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1.
Heliyon ; 10(9): e30581, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742053

RESUMO

This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan-Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients.

3.
Quant Imaging Med Surg ; 13(8): 5153-5167, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581029

RESUMO

Background: Lower extremity venous disease (LEVD) is a complex disorder, and determining the etiology of LEVD is paramount for treatment selection. Two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI) can provide an objective measure of hemodynamic status and may help differentiate between different etiologies of LEVD. A total of 271 participants, including 256 symptomatic patients with venous lower extremity disease and 15 healthy volunteers, were collected in this cohort study. Methods: It is a single-center prospective observational study using 2D PC-MRI analysis to assess the hemodynamic characteristics of patients with LEVD among participants recruited between April 2017 and October 2021 at a tertiary hospital. The approval institutional review board number for this study were 201802137B0, 201901058B0, 202100938B0, and 202102344B0. Participants were classified as venous reflux (VR) and venous obstruction (VO) by standard ultrasonography. 2D PC-MRI by 1.5 T scanner revealed stroke volume (SV), forward flow volume (FFV), absolute stroke volume (ASV), mean flux (MF), velocity time integral (VTI), and mean velocity (MV) for each selected venous segments. Results: 2D PC-MRI assessed 167 diseased legs from the 116 VR patients [mean age ± standard deviation (SD): 57.9±12.8 years; 39 males] and 113 diseased legs from the 95 VO patients (mean age ± SD: 66.4±12.8 years; 42 males). 2D PC-MRI analysis demonstrated discrimination ability to differentiate from VR to VO [SV, FFV, ASV, MF, VTI, and MV in the various venous segments, respectively, P≤0.001; area under the curve (AUC) =62-68.8%, P≤0.001 by Mann-Whitney U test]. The ratio data (morbid limb to normal limb) in the same individual with single-leg disease revealed differences between VR and VO (SV, FFV, ASV, and MF in the various venous segments, respectively; P<0.05; AUC =60.2-68.7%, P≤0.05 by Mann-Whitney U test). The most favorable differentiating variables of ratios were FFV in the great saphenous veins [AUC =68.7%, 95% confidence interval (CI): 59.8-77.6%] and ASV in the external iliac veins (AUC =67.4%, 95% CI: 58.7-76.2%). Conclusions: Quantitative 2D PC-MRI analysis is capable of differentiating VR from VO. It also provides an important diagnostic capability for preoperative evaluation.

4.
Brain Sci ; 13(7)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37509017

RESUMO

Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.

5.
Ann Thorac Surg ; 116(1): 111-119, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36739067

RESUMO

BACKGROUND: No published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery. METHODS: This study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed. RESULTS: There were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%. CONCLUSIONS: The presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Receptores ErbB/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Progressão da Doença
6.
J Mol Diagn ; 24(11): 1195-1206, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35963521

RESUMO

Identification of specific leukemia subtypes is a key to successful risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the best approach to identify virtually all specific leukemia subtypes, the routine use of this method is too costly for patients in resource-limited countries. This study enrolled 295 patients with pediatric ALL from 2010 to 2020. Routine screening could identify major cytogenetic alterations in approximately 69% of B-cell ALL (B-ALL) cases by RT-PCR, DNA index, and multiplex ligation-dependent probe amplification. STIL-TAL1 was present in 33% of T-cell ALL (T-ALL) cases. The remaining samples were submitted for RNA-seq. More than 96% of B-ALL cases and 74% of T-ALL cases could be identified based on the current molecular classification using this sequential approach. Patients with Philadelphia chromosome-like ALL constituted only 2.4% of the entire cohort, a rate even lower than those with ZNF384-rearranged (4.8%), DUX4-rearranged (6%), and Philadelphia chromosome-positive (4.4%) ALL. Patients with ETV6-RUNX1, high hyperdiploidy, PAX5 alteration, and DUX4 rearrangement had favorable prognosis, whereas those with hypodiploid and KMT2A and MEF2D rearrangement ALL had unfavorable outcomes. With the use of multiplex ligation-dependent probe amplification, DNA index, and RT-PCR in B-ALL and RT-PCR in T-ALL followed by RNA-seq, childhood ALL can be better classified to improve clinical assessments.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Criança , Humanos , Proteínas de Fusão Oncogênica/genética , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Aneuploidia , DNA
7.
Am J Cancer Res ; 12(3): 1088-1101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35411222

RESUMO

Liquid biopsy test has a better uptake for colorectal cancer (CRC) screening. However, suboptimal detection of early-staged colorectal neoplasia (CRN) limits its application. Here, we established an early-staged CRN blood test using error-corrected sequencing by comparing clonal hematopoiesis (CH) of 63 CRN patients and that of 32 controls. We identified 1,446 variants and classified the uniqueness in CRN patients. There was no significance difference in the amount of variant between CRNs and controls, but the uniqueness of variants with defective DNA mismatch repair-related mutational signature was addressed from peripheral blood in early-staged CRN patients. By machine learning approach, the early-staged CRNs was discriminated from controls with an AUC of 0.959 and an accuracy of 0.937 (95% CI, 0.863 to 0.968). The CRN predictive model was further validated by additional 20 CRNs and 10 controls and showed the accuracy, sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) of 0.933 (95% CI: 0.779 to 0.992), 0.95, 0.90, 0.95 and 0.90, respectively. In summary, we develop a CH-based liquid biopsy test with machine learning approach, which not only increase screening uptake but also improve the detection rate of early-staged CRN.

10.
Diagnostics (Basel) ; 11(10)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34679608

RESUMO

(1) Background: We used four-dimensional phase-contrast magnetic resonance imaging (4D PC-MRI) to evaluate the impact of an endovascular aortic repair (TEVAR) on aortic dissection. (2) Methods: A total of 10 patients received 4D PC-MRI on a 1.5-T MR both before and after TEVAR. (3) Results: The aortas were repaired with either a GORE TAG Stent (Gore Medical; n = 7) or Zenith Dissection Endovascular Stent (Cook Medical; n = 3). TEVAR increased the forward flow volume of the true lumen (TL) (at the abdominal aorta, p = 0.047). TEVAR also reduced the regurgitant fraction in the TL at the descending aorta but increased it in the false lumen (FL). After TEVAR, the stroke distance increased in the TL (at descending and abdominal aorta, p = 0.018 and 0.015), indicating more effective blood transport per heartbeat. Post-stenting quantitative flow revealed that the reductions in stroke volume, backward flow volume, and absolute stroke volume were greater when covered stents were used than when bare stents were used in the FL of the descending aorta. Bare stents had a higher backward flow volume than covered stents did. (4) Conclusions: TEVAR increased the stroke volume in the TL and increased the regurgitant fraction in the FL in patients with aortic dissection.

11.
J Pers Med ; 11(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34575634

RESUMO

Imaging characteristics of stasis leg ulcers (SLUs) are not easily demonstrated through existing diagnostic tools. Early diagnosis and treatment are crucial. This pilot study was conducted to assess the quantitative flow (QFlow) in triggered angiography noncontrast enhanced (TRANCE) magnetic resonance imaging (MRI) to identify the hemodynamics of victims with stasis leg ulcers (SLUs). This study included 33 patients with SLUs and 14 healthy controls (HC). The 33 patients with SLUs were divided into a reflux (15 patients) and a nonreflux group (18 patients). QFlow was done in the reflux, the nonreflux, and the HC. The stroke volume (SV), forward flow volume (FFV), absolute flow volume (AFV), mean flow (MF), and mean velocity (MV) were higher in the reflux than in the HC group in most segments, namely the external iliac vein (EIV), popliteal vein (PV), and great saphenous vein (GSV) (SV, p = 0.008; FFV, p = 0.008; absolute stroke volume (ASV), p = 0.008; MF, p = 0.002; MV, p = 0.009). No differences in the QFlow patterns were found in the GSV segment between the nonreflux group and the HC. Excellent performance in discriminating SLU with superficial venous reflux was reported for SV in the EIV and the PV (area under the curve (AUC) = 0.851 and 0.872), FFV in the EIV and PV (AUC = 0.854 and 0.869), ASV in the EIV and PV (AUC = 0.848 and 0.881), and MF in the EIV and PV (AUC = 0.866 and 0.868). The cutoff levels of SV/FFV/ASV/MF in the EIV/FV/PV/GSV for discriminating the SLU with superficial venous reflux were identified (p < 0.005). In conclusion, SLUs present different QFlow patterns by different etiology. The QFlow parameters of all vessel segments were higher in the morbid limbs of the reflux group than HC. The GSV segment of the nonreflux group displayed a pattern like the HC.

12.
Diagnostics (Basel) ; 11(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34441326

RESUMO

BACKGROUND: Venous interventions of the legs are less predictable owing to a lock of objective tools. METHODS: One hundred and twenty patients with lower extremity venous disease were evaluated anatomically using TRANCE MRI. Then, a QFlow analysis was performed in 53 patients with only one leg affected for hemodynamic evaluation. Those patients with complete QFlow were classified into obstructive and nonobstructive. RESULTS: The QFlow-namely, stroke volume, forward flow volume, mean flux, stroke distance (SD), and mean velocity (MV) in the external iliac vein (EIV), femoral vein (FV), popliteal vein (PV), and great saphenous vein (GSV). The obstructed group had a shorter SD and lower MV in the EIV, EIV/FV, and GSV/PV (SD: p-values of 0.025, 0.05, and 0.043, respectively; MV: p-values of 0.02, 0.05, and 0.048, respectively). A good performance in discriminating obstructive venous disease was reported for SD in the EIV (area under the curve (AUC) = 67.9%, 95% confidence interval (CI) = 53.2-82.7%), EIV/FV (AUC = 72.4%, 95% CI = 58.2-86.5%), and GSV/PV (AUC = 67.9%, 95% CI = 51.7-84.1%). The SD in the EIV, EIV/FV, and GSV/PV had the ability to discriminate between obstructive and nonobstructive diseases (p-values of 0.025, 0.005, and 0.043). The MV in the EIV, EIV/FV, and GSV/PV had ability to discriminate between obstructive and nonobstructive venous diseases (p-values of 0.02, 0.005, and 0.048). CONCLUSIONS: The SD and MV were lower for obstructive than nonobstructive disease in the EIV.

13.
Medicine (Baltimore) ; 100(20): e25809, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011044

RESUMO

ABSTRACT: Although venous duplex ultrasonography (USG) is reliable for diagnosing lower extremity venous disease (LEVD), cross-sectional imaging studies were usually required before intervention or surgery. Patients of LEVD with renal insufficiency usually restrict the use of contrast-enhanced imaging modalities. In seeking an alternative imaging solution for these patients, we explore the clinical utility of triggered angiography non-contrast-enhanced magnetic resonance imaging (TRANCE-MRI) in the assessment of LEVD.We collected data from patients presenting to a tertiary wound-care center with symptoms of LEVD from April 2017-November 2019. Each participant underwent baseline USG followed by TRANCE-MRI on a 1.5T MR scanner (Philips Ingenia, Philips Healthcare, Best, The Netherlands). Inter-rater reliability was measured using Cohen's kappa (κ).All 80 participants (mean age, 61.9 ±â€Š14.8 years; 35 males, 45 females) were assessed and were classified into one of five disease groups, deep vein thrombosis (n = 38), venous static ulcer (n = 16), symptomatic varicose veins (n = 18), recurrent varicose veins (n = 3), and lymphoedema (n = 5). The inter-rater reliability between TRANCE-MRI and doppler USG showed substantial agreement (κ, 0.73). The sensitivity, specificity, and accuracy of TRANCE-MRI were 90.5%, 88.1%, and 88.8%, respectively. In 59 (73.8%) USG-negative patients, we were able to diagnose positive findings (deep venous thrombosis, n = 7; varicose veins, n = 15; lymphedema, n = 10; iliac vein compression with thrombosis, n = 6; external venous compression, n = 5; vena cava anomaly, n = 2; occult peripheral artery disease, n = 5; ccluded bypass graft, n = 1) by using TRANCE-MRI. Of these, 9 (15.3%) patients underwent additional vascular surgery based on positive TRANCE-MRI findings.TRANCE technique provides the limb's entire venous drainage in clear images without background contamination by associated arterial imaging. Additionally, simultaneous evaluation of bilateral lower extremities can help determine the lesion's exact site. Although TRANCE-MRI can provide MR arteriography and MR venography, we recommend performing only MR venography in symptomatic LEVD patients because the incidence of occult arterial disease is low.


Assuntos
Angiografia por Ressonância Magnética/métodos , Úlcera Varicosa/diagnóstico , Varizes/diagnóstico , Veias/diagnóstico por imagem , Trombose Venosa/diagnóstico , Idoso , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
14.
Sci Rep ; 11(1): 5802, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707599

RESUMO

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.


Assuntos
Proteínas de Fusão Oncogênica/metabolismo , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Proteínas Quinases/metabolismo , Sequência de Bases , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Deleção de Genes , Rearranjo Gênico/genética , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Lactente , Masculino , Proteínas de Neoplasias/metabolismo , Intervalo Livre de Progressão , Taiwan
15.
Aging (Albany NY) ; 13(1): 646-674, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33293474

RESUMO

Microphthalamia-associated transcription factor (MITF) is a critical mediator in melanocyte differentiation and exerts oncogenic functions in melanoma progression. However, the role of MITF in non-small cell lung cancer (NSCLC) is still unknown. We found that MITF is dominantly expressed in the low-invasive CL1-0 lung adenocarcinoma cells and paired adjacent normal lung tissues. MITF expression is significantly associated with better overall survival and disease-free survival in NSCLC and serves as an independent prognostic marker. Silencing MITF promotes tumor cell migration, invasion and colony formation in lung adenocarcinoma cells. In xenograft mouse model, MITF knockdown enhances metastasis and tumorigenesis, but decreases angiogenesis in the Matrigel plug assay. Whole transcriptome profiling of the landscape of MITF regulation in lung adenocarcinoma indicates that MITF is involved in cell development, cell cycle, inflammation and WNT signaling pathways. Chromatin immunoprecipitation assays revealed that MITF targets the promoters of FZD7, PTGR1 and ANXA1. Moreover, silencing FZD7 reduces the invasiveness that is promoted by silencing MITF. Strikingly, MITF has significantly inverse correlations with the expression of its downstream genes in lung adenocarcinoma. In summary, we demonstrate the suppressive role of MITF in lung cancer progression, which is opposite to the canonical oncogenic function of MITF in melanoma.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Fator de Transcrição Associado à Microftalmia/genética , Adenocarcinoma de Pulmão/irrigação sanguínea , Adenocarcinoma de Pulmão/patologia , Idoso , Oxirredutases do Álcool/genética , Animais , Anexina A1/genética , Carcinogênese , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular , Feminino , Receptores Frizzled/genética , Técnicas de Silenciamento de Genes , Genes Supressores de Tumor , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Transplante de Neoplasias , Neovascularização Patológica , Ensaio Tumoral de Célula-Tronco , Sequenciamento do Exoma , Via de Sinalização Wnt
16.
BMC Cancer ; 20(1): 1023, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092589

RESUMO

BACKGROUND: This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. METHODS: This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. RESULTS: At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN (P = 0.01). The two most important predictors used by the ANN for predicting lung cancer were the documented sizes of partially solid nodules and ground-glass nodules. CONCLUSIONS: Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Estudos Prospectivos , Sensibilidade e Especificidade
17.
Sci Rep ; 10(1): 16777, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033326

RESUMO

As the performance of current fall risk assessment tools is limited, clinicians face significant challenges in identifying patients at risk of falling. This study proposes an automatic fall risk prediction model based on eXtreme gradient boosting (XGB), using a data-driven approach to the standardized medical records. This study analyzed a cohort of 639 participants (297 fall patients and 342 controls) from Chang Gung Memorial Hospital, Chiayi Branch, Taiwan. A derivation cohort of 507 participants (257 fall patients and 250 controls) was collected for constructing the prediction model using the XGB algorithm. A comparative validation of XGB and the Morse Fall Scale (MFS) was conducted with a prospective cohort of 132 participants (40 fall patients and 92 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. This machine learning method provided a higher sensitivity than the standard method for fall risk stratification. In addition, the most important predictors found (Department of Neuro-Rehabilitation, Department of Surgery, cardiovascular medication use, admission from the Emergency Department, and bed rest) provided new information on in-hospital fall event prediction and the identification of patients with a high fall risk.


Assuntos
Acidentes por Quedas , Modelos Teóricos , Admissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Taiwan
18.
Sci Rep ; 10(1): 12074, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694622

RESUMO

Although the cure rate for childhood acute lymphoblastic leukemia (ALL) has exceeded 80% with contemporary therapy, relapsed ALL remains a leading cause of cancer-related death in children. Relapse-specific mutations can be identified by comprehensive genome sequencing and might have clinical significance. Applying whole-exome sequencing to eight triplicate samples, we identified in one patient relapse-specific mutations in the folylpolyglutamate synthetase (FPGS) gene, whose product catalyzes the addition of multiple glutamate residues (polyglutamation) to methotrexate upon their entry into the cells. To determine the prevalence of mutations of the FPGS mutations, and those of two important genes in the thiopurine pathway, NT5C2 and PRPS1, we studied 299 diagnostic and 73 relapsed samples in 372 patients. Three more FPGS mutants were identified in two patients, NT5C2 mutations in six patients, and PRPS1 mutants in two patients. One patient had both NT5C2 and PRPS1 mutants. None of these alterations were detected at diagnosis with a sequencing depth of 1000X, suggesting that treatment pressure led to increased prevalence of mutations during therapy. Functional characterization of the FPGS mutants showed that they directly resulted in decreased enzymatic activity, leading to significant reduction in methotrexate polyglutamation, and therefore likely contributed to drug resistance and relapse in these cases. Thus, besides genomic alterations in thiopurine metabolizing enzymes, the relapse-specific mutations of FPGS represent another critical mechanism of acquired antimetabolite drug resistance in relapsed childhood ALL.


Assuntos
Biomarcadores Tumorais , Mutação , Peptídeo Sintases/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Alelos , Criança , Pré-Escolar , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico
19.
Cancers (Basel) ; 12(6)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532105

RESUMO

Depressed colorectal neoplasm exhibits high malignant potential and shows rapid invasiveness. We investigated the genomic profile of depressed neoplasms and clarified the survival outcome and treatment response of the cancers arising from them. We examined 20 depressed and 13 polypoid neoplasms by genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations (CNAs) in an independent cohort of 37 depressed and 42 polypoid neoplasms. Finally, the CNAs were tested as biomarkers in 530 colorectal cancers (CRCs) to clarify the clinical outcome of depressed neoplasms. CNAs in MYC, CCNA1, and BIRC7 were significantly enriched in depressed neoplasms and designated as the D-marker panel. CRCs with a D-marker panel have significantly shorter progression-free survival compared with those without (p = 0.012), especially in stage I (p = 0.049), stages T1+2 (p = 0.027), and proximal cancers (p = 0.002). The positivity of the D-marker panel was an independent risk factor of cancer progression (hazard ratio (95% confidence interval) = 1.52 (1.09-2.11)). Furthermore, the proximal CRCs with D-marker panels had worse overall and progression-free survival when taking oxaliplatin as chemotherapy than those that did not. The D-marker panel may help to optimize treatment and surveillance in proximal CRC and develop a molecular test. However, the current result remains preliminary, and further validation in prospective trials is warranted in the future.

20.
Medicine (Baltimore) ; 98(52): e18427, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876719

RESUMO

RATIONALE: Contrast-enhanced computed tomographic venography (CTV) or magnetic resonance venography (MRV) are usually used to detect May-Thurner syndrome (MTS). However, both are associated with contrast-induced nephrotoxicity. For patients who cannot receive contrast media, non-contrast-enhanced MRV using three-dimensional (3D) turbo spin-echo (TSE) is considered an alternative. We report a case of MTS to describe its clinical utility and advantages. PATIENT CONCERNS: A 49-year-old male experienced isolated left leg swelling and pain for half a month. He had a history of chronic renal insufficiency that made contrast-enhanced imaging studies inadequate. DIAGNOSES: A lower extremity venous Duplex scan showed a thrombus extending from the left distal femoral vein to the popliteal vein with valvular reflux, consistent with infrainguinal deep vein thrombosis (DVT). The suprainguinal DVT was evaluated by non-contrast-enhanced MRV. The results showed sandwich external compression of the left common iliac vein between the right common iliac artery and lumbar vertebrae, consistent with DVT of the left common iliac vein caused by MTS. INTERVENTIONS: The patient received angioplasty with the implantation of a balloon-expandable stent over the left common iliac vein. OUTCOMES: Excellent recanalization of the left iliac vein was noted postoperatively. LESSONS: In the evaluation of suprainguinal venous lesions, non-contrast-enhanced MRV presents the venous structure alone at high resolution without the accompanying arterial structure, which makes it an excellent diagnostic imaging tool for MTS. These findings indicate that non-contrast-enhanced MRV could be useful for detecting systemic venous pathologies in patients with renal insufficiency.


Assuntos
Angiografia por Ressonância Magnética/métodos , Síndrome de May-Thurner/diagnóstico por imagem , Insuficiência Renal/diagnóstico por imagem , Veia Femoral/diagnóstico por imagem , Humanos , Masculino , Síndrome de May-Thurner/complicações , Pessoa de Meia-Idade , Veia Poplítea/diagnóstico por imagem , Insuficiência Renal/etiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
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