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1.
Medicine (Baltimore) ; 100(9): e24724, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655937

RESUMO

ABSTRACT: Brain metastasis is a common site of distant metastasis of non-small-cell lung cancer (NSCLC) that greatly reduces the prognosis of patients. In this study, we explored the correlation between different clinical factors and secondary brain metastases in NSCLC in an attempt to identify NSCLC patient populations at high risk of metastasis to the central nervous system.We collected data for 350 NSCLC patients from the medical record system of the First Affiliated Hospital of Nanchang University from June 2015 to June 2019, and these patients had pathologically verified diagnoses. The correlations between age at the time of diagnosis, sex, histological type, calcium concentration, hemoglobin (HB), fibrinogen (Fbg), activated partial thromboplastin time (APTT), alkaline phosphatase (ALP), carcinoembryonic antigen (CEA), CA125, and CA199 levels and brain metastasis were analyzed. Multivariate logistic regression analysis was used to identify risk factors for NSCLC brain metastasis. A receiver operating characteristic (ROC) curve was used to calculate the cutoff, sensitivity, and specificity of the independent related factors.Of the 350 patients, 57 were diagnosed with brain metastases. Univariate and multivariate logistic regression analysis indicated that lesion diameter, calcium concentration, and CEA level were independent risk factors correlated with brain metastasis (P < .05). There were no significant differences in age, sex, type of histopathology, presence or absence of mediastinal lymph node metastasis, HB, Fbg, APTT, ALP, cancer antigen 125 (CA-125), or cancer antigen 199 (CA-199) levels between patients with brain metastases and patients without brain metastases (P > .05, respectively). ROC curves demonstrated that these factors had comparable accuracy in predicting brain metastasis (area under the curve [AUCs] were 0.620, 0.661, and 0.729, respectively). The cutoff values for lesion diameter, calcium, and CEA were 5.050 cm, 2.295 mmol/L, and 11.160 ng/mL, respectively. The sensitivities for prediction brain metastasis were 59.6%, 64.9%, and 73.3%, with specificities of 63.1%, 59.2%, and 70.3%, respectively.According to our study, lesion diameter, calcium concentration, and CEA level are independent risk factors for brain metastases in NSCLC patients. Thus, we can strengthen the regular follow-up of NSCLC patients with tumor diameter > 5.050 cm, calcium > 2.295 mmol/L, CEA > 11.160 ng/mL, and use these factors as a reference for preventive treatments.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Idoso , Fosfatase Alcalina/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Ca-125/sangue , Cálcio/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Fibrinogênio/análise , Hemoglobinas/análise , Humanos , Modelos Logísticos , Pulmão/patologia , Neoplasias Pulmonares/sangue , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Carga Tumoral
2.
Cell Prolif ; 54(2): e12968, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33332660

RESUMO

OBJECTIVES: Pre-eclampsia is a leading cause of morbidity and mortality during pregnancy. Although the two forms of this disorder, early- (EOPE) and late-onset of pre-eclampsia (LOPE) are different, the underlying pathology remains elusive. We aim to unravel the difference and to identify novel biomarkers for EOPE and LOPE. MATERIALS AND METHODS: A complete comparison of both placental and peripheral blood transcriptomes was performed to investigate the pathology of pre-eclampsia. Single-cell transcriptomics of the maternal-fetal interface were integrated to identify novel biomarkers for EOPE and LOPE which were further verified at protein or mRNA level in patients. RESULTS: We found that the transcriptomes of placentae from EOPE, but not LOPE, were significantly different from their respective controls. Conversely, the transcriptomes of peripheral blood from LOPE were more different from their controls than EOPE. Importantly, we identified that several classical biomarkers of pre-eclampsia were expressed specifically in extravillous trophoblast and syncytiotrophoblast and only upregulated in EOPE, suggesting they should not be applied to all pre-eclampsia patients in general. We further identified novel biomarkers for EOPE and LOPE from differentially expressed genes (DEGs) of placental and peripheral blood, respectively. The new biomarkers EBI3, IGF2, ORMDL3, GATA2 and KIR2DL4 were experimentally verified with patient blood samples. CONCLUSION: Our data demonstrate distinct pathology of EOPE and LOPE, and uncover new biomarkers that can be applied in diagnosis for pre-eclampsia.


Assuntos
Biomarcadores/metabolismo , Pré-Eclâmpsia/patologia , Transcriptoma , Biomarcadores/sangue , Estudos de Casos e Controles , Biologia Computacional , Feminino , Fator de Transcrição GATA2/sangue , Fator de Transcrição GATA2/metabolismo , Humanos , Interleucinas/sangue , Interleucinas/metabolismo , Transtornos de Início Tardio , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismo , Antígenos de Histocompatibilidade Menor/sangue , Antígenos de Histocompatibilidade Menor/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Mapas de Interação de Proteínas , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única
3.
Cytokine ; 137: 155354, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33113474

RESUMO

BACKGROUND AND AIMS: The interferon-induced transmembrane proteins play an important antiviral role by preventing viruses from traversing the cellular lipid bilayer. IFITM3 gene variants have been associated with the clinical response to influenza and other viruses. Our aim was to determine whether the IFITM3 rs12252 polymorphism was associated with the risk of developing severe symptoms of COVID-19 in our population. METHODS: A total of 288 COVID-19 patients who required hospitalization (81 in the intensive care unit) and 440 age matched controls were genotyped with a Taqman assay. Linear regression models were used to compare allele and genotype frequencies between the groups, correcting for age and sex. RESULTS: Carriers of the minor allele frequency (rs12252 C) were significantly more frequent in the patients compared to controls after correcting by age and sex (p = 0.01, OR = 2.02, 95%CI = 1.19-3.42). This genotype was non-significantly more common among patients who required ICU. CONCLUSIONS: The IFITM3 rs12252 C allele was a risk factor for COVID-19 hospitalization in our Caucasian population. The extent of the association was lower than the reported among Chinese, a population with a much higher frequency of the risk allele.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Proteínas de Membrana/genética , Proteínas de Ligação a RNA/genética , Idoso , /epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Lineares , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Polimorfismo Genético , Proteínas de Ligação a RNA/sangue , Fatores de Risco
4.
Int J Mol Sci ; 21(24)2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33322837

RESUMO

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , Metilação de DNA , Genes Supressores de Tumor , Proteínas de Membrana/sangue , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Regulação para Cima
5.
Maturitas ; 140: 64-71, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32972637

RESUMO

OBJECTIVES: Progesterone receptor membrane component-1 (PGRMC1) in breast cancer tissue has been suggested to predict a worse prognosis. The aim of this study was to assess for the first time whether PGRMC1 expressed in cancer tissue is associated with PGRMC1 blood concentrations and whether both are correlated with clinical tumour characteristics known to predict a worse outcome. METHODS: In total, 201 patients with invasive breast cancer and 65 with benign breast disease (control group) were recruited. PGRMC1 blood concentrations were measured by a recently developed ELISA, PGRMC1 in breast cancer tissue was assessed by immunohistochemistry, and the correlation between the two was calculated. Receiver-operating characteristic (ROC) curve analysis was used to assess area under the curve (AUC). Furthermore, PGRMC1 was correlated with tumour characteristics such as tumour diameter, tumour grade and metastatic status, and with known blood tumour markers. RESULTS: AUC for the breast cancer group was 0.713, which was significantly higher than in the control group (p < 0.01). Blood PGRMC1 concentrations had a strong (positive) correlation with tissue PGRMC1 expression (p < 0.01) but were not associated with serum tumour markers CEA, CA125, CA153 and TPS. Tissue PGRMC1, ER and cancer stage were positively associated with blood PGRMC1 (p < 0.05). CONCLUSIONS: As PGRMC1 expression levels in cancer tissue were significantly correlated with PGRMC1 in blood, and because concentrations in blood were also positively associated with breast tumour characteristics known to predict a worse prognosis, PGRMC1 may be valuable as a new tumour marker and may be superior to known tumour markers such as CEA, CA125, CA153 and TPS.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismo , Receptores de Progesterona/sangue , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
6.
Medicine (Baltimore) ; 99(38): e21840, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957308

RESUMO

BACKGROUND: The prognostic significance of preoperative prognostic nutritional index (PNI) in ovarian cancer (OC) is uncertain, and this study is aimed to clarify the prognostic significance. METHODS: We used 4 common databases for conducting a systematic review and meta-analysis, and eligible studies were included in the analysis. The association of preoperative PNI with overall survival (OS), progression-free survival (PFS), and clinicopathological parameters was analyzed. RESULTS: A total of 2050 patients with OC receiving the surgical treatment were analyzed in this study. Patients with low PNI tended to have a shorter OS (hazard ratio [HR] = 1.82, 95% CI = 1.30-2.55, P < .01) and PFS (HR = 1.91, 95% CI = 1.53-2.39, P < .01) compared with those with high PNI. Besides, low PNI was significantly associated with more advanced International Federation of Gynecology and Obstetrics stage (P < .01), the occurrence of ascites (P < .01), larger residual tumor (P < .01), insensitive to chemotherapy (P < .01), and higher CA125 (P < .01) compared with high PNI in OC. CONCLUSION: Low preoperative PNI is associated with shorter OS, shorter PFS, and worse clinicopathological parameters in OC. Low preoperative PNI is an unfavorable prognostic indicator of patients with OC.


Assuntos
Estado Nutricional/fisiologia , Neoplasias Ovarianas/mortalidade , Antígeno Ca-125/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Proteínas de Membrana/sangue , Prognóstico , Modelos de Riscos Proporcionais
7.
PLoS One ; 15(8): e0237074, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790694

RESUMO

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087-2,408) pg/ml as compared to CAD controls 2,259 (1,533-3,778) pg/ml and healthy adults 3,904 (2,732-5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-α, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Proteínas de Membrana/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
8.
BMJ ; 370: m2614, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732303

RESUMO

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.


Assuntos
Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Modelos Logísticos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Calibragem , Tratamento Conservador , Neoplasias das Tubas Uterinas/terapia , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Ovariectomia , Estudos Prospectivos , Medição de Risco/métodos , Ultrassonografia , Adulto Jovem
9.
PLoS One ; 15(6): e0234465, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544194

RESUMO

Obesity leads a crucial importance in metabolic disorders, as well as type 2 diabetes mellitus. Our present study was designed to assess the potential role of irisin, adiponectin, leptin and gene polymorphism of PNPLA3, leptin and adiponectin as predictive markers of diabetes associated with obesity. One hundred eighty subjects were distributed to three groups including; healthy non-diabetic non obese volunteers as a control group, diabetic non obese group, and diabetic obese group (n = 60 for each group). Fasting blood samples of all groups were collected to determine fasting blood glucose, insulin levels, insulin resistance, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triacylglycerol, irisin, adiponectin, leptin; as well as, polymorphism of PNPLA3, adiponectin and leptin. The results showed that glucose, insulin resistance, total cholesterol, irisin, leptin, LDL-C, triacylglycerol concentrations were significantly increased, however, insulin, HDL-C, adiponectin were significantly decreased in diabetic obese patients in relation to diabetic non-obese patients as well as in healthy volunteers. The polymorphism of PNPLA3 rs738409 was linearly related to irisin and leptin but was not related with circulating concentrations of adiponectin. We concluded that increased irisin and leptin levels can predict the insulin resistance in obese patients. Moreover, patients who have mutant genotype of PNPLA3 I148 gene (rs738409) C>G, ADIPOQ gene (rs266729) G>C and LEP gene (rs2167270) G>A showed a significant higher susceptibility rate for DM in obese people than those with wild type. This could be considered as an adjustable retort to counter the impact of obesity on glucose homeostasis.


Assuntos
Adiponectina/genética , Diabetes Mellitus Tipo 2/etiologia , Predisposição Genética para Doença , Resistência à Insulina/genética , Leptina/genética , Lipase/genética , Proteínas de Membrana/genética , Obesidade/complicações , Obesidade/genética , Adiponectina/sangue , Adulto , Feminino , Fibronectinas/sangue , Fibronectinas/genética , Marcadores Genéticos , Humanos , Leptina/sangue , Lipase/sangue , Masculino , Proteínas de Membrana/sangue , Polimorfismo Genético , Adulto Jovem
10.
Neurology ; 94(22): e2290-e2301, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32424051

RESUMO

OBJECTIVE: To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies. METHODS: Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease. RESULTS: Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy. CONCLUSION: High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.


Assuntos
Autoanticorpos/sangue , Autoimunidade/fisiologia , Encefalopatias/sangue , Hipertensão/sangue , Proteínas de Membrana/sangue , Proteínas do Tecido Nervoso/sangue , Siringomielia/sangue , Adolescente , Autoanticorpos/imunologia , Encefalopatias/imunologia , Encefalopatias/terapia , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/imunologia , Hipertensão/terapia , Imunoterapia/métodos , Lactente , Masculino , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Estudos Retrospectivos , Siringomielia/imunologia , Siringomielia/terapia
11.
Pediatrics ; 145(6)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32444380

RESUMO

A previously healthy 15-year-old boy presented with 3 months of progressive psychosis, insomnia, back and groin pain, and hyperhidrosis. On examination, the patient was disheveled, agitated, and soaked with sweat, with systolic blood pressure in the 160s and heart rate in the 130s. Aside from occasional auditory and visual hallucinations, his neurologic examination was normal. The patient was admitted for an extensive workup, including MRI of the brain and spine and lumbar puncture, which were normal. Through collaboration with various pediatric specialists, including psychiatry and neurology, a rare diagnosis was ultimately unveiled.


Assuntos
Autoanticorpos/sangue , Hiperidrose/sangue , Proteínas de Membrana/sangue , Proteínas do Tecido Nervoso/sangue , Transtornos Psicóticos/sangue , Índice de Gravidade de Doença , Siringomielia/sangue , Doença Aguda , Adolescente , Diagnóstico Diferencial , Humanos , Hiperidrose/diagnóstico por imagem , Hiperidrose/etiologia , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/etiologia , Siringomielia/complicações , Siringomielia/diagnóstico por imagem
12.
Zhonghua Zhong Liu Za Zhi ; 42(4): 331-335, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375450

RESUMO

Objective: To investigate the clinicopathological characteristics and outcomes of a series of ovarian metastases of pancreatic ductal adenocarcinoma. Methods: Data of clinical manifestation, pathological characteristic, treatment and follow-up result from ten patients with ovarian metastases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed. Results: The median age of onset was 46 years (38~79 years). The primary tumors were located in the body and tail of the pancreas in 8 cases. Bilateral ovarian metastasis occurred in 8 patients at the time of diagnosis. The median time from patients with clinical symptom to ovarian metastases was 2.5 months (0~12 months). Peritoneal metastasis was found in all of 10 cases. Nine cases were accompanied by CA125 elevation. The major features of metastatic carcinoma in the ovary were cystic-solid appearance (8 cases) and mucinous adenocarcinoma (6 cases) with no obvious immunohistochemical features in pathological observation. All patients underwent palliative ovariectomy at onset, and one patient underwent primary tumor resection simultaneously. Seven patients received chemotherapy. The median survival time of the 10 patients was 10.3 months. Conclusions: Ovarian metastases of pancreatic ductal adenocarcinoma are easily misdiagnosed. The final diagnosis depends on clinical manifestations, imaging and histopathological observation. Ovariectomy may be associated with better outcome.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Tumor de Krukenberg/patologia , Metástase Neoplásica/patologia , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/mortalidade , Adulto , Idoso , Antígeno Ca-125/sangue , Carcinoma Ductal Pancreático/mortalidade , China/epidemiologia , Feminino , Humanos , Tumor de Krukenberg/mortalidade , Tumor de Krukenberg/secundário , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/secundário , Ovário/patologia , Estudos Retrospectivos
13.
PLoS One ; 15(4): e0231555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315321

RESUMO

The proline-specific enzymes dipeptidyl peptidase 4 (DPP4), prolylcarboxypeptidase (PRCP), fibroblast activation protein α (FAP) and prolyl oligopeptidase (PREP) are known for their involvement in the immune system and blood pressure regulation. Only very limited information is currently available on their enzymatic activity and possible involvement in patients with sepsis and septic-shock. The activity of the enzymes was measured in EDTA-plasma of patients admitted to the intensive care unit (ICU): 40 septic shock patients (sepsis-2) and 22 ICU control patients after major intracranial surgery. These data were used to generate receiver operating characteristic (ROC) curves. A survival analysis (at 90 days) and an association study with other parameters was performed. PRCP (day 1) and PREP (all days) enzymatic activities were higher in septic shock patients compared to controls. In contrast, FAP and DPP4 were lower in these patients on all studied time points. Since large differences were found, ROC curves were generated and these yielded area under the curve (AUC) values for PREP, FAP and DPP4 of 0.88 (CI: 0.80-0.96), 0.94 (CI: 0.89-0.99) and 0.86 (CI: 0.77-0.95), respectively. PRCP had a lower predicting value with an AUC of 0.71 (CI: 0.58-0.83). A nominally significant association was observed between survival and the DPP4 enzymatic activity at day 1 (p<0.05), with a higher DPP4 activity being associated with an increase in survival. All four enzymes were dysregulated in septic shock patients. DPP4, FAP and PREP are good in discriminating between septic shock patients and ICU controls and should be further explored to see whether they are already dysregulated in earlier stages, opening perspectives for their further investigation as biomarkers in sepsis. DPP4 also shows potential as a prognostic biomarker. Additionally, the associations found warrant further research.


Assuntos
Carboxipeptidases/sangue , Dipeptidil Peptidase 4/sangue , Gelatinases/sangue , Proteínas de Membrana/sangue , Serina Endopeptidases/sangue , Choque Séptico/sangue , Choque Séptico/enzimologia , Área Sob a Curva , Biomarcadores/sangue , Cuidados Críticos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prolina/metabolismo , Estudos Prospectivos , Curva ROC , Choque Séptico/mortalidade , Choque Séptico/terapia , Análise de Sobrevida
14.
Gynecol Oncol ; 157(2): 521-528, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145911

RESUMO

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.


Assuntos
Antígeno Ca-125/sangue , Proteínas de Membrana/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico por imagem , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Adulto , Algoritmos , Biomarcadores Tumorais/sangue , Estudos de Viabilidade , Feminino , Humanos , Cooperação do Paciente , Projetos Piloto , Risco , Ultrassonografia , Conduta Expectante/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-32139603

RESUMO

BACKGROUND AND AIM: Imaging-confirmed non-alcoholic fatty liver disease (NAFLD) with normal alanine aminotransferase (nALT) levels is infrequently the subject for further evaluation. Early diagnosis of non-alcoholic steatohepatitis (NASH) is needed to prevent disease progression. Thus, we tested the clinical utility of serum Golgi protein 73 (GP73) levels and developed a new non-invasive score to diagnose NASH in patients with biopsy-confirmed NAFLD and persistent nALT levels. METHODS: Serum GP73 and cytokeratin-18 M30 fragments (CK18-M30) levels were measured in 345 patients with biopsy-proven NAFLD. We developed a new score, named G-NASH model (by incorporating serum GP73), and combined it with serum CK18-M30 measurement in a sequential non-invasive approach to accurately identify NASH among patients with NAFLD and persistent nALT levels. RESULTS: 105 (30.4%) patients had persistent nALT, 53 of whom had histologically confirmed NASH. Both serum GP73 and CK18-M30 levels alone had poor diagnostic accuracy in identifying NASH (55.2% and 51.6%, respectively) in these patients. Conversely, G-NASH model performed better than other established non-invasive scoring systems, and by using our proposed sequential non-invasive approach 82.9% of patients with NASH were correctly identified. CONCLUSIONS: NASH is highly prevalent in patients with NAFLD with persistent nALT levels. The G-NASH model accurately identifies NASH in this patient group.


Assuntos
Alanina Transaminase/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Queratina-18/sangue , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Sensibilidade e Especificidade
16.
Gynecol Oncol ; 157(2): 398-404, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32063274

RESUMO

OBJECTIVE: To compare the efficacy of ascitic fluid cell block (ACB) with that of core needle biopsy (CNB) or the CA125/CEA ratio in diagnosing primary tubo-ovarian cancer in female patients with peritoneal carcinomatosis (PC) with ascites. METHODS: This retrospective study examined female patients with PC with ascites who had available results for ACB, peritoneal tumor CNB, and the CA125/CEA ratio. Several measures of the accuracy of ACB and the CA125/CEA ratio were calculated and compared, with CNB as the reference standard. RESULTS: Of 81 patients with available results, 57 were clinically diagnosed with primary tubo-ovarian cancer. Overall, 52, 47, and 64 patients were diagnosed via CNB, ACB, and CA125/CEA ratio > 25, respectively. CNB and ACB identified the cancer origin in 91.4% and 82.7% cases, respectively. The concordance ratio of the immunohistochemical findings between ACB and CNB was 93.6%. Two patients with inconclusive CNB results were diagnosed with primary tubo-ovarian cancer via ACB. The sensitivity, specificity, positive predictive value, negative predictive value, and positive likelihood ratio were 86.5%, 93.1%, 95.7%, 79.4%, and 12.5, respectively, for ACB and 94.2%, 48.3%, 76.6%, 82.4%, and 1.82, respectively, for CA125/CEA ratio > 25. CONCLUSIONS: ACB is not inferior to CNB in diagnosing primary tubo-ovarian cancer; the two methods complement each other. ACB can substitute CNB in diagnosing primary tubo-ovarian cancer in selected PC patients. ACB is superior to a CA125/CEA ratio of >25 in diagnosing primary tubo-ovarian cancer. ACB is effective, reliable, and convenient for diagnosing primary tubo-ovarian cancer in PC patients with ascites.


Assuntos
Adenocarcinoma/patologia , Líquido Ascítico/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Antígeno Ca-125/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/diagnóstico , Estudos Retrospectivos
17.
Dis Markers ; 2020: 6036904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089754

RESUMO

Aims: Persistent hepatic necroinflammatory damage almost always results in fibrosis/cirrhosis or even hepatocellular carcinoma. Therefore, the presence of active necroinflammation in the liver suggests that nonalcoholic fatty liver disease (NAFLD) patients are in urgent need of treatment. Unfortunately, alanine transaminase (ALT), a routine indicator of liver inflammatory damage, showed a poor performance in nonalcoholic steatohepatitis (NASH) patients. Thus, it will be valuable to find an alternative indicator to identify patients with hepatic necroinflammatory damage. In this study, we evaluated the diagnostic value of serum Golgi protein 73 (GP73) for hepatic necroinflammatory damage in patients with NASH. Methods: The clinical data of 201 patients with NASH diagnosed by liver biopsy according to the Brunt staging system were collected retrospectively. The in situ expression of GP73 protein was measured by immunohistochemistry. The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUROC) of serum GP73 for diagnosing hepatic necroinflammatory damage. Results: The serum GP73 levels of NASH patients increased with the aggravation of liver necroinflammation. The median levels significantly increased from 49.98 ng/ml (31.49, 75.05) for G0-1 to 76.61 ng/ml (48.68, 110.03) for G2 and to 116.44 ng/ml (103.41, 162.17) for G3 patients (G0-1 vs. G2, P < 0.0001; G2 vs. G2, P < 0.0001; G2. Conclusions: GP73 is a valuable alternative serum marker reflecting the severity of hepatic necroinflammation in NASH patients.


Assuntos
Biomarcadores/sangue , Inflamação/diagnóstico , Cirrose Hepática/diagnóstico , Proteínas de Membrana/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Curva ROC , Estudos Retrospectivos , Adulto Jovem
18.
Cancer Biomark ; 27(4): 485-491, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32065786

RESUMO

BACKGROUND: Ovarian cancer (OC) is one of the most common malignancy worldwide. Emerging evidences have demonstrated that microRNAs (miRNAs) play an important role in regulating the initiation and development of OC. OBJECTIVE: The present study was to explore the clinical significance of serum exosomal miR-484 in OC. METHODS: A total of 113 OC patients and 60 healthy volunteers were enrolled in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure serum exosomal miR-484 levels in blood samples. RESULTS: Our results showed that serum exosomal miR-484 levels were significantly lower in OC patients. Serum exosomal miR-484 was able to discriminate OC cases from controls, with an area under the receiver-operating characteristics (ROC) curve (AUC) of 0.821. Combination of serum exosomal miR-484 with CA-125 showed an elevated AUC of 0.912 in identifying OC patients from controls. Moreover, decreased serum exosomal miR-484 expression was significantly associated with aggressive clinical variables as well as shorter overall survival and progression-free survival. The OC patients with simultaneously low serum exosomal miR-484 expression and high serum CA-125 levels tended to suffer the worst clinical outcomes. The multivariate analysis confirmed that low serum exosomal miR-484 level was an independent indicator. CONCLUSIONS: Collectively, serum exosomal miR-484 could serve as a reliable and non-invasive marker for predicting the prognosis of OC.


Assuntos
Exossomos/metabolismo , MicroRNAs/sangue , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Antígeno Ca-125/sangue , Estudos de Casos e Controles , Exossomos/genética , Feminino , Humanos , Proteínas de Membrana/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Prognóstico , Curva ROC , Taxa de Sobrevida
19.
J Ovarian Res ; 13(1): 17, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050995

RESUMO

OBJECTIVE: The aim of this study is to establish a noninvasive preoperative model for predicting primary optimal cytoreduction in advanced epithelial ovarian cancer by HE4 and CA125 combined with clinicopathological parameters. METHODS: Clinical data including preoperative serum HE4 and CA125 level of 83 patients with advanced epithelial ovarian cancer were collected. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of each clinical parameter were calculated. The Predictive Index score model and the logistic model were constructed to predict the primary optimal cytoreduction. RESULTS: Optimal surgical cytoreduction was achieved in 62.65% (52/83) patients. Cutoff values of preoperative serum HE4 and CA125 were 777.10 pmol/L and 313.60 U/ml. (1) Patients with PIV ≥ 6 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing suboptimal cytoreduction were 71, 100, 68, and 100%, respectively. (2) The logistic model was: logit p = 0.12 age - 2.38 preoperative serum CA125 level - 1.86 preoperative serum HE4 level-2.74 histological type-3.37. AUC of the logistic model in the validation group was 0.71(95%CI 0.54-0.88, P = 0.025). Sensitivity and specificity were 1.00 and 0.44, respectively. CONCLUSION: Age, preoperative serum CA125 level and preoperative serum HE4 level are important non-invasive predictors of primary optimal surgical cytoreduction in advanced epithelial ovarian cancer. Our PIV and logistic model can be used for assessment before expensive and complex predictive methods including laparoscopy and diagnostic imaging. Further future clinical validation is needed.


Assuntos
Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/cirurgia , Proteínas de Membrana/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Resultado do Tratamento
20.
Zhonghua Gan Zang Bing Za Zhi ; 28(1): 47-52, 2020 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-32023699

RESUMO

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.


Assuntos
Biomarcadores/metabolismo , Cirrose Hepática/diagnóstico , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Aspartato Aminotransferases/metabolismo , Biópsia , Fibrose , Hepatite B , Humanos , Fígado/patologia , Proteínas de Membrana/sangue , Curva ROC , Índice de Gravidade de Doença
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