting of LCS. These opacities are commonly multifocal and resolve on follow-up. Less than 1% are associated with malignancy. CLINICAL IMPACT. Adoption of a conservative management algorithm can standardize recommendations and reduce unnecessary imaging without increasing the risk of missing a malignancy.


Assuntos
Detecção Precoce de Câncer , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento , Pneumonia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos
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