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1.
Eur J Cardiothorac Surg ; 66(1)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38970382

RESUMO

OBJECTIVES: To evaluate the impact of previous cardiac surgery (PCS) on clinical outcomes after reoperative extended arch repair for acute type A aortic dissection. METHODS: This study included 37 acute type A aortic dissection patients with PCS (PCS group) and 992 without PCS (no-PCS group). Propensity score-matching yielded a subgroup of 36 pairs (1:1). In-hospital outcomes and mid-term survival were compared between the 2 groups. RESULTS: The PCS group was older (56.7 ± 14.2 vs 52.2 ± 12.6 years, P = 0.036) and underwent a longer cardiopulmonary bypass (median, 212 vs 183 min, P < 0.001) compared with the no-PCS group. Operative death occurred in 88 (8.6%) patients, exhibiting no significant difference between groups (13.5% vs 8.4%, P = 0.237). Major postoperative morbidity was observed in 431 (41.9%) patients, also showing no difference between groups (45.9% vs 41.7%, P = 0.615). Moreover, the multivariable logistic regression analysis revealed that PCS was not significantly associated with operative mortality (adjusted odds ratio 2.58, 95% confidence interval 0.91-7.29, P = 0.075) or major morbidity (adjusted odds ratio 1.92, 95% confidence interval 0.88-4.18, P = 0.101). The 3-year cumulative survival rates were 71.1% for the PCS group and 83.9% for the no-PCS group (log-rank P = 0.071). Additionally, Cox regression indicated that PCS was not significantly associated with midterm mortality (adjusted hazard ratio 1.40, 95% confidence interval 0.44-4.41, P = 0.566). After matching, no significant differences were found between groups in terms of operative mortality (P > 0.999), major morbidity (P > 0.999) and midterm survival (P = 0.564). CONCLUSIONS: No significant differences were found between acute type A aortic dissection patients with PCS and those without PCS regarding in-hospital outcomes and midterm survival after extended arch repair.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Procedimentos Cirúrgicos Cardíacos , Reoperação , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/mortalidade , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Complicações Pós-Operatórias/epidemiologia , Aorta Torácica/cirurgia , Resultado do Tratamento , Doença Aguda , Adulto , Implante de Prótese Vascular/métodos , Implante de Prótese Vascular/efeitos adversos , Pontuação de Propensão
2.
Cell ; 187(14): 3712-3725.e34, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38810646

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, whereas its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, ivacaftor, has suboptimal pharmacokinetics and inhibitors have yet to be clinically developed. Here, we combine molecular docking, electrophysiology, cryo-EM, and medicinal chemistry to identify CFTR modulators. We docked ∼155 million molecules into the potentiator site on CFTR, synthesized 53 test ligands, and used structure-based optimization to identify candidate modulators. This approach uncovered mid-nanomolar potentiators, as well as inhibitors, that bind to the same allosteric site. These molecules represent potential leads for the development of more effective drugs for cystic fibrosis and secretory diarrhea, demonstrating the feasibility of large-scale docking for ion channel drug discovery.


Assuntos
Aminofenóis , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Simulação de Acoplamento Molecular , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/química , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/metabolismo , Aminofenóis/farmacologia , Aminofenóis/química , Aminofenóis/uso terapêutico , Descoberta de Drogas , Microscopia Crioeletrônica , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/uso terapêutico , Sítio Alostérico/efeitos dos fármacos , Animais , Ligantes
3.
JAMA Cardiol ; 9(7): 649-658, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38809565

RESUMO

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions. Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics. Design, Setting, and Participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023. Exposures: Protein aptamers, measured at study V3 and V5. Main Outcomes and Measures: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty. Results: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF. Conclusions and Relevance: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.


Assuntos
Fragilidade , Insuficiência Cardíaca , Proteômica , Humanos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/sangue , Feminino , Masculino , Idoso , Fragilidade/epidemiologia , Fragilidade/sangue , Incidência , Fatores de Risco , Pessoa de Meia-Idade , Biomarcadores/sangue
4.
Eur J Med Res ; 29(1): 206, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539263

RESUMO

OBJECTIVE: It has been demonstrated that IDO1, a target of immune checkpoint inhibition, functions as an oncogene in the majority of human malignancies. IDO1's function in human pan-cancers hasn't been thoroughly studied, though. MATERIALS AND METHODS: The Kaplan-Meier (K-M) and COX analyses were applied to the survival analysis. Furthermore, we used Spearman's correlation analysis to examine the associations between IDO1 and microsatellite instability (MSI), DNA methyltransferases (DNMTs), tumor mutational burden (TMB), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers. Moreover, immunohistochemical analysis and qRT-PCR were used to evaluate IDO1's expression in pan-cancer cells. RESULTS: The findings of this study reveal that IDO1 has abnormal expression in a number of malignancies and is related to the prognosis for UVM, LGG, KIRP, GBM, LAML, OV, READ, MESO, SARC, SKCM, and HNSC. Furthermore, the aberrant IDO1 expression was connected to the TMB, MSI, MMR, drug sensitivity, immune cells infiltrating, and tumor immune microenvironment across a variety of cancer types. The PCR results showed that in contrast to normal cells, IDO1 was found to be significantly highly expressed in breast cancer cells and hepatocellular carcinoma cells, and significantly lowly expressed in gastric cancer cells. CONCLUSION: The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study.


Assuntos
Neoplasias Gástricas , Humanos , Prognóstico , Linhagem Celular , Metilação de DNA , Microambiente Tumoral/genética
5.
BMC Cancer ; 24(1): 20, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166842

RESUMO

OBJECTIVE: PD-L1, a target of immune checkpoint blockade, has been proven to take the role of an oncogene in most human tumors. However, the role of PD-L1 in human pan-cancers has not yet been fully investigated. MATERIALS AND METHODS: Pan-cancer analysis was conducted to analyze expression, genetic alterations, prognosis analysis, and immunological characteristics of PD-L1. Estimating the correlation between PD-L1 expression and survival involved using pooled odds ratios and hazard ratios with 95% CI. The Kaplan-Meier (K-M) technique, COX analysis, and receiver operating characteristic (ROC) curves were applied to the survival analysis. Additionally, we investigated the relationships between PD-L1 and microsatellite instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers using Spearman's correlation analysis. Also, immunohistochemical analysis and qRT-PCR were employed in evaluating PD-L1's protein and mRNA expression in pan-caner. RESULTS: PD-L1 showed abnormal mRNA and protein expression in a variety of cancers and predicted prognosis in cancer patients. Furthermore, across a variety of cancer types, the aberrant PD-L1 expression was connected to the MSI, MMR, TMB, drug sensitivity, and tumor immune microenvironment (TIME). Moreover, PD-L1 was significantly correlated with infiltrating levels of immune cells (T cell CD8 + , neutrophil, and so on). CONCLUSION: Our study provides a better theoretical basis and guidance for the clinical treatment of PD-L1.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Prognóstico , Antígeno B7-H1/metabolismo , Neoplasias/genética , Análise de Sobrevida , Instabilidade de Microssatélites , RNA Mensageiro , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Microambiente Tumoral/genética
6.
J Cancer ; 15(2): 508-525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169519

RESUMO

Background: CD27 is an immunological checkpoint gene, plays a critical function inInhibition or activation of cancer immunity. The CD27/CD27L axis is its pathway of action. Therefore, our goal was to examine the predictive role of CD27 in the clinical prognosis of 33 cancer types and its functions in cancer progression, as well as explore the link between pan-cancer CD27 gene expression and immune infiltration. Methods: By comprehensive use of datasets and methods from TCGA, cBioPortal, GTEx, HPA, KM-plotter, Spearman, CellMinerTM, R packages and RT-qPCR, we delved deeper into the potential impact of the CD27 on cancer development. These include expression differences, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways, TMB, MSI, and prognosis. Also, we explored CD27 interactions with different drugs. Results: The results showed that, mutated CD27 was highly expressed in most cancers. The CD27 showed strong diagnostic value in 4 cancers and marked a positive prognosis for CESC, intracervical adenocarcinoma, HNSC, and endometrial cancer, and a poor prognosis for UVM. In addition, CD27 affects multiple immune and inflammatory signaling pathways and is positively correlated with immune cell infiltration, T cell differentiation, macrophage M1 polarization, stromal infiltration, and drug sensitivity. DNA methylation is involved in CD27 expression in cancer. Conclusion: CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers.

7.
bioRxiv ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37745391

RESUMO

The cystic fibrosis transmembrane conductance regulator (CFTR) is a crucial ion channel whose loss of function leads to cystic fibrosis, while its hyperactivation leads to secretory diarrhea. Small molecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, ivacaftor, has suboptimal pharmacokinetics and inhibitors have yet to be clinically developed. Here we combine molecular docking, electrophysiology, cryo-EM, and medicinal chemistry to identify novel CFTR modulators. We docked ~155 million molecules into the potentiator site on CFTR, synthesized 53 test ligands, and used structure-based optimization to identify candidate modulators. This approach uncovered novel mid-nanomolar potentiators as well as inhibitors that bind to the same allosteric site. These molecules represent potential leads for the development of more effective drugs for cystic fibrosis and secretory diarrhea, demonstrating the feasibility of large-scale docking for ion channel drug discovery.

8.
Front Oncol ; 13: 1290434, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074656

RESUMO

Objectives: The purpose of this study is to evaluate the potential of the flattening filter free (FFF) mode of a linear accelerator for patients with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) by comparison with flattened beams (FF) technique in the application of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) using dosimetric and radiobiological indexes based on the volume of hippocampus and target. Methods: 2 VMAT- and 2 IMRT- plans were optimized in Eclipse planning system with 2 different delivery modes (6 MV standard vs. 6 MV FFF) for each of 25 patients. Dose distributions of the target and organs at risk (OARs), normal tissue complication probability (NTCP) of the hippocampus, monitor units, treatment time and quality assurance results were evaluated to compare the normal and FFF beam characteristics by Wilcoxon matched-pair signed-rank test with a significance level of 0.05. Results: VMAT-FFF provided the significantly best homogeneity and conformity of the target, delivered the lowest dose to hippocampus and the other OARs, and led to the lowest NTCP of the hippocampus among all modalities, which has the potential to alleviate neurocognitive decline after WBRT. IMRT-FFF reduced the dose to the lens with similar dose distributions of the target compared with IMRT-FF, whereas the lower dose to the hippocampus was achieved using the conventional beams. The monitor units were obviously increased by 19.2% for VMAT and 33.8% for IMRT, when FFF beams w ere used. The removal of flattening filter for IMRT resulted in a 26% reduction in treatment time, but VMAT had the similar treatment time for the two modes owing to the limitation of gantry rotation speed. Gamma analysis showed an excellent agreement for all plans at 3%/2 mm, and no statistical differences were found between FF and FFF. Conclusion: In conclusion, this study suggests that FFF mode is feasible and advantageous in HA-WBRT and VMAT-FFF is the optimal solution in terms of dose distribution of the target, OARs sparing, NTCP of the hippocampus and delivery efficiency compared to the other three techniques. Additionally, the advantages of the FFF technique for VMAT are more prominent in cases with small hippocampal volumes.

9.
World J Surg Oncol ; 21(1): 302, 2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37741975

RESUMO

BACKGROUND: Treatment options for advanced colon cancer are mainly combinations of chemotherapy and targeted drugs. However, poor physical health and medication intolerance limit the choice of anticancer drugs. Colon cancer with cirrhosis is a particular patient group that poses a challenge to clinical treatment. CASE PRESENTATION: This article presents a case of a patient in the decompensated stage of cirrhosis who was diagnosed with advanced colon cancer. The initial presentation was a nodule on his navel named the Sister Mary Joseph's nodule, which was later confirmed by biopsy and PET-CT as one of the metastases of colon cancer. The patient was treated with cetuximab and 5-fluorouracil at a below-guideline dose; however, portal vein thrombosis developed and led to death. This entire process, from diagnosis to death, occurred within a span of three months. CONCLUSION: Cancers with cirrhosis are a special group that deserves more attention. There is no unified treatment guideline for these patients, especially those with extrahepatic primary tumors. We should be more cautious when choosing treatment for such patients in the future. Both chemotherapy and targeted treatment may potentially induce portal vein thrombosis, which appears to have a higher incidence and worse prognosis than cancers without cirrhosis.


Assuntos
Neoplasias do Colo , Hepatopatias , Trombose , Humanos , Fluoruracila/efeitos adversos , Cetuximab/efeitos adversos , Veia Porta , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Colo/tratamento farmacológico , Cirrose Hepática/complicações
10.
Heliyon ; 9(8): e18840, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37636355

RESUMO

Objective: To conduct a bibliometric analysis of literature on hemorrhagic shock published between 2000 and 2021 with the help of Citespace to explore the current status, hotspots and research trends in this regard, with the results presented in a visualized manner. Methods: The data over the past 22 years were retrieved from the Web of Science (WOS) Core Collection database and downloaded as the "Full Record and Cited References". Cooperative analysis, cluster analysis, co-citation analysis, and burst analysis were performed based on the data on countries/regions, institutions, journals, authors, and keywords through Citespace. Results: A total of 2027 articles were retrieved. The number of annual publications fluctuated but was generally on an upward trend. The United States stands out as the most productive country (989 articles), the University of Pittsburgh the most productive publishing institution (109 articles), SHOCK the most cited journal (1486 articles), TAO LI the most productive author (40 articles), DEITCH EA the most cited author (261 times of citation), hemorrhagic shock the most frequent keyword (725 times of occurrence), and "traumatic brain injury" the most covered article in keyword clustering (29 articles). The burst analysis revealed Harvard University as the institution with the highest strength value and the Journal of Trauma and Acute Care Surgery the most important journal. It was also concluded that HASAN B ALAM, AARON M WILLIAMS, and LIMIN ZHANG may continue to publish high-quality articles in the future. In the meanwhile, both "protect" and "transfusion" were considered the hotspots and trends in current research. Conclusions: The United States has been a major contributor to the publication of the articles over the past 22 years, with the most productive publishing institution, the most cited journal, and the most cited author all coming from the US. Hemorrhagic shock, injury, resuscitation, trauma, models, activation, expression, fluid resuscitation, rats, and nitric oxide are hot topics in relevant research. According to the keyword burst analysis, the areas related to "protect" and "transfusion" may rise as the research directions in the future. However, since the hotspots in the research of hemorrhagic shock are short-lived and fast-changing, the researchers should pay more attention to the development trend in this field.

11.
Exp Neurol ; 368: 114507, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37598880

RESUMO

Despite decades of intensive research, there are still very limited options for the effective treatment of intracerebral hemorrhage (ICH). Recently, mounting evidence has indicated that the ultra-early stage (<3 h), serving as the primary phase of ICH, plays a pivotal role and may even surpass other stages in terms of its significance. Therefore, uncovering the metabolic alterations induced by ICH in the ultra-early stage is of crucial importance. To investigate this, the collagenase ICH mouse model was employed in this study. ICH or sham-operated mice were euthanized at the ultra-early stage of 3 h and the acute stage of 24 h and 72 h after the operation. Then, the metabolic changes in the perihematomal tissues were detected by liquid chromatography coupled with tandem mass spectrometry. In total, alterations in the levels of 465 metabolites were detected. A total of 136 metabolites were significantly changed at 3 h. At 24 h and 72 h, the amounts were 132 and 126, respectively. Additionally, the key corresponding metabolic pathways for these time points were analyzed through KEGG. To gather additional information, quantitative real-time transcription polymerase chain reaction, enzyme-linked immunosorbent assay and Western blots were performed to validate the metabolic changes. Overall, ICH significantly alters important physiological functions such as cysteine metabolism, purine metabolism, synaptic alterations, the synaptic vesicle cycle, and the ATP-binding cassette transporter system. These might be the key pathologic mechanisms of the ultra-early stage induced by ICH.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Metabolômica , Animais , Camundongos , Hemorragia Cerebral , Cromatografia Líquida , Modelos Animais de Doenças
12.
Pathol Res Pract ; 242: 154291, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36696806

RESUMO

BACKGROUND: Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. In this meta-analysis, data from diverse malignancies were analyzed to determine whether LINC00963 expression levels were associated with clinical prognosis and immune infiltration in pan-cancer. MATERIALS AND METHODS: The eligible studies were identified from several electronic databases from the inception to July 2022 through systematic research. LINC00963 expression and survival were estimated using pooled odds ratios and hazard ratios with 95% CI. We used the Kaplan-Meier method and COX analysis for survival analysis. In addition, Spearman's correlation analysis was used to uncover any correlation between LINC00963 and microsatellites instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), immune checkpoint biomarkers, and the related genes of mismatch repair (MMR). RESULTS: Our findings indicated that overexpression of LINC00963 was related to poor overall survival (OS) (HR =1.32, 95% CI, 1.09-1.59, P = 0.004). The TCGA database also found that abnormal expression of LINC00963 was linked to overall survival in various cancers. Moreover, there is an association between LINC00963 expression and MSI, TMB, and MMR in malignancies of various types. CONCLUSION: The results of this study indicate that LINC00963 may serve as a prognostic biomarker and a therapeutic target for cancer. By using it, cancer diagnoses can be improved, treatment targets discovered, and prognostic questions improved.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Neoplasias/patologia , Prognóstico , Análise de Sobrevida , Biomarcadores Tumorais/análise
13.
Front Oncol ; 12: 1008326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338725

RESUMO

Background: The purpose of this study was to analyze the clinical characteristics and prognosis of EPEC and to construct a prediction model based on the SEER database. Methods: All EPECs from the SEER database were retrospectively analyzed. A comprehensive and practical nomogram that predicts the overall survival (OS) of EPEC was constructed. Univariate and multivariate Cox regression analysis was performed to explore the clinical factors influencing the prognosis of EPEC, and finally, the 1 -, 3 - and 5-year OS were predicted by establishing the nomogram. The discriminant and predictive ability of the nomogram was evaluated by consistency index (C-index), calibration plot, area under the curve (AUC), and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to evaluate the clinical value of the nomogram. Results: A total of 3478 patients diagnosed with EPEC were extracted from the SEER database, and the data were randomly divided into the training group (n=2436) and the validation group (n=1402). T stage, N stage, M stage, surgery, chemotherapy, radiotherapy, age, grade, and tumor size were independent risk factors for 1 -, 3 - and 5-year OS of EPEC (P< 0.05), and these factors were used to construct the nomogram prediction mode. The C-index of the validation and training cohorts was 0.718 and 0.739, respectively, which were higher than those of the TNM stage system. The AUC values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, and 3-year OS showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, and 3-year DCA compared with the AJCC stage system. Conclusions: This study shows that the nomogram prediction model for EPEC based on the SEER database has high accuracy and its prediction performance is significantly better than the TNM staging system, which can accurately and individually predict the OS of patients and help clinicians to formulate more accurate and personalized treatment plans.

14.
Medicine (Baltimore) ; 101(42): e31000, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281112

RESUMO

Distant metastases of small-cell lung cancer (DM-SCLC) is an important factor in the selection of treatment strategies. In this study, we established a nomogram to predict DM-SCLC and determine the benefit of radiotherapy (RT) for DM-SCLC. We analyzed DM-SCLC prognosis based on surveillance, epidemiology, and end result database (SEER) data. A comprehensive and practical nomogram that predicts the overall survival (OS) of DM-SCLC was constructed and the results were compared with the 7th edition of the American Joint Committee on Cancer (AJCC) TNM stage system. A concordance index (C-index) and receiver operating characteristic plot were generated to evaluate the nomogram discrimination. The calibration was evaluated with a calibration plot, and its effectiveness was evaluated by a decision curve analysis (DCA). A score was assigned to each variable, and a total score was established for the risk stratification model. A total of 13,403 DM-SCLC patients were included. Eight characteristic variables were identified as independent prognostic variables. The C-index of the validation and training cohorts was 0.716 and 0.734, respectively. The area under the receiver operating characteristic curve (AUC) values of the nomogram used to predict 1-, 2-, and 3-year OS were 0.751, 0.744, and 0.786 in the validation cohorts (0.761, 0.777, 0.787 in the training cohorts), respectively. The calibration curve of 1-, 2-, 3-year survival rates showed that the prediction of the nomogram was in good agreement with the actual observation. The nomogram exhibited higher clinical utility after evaluation with the 1-, 2-, 3-year DCA compared with the AJCC stage system. A predictive nomogram and risk stratification model have been constructed to evaluate the prognosis of DM-SCLC effectively and accurately. This nomogram may provide a reference for prognosis stratification and treatment decisions.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Prognóstico , Programa de SEER , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/patologia , Nomogramas , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Medição de Risco
15.
Medicine (Baltimore) ; 101(36): e30510, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086681

RESUMO

Due to extensive tumor spread, systemic chemotherapy is the main treatment for distant metastatic small-cell lung cancer (DM-SCLC). It is still unclear whether adding local radiotherapy (RT) on the basis of chemotherapy can improve the long-term survival of patients with DM-SCLC. This study aims to explore the population with DM-SCLC who can benefit from RT. Patients with metastatic SCLC with complete data were collected from the Surveillance, Epidemiology, and End Results database and divided into 2 groups according to whether RT was given or not. The propensity score matching method was used to balance the covariate differences between the RT group and the non-RT group. Lasso Cox regression model and Cox proportional hazards regression analyses were used to identifying independent risk factors affecting survival. Kaplan-Meier method was used to calculate the survival rate. P < .05 was considered statistically significant. After matching, there were 3150 patients in both groups. Sex, tumor size, N stage, RT, chemotherapy, brain metastasis, liver metastasis, age, and site metastasis were independent factors of survival in DM-SCLC. The 1- and 2-year survival rates were 24.5% and 5.8% in the RT group and 14.8% and 2.3% in the non-RT group (P < .001). The median survival time of the RT group was 9 months, and that of the non-RT group was 7 months, and the difference was statistically significant (P < .001). RT improved survival in all sex subgroups, any N stage subgroup, any tumor size subgroup, no brain metastases subgroup, no liver metastases subgroup, any age subgroup, and 1-2 organ metastases subgroup. RT improves 1- and 2-year survival in DM-SCLC.


Assuntos
Neoplasias Hepáticas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Pontuação de Propensão , Estudos Retrospectivos , Programa de SEER , Carcinoma de Pequenas Células do Pulmão/radioterapia
16.
J Sep Sci ; 45(14): 2520-2528, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35569141

RESUMO

A novel method for detecting pesticide multi-residue in grass forage (alfalfa and oat) was established based on the one-step automatic extraction and purification technology of quick, easy, cheap, effective, rugged, and safe combined with ultrahigh-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry. The crushed sample was extracted with acetonitrile with 1% acetate, followed by a cleanup step with a primary-secondary amine, octadecylsilane, and graphitized carbon black. The extraction and purification were carried out using the one-step automatic pretreatment equipment. The target pesticides were acquired in positive ion electrospray ionization mode and full scan/data dependent secondary scan mode. The calibration curve shows good linearity over the corresponding concentration range, with the coefficient of determination greater than 0.99. The screening detection limits were 0.5-50 µg/kg, and the limit of quantification for the 206 pesticides was set at 1-50 µg/kg. At the spiking levels of one, two, and 10 times of limit of quantification, more than 95% of pesticides had recovery between 70-120%, with a relative standard deviation ≤20%. The method was proved to be simple, rapid, high-sensitivity, and could be routinely used for the high throughput screening and quantitative analysis of pesticide residues in alfalfa and oat.


Assuntos
Resíduos de Praguicidas , Praguicidas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Resíduos de Praguicidas/análise , Praguicidas/análise , Poaceae
17.
Front Cardiovasc Med ; 9: 841472, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310990

RESUMO

Objectives: A right minithoracotomy approach with a sternal sparing technique is a minimally invasive option for surgeons performing aortic root surgery. This report presents our initial clinical results of the right minithoracotomy Bentall procedure. Methods: Clinical data of 15 patients were retrospectively analyzed who underwent the minimally invasive Bentall procedure through the right anterior thoracotomy via the second intercostal incision without any costochondral cartilage invasion at our institution between October, 2019 and June, 2021. The operative time, length of intensive care unit stay and postoperative hospital stay, perioperative outcomes, and follow-up results were analyzed. Results: The median aortic cross-clamping time was 95.0 (85.5-98.8) min. Three (21.4%) patients received blood transfusion. The median drainage volume in the first 24 h was 200.0 ml, with no redo for bleeding. The median duration of mechanical ventilation was 12.5 (11.0-25.0) h, and median length of intensive care unit stay was 1.5 (1.0-3.0) day. All patients discharged 5.8 ± 1.2 days following surgery, with no dead patients found. At 6 months following surgery, all patients survived with an improved New York Heart Association (NYHA) functional class. Conclusion: The right minithoracotomy Bentall procedure may be performed safely with low morbidity and mortality. This approach should be considered as an option in carefully selected patients requiring aortic root replacement.

18.
Graefes Arch Clin Exp Ophthalmol ; 260(7): 2249-2260, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35133487

RESUMO

PURPOSE: To study serial changes in branching neovascular networks (BNN) by using optical coherence tomography angiography (OCTA) in patients with polypoidal choroidal vasculopathy (PCV) who underwent combined photodynamic therapy (PDT) and anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: In this retrospective study of 30 PCV patients who underwent combined therapy, OCTA images obtained at baseline and 1, 3, and 6 months after treatment were collected. The vessel area, vessel percentage area, average vessel length, and presence of polypoidal lesions on OCTA images as well as best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT) were recorded at each time point. RESULTS: The BNN- and polypoidal lesion-detection rates on baseline OCTA images were 100% and 71%, respectively. The vessel area decreased during the first 3 months, and increased 6 months post-treatment, showing significant differences from baseline (p = 0.031). The vessel percentage area also reduced 1 and 3 months post-treatment (p = 0.025) and increased 6 months post-treatment. Continuous polypoidal lesion regression was observed from 1 to 3 and 6 months post-treatment (p = 0.031, p = 0.004, p = 0.002, respectively, in comparison with baseline). Patients with a decreasing vessel area over 6 months showed greater choroidal thickness than those with increasing vessel area (p = 0.004). CONCLUSIONS: The BNN showed initial regression but were enlarged at 6 months after therapy. Patients showing continuous BNN regression showed a thicker choroid at baseline. This difference should be considered during treatment for PCV, and OCTA could be used for follow-up evaluations of PCV patients.


Assuntos
Doenças da Coroide , Oftalmopatias , Fotoquimioterapia , Pólipos , Corioide/patologia , Doenças da Coroide/diagnóstico , Angiofluoresceinografia/métodos , Humanos , Injeções Intravítreas , Fotoquimioterapia/métodos , Pólipos/diagnóstico , Pólipos/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Fatores de Crescimento do Endotélio Vascular
19.
Medicina (Kaunas) ; 58(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35056386

RESUMO

Background: The Caldwell-Luc (CL) procedure, an outdated operative procedure that is used to treat inflammatory sinus diseases, is rarely performed presently. However, physicians may encounter patients with a history of CL surgery who develop considerable postoperative changes that may lead to diagnostic confusion in imaging evaluation; increase the difficulty of future surgery, such as sinonasal surgery; and increase the incidence of future intraoperative complications. Case summary: A 67-year-old man with a surgical history of chronic sinusitis reported epiphora of the left eye for five years. Balloon dacryocystoplasty was attempted but failed. Endo-DCR (Endoscopic dacryocystorhinostomy) was indicated; however, preoperative CT (computed tomography) imaging and nasal endoscopic examination showed sinonasal anomalies and the loss of internal landmarks for localizing the lacrimal sac. Preoperative CT results indicated previous CL surgery. Endo-DCR was performed with the aid of nasal forceps and a 20-gauge vitreoretinal fiberoptic endoilluminator. A six-month follow-up revealed the complete resolution of symptoms and no signs of recurrence. Conclusions: Epiphora might be a delayed complication of the CL procedure. Before performing endo-DCR, ophthalmologists should be familiar with the sinonasal anatomy and carefully assess preoperative imaging to identify anatomical variations. Nasal forceps and transcanalicular illumination can assist in determining the precise location of the lacrimal sac during endo-DCR.


Assuntos
Dacriocistorinostomia , Ducto Nasolacrimal , Sinusite , Idoso , Endoscopia , Humanos , Masculino , Ducto Nasolacrimal/diagnóstico por imagem , Ducto Nasolacrimal/cirurgia , Nariz
20.
J Cardiol ; 79(1): 42-49, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34551867

RESUMO

BACKGROUND: The role of mitral subvalvular anomalies in the etiology of latent left ventricular outflow tract (LVOT) obstruction has rarely been reported; and the results of surgical treatment for latent LVOT obstruction have been infrequently reported as a separate group by other medical centers other than Mayo clinic. METHODS: Among 292 eligible patients, 45 with resting gradients <30 mmHg had provoked obstruction. Their clinical characteristics and surgical results were compared with those of 247 patients with resting LVOT obstruction. The patients were followed up for a median of 13 months. RESULTS: Comparatively, patients with latent obstruction were younger (51.6±12.1 years vs. 57.2±11.6 years, p=0.003) and had higher prevalence of mitral subvalvular abnormalities (73.3% vs. 16.2%, p<0.001) and basal variant of hypertrophic cardiomyopathy (84.5% vs. 62.0%, p=0.014), less marked septal thickness (16.9±2.8 mm vs. 18.6±3.8 mm, p=0.005), lower resting gradients (22.2±5.7 mmHg vs. 93.0±25.7 mmHg, p < 0.001), and lower mitral regurgitation severity (median, 2.0 vs. 3.0, p<0.001). After surgery, no surgical death occurred in patients with latent LVOT obstruction. Only one (2.2%) patient from the latent group developed complete atrioventricular block. No follow-up death or reoperation was recorded with a significant improvement in New York Heart Association functional status in either group. The provoked LVOT gradients of patients with latent obstruction decreased sharply from the preoperative value (11.8±3.7 mmHg vs. 89.8±16.4 mmHg, p < 0.001), with no occurrence of residual obstruction. CONCLUSIONS: Symptomatic patients with latent LVOT obstruction may have a higher prevalence of mitral subvalvular abnormalities and have less marked septal hypertrophy; and concomitant mitral management during myectomy for the treatment of this patient group achieved excellent results.


Assuntos
Cardiomiopatia Hipertrófica , Insuficiência da Valva Mitral , Obstrução do Fluxo Ventricular Externo , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/cirurgia , Septos Cardíacos/cirurgia , Humanos , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/cirurgia
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