Worse Prognosis
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2021 ◽  
Vol 21 (1) ◽  
Athanasios Samaras ◽  
Eleni Vrana ◽  
Anastasios Kartas ◽  
Dimitrios V. Moysidis ◽  
Andreas S. Papazoglou ◽  

Abstract Background Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF. Methods This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction. Results In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17–2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09–2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35–4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization. Conclusion Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis.

2021 ◽  
Kaname Uno ◽  
Nobuhisa Yoshikawa ◽  
Akira Tazaki ◽  
Shoko Ohnuma ◽  
Kazuhisa Kitami ◽  

Abstract Most advanced ovarian cancer patients experience recurrence and develop resistance to platinum-based agents. However, the diagnosis of platinum resistance based on platinum-free interval is not always accurate and timely. In this study, we employed laser ablation inductively coupled plasma mass spectrometry to visualize platinum distribution in the tissues at the time of interval debulking surgery following neoadjuvant chemotherapy. Twenty seven patients with advanced high grade serous ovarian cancer were enrolled. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum through tumor and adjacent stroma. Type A was significantly correlated with worse prognosis (P = 0.031). Patients classified in type A and treated with platinum-based adjuvant chemotherapy after operation were significantly shorter period of recurrence after last platinum-based chemotherapy (P = 0.020) and diagnosed with “platinum-resistant recurrence”. Treatment with non-platinum-based chemotherapy after operation could be effective for the patients who were classified in type A. Our data indicate that the platinum resistance can be predicted prior to recurrence with platinum distribution. Thus, we will be able to select more appropriate adjuvant chemotherapy, which may possibly lead to improve patient’s prognosis.

2021 ◽  
Vol 10 (18) ◽  
pp. 4218
Arik Eisenkraft ◽  
Yasmin Maor ◽  
Keren Constantini ◽  
Nir Goldstein ◽  
Dean Nachman ◽  

COVID-19 exerts deleterious cardiopulmonary effects, leading to a worse prognosis in the most affected. This retrospective multi-center observational cohort study aimed to analyze the trajectories of key vitals amongst hospitalized COVID-19 patients using a chest-patch wearable providing continuous remote patient monitoring of numerous vital signs. The study was conducted in five COVID-19 isolation units. A total of 492 COVID-19 patients were included in the final analysis. Physiological parameters were measured every 15 min. More than 3 million measurements were collected including heart rate, systolic and diastolic blood pressure, cardiac output, cardiac index, systemic vascular resistance, respiratory rate, blood oxygen saturation, and body temperature. Cardiovascular deterioration appeared early after admission and in parallel with changes in the respiratory parameters, showing a significant difference in trajectories within sub-populations at high risk. Early detection of cardiovascular deterioration of COVID-19 patients is achievable when using frequent remote patient monitoring.

2021 ◽  
Tao Yang ◽  
Lizheng Hao ◽  
Jian Chen ◽  
Xueying Zhu ◽  
Keyi Sun ◽  

Abstract Background: Cancer poses a serious threat to human health. Clarifying the potential significance of Bruton's tyrosine kinase (BTK)in cancer has potential clinical value. This study examined the prognostic and immunological value of BTK gene expression in pan-cancer.Methods: We evaluated the gene expression of BTK in tumor tissues and normal tissues in different cancers. Survival analysis, including Kaplan–Meier analysis and Cox analysis, were performed to explore the prognostic value of BTK for pan-cancer based on survival data from The Cancer Genome Atlas (TCGA) database. Spearman’s method was conducted to analyze the interrelation between BTK gene expression and tumor mutational burden (TMB)and microsatellite instability (MSI). We explored the association of BTK expression with the tumor microenvironment based on Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Co-expression analysis of BTK expression and immune-related genes was performed. We used Gene Set Enrichment Analysis (GSEA) to examine the molecular mechanisms and pathways of BTK in pan-cancer.Results: High BTK expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) was positively correlated with patient prognosis, while high expression of BTK in lymphoid neoplasm diffuse large B cell lymphoma (DLBC), brain lower grade glioma (LGG) and esophageal carcinoma (ESCA) corresponded with a worse prognosis. Cox analysis showed that BTK was closely associated to the prognosis of HNSC, LGG, SKCM and LUAD. BTK expression was correlated with clinical stage, TMB and MSI of 10 types of tumors. In HNSC, LGG, LUAD and SKCM, the expression of BTK was positive correlated with immune and stromal scores. Conclusion: BTK expression can act as a prognostic factor in various cancers, especially in HNSC, LGG, LUAD and SKCM, and this may be from its close association with TMB, MSI and immune cell infiltration.

2021 ◽  
Vol 11 ◽  
Zigao Huang ◽  
Hao Lai ◽  
Jiankun Liao ◽  
Jinghua Cai ◽  
Baojia Li ◽  

BackgroundA disintegrin and metalloprotease 12 (ADAM12) is a member of the multidomain protein family, but the mechanisms by which it affects prognosis and immune cell infiltration in patients with colon adenocarcinoma (COAD) remain unclear. Here, our study aimed to analyze the prognostic value of ADAM12 and investigate the correlation between ADAM12 expression and immune cell infiltration in patients with COAD.MethodsDifferential expression analyses were performed using the Oncomine and UALCAN databases, and prognostic analyses were conducted using PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan–Meier Plotter. Then, the cBioPortal database was used to analyze alterations in the ADAM12 gene, and the STRING and Metascape websites were used to conduct Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Additionally, relationships between ADAM12 and the immune microenvironment were evaluated based on the TIMER, GEPIA, and TISIDB databases.ResultsADAM12 was overexpressed in COAD tissues, and higher ADAM12 expression correlated with a worse prognosis for patients with COAD. The gene regulatory network suggested that ADAM12 was mainly enriched in extracellular matrix (ECM) organization, ECM proteoglycans, skeletal system development, and ossification, among other pathways. Moreover, ADAM12 expression significantly correlated with the abundance of CD4+ T cells, B cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, and their markers, as well as lymphocytes, immunomodulators, and chemokines.ConclusionsIn colorectal tumors, ADAM12 may play vital roles in regulating the ECM and the recruitment of immune cells, and we suggest that ADAM12 will become a reliable biomarker for determining response to immunotherapy and the prognosis of patients with COAD.

2021 ◽  
Vol 21 (1) ◽  
Zongxian Zhao ◽  
Shuliang Li ◽  
Shilong Li ◽  
Jun Wang ◽  
Hai Lin ◽  

Abstract Background Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. Methods The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. Results CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). Conclusion CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257195
Tim Muilwijk ◽  
Murat Akand ◽  
Sofie Daelemans ◽  
Koen Marien ◽  
Yannick Waumans ◽  

Fibroblast activation protein-α (FAP) is a transmembrane peptidase and a surrogate marker for cancer-associated fibroblasts (CAFs). FAP has been linked to worse prognosis and therapy resistance in several cancers. We hypothesised that FAP might have a prognostic 3biomarker potential to stratify patients with high-grade (HG) T1 non-muscle-invasive bladder cancer (NMIBC). We selected 30 patients with HG T1 NMIBC that progressed to ≥T2 disease which were pair-matched based on CUETO progression score variables with 90 patients that did not progress. After revision a final cohort of 86 patients was retained. Slides were stained for FAP, the luminal marker GATA3 and the basal marker CK5. All HG T1 tumour regions of interest (ROIs) within each patient were annotated, analysed and scored using image analysis software. FAP expression in HG T1 ROIs was significantly higher in progressors vs. non-progressors and was prognostic for recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival. FAP expression in HG T1 ROIs remained strongly prognostic for these outcomes in a bivariable model corrected for adequate BCG per FDA definition. Expression of GATA3 and CK5 did not differ between progressors vs. non-progressors, and were not prognostic for these outcomes. FAP might serve as an easily applicable prognostic biomarker to risk-stratify patients with HG T1 NMIBC if these results are prospectively validated in a larger series.

2021 ◽  
Vol 11 (9) ◽  
pp. 917
Florian Reichl ◽  
Daniela Muhr ◽  
Katharina Rebhan ◽  
Gero Kramer ◽  
Shahrokh F. Shariat ◽  

BACKGROUND: Men with germline BRCA1/2 mutations are not well studied compared to their female counterparts. This study evaluates the cancer characteristics, family history of cancer, and outcomes of male BRCA1/2 mutation carriers. METHODS: All men with germline BRCA1/2 mutations who attended genetic assessment between October 1995 and October 2019 at the Medical University of Vienna were identified. Clinicohistopathological features, family history of cancer, and outcomes were assessed by mutation status. RESULTS: Of the 323 men included, 45 (13.9%) had a primary cancer diagnosis, many of whom were BRCA2 carriers (75.5%). Breast cancer (BC) was the most common cancer (57.8%) followed by prostate cancer (15.6%). Invasive ductal carcinoma and hormone receptor positive tumors were the most common. Among 26 BC-affected patients, 42% did not have any relatives with cancer. Parent of origin was only known in half of the 26 men, with 42% of them inherited through the maternal lineage versus 8% through the paternal. BRCA2 carriers and those with a family history of BC had worse overall survival (20 y vs. 23 y BRCA1 carriers; P = 0.007; 19 y vs. 21 y for those without family history of BC; P = 0.036). CONCLUSION: Male BRCA2 carriers were most likely to develop cancer and had worse prognosis. In our dataset, BC was the most common cancer, likely due to referral bias. Not all mutation carriers present with BC or have a family history of cancer to warrant genetic testing.

2021 ◽  
Vol 28 (5) ◽  
pp. 3554-3572
Yanyu Chen ◽  
Wenyun Hou ◽  
Miner Zhong ◽  
Bin Wu

To clarify the molecular mechanisms underlying the poor prognosis of right-sided and mucinous colon cancer at the proteomic level. A tandem mass tag-proteomics approach was used to identify differentially expressed proteins (DEPs) in colon carcinoma tissues from different locations and with different histological types to reveal the underlying mechanisms of these differences at the protein level. In additional, the DEPs were analyzed using bioinformatics methods. The proteomics profiles among colon cancers with different tumor locations and histological types were dramatically distinguished. In terms of tumor locations, the right-sided carcinoma specific DEPs may promote the tumor progression via activating inflammation, metastasis associated pathways. When referring to histological types, the mucinous colon cancers perhaps increased the invasion and metastasis through distinct mechanisms in different tumor locations. For mucinous cancer located in right-sided colon, the mucinous specific DEPs were mainly associated with ECM-related remodeling and the IL-17 signal pathway. For mucinous cancer located in left-sided colon, the mucinous specific DEPs showed a strong relationship with ACE2/Ang-(1–7)/MasR axis. The proteomics profiles of colon cancers showed distinct differences related to locations and histological types. These results suggested a distinct mechanism underlying the diverse subtypes of colon cancers.

2021 ◽  
Vol 11 (1) ◽  
A. M. L. Meesters ◽  
K. ten Duis ◽  
J. Kraeima ◽  
H. Banierink ◽  
V. M. A. Stirler ◽  

AbstractThe assessment of gaps and steps in acetabular fractures is challenging. Data from various imaging techniques to enable accurate quantification of acetabular fracture displacement are limited. The aim of this study was to assess the accuracy of pelvic radiographs, intraoperative fluoroscopy, and computed tomography (CT) in detecting gaps and step-offs in acetabular fractures. Sixty patients, surgically treated for acetabular fractures, were included. Five observers (5400 measurements) measured the gaps and step-offs on radiographs and CT scans. Intraoperative fluoroscopy images were reassessed for the presence of gaps and/or step-offs. Preoperatively, 25% of the gaps and 40% of the step-offs were undetected on radiographs compared to CT. Postoperatively, 52% of the gaps and 80% of the step-offs were missed on radiographs compared to CT. Radiograph analysis led to a significantly smaller gap and step-off compared to the CT measurements, an underestimation by a factor of two. Approximately 70% of the residual gaps and step-offs was not detected using intraoperative fluoroscopy. Gaps and step-offs that exceed the critical cut-off indicating worse prognosis often remained undetected on radiographs compared to CT scans. Less-experienced observers tend to overestimate gaps and step-offs compared to the more-experienced observers. In acetabular fracture treatment, gaps and step-offs were often undetected and underestimated on radiographs and intraoperative fluoroscopy in comparison with CT scans. This means that CT is superior to radiographs in detecting acetabular fracture displacement, which is clinically relevant for patient counselling regarding treatment decisions and prognosis.

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