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1.
Transfusion ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650381

RESUMO

BACKGROUND: For many years, there has been concern about the risk of transmission of classic forms of Creutzfeldt-Jakob disease (CJD) by blood transfusion, particularly after the recognition of such transmission of variant CJD (vCJD). We report on a 28-year lookback study of recipients of blood from donors who subsequently developed CJD. METHODS: Patients with diagnosed CJD and a history of blood donation were identified. Blood centers were asked to provide information about the distribution of the donations and consignees were requested to provide information about the recipients of the donations. Vital status of each available recipient was determined and, if deceased, the reported cause(s) of death were obtained primarily from the National Death Index. All recipients included in the study database contributed person-time up to the last recorded review of vital status. RESULTS: There were 84 eligible donors who gave 3284 transfusable components, and it was possible to evaluate 1245 recipients, totaling 6495 person-years of observation. The mean observation period per recipient was 5.5 years with a maximum of 51 years. No case of CJD or prion disease was reported among the recipient population. DISCUSSION: The study suggests that CJD may not be transfusion-transmissible, a position in agreement with similar findings from two similar European reports amounting to an overall observation period of 15,500 person-years. These studies have supported the conclusion that the risk, if any, of transmission of CJD by blood products is extremely small and remains theoretical.

2.
Transfusion ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661249

RESUMO

BACKGROUND: The COVID-19 pandemic impacted the US blood supply. We compared blood donor demography and infectious disease prevalence before and during the pandemic using a large multicenter database. METHODS: Data were categorized as "Before COVID-19" (March 2018-February 2020) or "During COVID-19" (March 2020-February 2022). Donor demographics, donation frequency, and infectious marker prevalence of HIV, HBV, and HCV were compared for the two time periods. The odds of a donor testing positive for these infections among the two time periods were calculated using multivariable logistic regression. RESULTS: Our study assessed a total of 26,672,213 donations including 13,430,380 before and 13,241,833 during COVID-19. There were significantly more donations from donors who were female, aged 40 and older, white, and repeat, during COVID-19. Donation frequency comparison quantified the increase in donations from donors who were white, female, older, and repeat during the pandemic. The prevalence of HIV and HCV decreased significantly during COVID-19 compared to before, but not for HBV. For HIV, the adjusted odds of infection during the pandemic did not differ but for HBV, the odds were significantly more likely during the pandemic and were significantly lower for HCV. DISCUSSION: Demographics and infectious disease marker prevalence changed during the COVID-19 pandemic in the United States. Prevalence of each infection in the donor population will continue to be monitored to determine if changes were specific to the pandemic period.

3.
Cancer Biomark ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38427470

RESUMO

Pulmonary nodules are ubiquitously found on computed tomography (CT) imaging either incidentally or via lung cancer screening and require careful diagnostic evaluation and management to both diagnose malignancy when present and avoid unnecessary biopsy of benign lesions. To engage in this complex decision-making, clinicians must first risk stratify pulmonary nodules to determine what the best course of action should be. Recent developments in imaging technology, computer processing power, and artificial intelligence algorithms have yielded radiomics-based computer-aided diagnosis tools that use CT imaging data including features invisible to the naked human eye to predict pulmonary nodule malignancy risk and are designed to be used as a supplement to routine clinical risk assessment. These tools vary widely in their algorithm construction, internal and external validation populations, intended-use populations, and commercial availability. While several clinical validation studies have been published, robust clinical utility and clinical effectiveness data are not yet currently available. However, there is reason for optimism as ongoing and future studies aim to target this knowledge gap, in the hopes of improving the diagnostic process for patients with pulmonary nodules.

4.
Transfusion ; 64(2): 325-333, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38180267

RESUMO

BACKGROUND: HIV, HBV, and HCV infections for ~60% of the US blood supply are monitored by TTIMS with syphilis added in 2020. STUDY DESIGN AND METHODS: Data were compiled from October 2020 to September 2022. Syphilis prevalence was estimated for allogeneic and directed donors who were consensus positive (CP) and the subset of those with confirmed-active infections (AI). Prevalence and incidence were stratified by demographics for two consecutive 1-year periods, starting October 1, 2020 and for both years combined. Incidence was estimated for repeat donors. Associations between syphilis positivity and other infections were evaluated. RESULTS: Among 14.75 million donations, syphilis prevalence was 28.4/100,000 donations and significantly higher during the second year compared to the first year. Overall, syphilis incidence for the two-year period was 10.8/100,000 person-years. The adjusted odds of a CP infection were 1.18 (95% CI: 1.11, 1.26) times higher in the second year compared to the first, and for AI, 1.22 (95% CI: 1.10, 1.35) times higher in year 2. Highest rates occurred among males, first-time, Black, and younger (ages 18-39) donors, and those in the South US Census region. Syphilis CP donors were 64 (95% CI: 46, 89) times more likely to be HIV CP, and AI donors 77 (95% CI: 52, 114) times more likely to be HIV CP than non-CP donors, when controlling for confounders. SUMMARY/CONCLUSIONS: Syphilis prevalence increased over the study period mirroring national trends reported by CDC and is significantly associated with HIV CP.


Assuntos
Infecções por HIV , Sífilis , Masculino , Humanos , Sífilis/epidemiologia , Estudos Soroepidemiológicos , Incidência , Doadores de Sangue , Infecções por HIV/epidemiologia , Prevalência
5.
Int J Equity Health ; 23(1): 8, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233876

RESUMO

BACKGROUND: Female migrant domestic workers (MDW), approximately 8.5 million globally, often live in their employer's home under vulnerable conditions. In Hong Kong, MDWs currently comprise 5% of the population. This study was conducted to assess the association between employment conditions and mental health, and the mediating roles stress and job satisfaction have, among female MDWs in Hong Kong. METHODS: Participants completed an online cross-sectional survey. A total of 1,965 survey were collected between August 2020 and August 2021. Questions in the survey were related to MDWs background information, employment conditions, stress, job satisfaction, and two mental health outcomes: anxiety and depression. An employment conditions score was created to assess the cumulative effect poor employment conditions had on mental health. A multicategorical parallel mediation analysis was used to assess the direct effect employment conditions have on mental health and the indirect effects through stress and job satisfaction. RESULTS: Overall, 17.7% of MDWs were reported to be suffering from anxiety and 30.8% from depression. An increase in poor employment conditions was statistically associated with an increase in both outcomes, while stress levels and job satisfaction mediated this association. CONCLUSIONS: The findings call for increased scrutiny of employment conditions and mental well-being of MDWs.


Assuntos
Saúde Mental , Migrantes , Humanos , Feminino , Hong Kong/epidemiologia , Estudos Transversais , Análise de Mediação , Emprego/psicologia
6.
Ann Intern Med ; 177(1): 18-28, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163370

RESUMO

BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials. OBJECTIVE: To identify rates of downstream procedures and complications associated with LCS. DESIGN: Retrospective cohort study. SETTING: 5 U.S. health care systems. PATIENTS: Individuals who completed a baseline LDCT scan for LCS between 2014 and 2018. MEASUREMENTS: Outcomes included downstream imaging, invasive diagnostic procedures, and procedural complications. For each, absolute rates were calculated overall and stratified by screening result and by lung cancer detection, and positive and negative predictive values were calculated. RESULTS: Among the 9266 screened patients, 1472 (15.9%) had a baseline LDCT scan showing abnormalities, of whom 140 (9.5%) were diagnosed with lung cancer within 12 months (positive predictive value, 9.5% [95% CI, 8.0% to 11.0%]; negative predictive value, 99.8% [CI, 99.7% to 99.9%]; sensitivity, 92.7% [CI, 88.6% to 96.9%]; specificity, 84.4% [CI, 83.7% to 85.2%]). Absolute rates of downstream imaging and invasive procedures in screened patients were 31.9% and 2.8%, respectively. In patients undergoing invasive procedures after abnormal findings, complication rates were substantially higher than those in NLST (30.6% vs. 17.7% for any complication; 20.6% vs. 9.4% for major complications). LIMITATION: Assessment of outcomes was retrospective and was based on procedural coding. CONCLUSION: The results indicate substantially higher rates of downstream procedures and complications associated with LCS in practice than observed in NLST. Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms. PRIMARY FUNDING SOURCE: National Cancer Institute and Gordon and Betty Moore Foundation.


Assuntos
Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/métodos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos
7.
J Phys Chem A ; 128(1): 182-190, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38118433

RESUMO

We present a comprehensive theoretical study of valence-shell photoionization of the CO2 molecule by using the XCHEM methodology. This method makes use of a fully correlated molecular electronic continuum at a level comparable to that provided by state-of-the-art quantum chemistry packages in bound-state calculations. The calculated total and angularly resolved photoionization cross sections are presented and discussed, with particular emphasis on the series of autoionizing resonances that appear between the first and the fourth ionization thresholds. Ten series of Rydberg autoionizing states are identified, including some not previously reported in the literature, and their energy positions and widths are provided. This is relevant in the context of ongoing experimental and theoretical efforts aimed at observing in real-time (attosecond time scale) the autoionization dynamics in molecules.

8.
bioRxiv ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38076839

RESUMO

Neuronal extracellular matrix (ECM) and a specific form of ECM called the perineuronal net (PNN) are important structures for central nervous system (CNS) integrity and synaptic plasticity. PNNs are distinctive, dense extracellular structures that surround parvalbumin (PV)-positive inhibitory interneurons with openings at mature synapses. Enzyme-mediated PNN disruption can erase established memories and re-open critical periods in animals, suggesting that PNNs are important for memory stabilization and conservation. Here, we characterized the structure and distribution of several ECM/PNN molecules around neurons in culture, brain slice, and whole mouse brain. While specific lectins are well-established as PNN markers and label a distinct, fenestrated structure around PV neurons, we show that other CNS neurons possess similar extracellular structures assembled around hyaluronic acid, suggesting a PNN-like structure of different composition that is more widespread. We additionally report that genetically encoded labeling of hyaluronan and proteoglycan link protein 1 (HAPLN1) reveals a PNN-like structure around many neurons in vitro and in vivo. Our findings add to our understanding of neuronal extracellular structures and describe a new mouse model for monitoring live ECM dynamics.

9.
J Cancer Policy ; 38: 100453, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37977216

RESUMO

INTRODUCTION: Lung cancer is a major cause of death in the United States. Social determinants of health (SDOH) are important factors that impact the treatment and prognosis of lung cancer. The social vulnerability index (SVI) is a validated measure of SDOH. This cross-sectional study aimed to investigate the impact of the SVI on lung cancer mortality using descriptive epidemiology. METHODS: Mortality data for lung malignancies from 2014 to 2018 was obtained from the CDC database and was age-adjusted and standardized to the population in the year 2000. The SVI for the same years was obtained from the CDC Agency for Toxic Substances and Disease Registry database. Age-adjusted mortality rates (AAMR) were estimated for each SVI quartile (SVI-Q) and demographic subgroup. RESULTS: We found that counties in SVI-Q4 (most vulnerable) had a higher cumulative AAMR compared to counties in SVI-Q1 (least vulnerable), accounting for a 4.48 excess death rate per 100,000 person-years. AAMR among males in SVI-Q4 was higher compared to SVI-Q1, accounting for a 9.96 excess death rate per 100,000 person-years, whereas no mortality differences were observed for female populations between SVI-Q4 and SVI-Q1. AAMR in SVI-Q4 was higher for both Hispanic and non-Hispanic populations, except for American Indian/Alaska Native populations. Similar trends were observed in both metropolitan and non-metropolitan counties. CONCLUSION: Our study suggests that the SVI may play a significant role in lung cancer mortality and highlights the need for interventions targeting vulnerable populations to improve outcomes.


Assuntos
Neoplasias Pulmonares , Masculino , Feminino , Humanos , Vulnerabilidade Social , Estudos Transversais , Populações Vulneráveis
10.
MAbs ; 15(1): 2239405, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497986

RESUMO

Monoclonal antibody (mAb) production using non-human cells can introduce non-human glycan epitopes including terminal galactosyl-α1-3-galactose (α1-3-Gal) moieties. Cetuximab is a commercial mAb associated with causing anaphylaxis in some patients due to the binding of endogenous anti-α1-3-Gal IgE to the Fab (containing bi-α1-3-galactosylated glycans) but not to the Fc region (containing mono-α1-3-galactosylated glycans). Despite being low in abundance in typical commercial mAbs, the inherent sensitivity of cell culture conditions on glycosylation profiles, and the development of novel glycoengineering strategies, novel antibody-based modalities, and biosimilars by various manufacturers with varying procedures, necessitates a better understanding of the structural requirements for anti-α1-3-Gal IgE binding to the Fc region. Herein, we synthesized mAb glycoforms with varying degrees and regioisomers of α1-3-galactosylation and tested their binding to two commercial anti-α1-3-Gal human IgE antibodies derived from a human patient with allergies to red meat (comprising α1-3-Gal epitopes), as well as to the FcγRIIIA receptor. Our results demonstrate that unexpectedly, anti-α1-3-Gal human IgE antibodies can bind to Fc glycans, with bi-α1-3-galactosylation being the most important factor, highlighting that their presence in the Fc region may be considered as a potential critical quality attribute, particularly when using novel platforms in mAb-based biotherapeutics.


Assuntos
Anticorpos Monoclonais , Medicamentos Biossimilares , Humanos , Anticorpos Monoclonais/química , Epitopos , Galactose/química , Polissacarídeos/química , Imunoglobulina E
11.
Nat Commun ; 14(1): 4155, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438348

RESUMO

The small Ultra-Red Fluorescent Protein (smURFP) represents a new class of fluorescent protein with exceptional photostability and brightness derived from allophycocyanin in a previous directed evolution. Here, we report the smURFP crystal structure to better understand properties and enable further engineering of improved variants. We compare this structure to the structures of allophycocyanin and smURFP mutants to identify the structural origins of the molecular brightness. We then use a structure-guided approach to develop monomeric smURFP variants that fluoresce with phycocyanobilin but not biliverdin. Furthermore, we measure smURFP photophysical properties necessary for advanced imaging modalities, such as those relevant for two-photon, fluorescence lifetime, and single-molecule imaging. We observe that smURFP has the largest two-photon cross-section measured for a fluorescent protein, and that it produces more photons than organic dyes. Altogether, this study expands our understanding of the smURFP, which will inform future engineering toward optimal FPs compatible with whole organism studies.


Assuntos
Biliverdina , Corantes , Proteínas Luminescentes/genética , Engenharia
12.
Adv Sci (Weinh) ; 10(26): e2302611, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37400371

RESUMO

Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates. Biomimetic hydrogel culture of LAM cells is found to recapitulate the molecular and phenotypic characteristics of human disease more faithfully than culture on plastic. A 3D drug screen is conducted, identifying histone deacetylase (HDAC) inhibitors as anti-invasive agents that are also selectively cytotoxic toward TSC2-/- cells. The anti-invasive effects of HDAC inhibitors are independent of genotype, while selective cell death is mTORC1-dependent and mediated by apoptosis. Genotype-selective cytotoxicity is seen exclusively in hydrogel culture due to potentiated differential mTORC1 signaling, a feature that is abrogated in cell culture on plastic. Importantly, HDAC inhibitors block invasion and selectively eradicate LAM cells in vivo in zebrafish xenografts. These findings demonstrate that tissue-engineered disease modeling exposes a physiologically relevant therapeutic vulnerability that would be otherwise missed by conventional culture on plastic. This work substantiates HDAC inhibitors as possible therapeutic candidates for the treatment of patients with LAM and requires further study.


Assuntos
Neoplasias Pulmonares , Linfangioleiomiomatose , Animais , Humanos , Linfangioleiomiomatose/tratamento farmacológico , Linfangioleiomiomatose/genética , Linfangioleiomiomatose/metabolismo , Neoplasias Pulmonares/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Engenharia Tecidual , Peixe-Zebra , Alvo Mecanístico do Complexo 1 de Rapamicina
13.
Emerg Infect Dis ; 29(7): 1323-1329, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37163762

RESUMO

We evaluated antibodies to the nucleocapsid protein of SARS-CoV-2 in a large cohort of blood donors in the United States who were recently infected with the virus. Antibodies to the nucleocapsid protein of SARS-CoV-2 indicate previous infection but are subject to waning, potentially affecting epidemiologic studies. We longitudinally evaluated a cohort of 19,323 blood donors who had evidence of recent infection by using a widely available serologic test to determine the dynamics of such waning. We analyzed overall signal-to-cutoff values for 48,330 donations (average 2.5 donations/person) that had an average observation period of 102 days. The observed peak signal-to-cutoff value varied widely, but the waning rate was consistent across the range, with a half-life of 122 days. Within the cohort, only 0.75% of persons became seronegative. Factors predictive of higher peak values and longer time to seroreversion included increasing age, male sex, higher body mass index, and non-Caucasian race.


Assuntos
COVID-19 , SARS-CoV-2 , Masculino , Humanos , Estados Unidos/epidemiologia , COVID-19/epidemiologia , Doadores de Sangue , Anticorpos Antivirais , Nucleocapsídeo , Proteínas do Nucleocapsídeo , Demografia , Glicoproteína da Espícula de Coronavírus
15.
bioRxiv ; 2023 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-37066274

RESUMO

Perineuronal nets (PNN), a specialized form of ECM (?), surround numerous neurons in the CNS and allow synaptic connectivity through holes in its structure. We hypothesis that PNNs serve as gatekeepers that guard and protect synaptic territory, and thus may stabilize an engram circuit. We present high-resolution, and 3D EM images of PNN- engulfed neurons showing that synapses occupy the PNN holes, and that invasion of other cellular components are rare. PNN constituents are long-lived and can be eroded faster in an enriched environment, while synaptic proteins have high turnover rate. Preventing PNN erosion by using pharmacological inhibition of PNN-modifying proteases or MMP9 knockout mice allowed normal fear memory acquisition but diminished remote-memory stabilization, supporting the above hypothesis. Significance: In this multidisciplinary work, we challenge the hypothesis that the pattern of holes in the perineuronal nets (PNN) hold the code for very-long-term memories. The scope of this work might lead us closer to the understanding of how we can vividly remember events from childhood to death bed. We postulate that the PNN holes hold the code for the engram. To test this hypothesis, we used three independent experimental strategies; high-resolution 3D electron microscopy, Stable Isotop Labeling in Mammals (SILAM) for proteins longevity, and pharmacologically and genetically interruption of memory consolidation in fear conditioning experiments. All of these experimental results did not dispute the PNN hypothesis.

16.
Open Forum Infect Dis ; 10(2): ofac697, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36751647

RESUMO

Background: Blood donors were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); resulting antibody levels were monitored over time. Methods: Donors reactive to anti-SARS-CoV-2 spike protein (S1-total antibodies) participated in a follow-up study of 18 months. Testing for nucleocapsid antibodies distinguished between vaccination and infection. Vaccination and symptom information were collected for anti-S1-reactive donors by completing a survey. Results: The majority of 249 followed donors were over 60 years old (54%), White (90%), and female (58%); 83% had not been vaccinated at enrollment, but by study completion, only 29% remained nonvaccinated. Of the 210 (84%) anti-N-reactive donors, 138 (66%) reported vaccination, whereas 37 (95%) of donors vaccinated and anti-N negative at enrollment remained uninfected. Vaccinated (2 doses) and infected donors showed a steady increase in anti-S1 that increased markedly for vaccinated donors after a booster and infected donors after vaccination (slightly higher for those with hybrid immunity), whereas anti-N levels declined. Most surveyed nonvaccinated donors (65%) reported symptoms, whereas 85% of vaccinated donors were asymptomatic. A coronavirus disease 2019 (COVID-19) diagnosis was reported by 48 (31%) nonvaccinated and 3 (8%) vaccinated donors. Of asymptomatic donors, 38% never tested diagnostically for COVID-19, and 35% tested negative, suggesting an absence of knowledge of the infection. Conclusions: Healthy blood donors were vaccinated at high rates and remained mostly asymptomatic and noninfected, whereas approximately two thirds of infected donors reported symptoms. Anti-S1 levels increased while anti-N decreased over 18 months but remained comparable between vaccinated and hybrid immune individuals with dramatic anti-S1 increases after vaccination or boosting.

17.
Transfusion ; 63(4): 764-773, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36794656

RESUMO

BACKGROUND: U.S. blood donors are tested at each donation for human T-lymphotropic virus (HTLV) antibodies. Depending on donor incidence and other mitigation/removal technologies, a strategy of one-time selective donor testing should be considered. METHODS: Antibody seroprevalence was calculated for HTLV-confirmed-positive American Red Cross allogeneic blood donors from 2008 to 2021. Incidence was estimated for seven 2-year time periods using confirmed-positive repeat donors having seroconverted in 730 days. Leukoreduction failure rates were obtained from internal data from July 1, 2008-June 30, 2021. Residual risks were calculated using a 51-day window period. RESULTS: Between 2008 and 2021, >75 million donations (>18 million donors) yielded 1550 HTLV seropositives. HTLV seroprevalence was 2.05 antibody-positives per 100,000 donations (0.77 HTLV-1, 1.03 HTLV-2, 0.24 HTLV-1/2), and 10.32 per 100,000 among >13.9 million first-time donors. Seroprevalence differed significantly by virus type, sex, age, race/ethnicity, donor status, and U.S. census region. Over 14 years and 24.8 million person-years of observation, 57 incident donors were identified (25 HTLV-1, 23 HTLV-2, and 9 HTLV-1/2). Incidence decreased from 0.30 (13 cases) in 2008-2009 to 0.25 (7 cases) in 2020-2021. Female donors accounted for most incident cases (47 vs. 10 males). In the last 2-year reporting period, the residual risk was 1 per 2.8 million donations and 1 per 3.3 billion donations when coupled with successful leukoreduction (0.085% failure rate). CONCLUSIONS: HTLV donation seroprevalence for the years 2008-2021 varied by virus type and donor characteristics. Low HTLV residual risk and use of leukoreduction processes support the conclusion that a selective one-time donor testing strategy should be considered.


Assuntos
Infecções por HTLV-I , Infecções por HTLV-II , Vírus Linfotrópico T Tipo 1 Humano , Masculino , Humanos , Feminino , Infecções por HTLV-I/epidemiologia , Doadores de Sangue , Estudos Soroepidemiológicos , Vírus Linfotrópico T Tipo 2 Humano , Infecções por HTLV-II/epidemiologia
18.
Clin Lung Cancer ; 24(2): e105-e112, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36599742

RESUMO

INTRODUCTION/BACKGROUND: Samples from endobronchial ultrasound-guided fine needle aspiration (EBUS-TBNA) are frequently used for next generation sequencing (NGS) in patients with non-small cell lung cancer (NSCLC) to look for genetic driver mutations. The objective of the current study was to evaluate the performance of extended NGS panels using EBUS-TBNA samples in a real-world setting and identify factors associated with the success of NGS. MATERIALS AND METHODS: This study included all patients who underwent EBUS and were diagnosed with non-squamous NSCLC with mediastinal metastasis from 2016 to 2019 at the University of Pennsylvania. We reviewed demographic information, imaging studies, procedure reports, pathology and NGS reports. Logistic regression was used to analyze factors associated with the success of NGS panels. RESULTS: The success rates of NGS using EBUS-TBNA samples were 92.5%, and 91.5% for DNA and RNA NGS panels respectively. Samples from higher N stage (N2 and N3 lymph nodes) and with higher tumor cellularity (>25%) resulted in higher success rate for DNA NGS. The effect of tumor cellularity remained borderline significant after entering multivariable logistic regression. The short-axis diameter of the sampled lymph node on CT scan, FDG-avidity on PET CT and >3 EBUS passes per lymph node during the procedure were not associated with NGS success. CONCLUSION: Both DNA and RNA extended-panel NGS had high performance using EBUS-TBNA samples. Sampling more advanced nodal stations and obtaining samples with higher tumor cellularity were associated with higher success rate of DNA NGS. Other imaging or procedural factors did not affect NGS performance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
19.
J Chem Phys ; 158(2): 024303, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641397

RESUMO

We present an experimental and theoretical energy- and angle-resolved investigation on the non-dissociative photoionization dynamics of near-resonant, one-color, two-photon, single valence ionization of neutral O2 molecules. Using 9.3 eV femtosecond pulses produced via high harmonic generation and a 3-D momentum imaging spectrometer, we detect the photoelectrons and O2 + cations produced from one-color, two-photon ionization in coincidence. The measured and calculated photoelectron angular distributions show agreement, which indicates that a superposition of two intermediate electronic states is dominantly involved and that wavepacket motion on those near-resonantly populated intermediate states does not play a significant role in the measured two-photon ionization dynamics. Here, we find greater utility in the diabatic representation compared to the adiabatic representation, where invoking a single valence-character diabat is sufficient to describe the underlying two-photon ionization mechanism.

20.
Am J Prev Med ; 65(1): 126-130, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36707314

RESUMO

INTRODUCTION: Authors aimed to calculate the percentage up-to-date with testing in the context of lung cancer screening across 5 healthcare systems and evaluate differences according to patient and health system characteristics. METHODS: Lung cancer screening‒eligible individuals receiving care within the five systems in the Population-based Research to Optimize the Screening Process Lung consortium from October 1, 2018 to September 30, 2019 were included in analyses. Data collection was completed on June 15, 2021; final analyses were completed on April 1, 2022. Chest computed tomography scans and patient characteristics were obtained through electronic health records and used to calculate the percentage completing a chest computed tomography scan in the previous 12 months (considered up-to-date). The association of patient and healthcare system factors with being up-to-date was evaluated with adjusted prevalence ratios and 95% CIs using log-binomial regression models. RESULTS: There were 29,417 individuals eligible for lung cancer screening as of September 30, 2019; 8,333 (28.3%) were up-to-date with testing. Those aged 65-74 years (prevalence ratio=1.19; CI=1.15, 1.24, versus ages 55-64), those with chronic obstructive pulmonary disease (prevalence ratio=2.05; CI=1.98, 2.13), and those in higher SES census tracts (prevalence ratio=1.22; CI=1.16, 1.30, highest quintile versus lowest) were more likely to be up-to-date. Currently smoking (prevalence ratio=0.91; CI=0.88, 0.95), having a BMI ≥30 kg/m2 (prevalence ratio=0.83; CI=0.77, 0.88), identifying as Native Hawaiian or other Pacific Islander (prevalence ratio=0.79; CI=0.68, 0.92), and having a decentralized lung cancer screening program (prevalence ratio=0.77; CI=0.74, 0.80) were inversely associated with being up-to-date. CONCLUSIONS: The percentage up-to-date with testing among those eligible for lung cancer screening is well below up-to-date estimates for other types of cancer screening, and disparities in lung cancer screening participation remain.


Assuntos
Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Detecção Precoce de Câncer , Tomografia Computadorizada por Raios X/métodos , Fumar/epidemiologia , Programas de Rastreamento/métodos
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