scholarly journals The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study

2020 ◽  
Vol 27 (10) ◽  
pp. 541-550
Author(s):  
S G Creemers ◽  
R A Feelders ◽  
N Valdes ◽  
C L Ronchi ◽  
M Volante ◽  
...  
Keyword(s):  
Cohort Study ◽  
Tumor Size ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Adrenocortical Tumor ◽  
Adrenocortical Cancer ◽  
Tumor Patients ◽  
Cox Regression Analysis ◽  
Methylation Score

Adrenocortical carcinoma (ACC) is diagnosed using the histopathological Weiss score (WS), but remains clinically elusive unless it has metastasized or grows locally invasive. Previously, we proposed the objective IGF2 methylation score as diagnostic tool for ACC. This multicenter European cohort study validates these findings. Patient and tumor characteristics were obtained from adrenocortical tumor patients. DNA was isolated from frozen specimens, where after DMR2, CTCF3, and H19 were pyrosequenced. The predictive value of the methylation score for malignancy, defined by the WS or metastasis development, was assessed using receiver operating characteristic curves and logistic and Cox regression analyses. Seventy-six ACC patients and 118 patients with adrenocortical adenomas were included from seven centers. The methylation score and tumor size were independently associated with the pathological ACC diagnosis (OR 3.756 95% CI 2.224–6.343; OR 1.467 95% CI 1.202–1.792, respectively; Hosmer–Lemeshow test P = 0.903), with an area under the curve (AUC) of 0.957 (95% CI 0.930–0.984). The methylation score alone resulted in an AUC of 0.910 (95% CI 0.866–0.952). Cox regression analysis revealed that the methylation score, WS and tumor size predicted development of metastases in univariate analysis. In multivariate analysis, only the WS predicted development of metastasis (OR 1.682 95% CI 1.285–2.202; P < 0.001). In conclusion, we validated the high diagnostic accuracy of the IGF2 methylation score for diagnosing ACC in a multicenter European cohort study. Considering the known limitations of the WS, the objective IGF2 methylation score could potentially provide extra guidance on decisions on postoperative strategies in adrenocortical tumor patients.

scholarly journals Identification of prognostic alternative splicing events in sarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongshuai Li ◽  
Jie Yang ◽  
Guohui Yang ◽  
Jia Ren ◽  
Yu Meng ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

scholarly journals Prognostic Nomogram for Patients With Pancreatic Ductal Adenocarcinoma of Pancreatic Head After Pancreaticoduodenectomy

2021 ◽  
Vol 15 ◽  
pp. 117955492110241
Author(s):  
Hongkai Zhuang ◽  
Zixuan Zhou ◽  
Zuyi Ma ◽  
Shanzhou Huang ◽  
Yuanfeng Gong ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Perineural Invasion ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Cox Regression Analysis ◽  
Ajcc Stage

Background: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) of pancreatic head remains poor, even after potentially curative R0 resection. The aim of this study was to develop an accurate model to predict patients’ prognosis for PDAC of pancreatic head following pancreaticoduodenectomy. Methods: We retrospectively reviewed 112 patients with PDAC of pancreatic head after pancreaticoduodenectomy in Guangdong Provincial People’s Hospital between 2014 and 2018. Results: Five prognostic factors were identified using univariate Cox regression analysis, including age, histologic grade, American Joint Committee on Cancer (AJCC) Stage 8th, total bilirubin (TBIL), CA19-9. Using all subset analysis and multivariate Cox regression analysis, we developed a nomogram consisted of age, AJCC Stage 8th, perineural invasion, TBIL, and CA19-9, which had higher C-indexes for OS (0.73) and RFS (0.69) compared with AJCC Stage 8th alone (OS: 0.66; RFS: 0.67). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the nomogram for OS and RFS were significantly higher than other single parameter, which are AJCC Stage 8th, age, perineural invasion, TBIL, and CA19-9. Importantly, our nomogram displayed higher C-index for OS than previous reported models, indicating a better predictive value of our model. Conclusions: A simple and practical nomogram for patient prognosis in PDAC of pancreatic head following pancreaticoduodenectomy was established, which shows satisfactory predictive efficacy and deserves further evaluation in the future.

scholarly journals Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Yen-Chu Huang ◽  
Meng-Che Wu ◽  
Yu-Hsun Wang ◽  
James Cheng-Chung Wei
Keyword(s):  
Cohort Study ◽  
Cox Regression ◽  
Population Based ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Research Database ◽  
Real World Data ◽  
Childhood Disorders ◽  
Cox Regression Analysis ◽  
Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p &lt; 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within &lt; 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p &lt; 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

scholarly journals Evaluation of independent predictors of in-hospital mortality in patients with severe trauma

2019 ◽  
Vol 147 (7-8) ◽  
pp. 455-460
Author(s):  
Marija Milenkovic ◽  
Zaneta Terzioski ◽  
Adi Hadzibegovic ◽  
Jovana Stanisavljevic ◽  
Ksenija Petrovic ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Cox Regression ◽  
Arterial Oxygen Saturation ◽  
Area Under The Curve ◽  
Case Fatality ◽  
Scoring Systems ◽  
Severe Trauma ◽  
Arterial Oxygen ◽  
Emergency Center ◽  
Cox Regression Analysis

Introduction/Objective. The aim of this study was to determine independent predictors and the best trauma scoring system (REMS, RTS, GSC, SOFA, APPACHE II) of in-hospital mortality in patients with severe trauma at the Department of Emergency, Emergency Center, Clinical Center of Serbia, Belgrade. Methods. Longitudinal study included 208 consecutive patients with severe trauma. In order to determine independent survival contributors, univariate and multivariate Cox regression analyses were performed. The power of above-mentioned scoring systems (measured at admission to the Emergency center) to predict mortality was compared using the area under the curve (AUC). Results. There were 208 patients (159 male, 49 female), with the average age of 47.3 ? 20.7 years. Majority of patients were initially intubated (86.1%) on admission to the emergency department, and 59.6% patients were sedated before intubation. After finishing of diagnostic procedures, 17 patients were additionally intubated, and, at that time, 94.2% patients were on mechanic ventilation. The majority of patients was traumatized in a car crash (33.2%), followed by falls from height (26.4%) and as pedestrians (22.6%). Patients had an average of 24.7 ? 21.2 days spent in intensive care unit. The overall case-fatality ratio was 17/208 (8.2%). In Cox regression analysis only elevated heart rate (HR = 1.03, p = 0.012) and decreased arterial oxygen saturation (SpO2) (HR = 0.91, p = 0.033) singled out as independent contributors to in-hospital mortality of patients with severe trauma. REMS (AUC 0.72 ? 0.64) and SOFA (AUC 0.716 ? 0.067) scores were found fair and similar predictor of in-hospital mortality, while APACHE II (AUC 0.614 ? 0.062) and RTS (0.396 ? 0.068) were poor predictors. Conclusion. Results of this study showed an important role of REMS, which appears to provide balance between the predictive ability and the practical application, and components of REMS in prediction of outcome in patients with severe trauma and that HR and SpO2 are independent predictors of in-hospital mortality.

scholarly journals Endobronchial Therapy With Gentamicin and Dexamethasone After Airway Clearance by Bronchoscopy in Exacerbation of Non-Cystic Fibrosis Bronchiectasis: A Real-World Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiuhong Li ◽  
Beijie Huang ◽  
Hongyan Gu ◽  
Ying Zhou ◽  
Xizheng Shan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Intratracheal Instillation ◽  
Drug Group ◽  
Control Group ◽  
Cox Regression Analysis ◽  
Airway Clearance ◽  
Significant Prolongation

Background: The exacerbation of non-cystic fibrosis bronchiectasis (NCFB) may lead to poor prognosis. The objective of this study was to retrospectively analyze the clinical efficacy and safety of endobronchial therapy with gentamicin and dexamethasone after airway clearance by bronchoscopy in the exacerbation of NCFB.Methods: We retrospectively reviewed 2,156 patients with NCFB between January 2015 and June 2016 and 367 consecutive patients with exacerbation of bronchiectasis who had complete data and underwent airway clearance (AC) by bronchoscopy. The final cohort included 181 cases of intratracheal instillation with gentamicin and dexamethasone after AC (a group with airway drugs named the drug group) and 186 cases of AC only (a group without airway drugs named the control group). The last follow-up was on June 30, 2017.Results: The total cough score and the total symptom score in the drug group were improved compared to those in the control group during 3 months after discharge (p &lt; 0.001). Re-examination of chest HRCT within 4–6 months after discharge revealed that the improvements of peribronchial thickening, the extent of mucous plugging, and the Bhalla score were all significantly improved in the drug group. Moreover, the re-exacerbations in the drug group were significantly decreased within 1 year after discharge. Univariate analysis showed a highly significant prolongation of the time to first re-exacerbation in bronchiectasis due to treatment with airway drugs compared with that of the control group. Multivariate Cox regression analysis showed that the risk of first re-exacerbation in the drug group decreased by 29.7% compared with that of the control group.Conclusion: Endobronchial therapy with gentamicin and dexamethasone after AC by bronchoscopy is a safe and effective method for treating NCFB.

scholarly journals Construction and Validation of a Prognostic Risk Model Based on Autophagy-Related Genes in Hepatocellular Carcinoma Cells

2021 ◽  
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Differential Expression ◽  
Prognostic Model ◽  
Risk Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Differential Expression Analysis ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

scholarly journals Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110588
Author(s):  
Tomonori Aratani ◽  
Hitoshi Tsukamoto ◽  
Takashi Higashi ◽  
Takaaki Kodawara ◽  
Ryoichi Yano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Regression Analysis ◽  
Cox Regression ◽  
Methicillin Resistance ◽  
Univariate Analysis ◽  
Cox Regression Analysis ◽  
Staphylococcus Aureus Bacteremia ◽  
Mortality Outcome ◽  
Delayed Initiation ◽  
Hospital Acquired

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

Intra-Abdominal Hypertension is a Risk Factor for Increased VAP Incidence: A Prospective Cohort Study in the ICU of a Tertiary Hospital

2018 ◽  
Vol 35 (7) ◽  
pp. 700-707 ◽  
Author(s):  
Eleni Papakrivou ◽  
Demosthenes Makris ◽  
Efstratios Manoulakas ◽  
Marios Karvouniaris ◽  
Epaminondas Zakynthinos
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cohort Study ◽  
Cox Regression ◽  
Tertiary Hospital ◽  
University Hospital ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cox Regression Analysis ◽  
Abdominal Hypertension

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period. Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P = .053), while there was an indication for an independent association between VAP and abdominal surgery (1.62 [0.87-3.03]; P = .11] and chronic obstructive pulmonary disease (1.79 [0.96-3.37]; P = .06). Conclusions: Intra-abdominal hypertension is an independent risk factor for increased VAP incidence in critically ill patients who present risk factors for IAH at admission to the ICU.

Clinical Characteristics, Pathology and Outcome of 237 Patients With Synovial Sarcoma: Single Center Experience

2021 ◽  
pp. 106689692110560
Author(s):  
Hao Cheng ◽  
Chi Yihebali ◽  
Hongtu Zhang ◽  
Lei Guo ◽  
Susheng Shi
Keyword(s):  
Overall Survival ◽  
Synovial Sarcoma ◽  
Tumor Size ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Tumor Diameter ◽  
Single Center ◽  
Primary Tumors ◽  
Cox Regression Analysis

Background Synovial sarcoma (SS) is a rare soft tissue sarcoma. Available data regarding survival outcomes of patients with SS still remains limited. In this study, a single center retrospective analysis was performed to investigate the clinical characteristics, pathology and survival outcomes in patients with SS in China. Methods Patient data were systematically reviewed at the National Cancer Center from January 2015 to December 2020. The general information and treatment condition of patients were collected. Overall survival (OS) was evaluated using the Kaplan-Meier and Cox regression method. Results A total of 237 consecutive patients were included in this study (follow-up cut-off date: December, 2020). The median age of patients involved was 35 years (ranging from 5 to 83 years) and the mean tumor diameter was 5.3 cm (ranging from .2 to 26.0 cm). The main findings of the immunohistochemical staining analyses were EMA (111/156) (71%), keratin (32/64) (50.0%), keratin (12/20) (60%), keratin (42/70) (60%), S-100 (18/160) (11%), BCL-2 (128/134) (96%), CD99 (137/148) (93%) and TLE1 (23/26) (88%). It was found that 109 patients (66%) were presented with monophasic subtype and 55 (34%) with biphasic subtype. A total of 137 patients were tested by FISH method and 119 patients (87%) demonstrated SS18 rearrangement, whereas 18 patients (13%) did not show SS18 rearrangement. Generally, it was found that the 3-year OS rate was 86% and the 3-year DFS was 55%. Results of univariate analysis revealed that age, tumor size, tumor site, radiotherapy and targeted therapy were significantly correlated with the overall survival ( P < .05). Further, multivariate Cox regression analysis revealed that age, tumor size and radiotherapy were significantly associated with OS ( P < .05). Conclusions In conclusion, this study shows that the outcomes of patients with SS significantly decrease with age and tumor size. It was evident that radiotherapy is an independent and positive prognostic factor for patients with SS. In addition, it was shown that the prognosis of SS varies with tumor location. For instance, primary tumors in lower extremities have a higher prognosis, whereas tumors located in thorax have a lower prognosis.

Abstract P207: Incidence of Hypertension in Colombia Similar to That Observed Decades Ago in Developed Countries: An Observation From the Chicamocha Cohort Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Juan C Villar ◽  
Luz X Martínez ◽  
Yeny Z Castellanos ◽  
Skarlet M Vásquez ◽  
Víctor M Herrera
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Incidence Rate ◽  
Latin American ◽  
Cox Regression ◽  
Population Attributable Fraction ◽  
Developed Countries ◽  
Cox Regression Analysis ◽  
Incident Cases ◽  
The Impact

Background: Overweight is a modifiable risk factor for high blood pressure (BP). Despite the increasing prevalence of both conditions in the Latin American population, there are no estimates of either the incidence of hypertension or the impact of overweight on it that inform the design and evaluation of individual and community-based preventive interventions in the region. Methods: We conducted a prospective cohort study in a sample of normotensive, blood donors from Bucaramanga, Colombia, who were free of transfusion-transmitted infectious and cardiovascular diseases at baseline. Participants were re-evaluated after a median follow-up of 12 years to determine the incidence of hypertension defined as: 1) Self-reported diagnosis with evidence of pharmacological treatment; 2) Systolic BP >140 mmHg or diastolic BP >90 mmHg (average of two measures in seated position); or 3) Current systolic/diastolic BP >120/80 mmHg with evidence of increments >10/5 mmHg from baseline. We estimated crude incidence rates of hypertension and age- and sex-adjusted hazard ratios (HRs) for baseline overweight (body mass index ≥25 kg/m2) using Cox regression analysis. The population attributable fraction (PAF) for overweight was also assessed. Results: We followed 594 participants (baseline mean age = 38.0 years; 64% male; adherence rate = 78%) at risk of hypertension among which we observed 164 incident cases: Cumulative incidence of 27.6%; incidence rate of 23.4 cases per 1,000 person-years. Incidence rate was similar in men and women (23.4 vs. 23.2 per 1,000 person-years; p>0.05) and tended to increase with age (17.4, 21.2, and 27.8 per 1,000 person-years among participants <30, 30-39, and ≥40 years old, respectively; p>0.05). Participants with overweight at baseline had twice the risk of developing hypertension than participants with normal weight (adjusted-HR = 2.00, 95%CI: 1.11, 3.61). The estimated PAF was 25.7%, considering a national prevalence of overweight equal to 34.6%. Conclusion: The incidence of hypertension in our study is similar to that reported two decades ago in cohorts from developed countries, which is consisting with the ongoing epidemiological transition in Latin America. We also confirmed the role of overweight as a risk factor for hypertension, accounting for about 1 out 4 incident cases. This finding highlights the importance of addressing overweight in our population.

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