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This article reported a case of an elderly female patient with diffuse lung lesions and multiple enlarged lymph nodes. In the early stages of diagnosis, many clues, obtained through cellular immunology and molecular biology tests on a variety of samples including blood and bronchoalveolar lavage fluid, pointed to the diagnosis of tuberculosis. At the same time, a peripheral lymph node biopsy was conducted, which led to the diagnosis of lymphoma coexisting with tuberculosis, a"dual-diagnosis". In the subsequent treatment, lymphoma therapy was actively pursued while the patient's tuberculosis infection was treated, with good results observed in the follow-up treatments. When diagnosing the disease, the differential diagnosis must be integrated into the overall disease process, and avoiding rigid adherence to a "unitary"diagnostic concept.
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Linfonodos , Humanos , Feminino , Linfonodos/patologia , Diagnóstico Diferencial , Idoso , Pulmão/patologia , Pulmão/diagnóstico por imagem , Linfoma/diagnóstico , Linfoma/patologia , Tuberculose Pulmonar/diagnósticoRESUMO
OBJECTIVE: To explore the mechanism underlying the protective effect of Lonicerae japonicae flos (LJF) extract against doxorubicin (DOX) -induced liver injury in mice. METHODS: Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets, based on which the protein-protein interaction (PPI) network was constructed using STRING database for screening the core targets using Cytoscape software. DAVID database was used for bioinformatics analysis, and the core components and core targets were verified using molecular docking study. In a mouse model of DOX-induced liver injury, the effect of LJF extract on liver pathologies, serum levels of ALT and AST, and hepatic expressions of HYP, ROS, TNF-α, IL-6, COL-â £ and P53 proteins were evaluated using HE and Masson staining, ELISA, and Western blotting. RESULTS: We identified 12 core targets from 43 intersection genes involving cancer pathway, IL-17 signaling pathway, and TNF signaling pathways. Molecular docking study suggested that 10 core components of LJF could bind to different core targets. The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis, increased ROS content, and enhanced expressions of TNF-α, IL-6, HYP, COL-â £ and P53 proteins in the liver tissue. All these changes in the mouse models were significantly alleviated by treatment with LJF extract, suggesting obviously lowered levels of oxidative stress, inflammation and fibrosis in the liver tissues. CONCLUSION: LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53, TNF and IL-6 to reduce liver oxidative stress, inflammation and fibrosis.
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Doença Hepática Induzida por Substâncias e Drogas , Doxorrubicina , Interleucina-6 , Lonicera , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa , Animais , Doxorrubicina/efeitos adversos , Camundongos , Lonicera/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Proteína Supressora de Tumor p53/metabolismo , Substâncias Protetoras/farmacologia , Mapas de Interação de Proteínas , Transdução de Sinais/efeitos dos fármacos , Farmacologia em RedeRESUMO
BACKGROUND AND AIMS: In autoimmune hepatitis, achieving complete biochemical remission (CBR) with current weight-based thiopurine dosing is challenging. We investigated whether patients could be stratified regarding CBR according to a target range of thiopurine metabolites. Moreover, we explored the effects of azathioprine dosage increases and co-therapy of allopurinol with low-dose thiopurines on metabolite profiles and treatment response. APPROACH AND RESULTS: The relation between metabolites and treatment response was assessed in 337 individuals from 4 European centers. In a global, cross-sectional analysis, active metabolites 6-thioguanine nucleotides (6TGN) were similar in those with and without CBR. However, analyzing patients with sequential measurements over 4 years (N = 146) revealed higher average 6TGN levels in those with stable CBR (260 pmol/0.2 mL) compared to those failing to maintain CBR (181 pmol/0.2 mL; p = 0.0014) or never achieving CBR (153 pmol/0.2 mL; p < 0.0001), with an optimal 6TGN cutoff of ≥223 pmol/0.2 mL (sensitivity: 76% and specificity: 78%). Only 42% exhibited 6TGN ≥223 pmol/0.2 mL following weight-based dosing, as doses weakly correlated with 6TGN but with 6-methylmercaptopurine (6MMP), a metabolite associated with toxicity. Azathioprine dose increases led to preferential 6MMP formation (+127% vs. 6TGN +34%; p < 0.0001). Conversely, adding allopurinol to thiopurines in difficult-to-treat patients (N = 36) raised 6TGN (168â321 pmol/0.2 mL; p < 0.0001) and lowered 6MMP (2125â184 pmol/0.2 mL; p < 0.0001), resulting in improved transaminases in all patients and long-term CBR in 75%. CONCLUSIONS: Maintaining CBR in autoimmune hepatitis was associated with 6TGN ≥223 pmol/0.2 mL. For patients who fail to achieve CBR and therapeutic 6TGN levels despite thiopurine dose increase due to preferential 6MMP formation, comedication of allopurinol alongside low-dose thiopurines represents an efficient alternative.
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Alopurinol , Azatioprina , Quimioterapia Combinada , Hepatite Autoimune , Imunossupressores , Mercaptopurina , Humanos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/sangue , Hepatite Autoimune/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Azatioprina/administração & dosagem , Azatioprina/uso terapêutico , Estudos Transversais , Adulto , Mercaptopurina/análogos & derivados , Mercaptopurina/administração & dosagem , Mercaptopurina/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Idoso , Tionucleotídeos/sangue , Nucleotídeos de Guanina/sangue , Nucleotídeos de Guanina/metabolismo , Monitoramento de Medicamentos/métodos , Resultado do Tratamento , Indução de Remissão/métodosRESUMO
The aim of this study was to investigate the survival effect of palliative surgery in advanced tongue squamous cell carcinoma (TSCC). A retrospective analysis of data in the SEER database for 6151 patients with stage III/IV TSCC (American Joint Committee on Cancer (AJCC) staging), diagnosed between 2004 and 2015, was performed. The patients were divided into two groups: palliative surgery and no surgery. Kaplan-Meier and Cox proportional hazards regression analyses were applied to determine risk factors for overall survival (OS) and cancer-specific survival (CSS). A further analysis was performed using 1:1 propensity score matching (PSM) to balance 13 patient variables (sex, age at diagnosis, race, marital status, primary tumour site, SEER stage, AJCC stage, pathological differentiation grade, tumour size, lymph node metastasis, previous lymph node removal, radiotherapy, and chemotherapy). Among the 6151 patients, 706 underwent palliative surgery; the other 5445 did not undergo any kind of surgery. Those who underwent palliative surgery had a higher 5-year survival rate. After PSM, 1274 patients were included in the matched cohort. Multivariate Cox regression analysis showed that patients who underwent palliative surgery had a lower risk of death than those who did not (OS: hazard ratio 0.58, 95% confidence interval 0.49-0.69, P < 0.001; CSS: hazard ratio 0.60, 95% confidence interval 0.49-0.74, P < 0.001). In this comparative study it was found that compared with no surgery, palliative surgery has a positive impact on the survival rate of patients with advanced TSCC.
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OBJECTIVES: This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. STUDY DESIGN: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. RESULTS: In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75-4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020-2030. CONCLUSIONS: The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge.
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Neoplasias Gastrointestinais , Humanos , China/epidemiologia , Pessoa de Meia-Idade , Neoplasias Gastrointestinais/epidemiologia , Masculino , Adulto , Feminino , Incidência , Fatores de Risco , Adulto Jovem , Anos de Vida Ajustados por Deficiência/tendências , Adolescente , Teorema de Bayes , Carga Global da Doença/tendências , Idade de InícioRESUMO
Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.
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Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration. We demonstrate the successful culture of primary human liver endothelial cells in organ-on-a-chip technology followed by perfusion of peripheral blood mononuclear cells. We confirm, with confocal and multiphoton imaging, the capture and adhesion of immune cells in response to pro-inflammatory cytokines in this model. This multicellular platform sets the foundation for testing the efficacy of new therapies in promoting leukocyte infiltration across liver endothelium as well as a model for testing cell therapy, such as chimeric antigen receptor (CAR)-T cell, capture and migration across human liver endothelium.
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BACKGROUND AND PURPOSE: To evaluate modern clinical outcomes for patients with brain-only metastatic non-small cell lung cancer (NSCLC) treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. MATERIALS AND METHODS: Patients with synchronously diagnosed NSCLC and brain-only metastatic disease treated with intracranial SRS at a single institution were retrospectively identified. Patients were stratified based on whether they did (A) or did not (B) receive definitive primary site treatment. Patient characteristics and clinical outcomes were compared. RESULTS: From 2008 to 2022, 103 patients were identified, 53 of whom received definitive primary site treatment. Median follow-up was 2.1 y (A) and 0.8 y (B) (p < 0.001). 28 (53 %) patients in Group A received immune checkpoint inhibitor (ICI) therapy versus 19 (38 %) in Group B (p = 0.13) and there were no other statistically significant baseline or treatment characteristic differences between the groups. 5-year local-PFS was 34.5 % (A) versus 0 % (B) (p < 0.001). 5-year regional-PFS was 33.0 % (A) versus 0 % (B) (p < 0.001). 5-year distant body-PFS was 34.0 % (A) versus 0 % (B) (p < 0.001). 5-year CNS-PFS was 14.7 % (A) versus 0 % (B) (p = 0.12). 5-year OS was 40.2 % (A) versus 0 % (B) (p = 0.001). 5-year CSS was 67.6 % (A) versus 0 % (B) (p = 0.002). On multivariable analysis, lack of definitive treatment to the primary site (HR = 2.40), AJCC T3-4 disease (HR = 2.73), and lack of ICI therapy (HR = 2.86) were significant predictors of death. CONCLUSION: Definitive treatment to the thoracic primary site in patients with brain-only metastatic NSCLC after intracranial radiosurgery was associated with slower progression of disease and improved survival.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Radiocirurgia/métodos , Masculino , Feminino , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adulto , Taxa de Sobrevida , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8+ T cell invasion into BEC. CD8+ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. They were also not contained within secondary vesicles. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8+ T cells were observed in both non-cirrhotic and cirrhotic diseased liver tissues but enriched in PBC patients, both during active disease and at the time of transplantation. E-cadherin expression by CD8+ T cells correlated with frequency of internalisation of these cells into BEC. E-cadherin+ CD8+ T cells formed ß-catenin-associated interactions with BEC, were larger than E-cadherin- CD8+ T cells and invaded into BEC more frequently. Overall, we unveil a distinct cell-in-cell structure process in the liver detailing the invasion of E-cadherin+ CD103+ CD69+ CD8+ T cells into BEC.
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Ductos Biliares , Cirrose Hepática Biliar , Humanos , Ductos Biliares/metabolismo , Cirrose Hepática Biliar/patologia , Linfócitos T CD8-Positivos/metabolismo , Células Epiteliais/metabolismo , Caderinas/metabolismoRESUMO
OBJECTIVE: Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells (HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor α and/or ß (TRα/ß). Here, we evaluated the influence of TH in hepatic fibrogenesis. DESIGN: Human liver tissue was obtained from explanted livers following transplantation. TRα-deficient (TRα-KO) and wild-type (WT) mice were fed a control or a profibrogenic methionine-choline deficient (MCD) diet. Liver tissue was assessed by qRT-PCR for fibrogenic gene expression. In vitro, HSC were treated with TGFß in the presence or absence of T3. HSC with stable TRα knockdown and TRα deficient mouse embryonic fibroblasts (MEF) were used to determine receptor-specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT-PCR. RESULTS: TRα and TRß expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TRα represents the dominant isoform in HSC. In vitro, T3 blunted TGFß-induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGFß signalling, which depended on TRα presence. In vivo, TRα-KO enhanced MCD diet-induced liver fibrogenesis. CONCLUSION: These observations indicate that TH action in non-parenchymal cells is highly relevant. The interaction of TRα with TH regulates the phenotype of HSC via the TGFß signalling pathway. Thus, the TH-TR axis may be a valuable target for future therapy of liver fibrosis.
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Fibroblastos , Células Estreladas do Fígado , Animais , Camundongos , Humanos , Células Estreladas do Fígado/metabolismo , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/farmacologia , Receptores alfa dos Hormônios Tireóideos/genética , Receptores alfa dos Hormônios Tireóideos/metabolismo , Fator de Crescimento Transformador betaRESUMO
OBJECTIVE: This study's aim was to investigate the expression changes of total type I procollagen amino-terminal peptide (t-PINP) and type I collagen C-terminal peptide (ß-CTX) in serum after vertebral osteoporotic fracture surgery and the clinical value of predicting the risk of refracture. PATIENTS AND METHODS: The clinical data of 100 patients with vertebral osteoporotic fractures treated in our hospital from January 2019 to January 2020 were retrospectively analyzed, and the patients were divided into the control group (patients without re-fracture, n = 68) and the observation group (patients with re-fracture, n = 32) according to whether they had re-fracture at 2-year follow-up. The risk factors of postoperative re-fracture were analyzed using Multivariate logistic regression analysis. The serum contents of t-PINP, ß-CTX, osteocalcin (BGP), and calcium (Ca) were measured. Bone mineral density (BMD) was measured by bone densitometer. The correlation between the t-PINP/ß-CTX ratio and the bone metabolic index was analyzed by Pearson correlation. The area under the curve (AUC), sensitivity, and specificity of t-PINP/ß-CTX in predicting the risk of re-fracture were determined by the receiver operating characteristic (ROC) curve. RESULTS: There was a significant difference in age, the number of vertebral bodies with initial fracture, and whether there was leakage of bone cement between the two groups (p < 0.05). Age, the number of vertebral bodies with primary fracture, and the leakage of bone cement were risk factors affecting re-fracture after operation (p < 0.05). Compared with those in the control group, the level of t-PINP and the ratio of t-PINP/ß-CTX were higher, and the ß-CTX level was lower in the observation group (p < 0.05). The BGP level was higher, and the levels of BMD and Ca were lower in the observation group than those in the control group (p < 0.05). Pearson correlation analysis showed that t-PINP had a positive correlation with BGP (r = 0.222, p < 0.05). ß-CTX was positively correlated with BMD and Ca (r = 0.230, 0.269, p < 0.05). The ratio of t-PINP/ ß-CTX was negatively correlated with BMD and Ca (r = -0.621 and -0.660, p < 0.05), but positively correlated with BGP (r = 0.517, p < 0.05). ROC curve analysis showed that the AUC of t-PINP, ß-CTX, and the ratio of t-PINP/ß-CTX in predicting the risk of re-fracture after vertebral osteoporotic fracture surgery was 0.724, 0.736, and 0.838, respectively. CONCLUSIONS: The t-PINP/ß-CTX ratio was significantly correlated with the bone metabolic indexes in patients with vertebral osteoporotic fractures. The detection of the changes in its index can help predict the risk of postoperative re-fracture, providing a new idea for clinical assessment of the risk of postoperative re-fracture.
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Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Cimentos Ósseos , Peptídeos , Colágeno , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/etiologia , Densidade Óssea , BiomarcadoresRESUMO
Objective: To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM). Methods: A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student's t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman's correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results: A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10-3 mm2/s vs. 7.35×10-3 mm2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score (r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score (r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion: IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Nefropatias Diabéticas/diagnóstico por imagem , Rim/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
AIMS: Autoantibodies against tumour-associated antigens (TAAs) are promising biomarkers for early immunodiagnosis of cancers. This study was designed to screen and verify autoantibodies against TAAs in sera as diagnostic biomarkers for oesophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The customised proteome microarray based on cancer driver genes and the Gene Expression Omnibus database were used to identify potential TAAs. The expression levels of the corresponding autoantibodies in serum samples obtained from 243 ESCC patients and 243 healthy controls were investigated by enzyme-linked immunosorbent assay (ELISA). In total, 486 serum samples were randomly divided into the training set and the validation set in the ratio of 2:1. Logistic regression analysis, recursive partition analysis and support vector machine were performed to establish different diagnostic models. RESULTS: Five and nine candidate TAAs were screened out by proteome microarray and bioinformatics analysis, respectively. Among these 14 anti-TAAs autoantibodies, the expression level of nine (p53, PTEN, GNA11, SRSF2, CXCL8, MMP1, MSH6, LAMC2 and SLC2A1) anti-TAAs autoantibodies in the cancer patient group was higher than that in the healthy control group based on the results from ELISA. In the three constructed models, a logistic regression model including four anti-TAA autoantibodies (p53, SLC2A1, GNA11 and MMP1) was considered to be the optimal diagnosis model. The sensitivity and specificity of the model in the training set and the validation set were 70.4%, 72.8% and 67.9%, 67.9%, respectively. The area under the receiver operating characteristic curve for detecting early patients in the training set and the validation set were 0.84 and 0.85, respectively. CONCLUSIONS: This approach to screen novel TAAs is feasible, and the model including four autoantibodies could pave the way for the diagnosis of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/genética , Proteoma , Metaloproteinase 1 da Matriz , Proteína Supressora de Tumor p53 , Biomarcadores Tumorais/genética , Antígenos de Neoplasias/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Autoanticorpos , Expressão GênicaRESUMO
OBJECTIVE: To compare the performance of Clear Cell Likelihood Score (ccLS) v1.0 and v2.0 in diagnosing clear cell renal cell carcinoma (ccRCC) from small renal masses (SRM). METHODS: We retrospectively analyzed the clinical data and MR images of patients with pathologically confirmed solid SRM from the First Medical Center of the Chinese PLA General Hospital between January 1, 2018, and December 31, 2021, and from Beijing Friendship Hospital of Capital Medical University and Peking University First Hospital between January 1, 2019 and May 17, 2021. Six abdominal radiologists were trained for use of the ccLS algorithm and scored independently using ccLS v1.0 and ccLS v2.0. Random- effects logistic regression modeling was used to generate plot receiver operating characteristic curves (ROC) to evaluate the diagnostic performance of ccLS v1.0 and ccLS v2.0 for ccRCC, and the area under curve (AUC) of these two scoring systems were compared using the DeLong's test. Weighted Kappa test was used to evaluate the interobserver agreement of the ccLS score, and differences in the weighted Kappa coefficients was compared using the Gwet consistency coefficient. RESULTS: In total, 691 patients (491 males, 200 females; mean age, 54 ± 12 years) with 700 renal masses were included in this study. The pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ccLS v1.0 for diagnosing ccRCC were 77.1%, 76.8%, 77.7%, 90.2%, and 55.7%, as compared with 80.9%, 79.3%, 85.1%, 93.4%, 60.6% with ccLS v2.0, respectively. The AUC of ccLS v2.0 was significantly higher than that of ccLS v1.0 for diagnosis of ccRCC (0.897 vs 0.859; P < 0.01). The interobserver agreement did not differ significantly between ccLS v1.0 and ccLS v2.0 (0.56 vs 0.60; P > 0.05). CONCLUSION: ccLS v2.0 has better performance for diagnosing ccRCC than ccLS v1.0 and can be considered for use to assist radiologists with their routine diagnostic tasks.
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Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Carcinoma de Células Renais/diagnóstico , Estudos Retrospectivos , Rim , Neoplasias Renais/diagnósticoRESUMO
OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.
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COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T CD4-Positivos , Estado Terminal , Interleucina-6 , Prognóstico , Estudos Retrospectivos , Adulto , Idoso , Idoso de 80 Anos ou maisRESUMO
Objective: To evaluate the diagnostic value of multiparametric magnetic resonance imaging (mpMRI) based models in the assessment of extra-prostatic extension (EPE) of prostate cancer. Methods: This retrospective study included 168 consecutive men with prostate cancers [aged 48 to 82 (66.6±6.8) years] who underwent radical prostatectomy and preoperative mpMRI examinations at the First Medical Center of the PLA General Hospital from January 2021 to February 2022. According to European Society of Urogenital Radiology (ESUR) score, EPE grade and mEPE score, all cases were independently evaluated by two radiologists, with disagreement reviewed by a senior radiologist as the final result. The diagnostic performance of each MRI-based model for pathologic EPE prediction was assessed using receiver operating characteristic curve (ROC), and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. The weighted Kappa test was used to evaluate the inter-reader agreement of each MRI-based model. Results: A total of 62 (36.9%) prostate cancer patients had pathologic confirmed EPE after radical prostatectomy. The AUC of ESUR score, EPE grade and mEPE score for predicting pathologic EPE were 0.836 (95%CI: 0.771-0.888), 0.834 (95%CI: 0.769-0.887) and 0.785 (95%CI: 0.715-0.844), respectively. The AUC of ESUR score and EPE grade were both superior to that of mEPE score with significant differences (all P<0.05), while there was no significant difference between the ESUR score and EPE grade models (P=0.900). EPE grading and mEPE score had good inter-reader consistency, with weighted Kappa values of 0.65 (95%CI: 0.56-0.74) and 0.74 (95%CI: 0.64-0.84), respectively. The inter-reader consistency of ESUR score was moderate, and the weighted Kappa value was 0.52 (95%CI: 0.40-0.63). Conclusion: All MRI-based models showed good preoperative diagnostic value in predicting EPE, among which the EPE grade resulted in more reliable performance with substantial inter-reader agreement.
Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Próstata/patologia , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Prostatectomia/métodosRESUMO
OBJECTIVE: The aim of this study was to discuss the prognostic significance of peripheral interleukin-6 (IL-6) and CD4+ and CD8+ T cells in COVID-19. PATIENTS AND METHODS: Eighty-four COVID-19 patients were retrospectively analyzed and classified into three groups, including the moderate group (15 cases), the serious group (45 cases), and the critical group (24 cases). The levels of peripheral IL-6, CD4+, and CD8+ T cells and CD4+/CD8+ were determined for each group. It was assessed whether these indicators were correlated to the prognosis and death risks of COVID-19 patients. RESULTS: The three groups of COVID-19 patients differed significantly in the levels of peripheral IL-6 and CD4+ and CD8+ cells. The IL-6 levels in the critical, moderate, and serious groups were increased successively, but the changed levels of CD4+ and CD8+ T cells were just opposite to that of IL-6 (p<0.05). The peripheral IL-6 level increased dramatically in the death group, while the levels of CD4+ and CD8+ T cells decreased significantly (p<0.05). The peripheral IL-6 level was significantly correlated with the level of CD8+ T cells and CD4+/CD8+ ratio in the critical group (p<0.05). The logistic regression analysis indicated a dramatic increase in the peripheral IL-6 level in the death group (p=0.025). CONCLUSIONS: The aggressiveness and survival of COVID-19 were highly correlated with the increases in IL-6 and CD4+/CD8+ T cells. The fatalities of COVID-19 individuals remained at increased incidence due to elevated peripheral IL-6 levels.
Assuntos
COVID-19 , Interleucina-6 , Humanos , Linfócitos T CD4-Positivos , Prognóstico , Estudos Retrospectivos , Linfócitos T CD8-PositivosRESUMO
Objective: To explore the clinical effects of island posterior femoral composite tissue flaps in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter. Methods: The retrospective observational study was conducted. From December 2018 to December 2021, 23 patients with sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter who met the inclusion criteria were admitted to Ganzhou People's Hospital, including 16 males and 7 females, aged 45 to 86 years. The size of pressure ulcers in ischial tuberosity ranged from 1.5 cm×1.0 cm to 8.0 cm×5.0 cm, and the size of pressure ulcers in greater trochanter ranged from 4.0 cm×3.0 cm to 20.0 cm×10.0 cm before debridement. After treatment of underlying diseases, debridement and vacuum sealing drainage for 5 to 14 days were performed. All the wounds were repaired by island posterior femoral composite tissue flaps, with area of 4.5 cm×3.0 cm-24.0 cm×12.0 cm, pedicle width of 3-5 cm, pedicle length of 5-8 cm, and rotation radius of 30-40 cm. Most of the donor site wounds were sutured directly, and only 4 donor site wounds were repaired by intermediate thickness skin graft from the contralateral thigh. The survival of composite tissue flaps, wound healing of the donor and recipient sites and the complications were observed. The recurrence of pressure ulcers, and the appearance and texture of flaps were observed during follow-up. Results: A total of 32 wounds in 23 patients were repaired by island posterior femoral composite tissue flaps (including 3 fascio subcutaneous flaps, 24 fascial flaps+fascio subcutaneous flaps, 2 fascial flaps+fascial dermal flaps, 2 fascial flaps+fascio subcutaneous flaps+femoral biceps flaps, and one fascial flap+fascio subcutaneous flap+gracilis muscle flap). Among them, 31 composite tissue flaps survived well, and a small portion of necrosis occurred in one fascial flap+fascio subcutaneous flap post surgery. The survival rate of composite tissue flap post surgery was 96.9% (31/32). Twenty-nine wounds in the recipient sites were healed, and 2 wounds were torn at the flap pedicle due to improper postural changes, and healed one week after bedside debridement. One wound was partially necrotic due to the flap bruising, and healed 10 days after re-debridement. Thirty-one wounds in the donor sites (including 4 skin graft areas) were healed, and one wound in the donor site was torn due to improper handling at discharge, and healed 15 days after re-debridement and suture. The complication rate was 12.5% (4/32), mainly the incision dehiscence of the flap pedicle and the donor sites (3 wounds), followed by venous congestion at the distal end of flap (one wound). During the follow-up of 3 to 24 months, the pressure ulcers did not recur and the flaps had good appearance and soft texture. Conclusions: The island posterior femoral composite tissue flaps has good blood circulation, large rotation radius, and sufficient tissue volume. It has a high survival rate, good wound healing, low skin grafting rate in the donor site, few postoperative complications, and good long-term effect in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter.
Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Úlcera por Pressão , Lesões dos Tecidos Moles , Masculino , Feminino , Humanos , Úlcera por Pressão/cirurgia , Úlcera por Pressão/etiologia , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento , Transplante de Pele , Fêmur/cirurgia , Necrose/complicações , Necrose/cirurgiaRESUMO
Orbital inflammatory pseudotumor (OIP) is a kind of orbital idiopathic benign space-occupying lesion with no clear etiology and mainly characterized by inflammatory response. The clinical diagnosis of OIP should be based on exclusion of other diseases or surgical biopsy. Medication and surgical excision are both diagnostic and therapeutic methods. The choice of which is a problem that baffles clinicians. This article discusses a new strategy basing on the imaging features and classifications of OIP. It is expected to be further discussed and promoted in clinical practice to improve the diagnosis and treatment of OIP.