scholarly journals Plasma fibrinolysis, inflammatory markers, and postthrombotic syndrome: preliminary findings from the Kids-DOTT Biobank

2021 ◽  
Vol 5 (1) ◽  
pp. 233-239
Author(s):  
Marisol Betensky ◽  
Ernest K. Amankwah ◽  
Stephanie Brandal ◽  
Allen D. Everett ◽  
Neil A. Goldenberg

Abstract Plasma levels of markers of coagulation and inflammation have been identified as prognostic factors for adult postthrombotic syndrome (PTS). We aimed to determine whether plasma fibrinolytic capacity and cytokine levels during the first 3 months after provoked deep venous thrombosis (DVT) are associated with risk of PTS in young patients. We analyzed plasma biospecimens (6 weeks and 3 months after provoked DVT) and clinical data from a National Heart, Lung, and Blood Institute–sponsored multinational trial of anticoagulation for provoked venous thromboembolism in patients younger than age 21 years (Kids-DOTT). Patients with a provoked extremity DVT who had plasma samples available at both 6-week and 3-month post-DVT time points and PTS assessment at 1 year were included. We measured plasma fibrinolytic capacity using the Clot Formation and Lysis (CloFAL) assay and plasma cytokine levels by multiplex immunoassay. Logistic regression analyses evaluated prognostic associations with PTS. Seventy-nine patients were included (median age, 12.8 years; range, 0.04-20.8 years). PTS developed in 34%. Complete veno-occlusion at 6 weeks after diagnosis of DVT (odds ratio [OR], 3.12; 95% confidence interval [CI], 0.81-11.94; P = .097), low fibrinolytic capacity in plasma at 3 months post-DVT (OR, 2.71; 95% CI, 0.92-7.97; P = .07), and elevated serum amyloid A at 3 months post-DVT (OR, 2.85; 95% CI, 0.98-8.34; P = .055) were identified as putative prognostic factors for development of PTS. In multivariable logistic regression analysis, these factors did not retain a statistically significant independent association with PTS, but these preliminary results warrant further investigation in an independent data set to definitively evaluate these findings and identify additional potential prognostic factors for the development of PTS after a provoked DVT in young patients.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248829
Author(s):  
Marta Betti ◽  
Marinella Bertolotti ◽  
Daniela Ferrante ◽  
Annalisa Roveta ◽  
Carolina Pelazza ◽  
...  

Background Individual differences in susceptibility to SARS-CoV-2 infection, symptomatology and clinical manifestation of COVID-19 have thus far been observed but little is known about the prognostic factors of young patients. Methods A retrospective observational study was conducted on 171 patients aged ≤ 65 years hospitalized in Alessandria’s Hospital from 1st March to 30th April 2020 with laboratory confirmed COVID-19. Epidemiological data, symptoms at onset, clinical manifestations, Charlson Comorbidity Index, laboratory parameters, radiological findings and complications were considered. Patients were divided into two groups on the basis of COVID-19 severity. Multivariable logistic regression analysis was used to establish factors associated with the development of a moderate or severe disease. Findings A total of 171 patients (89 with mild/moderate disease, 82 with severe/critical disease), of which 61% males and a mean age (± SD) of 53.6 (± 9.7) were included. The multivariable logistic model identified age (50–65 vs 18–49; OR = 3.23 CI95% 1.42–7.37), platelet count (per 100 units of increase OR = 0.61 CI95% 0.42–0.89), c-reactive protein (CPR) (per unit of increase OR = 1.12 CI95% 1.06–1.20) as risk factors for severe or critical disease. The multivariable logistic model showed a good discriminating capacity with a C-index value of 0.76. Interpretation Patients aged ≥ 50 years with low platelet count and high CRP are more likely to develop severe or critical illness. These findings might contribute to improved clinical management.


2020 ◽  
Vol 29 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Yilun Xu ◽  
Yaqi Guan ◽  
Xingyi Yang ◽  
Ziqiang Xia ◽  
Jinming Wu

Background and Aims: Studies on the association between homocysteine and non-alcoholic fatty liver disease (NAFLD) have shown inconsistent results. Our study concerns the association of homocysteine with the histological severity of NAFLD, especially non-alcoholic steatohepatitis (NASH) and significant fibrosis (SF) after adjusting for other well-identified risk factors. Methods: This study enrolled 289 patients with biopsy proven NAFLD. The association of homocysteine with the severe histological features was examined using multivariable logistic regression analysis and subgroup analysis. The area under curves (AUC) and Hosmer-Lemeshow goodness-of-fit test for the adjusted logistic regression models was analyzed. Results: After multivariable regression analysis, homocysteine showed significant correlation with NASH (OR 0.79 95%CI: 0.69-0.89), p<0.001) and SF (OR 0.83 95%CI: 0.72-0.95, p=0.009). Spearman’s correlation analysis showed homocysteine levels were inversely correlated with the grade of hepatocellular ballooning and the stage of liver fibrosis (Spearman’s ρ=-0.13, p=0.033; Spearman’s ρ=-0.16, p=0.007), but had no correlation with the severity of steatosis and lobular inflammation. The subgroup analyses showed that homocysteine was strongly associated with NASH in females but was weaker in males (female OR: 0.61 95%CI: 0.45-0.84; male 0.86 95%CI: 0.75-0.99), and on SF showed no significant differences in the subgroups. The models showed good discrimination for NASH (AUC 0.789, 95% CI: 0.736-0.843) and for SF (0.784 95%CI: 0.719-0.848) and calibration (Hosmer-Lemeshow goodness-of-fit test, p=0.346 for NASH; p=0.908 for SF). Conclusion: Elevated serum homocysteine levels are negatively associated with NASH and SF in subjects with NAFLD.  


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 285-285
Author(s):  
C. Morizane ◽  
T. Okusaka ◽  
S. Morita ◽  
K. Tanaka ◽  
H. Ueno ◽  
...  

285 Background: The aim of the present study was to determine prognostic factors in patients with metastatic pancreatic adenocarcinoma (PC) receiving systemic chemotherapy and to construct and validate a prognostic index for metastatic PC. Methods: The relationship between patient characteristics and outcome was examined by multivariate regression analyses of data from 409 consecutive patients with metastatic pancreatic adenocarcinoma who had been treated with a gemcitabine- containing regimen (GEM alone: 302 patients, GEM + cisplatin (CDDP): 39, GEM + 5-flurorouracil (5-FU): 27, GEM + S-1:41), and we stratified the patients into three risk groups according to the number of prognostic factors they had for a poor outcome. A validation data set obtained from 145 patients who had been treated with agents other than GEM (5-FU + CDDP, MTX+5- FU, docetaxel, UFT, S-1, CPT-11) was analyzed. The prognostic index was applied the each of the patients. Results: The multivariate regression analyses revealed that the presence of pain (hazard ratio (HR): 1.692), peritoneal dissemination (HR:1.756), liver metastasis (HR:1.423), and an elevated serum CRP level by > 1.0 mg/dl (HR:1.540) significantly contributed to a shorter survival time. The patients were stratified into three groups according to their number of risk factors and their outcomes of the three groups were significantly different. The median survival times (MSTs) of the low-, intermediate-, and high-risk groups were 11.1, 7.3, and 3.2 months, respectively. When the prognostic index was applied to the validation data set, the respective outcomes of the three groups were found to be significantly differed from each other. The MSTs of the low-, intermediate-, and high-risk groups were 8.6, 5.2, and 2.3 months, respectively. Conclusions: Pain, peritoneal dissemination, liver metastasis, and an elevated serum CRP value are important prognostic factors for patients with metastatic pancreatic adenocarcinoma. No significant financial relationships to disclose.


2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.


2020 ◽  
Vol 21 (7) ◽  
pp. 541-547
Author(s):  
Bao Sun ◽  
Yue Yang ◽  
Mengzi He ◽  
Yanan Jin ◽  
Xiaoyu Cao ◽  
...  

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.


Author(s):  
Dhilsath Fathima.M ◽  
S. Justin Samuel ◽  
R. Hari Haran

Aim: This proposed work is used to develop an improved and robust machine learning model for predicting Myocardial Infarction (MI) could have substantial clinical impact. Objectives: This paper explains how to build machine learning based computer-aided analysis system for an early and accurate prediction of Myocardial Infarction (MI) which utilizes framingham heart study dataset for validation and evaluation. This proposed computer-aided analysis model will support medical professionals to predict myocardial infarction proficiently. Methods: The proposed model utilize the mean imputation to remove the missing values from the data set, then applied principal component analysis to extract the optimal features from the data set to enhance the performance of the classifiers. After PCA, the reduced features are partitioned into training dataset and testing dataset where 70% of the training dataset are given as an input to the four well-liked classifiers as support vector machine, k-nearest neighbor, logistic regression and decision tree to train the classifiers and 30% of test dataset is used to evaluate an output of machine learning model using performance metrics as confusion matrix, classifier accuracy, precision, sensitivity, F1-score, AUC-ROC curve. Results: Output of the classifiers are evaluated using performance measures and we observed that logistic regression provides high accuracy than K-NN, SVM, decision tree classifiers and PCA performs sound as a good feature extraction method to enhance the performance of proposed model. From these analyses, we conclude that logistic regression having good mean accuracy level and standard deviation accuracy compared with the other three algorithms. AUC-ROC curve of the proposed classifiers is analyzed from the output figure.4, figure.5 that logistic regression exhibits good AUC-ROC score, i.e. around 70% compared to k-NN and decision tree algorithm. Conclusion: From the result analysis, we infer that this proposed machine learning model will act as an optimal decision making system to predict the acute myocardial infarction at an early stage than an existing machine learning based prediction models and it is capable to predict the presence of an acute myocardial Infarction with human using the heart disease risk factors, in order to decide when to start lifestyle modification and medical treatment to prevent the heart disease.


2021 ◽  
Vol 13 ◽  
pp. 175628722098404
Author(s):  
Xudong Guo ◽  
Hanbo Wang ◽  
Yuzhu Xiang ◽  
Xunbo Jin ◽  
Shaobo Jiang

Aims: Management of inflammatory renal disease (IRD) can still be technically challenging for laparoscopic procedures. The aim of the present study was to compare the safety and feasibility of laparoscopic and hand-assisted laparoscopic nephrectomy in patients with IRD. Patients and methods: We retrospectively analyzed the data of 107 patients who underwent laparoscopic nephrectomy (LN) and hand-assisted laparoscopic nephrectomy (HALN) for IRD from January 2008 to March 2020, including pyonephrosis, renal tuberculosis, hydronephrosis, and xanthogranulomatous pyelonephritis. Patient demographics, operative outcomes, and postoperative recovery and complications were compared between the LN and HALN groups. Multivariable logistic regression analysis was conducted to identify the independent predictors of adverse outcomes. Results: Fifty-five subjects in the LN group and 52 subjects in the HALN group were enrolled in this study. In the LN group, laparoscopic nephrectomy was successfully performed in 50 patients (90.9%), while four (7.3%) patients were converted to HALN and one (1.8%) case was converted to open procedure. In HALN group, operations were completed in 51 (98.1%) patients and conversion to open surgery was necessary in one patient (1.9%). The LN group had a shorter median incision length (5 cm versus 7 cm, p < 0.01) but a longer median operative duration (140 min versus 105 min, p < 0.01) than the HALN group. There was no significant difference in blood loss, intraoperative complication rate, postoperative complication rate, recovery of bowel function, and hospital stay between the two groups. Multivariable logistic regression revealed that severe perinephric adhesions was an independent predictor of adverse outcomes. Conclusion: Both LN and HALN appear to be safe and feasible for IRD. As a still minimally invasive approach, HALN provided an alternative to IRD or when conversion was needed in LN.


2021 ◽  
Vol 12 ◽  
pp. 215013272110343
Author(s):  
Sewitemariam Desalegn Andarge ◽  
Abriham Sheferaw Areba ◽  
Robel Hussen Kabthymer ◽  
Miheret Tesfu Legesse ◽  
Girum Gebremeskel Kanno

Background Indoor air pollution from different fuel types has been linked with different adverse pregnancy outcomes. The study aimed to assess the link between indoor air pollution from different fuel types and anemia during pregnancy in Ethiopia. Method We have used the secondary data from the 2016 Ethiopian Demographic and Health Survey data. The anemia status of the pregnant women was the dichotomous outcome variable and the type of fuel used in the house was classified as high, medium, and low polluting fuels. Logistic regression was employed to determine the association between the exposure and outcome variables. Adjusted Odds Ratio was calculated at 95% Confidence Interval. Result The proportion of anemia in the low, medium, and high polluting fuel type users was 13.6%, 46%, 40.9% respectively. In the multivariable logistic regression analysis, the use of either kerosene or charcoal fuel types (AOR 4.6; 95% CI: 1.41-18.35) and being in the third trimester (AOR 1.72; 95% CI: 1.12-2.64) were significant factors associated with the anemia status of the pregnant women in Ethiopia. Conclusion According to our findings, the application of either kerosene or charcoal was associated with the anemia status during pregnancy in Ethiopia. An urgent intervention is needed to reduce the indoor air pollution that is associated with adverse pregnancy outcomes such as anemia.


2021 ◽  
pp. 135245852098863
Author(s):  
Frank Dahlke ◽  
Douglas L Arnold ◽  
Piet Aarden ◽  
Habib Ganjgahi ◽  
Dieter A Häring ◽  
...  

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients’ baseline age, using phase III study data (≈8000 patients). Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%–75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.


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