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1.
Iran Biomed J ; 25(6): 381-9, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34641641

RESUMO

Background: Lung injury is common in coronavirus disease 2019 (COVID-19) patients. The severity of lung injury appears to be reflected in serum Krebs von den Lungen-6 (KL-6), a glycoprotein expressed on type II alveolar epithelium. This study aims to assess the role of serum KL-6 in reflecting the severity of lung injury in COVID-19 patients. Methods: A systematic search was conducted in Scopus, PubMed, Wiley Online Library, and ProQuest. Articles were screened based on several eligibility criteria and assessed for study quality using Newcastle-Ottawa Scale. Results: This systematic review included four studies involving a total of 151 adult COVID-19 patients. Pooled analysis revealed that serum KL-6 was significantly higher in severe patients (SMD = 1.16; 95% CI = 0.69­1.63) with moderately high pooled sensitivity (79%; 95% CI = 61­91%) and specificity (86%; 95% CI = 72­95%). Conclusion: High serum KL-6 may depict more severe lung injury in COVID-19 patients with moderately high sensitivity and specificity.


Assuntos
COVID-19/complicações , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/virologia , Mucina-1/sangue , Índice de Gravidade de Doença , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , Humanos , Lesão Pulmonar/sangue , Sensibilidade e Especificidade
2.
Sci Rep ; 11(1): 19979, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620968

RESUMO

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.


Assuntos
COVID-19/sangue , Mucina-1/sangue , Fibrose Pulmonar/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores/sangue , COVID-19/complicações , COVID-19/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , SARS-CoV-2/isolamento & purificação
3.
Medicine (Baltimore) ; 100(43): e27693, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713867

RESUMO

ABSTRACT: The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, P < .001, and P < .001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, P < .001, P < .001, P = .032, P = .041, P < .001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15-3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001-1.005; OR = 1.025, 95% CI: 1.019-1.033; OR = 0.238, 95% CI: 0.112-0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15-3 and LDL were 16.78 0 U/mL, 63.175 U/mL, and 2.415 mmol/L, respectively. The combination of CA-125 and CA15-3 showed significant diagnostic value (area under the curve [AUC] = 0.982, P < .001). Our investigation suggests that CA-125, CA15-3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15-3 shows considerable diagnostic value.


Assuntos
Neoplasias da Mama/patologia , Antígeno Ca-125/sangue , Neoplasias Oculares/secundário , Lipoproteínas LDL/sangue , Mucina-1/sangue , Pós-Menopausa/fisiologia , Fatores Etários , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC
4.
Cytokine ; 148: 155513, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34507246

RESUMO

The clinical relevance of Krebs von den Lungen-6 (KL-6) levels in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to evaluate the correlation between KL-6 levels, laboratory parameters, and clinical outcomes. We enrolled 364 patients with confirmed COVID-19 who were hospitalized within 1 week of symptom onset. Their serum KL-6 level was measured on admission. Demographic data, symptoms, comorbidities, and laboratory parameters were recorded at the time of admission. Days to nucleic acid conversion and days of hospitalization were defined as clinical outcomes for evaluating the clinical relevance of serum KL-6 levels in COVID-19. Patients with elevated KL-6 levels were significantly older; had more reported instances of fever, cough, fatigue, and wheezing; and a longer hospital stays than those with normal KL-6 levels; the difference was statistically significant (p < 0.001). Furthermore, KL-6 levels was associated with the days of hospitalization and various laboratory parameters that influence the severity and prognosis of COVID-19. Elevated KL-6 levels have also been shown to be an independent risk factor for prolonged hospitalization. Our data suggest that serum KL-6 levels on admission can serve as an indicator for assessing the clinical outcomes of COVID-19.


Assuntos
COVID-19/sangue , Mucina-1/sangue , Idoso , COVID-19/virologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , SARS-CoV-2/fisiologia , Resultado do Tratamento
5.
Sci Rep ; 11(1): 16548, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400692

RESUMO

Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9-14.8, HR = 7.8 95% CI 2.4-25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6-52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Mucina-1/sangue , Cardiomiopatia de Takotsubo/sangue , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Doenças Cardiovasculares/mortalidade , Comorbidade , Feminino , Seguimentos , Ventrículos do Coração , Mortalidade Hospitalar , Hospitalização , Humanos , Interleucinas/sangue , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prognóstico , Edema Pulmonar/epidemiologia , Respiração Artificial/estatística & dados numéricos , Choque Cardiogênico/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Trombose/epidemiologia , Troponina I/sangue
6.
BMC Pulm Med ; 21(1): 165, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992083

RESUMO

BACKGROUND: Nintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes. METHODS: We analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined. RESULTS: Fifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13-10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89-19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63-12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16-24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06-73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline. CONCLUSIONS: For patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.


Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/uso terapêutico , Mucina-1/sangue , Proteína A Associada a Surfactante Pulmonar/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Fibrose Pulmonar Idiopática/sangue , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
7.
J Med Virol ; 93(9): 5405-5408, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33932304

RESUMO

The new type of coronavirus could cause severe acute respiratory syndrome and injuries in other systems as well. Multiple organ damage can occur rapidly in patients infected with coronavirus disease 2019 (COVID-19). Previous studies have shown that many laboratory biomarkers were not within the normal ranges in COVID-19 patients. We aimed to summarize laboratory parameters and the tumor markers in COVID-19 patients. This is a retrospective cohort study conducted on 53 women between the ages of 19-85 years infected with COVID-19 at a training and research hospital between May 2020 and August 2020. Of the 53 women, 16 (30.2%) had leukopenia. The mean C-reactive protein level was 18.42 ± 59.33 mg/L. The mean procalcitonin level was 0.1 ± 0.21 µg/L. The liver function tests were within normal limits. The mean creatinine level was 0.58 ± 0.37 mg/dl. Elevated levels of α-fetoprotein (AFP) in 1 patient, elevated levels of carcinoembryonic antigen (CEA) in 2 patients, elevated levels of cancer antigen 125 (CA125) in 4 patients, elevated levels of CA19-9 in 2 patients, and elevated levels of CA15-3 in 2 patients were detected. One of 4 patients who were taken to the intensive care unit had elevated levels of AFP. In addition, 2 of 4 patients who were taken to the intensive care unit had elevated levels of CA125 and CA15-3. Except for AFP, levels of all tumor markers of the patient who died were high. We found that COVID-19 had no effect on tumor markers (CA125, CA19-9, CA15-3, AFP, and CEA).


Assuntos
Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , COVID-19/sangue , Antígeno Carcinoembrionário/sangue , Leucopenia/sangue , Mucina-1/sangue , Pandemias , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Leucopenia/diagnóstico , Leucopenia/virologia , Linfócitos/virologia , Pessoa de Meia-Idade , Neutrófilos/virologia , Pró-Calcitonina/sangue , Estudos Retrospectivos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade , Troponina/sangue , Turquia/epidemiologia
8.
Anal Bioanal Chem ; 413(15): 4049-4061, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34057557

RESUMO

In the clinical diagnosis of tumors, a single-marker immunoassay may lead to false results. Thus there is a need for an effective and valid method for the simultaneous measurement of multiple tumor markers. In this work, an efficient fluorescence immunosensor for the simultaneous measurement of CA125 and CA15-3 tumor markers was fabricated by utilizing the high selectivity of magnetic molecularly imprinted polymers (MMIPs) and the high sensitivity of a fluorescence (FL) method. Ni nanoclusters (Ni NCs) and noble Cd nanoclusters (Cd NCs) were introduced as efficient and economic emitters, and magnetic graphene oxide (GO-Fe3O4) was applied as a support material for surface molecularly imprinted polymers. Under the most favorable experimental conditions, the fluorescence intensity of the Cd NCs and Ni NCs gradually increased with increasing concentration of CA125 and CA15-3 antigens at a range of 0.0005-40 U mL-1, respectively, with a limit of detection (LOD) of 50 µU mL-1. The developed method had excellent properties including a broad linear range, good reproducibility, and simple operation for the clinical diagnosis of CA 125 and CA 15-3 tumor markers. This molecularly imprinted fluorescence sensor has the potential to be an effective clinical tool for the timely screening of breast cancer in human serum samples and OVCAR-3 and MCF-7 cell lines, and can be applied in clinical diagnostics.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Cádmio/química , Corantes Fluorescentes/química , Mucina-1/sangue , Níquel/química , Espectrometria de Fluorescência/métodos , Linhagem Celular Tumoral , Humanos , Limite de Detecção , Impressão Molecular , Reprodutibilidade dos Testes
9.
BMC Cancer ; 21(1): 466, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902502

RESUMO

BACKGROUND: It is reported that appropriately 50% of early breast cancer patients with 1-2 positive sentinel lymph node (SLN) micro-metastases could not benefit from axillary lymph node dissection (ALND) or breast-conserving surgery with whole breast irradiation. However, whether patients with 1-2 positive SLN macro-metastases could benefit from ALND remains unknown. The aim of our study was to develop and validate nomograms for assessing axillary non-SLN metastases in patients with 1-2 positive SLN macro-metastases, using their pathological features alone or in combination with STMs. METHODS: We retrospectively reviewed pathological features and STMs of 1150 early breast cancer patients from two independent cohorts. Best subset regression was used for feature selection and signature building. The risk score of axillary non-SLN metastases was calculated for each patient as a linear combination of selected predictors that were weighted by their respective coefficients. RESULTS: The pathology-based nomogram possessed a strong discrimination ability for axillary non-SLN metastases, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.727 (95% CI: 0.682-0.771) in the primary cohort and 0.722 (95% CI: 0.653-0.792) in the validation cohort. The addition of CA 15-3 and CEA can significantly improve the performance of pathology-based nomogram in the primary cohort (AUC: 0.773 (0.732-0.815) vs. 0.727 (0.682-0.771), P < 0.001) and validation cohort (AUC: (0.777 (0.713-0.840) vs. 0.722 (0.653-0.792), P < 0.001). Decision curve analysis demonstrated that the nomograms were clinically useful. CONCLUSION: The nomograms based on pathological features can be used to identify axillary non-SLN metastases in breast cancer patients with 1-2 positive SLN. In addition, the combination of STMs and pathological features can identify patients with patients with axillary non-SLN metastases more accurately than pathological characteristics alone.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/patologia , Nomogramas , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Axila , Neoplasias da Mama/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Mucina-1/sangue , Micrometástase de Neoplasia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Biópsia de Linfonodo Sentinela
10.
J Med Virol ; 93(7): 4559-4563, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33811680

RESUMO

Coronavirus disease 2019 (COVID-19) is globally rampant, and to curb the growing burden of this disease, in-depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID-19 patients, based on disease severity. We included 72 consecutive COVID-19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild-Moderate I (mild) and Moderate II-Severe (severe) groups based on the COVID-19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d-dimer, lactate dehydrogenase, C-reactive protein, ferritin, Krebs von den Lungen-6, surfactant protein (SP)-D, and SP-A than the mild group. Strikingly, the levels of interleukin (IL)-28A/interferon (IFN)-λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN-λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.


Assuntos
COVID-19/sangue , Quimiocinas/sangue , Interferons/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Proteína C-Reativa/análise , COVID-19/patologia , Regulação para Baixo , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Interferons/biossíntese , Interleucinas/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Proteína A Associada a Surfactante Pulmonar/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Índice de Gravidade de Doença
11.
ACS Appl Mater Interfaces ; 13(18): 21030-21039, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33905228

RESUMO

The characterization of circulating tumor cells (CTCs) by liquid biopsy has a great potential for precision medicine in oncology. Here, a universal and tandem logic-based strategy is developed by combining multiple nanomaterials and nanopore sensing for the determination of mucin 1 protein (MUC1) and breast cancer CTCs in real samples. The strategy consists of analyte-triggered signal conversion, cascaded amplification via nanomaterials including copper sulfide nanoparticles (CuS NPs), silver nanoparticles (Ag NPs), and biomaterials including DNA hydrogel and DNAzyme, and single-molecule-level detection by nanopore sensing. The amplification of the non-DNA nanomaterial gives this method considerable stability, significantly lowers the limit of detection (LOD), and enhances the anti-interference performance for complicated samples. As a result, the ultrasensitive detection of MUC1 could be achieved in the range of 0.0005-0.5 pg/mL, with an LOD of 0.1 fg/mL. Moreover, we further tested MUC1 as a biomarker for the clinical diagnosis of breast cancer CTCs under double-blind conditions on the basis of this strategy, and MCF-7 cells could be accurately detected in the range from 5 to 2000 cells/mL, with an LOD of 2 cells/mL within 6 h. The detection results of the 19 clinical samples were highly consistent with those of the clinical pathological sections, nuclear magnetic resonance imaging, and color ultrasound. These results demonstrate the validity and reliability of our method and further proved the feasibility of MUC1 as a clinical diagnostic biomarker for CTCs.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , DNA/metabolismo , Mucina-1/sangue , Nanoporos , Células Neoplásicas Circulantes , Humanos , Limite de Detecção , Células MCF-7 , Reprodutibilidade dos Testes
12.
PLoS One ; 16(4): e0249607, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914762

RESUMO

INTRODUCTION: Acute presentations of COVID-19 infection vary, ranging from asymptomatic carriage through to severe clinical manifestations including acute respiratory distress syndrome (ARDS). Longer term sequelae of COVID-19 infection includes lung fibrosis in a proportion of patients. Krebs von den Lungen 6 (KL-6) is a mucin like glycoprotein that has been proposed as a marker of pulmonary epithelial cell injury. We sought to determine whether KL-6 was a marker of 1) the severity of acute COVID-19 infection, or 2) the persistence of symptoms/radiological abnormalities at medium term follow up. METHODS: Prospective single centre observational study. RESULTS: Convalescent KL-6 levels were available for 93 patients (male 63%, mean age 55.8 years) who attended an 12-week follow up appointment after being admitted to hospital with COVID-19. For 67 patients a baseline KL-6 result was available for comparison. There was no significant correlations between baseline KL-6 and the admission CXR severity score or clinical severity NEWS score. Furthermore, there was no significant difference in the baseline KL-6 level and an initial requirement for oxygen on admission or the severity of acute infection as measured at 28 days. There was no significant difference in the 12-week KL-6 level and the presence or absence of subjective breathlessness but patients with abnormal CT scans at 12 weeks had significantly higher convalescent KL-6 levels compared to the remainder of the cohort (median 1101 IU/ml vs 409 IU/ml). CONCLUSIONS: The association between high KL-6 levels at 12 weeks and persisting CT abnormalities (GGO/fibrosis), is a finding that requires further exploration. Whether KL-6 may help differentiate those patients with persisting dyspnoea due to complications rather than deconditioning or dysfunctional breathing alone, is an important future research question.


Assuntos
COVID-19/sangue , Mucina-1/sangue , Adulto , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico por imagem , COVID-19/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
13.
Sci Rep ; 11(1): 6564, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753802

RESUMO

Breast cancer (BC) is one of the most dangerous malignant diseases in females. However, the reliable serum biomarkers of BC still need to be explored. Chemerin levels have been found to be associated with different types of cancer. This study aimed to evaluate the role of serum chemerin as a biomarker of BC diagnosis, as well as the correlation between serum chemerin levels and clinicopathological features. The serum from 248 BC patients, 30 breast benign tumor patients, and 103 healthy controls were collected and serum chemerin levels were determined with enzyme-linked immunosorbent assay. We found that serum levels of chemerin in BC patients were higher than those in healthy control individuals (p < 0.05). The area under the ROC curve (AUC) for chemerin, CA15-3 and CEA was 0.703, 0.662 and 0.581, respectively, in distinguishing between breast cancer patients from healthy individuals, and the chemerin cutoff value was 100.327 ng/ml with a sensitivity of 56.60% and a specificity of 98.10%. The AUC for chemerin + CA15-3 was 0.822, which was higher than that for chemerin + CEA and CEA + CA15-3. Moreover, serum levels of chemerin were significantly associated with histologic grade, Ki67 expression, and menopausal status. However, no significant association was found between serum levels of chemerin and age, tumor size, metastase, ER status, PR status, and HER-2 status. Overall, our study suggested that the combination of chemerin with CA15-3 achieves relatively better diagnostic performance in the breast cancer. Elevated serum chemerin is associated with Ki67 expression levels and histologic grade.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/sangue , Quimiocinas/sangue , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Mucina-1/sangue , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Adulto Jovem
14.
Sci Rep ; 11(1): 6651, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758208

RESUMO

The purpose of this study is to evaluate the levels and clinical diagnosis value of CA15-3, CEA, and SF in canine mammary gland tumors (CMGTs). In this study, the levels of tissues/serum CA15-3, CEA, and SF in 178 CMGT patients or healthy dogs were determined by ELISA and qRT-PCR assay. CA15-3, CEA, and SF levels of the malignant tumor group were significantly higher than that of the benign tumor group and the healthy control group. In the malignant tumor group, CA15-3 held a sensitivity of 51.8%, a specificity of 93.9%, and an accuracy of 76.8%. The sensitivity, specificity, and accuracy of CEA were 44.6%, 84.1%, and 68.1% respectively. SF held a sensitivity of 62.5%, a specificity of 85.4%, and an accuracy of 76.1%. SF showed the highest sensitivity and CA15-3 showed the highest specificity. The sensitivity, specificity, and accuracy of the combined detection of the three biomarkers in malignant tumor groups were 80.4%, 78.0%, and 80.0%, respectively, therefore combined detection increased sensitivity and accuracy but decreased specificity. In conclusion, the combined detection of serum/tissue markers CA15-3, CEA, and SF may improve the detection sensitivity of CMGTs, providing reference value for clinical application.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/veterinária , Antígeno Carcinoembrionário/sangue , Doenças do Cão/sangue , Doenças do Cão/diagnóstico , Ferritinas/sangue , Mucina-1/sangue , Animais , Biópsia , Doenças do Cão/epidemiologia , Cães , Feminino , Imuno-Histoquímica , Curva ROC , Sensibilidade e Especificidade
15.
Medicine (Baltimore) ; 100(10): e25054, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725891

RESUMO

ABSTRACT: Waterproofing spray-associated pneumonitis (WAP) proceeds to acute respiratory failure and is characterized by diffuse bilateral ground-glass opacities on computed tomography; however, the detailed characteristics of WAP are unknown. Therefore, this study identified the characteristics of WAP from comparisons with those of acute eosinophilic pneumonia (AEP) and hypersensitivity pneumonitis (HP), which show similar features to WAP.Adult patients with WAP, AEP, and HP treated in Fukujuji Hospital from 1990 to 2018 were retrospectively enrolled. Furthermore, data from patients with WAP were collected from publications in PubMed and the Japan Medical Abstracts Society and combined with data from our patients.Thirty-three patients with WAP, eleven patients with AEP, and thirty patients with HP were reviewed. Regarding age, sex, smoking habit, and laboratory findings (white blood cell count, C-reactive protein level, and serum Krebs von den Lungen-6 level), WAP and AEP were not significantly different, while WAP and HP were significantly different. The duration from symptom appearance to hospital visit was shorter in patients with WAP (median 1 day) than in patients with AEP (median 3 days, P = .006) or HP (median 30 days, P < .001). The dominant cells in the bronchoalveolar lavage fluid of patients with WAP, AEP, and HP were different (macrophages, eosinophils, and lymphocytes, respectively).The characteristic features of WAP were rapid disease progression and macrophage dominance in the bronchoalveolar lavage fluid, and these characteristics can be used to distinguish among WAP, AEP, and HP.


Assuntos
Lesão Pulmonar Aguda/diagnóstico , Alveolite Alérgica Extrínseca/diagnóstico , Polímeros de Fluorcarboneto/efeitos adversos , Eosinofilia Pulmonar/diagnóstico , Insuficiência Respiratória/etiologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/complicações , Adolescente , Adulto , Idoso , Alveolite Alérgica Extrínseca/sangue , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Proteína C-Reativa/análise , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Exposição por Inalação/efeitos adversos , Contagem de Leucócitos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Eosinofilia Pulmonar/sangue , Estudos Retrospectivos , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-33672761

RESUMO

KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at >1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6: 1188 U/mL vs. 260 U/mL, p < 0.001). KL-6 > 1000 U/mL resulted independently associated with death (aOR: 11.29, p < 0.05) with a positive predictive value of 83.3%. Our results suggest that KL-6 is a reliable indicator of pulmonary function and unfavourable outcome in patients with COVID-19 pneumonia. A KL-6 value > 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome. KL-6 may thus represent a quick, inexpensive, and sensitive parameter to stratify the risk of severe respiratory failure and death.


Assuntos
COVID-19/diagnóstico , Mucina-1/sangue , Biomarcadores/sangue , COVID-19/sangue , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Biomarkers ; 26(3): 268-274, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33554683

RESUMO

PURPOSE: To evaluate the utilisation of CA-125, CA-15.3 and CA-19.9 in differentiating between ovarian neoplasms and endometriomas, and the best cut-off value for these tumour markers in this differentiation. MATERIALS AND METHODS: Preoperative serum values of CA-125, CA-15.3 and CA-19.9 were evaluated in 265 patients undergoing surgery for adnexal masses, being 32 non-neoplastic lesions, 134 benign neoplasms, 19 borderline tumours, 36 malignant neoplasms, and 44 endometriomas. ROC curves and Univariate and multivariate analyses were performed. RESULTS: Only CA-19.9 was useful in differentiating between endometriomas and ovarian neoplasms (benign and malignant tumours), being this marker found at higher levels in endometriomas. In multivariate analyses, CA-19.9 greater than 22.3 U/mL was considered an independent factor for the diagnosis of endometrioma, comparing endometrioma and ovarian cancer. Comparing endometrioma and all other groups, the clustering analysis using the combination CA-125 > 34.28 U/mL and CA-19.9 > 19.12 U/mL demonstrated that this association was considered an independent factor for the diagnosis of endometrioma. CONCLUSION: CA-9.9 is useful in distinguishing between endometriomas and ovarian cancer, and its combination with CA-125 is useful in differentiating endometrioma from other ovarian lesions.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Ca-125/sangue , Endometriose/sangue , Proteínas de Membrana/sangue , Mucina-1/sangue , Neoplasias Ovarianas/sangue , Adolescente , Adulto , Idoso , Criança , Diagnóstico Diferencial , Endometriose/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
18.
Clin Chim Acta ; 517: 48-53, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33631198

RESUMO

OBJECTIVE: Coronavirus Disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, which may progress to pulmonary fibrosis (PF), leading to the worsen outcome. As the markers of lung injury, the correlation of Krebs von den Lungen-6 (KL-6) and fibronectin (Fn) with pulmonary fibrosis in COVID-19 was still unclear. METHODS: 113 patients diagnosed as COVID-19 were enrolled in this retrospective study, and divided into three categories as mild, moderate and severe cases. The concentrations of serum KL-6 and Fn at hospital admission were tested using the method of latex agglutination assay and immunoturbidimetic assay, respectively. RESULTS: Compared with that in the non-severe COVID-19 cases and normal control subjects, serum KL-6 concentration on admission was significantly higher in the severe group, which was positively correlated with C-reactive protein, and negatively correlated with lymphocytes count. Whereas, no obvious elevation in serum Fn concentration was investigated in COVID-19 patients with the different phenotypes. The severe cases displayed the higher incident rate of pulmonary fibrosis at hospital discharge. Compared with non-PF patients, the COVID-19 cases with PF had the higher serum KL-6 values. CONCLUSION: Serum KL-6 concentration was significantly elevated in severe COVID-19 patients, which may be useful for evaluating the disease severity. For early prevention of the development of pulmonary fibrosis, high concentrations of serum KL-6 in the early stage of COVID-19 should be paid close attention.


Assuntos
COVID-19 , Fibronectinas/sangue , Mucina-1/sangue , Fibrose Pulmonar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/sangue , Fibrose Pulmonar/diagnóstico , Estudos Retrospectivos , Adulto Jovem
19.
Cytokine ; 141: 155455, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33548798

RESUMO

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.


Assuntos
Biomarcadores/sangue , COVID-19/sangue , COVID-19/imunologia , Citocinas/sangue , Pandemias , SARS-CoV-2 , Idoso , Peptídeo C/sangue , Proteína C-Reativa/metabolismo , COVID-19/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mucina-1/sangue , Prognóstico , Índice de Gravidade de Doença
20.
Medicine (Baltimore) ; 100(4): e24260, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530214

RESUMO

ABSTRACT: Interstitial pneumonia with autoimmune features (IPAF) is a special subtype of interstitial lung disease that has received worldwide attention. Krebs von den Lungen-6 (KL-6) and surfactant protein-A (SP-A) can be used as an important biomarker of interstitial lung disease, but its exact relationship with IPAF is poorly understood.A total of 65 IPAF patients were included in the study and were followed up for 52 weeks. The KL-6 and SP-A were evaluated by chemiluminescence enzyme immunoassay. The above indicators were tested at 2 time points, baseline (the first admission of patients) and 52 weeks. We also collected the indicators of antinuclear antibodies and rheumatoid factor. Based on high-resolution computed tomography evaluations, patients were divided into: aggravation, stable, and improvement group. At same time, 30 age-matched normal people as normal control were recruited, the same information was collected. Correlations among the groups were compared and analyzed.The KL-6 and SP-A level in IPAF patients were significantly higher than normal controls (fold increase = 11.35 and 1.39, both P < .001) and differed significantly at baseline and 52 weeks in IPAF (difference ratio = 37.7% and 21.3%, P < .05, both). There were significant differences at baseline and 52 weeks (r values of aggravation, improvement, and stable groups for KL-6 were 0.705, 0.770, and 0.344, P = .001, .001, and .163, and for SP-A the r value were 0.672, 0.375, and 0.316, P = .001, .126, and .152). In aggravation group, KL-6 and SP-A were correlated with CT scores (both P < .05). Diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC), % predicted showed a progressive downward trend, with a significant difference at baseline and 52 weeks in IPAF patients (difference ratio = 23.8% and 20.6%, both P < .05). There was a significant correlation between KL-6 and FVC % predicted and DLCO (both P < .05), SP-A showed negatively correlated with DLCO, but not significantly correlated with FVC % predicted (P < .05 and .47).This study demonstrated that KL-6 and SP-A can reflect disease progression, and both 2 play a key role at reflection of lung epithelial cell injury and fibrosis degree in IPAF.


Assuntos
Doenças Pulmonares Intersticiais/sangue , Mucina-1/sangue , Proteína A Associada a Surfactante Pulmonar/sangue , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangue
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