Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy

ObjectiveEndocrine complications characterised patients with β thalassaemia (βT). In particular, thyroid dysfunction occurs frequently in βT major, but its long-term natural history is poorly understood.DesignA total of 72 βT patients were followed for 8 years. The incidence of thyreopathies, defined as the primary study endpoint, was assessed. The aim of this study was to analyse the prognostic role of ferritin for thyreopathies in patients with major and intermedia βT. The power of different iron chelators to treat iron overload and to prevent or reverse thyreopathies was also assessed.MethodsPatients were treated with chelators with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying thyroid dysfunction in thalassaemic patients. Kaplan–Meier curves were generated to assess incidence of thyreopathy. Adjusted risk estimates for thyreopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis.ResultsPatients with thyroid dysfunction were characterised by higher ferritin when compared with patients without thyreopathies (1500 (872–2336) vs 513 (370–698) μg/l;P<0.0001). Patients with ferritin values above 1800 μg/l experienced a significantly faster evolution to endpoint (log-rank (χ2): 7.7;P=0.005). Ferritin predicted high risk of thyroid dysfunction independently of confounding factors (hazard ratio: 1.20;P<0.0001). The intensification of chelation therapy led to an amelioration of thyroid function.ConclusionsFerritin represents a prognostic marker for βT patients and a predictive factor for progression to thyroid dysfunction. Intensive chelation therapy allows the prevention and reversibility of thyroid complications.

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Abstract WP5: Outcomes Are Not Different Between Patients With Intermediate and High Dwi-aspects After Stent-retriever Thrombectomy

Stroke ◽

10.1161/str.47.suppl_1.wp5 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Woong Yoon ◽

Seul Kee Kim ◽

Tae Wook Heo ◽

Byung Hyun Baek ◽

Jaechan Park

Keyword(s):

Functional Outcome ◽

Time Window ◽

Multivariate Logistic Regression Analysis ◽

Area Under The Curve ◽

Stent Retriever ◽

Operating Characteristics ◽

Anterior Circulation ◽

Good Outcome ◽

Characteristics Analysis ◽

The Impact

Introduction: Few studies have investigated the association between pretreatment DWI-ASPECTS and functional outcome after stent-retriever thrombectomy in patients with acute anterior circulation stroke. Hypothesis: Patients with acute stroke and DWI-ASPECTS <7 might have a similar chance of a good outcome compared to those with a higher DWI-ASPECTS, if they are treated with a stent-retriever thrombectomy in a short time window. However, this hypothesis has not been tested. Thus, this study aimed to investigate the impact of DWI-ASPECTS on functional outcome in patients with acute anterior circulation stroke who received a stent-retriever thrombectomy. Methods: We retrospectively analyzed the clinical and DWI data from 171 patients with acute anterior circulation stroke who were treated with stent-retriever thrombectomy within 6 hours of symptom onset. The DWI-ASPECTS was assessed by two readers. A good outcome was defined as a modified Rankin Scale score of 0-2 at 3 months. Results: The median DWI-ASPECTS was 7 (interquartile range, 6-8). Receiver operating characteristics analysis revealed an ASPECTS ≥ 7 was the optimal cut-off to predict a good outcome at 3 months (area under the curve=0.57; sensitivity, 75.3%; specificity, 34.4%). The rates of good outcome, symptomatic hemorrhage, and mortality were not different between high DWI-ASPECTS (scores of 7-10) and intermediate (scores of 4-6) groups. In patients with an intermediate DWI-ASPECTS, good outcome was achieved in 46.5% (20/43) of patients with successful revascularization (modified TICI 2b or 3), whereas no patients without successful revascularization had a good outcome ( P =0.016). In multivariate logistic regression analysis, independent predictors of good outcome were age and successful revascularization. Conclusions: Our study suggested that treatment outcomes were not different between patients with a high DWI-ASPECTS and those with an intermediate DWI-ASPECTS who underwent stent-retriever thrombectomy for acute anterior circulation stroke. Thus, patients with an intermediate DWI-ASPECTS otherwise eligible for endovascular therapy should not be excluded for stent-retriever thrombectomy or stroke trials.

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Evaluation of cerebral glioma using 3T diffusion kurtosis tensor imaging and the relationship between diffusion kurtosis metrics and tumor cellularity

Journal of International Medical Research ◽

10.1177/0300060517712654 ◽

2017 ◽

Vol 45 (4) ◽

pp. 1347-1358 ◽

Cited By ~ 8

Author(s):

Chong Qi ◽

Song Yang ◽

Lanxi Meng ◽

Huiyuan Chen ◽

Zhenlan Li ◽

...

Keyword(s):

Mean Diffusivity ◽

Area Under The Curve ◽

Tumor Grade ◽

Superior Performance ◽

Cerebral Glioma ◽

Operating Characteristics ◽

Significant Difference ◽

Characteristics Analysis ◽

Sensitivity Specificity ◽

Diffusion Kurtosis

Purpose To evaluate the clinical utility of diffusion kurtosis tensor imaging in the characterization of cerebral glioma and investigate correlations between diffusion and kurtosis metrics with tumor cellularity. Materials and Methods A group of 163 patients (age: 40.5 ± 11.5 years) diagnosed with cerebral glioma underwent diffusion kurtosis tensor imaging with a 3 T scanner. Diffusion and kurtosis metrics were measured in the solid part of tumors, and their abilities to distinguish between tumor grades was evaluated. In addition, we analyzed correlations between the metrics and tumor cellularity. Results Mean kurtosis (MK) revealed a significant difference between each pair of tumor grades ( P < 0.05) and produced the best performance in a receiver operating characteristics analysis (area under the curve [AUC] = 0.89, sensitivity/specificity = 83.3/90). In contrast, mean diffusivity (MD) revealed a significant difference only for tumor grade II versus IV ( P < 0.05). No significant differences between grades were detected with fractional anisotropy (FA; P > 0.05). Thus, kurtosis metrics exhibited a positive and strong correlation with tumor cellularity, while MD exhibited a negative or weak correlation with tumor cellularity. Conclusion Diffusion kurtosis metrics, particularly MK, demonstrated superior performance in distinguishing cerebral glioma of different grades compared with conventional diffusion metrics, and were closely associated with tumor cellularity.

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Predicting backward erosion piping hazard, Lower Mississippi Valley, USA

Quarterly Journal of Engineering Geology and Hydrogeology ◽

10.1144/qjegh2020-035 ◽

2020 ◽

Vol 54 (1) ◽

pp. qjegh2020-035

Author(s):

S. Semmens ◽

W. Zhou

Keyword(s):

Logit Model ◽

Area Under The Curve ◽

Internal Erosion ◽

Mississippi Valley ◽

Operating Characteristics ◽

Final Model ◽

Lower Mississippi Valley ◽

Characteristics Analysis ◽

Backward Erosion Piping ◽

Using Data

Backward erosion piping (BEP) is a form of internal erosion and common failure mode along levees. Despite over a century of study, predicting where BEP will initiate is still a considerable challenge. This study proposes a new model for predicting BEP initiation focused on the widest range of applicability. A logit model is trained using data from 15 sites along the Lower Mississippi Valley. The included parameters are independent of geography or geological regime and exhibit recorded or suspected correlations to BEP. Three significant factors (95% confidence interval) are retained for the final model: cumulative clay thickness within the blanket (odds ratio (OR) 0.520), critical gradient (OR 0.001) and exit gradient (OR 63.15). Receiver operating characteristics analysis indicates an area under the curve of 0.823. The model demonstrates 71% classification accuracy, a dramatic 10% increase over previous logit model attempts. Model results are most applicable within 150 m of the levee toe to predict new incidents of BEP initiation. The final model is a useful tool for BEP assessment and mitigation efforts.

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P13.12 Development and validation of a radiomic model for the preoperative prediction of transsphenoidal surgical response in patients with acromegaly

Neuro-Oncology ◽

10.1093/neuonc/noz126.233 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii65-iii65

Author(s):

Y Fan ◽

M Feng ◽

R Wang

Keyword(s):

Clinical Features ◽

Validation Cohort ◽

Treatment Strategies ◽

Area Under The Curve ◽

Support Vector ◽

Individual Treatment ◽

Multivariable Logistic Regression Analysis ◽

Operating Characteristics ◽

Preoperative Prediction ◽

Characteristics Analysis

Abstract BACKGROUND The preoperative prediction of transsphenoidal surgical (TSS) response is important for determining individual treatment strategies for acromegaly. Therefore, this study aimed to predict TSS response in a non-invasive way based on radiomic analysis. MATERIAL AND METHODS 273 patients with acromegaly were enrolled and divided into primary (n=180) and validation cohorts (n=93) according to time point. Radiomic features were extracted from the MR images and determined using the ‘Elastic Net’ feature selection algorithm. A radiomic signature was built using a support vector machine. Subsequently, multivariable logistic regression analysis was used to select the most informative clinical features, and a radiomic model, incorporating the radiomic signature and selected clinical features, was constructed and used as the final predictive model. The performance of this radiomic model was validated using receiver operating characteristics analysis, and its calibration, discriminating ability, and clinical usefulness were assessed. RESULTS The radiomic signature, which was constructed with six radiomic features selected using the primary cohort, showed a favorable discriminatory ability in the validation cohort. The radiomic model incorporating the radiomic signature and three selected clinical features showed good discrimination abilities and calibration, with an area under the curve (AUC) of 0.93 for the primary cohort and 0.89 for the validation cohort. The radiomic model better estimated the treatment responses of patients with acromegaly than did the clinical features. Decision curve analysis showed the radiomic model was clinically useful. CONCLUSION This radiomic model could aid neurosurgeons in the preoperative prediction of TSS response in patients with acromegaly, and could contribute to determining individual treatment strategies.

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A phase II trial of neoadjuvant ABI-007, carboplatin, and gemcitabine (ACG) in patients with locally advanced carcinoma of the bladder.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.244 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 244-244 ◽

Cited By ~ 3

Author(s):

D. C. Smith ◽

P. Grivas ◽

S. Daignault ◽

K. Hafez ◽

D. P. Wood ◽

...

Keyword(s):

Bladder Cancer ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Area Under The Curve ◽

Invasive Disease ◽

Clinical Staging ◽

Study Endpoint ◽

Primary Study ◽

Target Area ◽

Upper Limit

244 Background: Neoadjuvant cisplatin-based chemotherapy benefits patients with bladder cancer, particularly in the 30% with pathologic complete response (pCR) at cystectomy. Many patients with bladder cancer are not candidates for cisplatin. Taxane-based regimens have activity in urothelial cancer. ABI-007 is an albumin-bound paclitaxel with increased activity and decreased toxicity compared to standard paclitaxel preparations. Methods: Eligible pts have T2-4,N0,M0 or Tany,N1- 3,M0 bladder cancer with ECOG PS 0-1, and adequate marrow (granulocyte count > 1,500/mm3, platelet > 100,000/mm3, and hemoglobin > 9.0 g/dl), hepatic (transaminases < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, and bilirubin < 1.5 mg/dl) and renal function (serum creatinine < 2.0 mg/dl and/or creatinine clearance > 40 ml/min). Pts are treated with intravenous ABI-007 260 mg/m2 and carboplatin (target area under the curve=5) on day 1 with gemcitabine 800 mg/m2 on days 1 and 8, followed by radical cystectomy after three cycles of therapy. The primary study endpoint is the proportion of patients with pCR at cystectomy. Results: 27 patients have been enrolled. By clinical staging, 20 had T2 disease, 5 had T3, 2 had T4, and 2 had nodal enlargement. All are evaluable for toxicity with 22 evaluable for response (exclusions-3 for change in dose schedule, 1 each for refusal of cystectomy and withdrawal from study). 25/27 patients received all three cycles (78 total cycles) with doses reduced in 26 cycles for toxicity. All patients had transient grade 3-4 neutropenia and 17 received filgrastim, but only two had febrile neutropenia. Six pts had pCR with an additional 5 having residual carcinoma in situ (CIS) and 1 with T1 disease at cystectomy. 54% of evaluable patients had no muscle invasive disease at cystectomy. Conclusions: Neoajuvant ACG is active in bladder cancer with pCR rate nearing 30% and nearly as many patients with CIS but no residual invasive disease. Marrow toxicity is significant but manageable. [Table: see text]

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MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis

AJP Renal Physiology ◽

10.1152/ajprenal.00148.2013 ◽

2013 ◽

Vol 305 (8) ◽

pp. F1220-F1227 ◽

Cited By ~ 121

Author(s):

Lin-Li Lv ◽

Yu-Han Cao ◽

Hai-Feng Ni ◽

Min Xu ◽

Dan Liu ◽

...

Keyword(s):

Renal Fibrosis ◽

Area Under The Curve ◽

Membrane Vesicles ◽

Tubulointerstitial Fibrosis ◽

Operating Characteristics ◽

Immunogold Staining ◽

Potential Biomarker ◽

Characteristics Analysis ◽

Urinary Exosome ◽

Average Size

Micro (mi)RNAs are frequently dysregulated in the development of renal fibrosis. Exosomes are small membrane vesicles that could be isolated from urine secreted from all nephron segments. Here we sought to observe for the first time whether miRNA in urine exosome could serve as a potential biomarker of renal fibrosis. Urine samples were collected from 32 chronic kidney disease (CKD) patients who underwent kidney biopsy and 7 controls. Exosome was isolated and confirmed by immunogold staining of exosome marker. Members of miR-29, miR-200, and RNU6B as endogenous control were detected by RT quantitative PCR. Electronic microscopy verified a typical shape of exosome with average size of 65.1 nm and labeled it with anti-CD9 and anti-aquaporin 2 antibody. Members of miR-29 and miR-200 are readily measured with reduced levels compared with controls ( P < 0.05) and can robustly distinguish CKD from controls [area under the curve (AUC) varied from 0.902 to 1 by receiver operating characteristics analysis]. miR-29c correlated with both estimated glomerular filtration rate ( r = 0.362; P < 0.05) and degree of tubulointerstitial fibrosis ( r = −0.359; P < 0.05) for CKD patients. Moreover, miRNA in exosome was decreased in mild fibrosis group compared with moderated to severe group. miR-29a and miR-29c could predict degree of tubulointerstitial fibrosis with AUC of 0.883 and 0.738 ( P < 0.05). The sensitivity and specificity for distinguishing mild from moderate to severe fibrosis were 93.8 and 81.3% with the use of miR-29a and 68.8 and 81.3% for miR-29c. Overall, miR-29c in urinary exosome correlates with both renal function and degree of histological fibrosis, suggesting it as a novel, noninvasive marker for renal fibrosis.

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C-reactive protein/albumin ratio is a prognostic indicator for predicting surgical intervention and mortality in neonates with necrotizing enterocolitis

Pediatric Surgery International ◽

10.1007/s00383-021-04879-1 ◽

2021 ◽

Author(s):

Amir T. Mohd Amin ◽

Rafdzah A. Zaki ◽

Florian Friedmacher ◽

Shazia P. Sharif

Keyword(s):

Necrotizing Enterocolitis ◽

Surgical Intervention ◽

Area Under The Curve ◽

Prognostic Indicator ◽

Operating Characteristics ◽

C Reactive Protein ◽

Critical Pathway ◽

Reactive Protein ◽

Characteristics Analysis ◽

Prolonged Hospital

Abstract Purpose The role of hypoalbuminemia and raised C-reactive protein (CRP) levels in predicting critical prognosis has been described extensively in adult literature. However, there are limited studies in pediatrics, particularly neonates. The CRP/albumin (CRP/ALB) ratio is often associated with higher mortality, organ failure and prolonged hospital stay. We hypothesized that the serum CRP/ALB ratio has a prognostic value in predicting surgery and mortality in neonates with necrotizing enterocolitis (NEC). Methods Retrospective review of all neonates with clinical and radiological evidence of non-perforated NEC that were treated in a tertiary-level referral hospital between 2009 and 2018. General patient demographics, laboratory parameters and outcomes were recorded. Receiver operating characteristics analysis was performed to evaluated optimal cut-offs and area under the curve (AUC) with 95% confidence intervals (CI). Results A total of 191 neonates were identified. Of these, 103 (53.9%) were born at ≤ 28 weeks of gestation and 101 (52.9%) had a birth weight of ≤ 1000 g. Eighty-four (44.0%) patients underwent surgical intervention for NEC. The overall survival rate was 161/191 (84.3%). A CRP/ALB ratio of ≥ 3 on day 2 of NEC diagnosis was associated with a statistically significant higher likelihood for surgery [AUC 0.71 (95% CI 0.63–0.79); p < 0.0001] and mortality [AUC 0.66 (95% CI 0.54–0.77); p = 0.0150], respectively. Conclusions A CRP/ALB ratio of ≥ 3 on day 2 is indicative of a critical pathway in neonates with radiologically confirmed, non-perforated NEC. This could be used as an additional criterion to guide parental counselling in NEC for surgical intervention and mortality.

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Autoantibodies to Mi-2 alpha and Mi-2 beta in patients with idiopathic inflammatory myopathy

Rheumatology ◽

10.1093/rheumatology/kez092 ◽

2019 ◽

Vol 58 (9) ◽

pp. 1655-1661 ◽

Cited By ~ 4

Author(s):

Michaelin Richards ◽

Ignacio García-De La Torre ◽

Yelitza C. González-Bello ◽

Mónica Vázquez-Del Mercado ◽

Lilia Andrade-Ortega ◽

...

Keyword(s):

Inflammatory Myopathy ◽

Area Under The Curve ◽

Idiopathic Inflammatory Myopathy ◽

Control Group ◽

Operating Characteristics ◽

High Area ◽

Characteristics Analysis ◽

Group 3 ◽

Low Levels ◽

Good Agreement

Abstract Objectives The objective of this study was to compare the results obtained from different assays for the detection of anti-Mi-2 antibodies, which are important markers in the diagnosis of DM. Methods The study included 82 patients (68 females/14 males), most of whom had DM (n = 57), followed by PM (n = 16) and juvenile DM (n = 9). All samples were tested using a novel particle-based multi-analyte technology (PMAT) (Inova Diagnostics, research use only) in parallel with a line immunoassay (LIA: Euroimmun). To assess clinical specificity for the PMAT assay, a total of 775 disease and healthy controls were tested. Results 29 samples were positive by at least one test for anti-Mi-2 antibodies. Of those, 24 were Mi-2β LIA+, five were Mi-2α LIA+ and 23 Mi-2 PMAT+. The comparison shows varying agreement between the different methods (kappa 0.27–0.77). When LIA results were used as reference for receiver operating characteristics analysis, high area under the curve values were found for both PMAT vs LIA Mi-2α and LIA Mi-2β. When analysing the results in the context of the myositis phenotype, PMAT associated closest with the DM phenotype. In the control group, 3/775 controls (all low levels) were anti-Mi-2+ resulting in a sensitivity and specificity of 28.1% and 99.6%, respectively. Conclusion Overall, good agreement was found between LIA and PMAT for anti-Mi-2 antibodies, which is important for the standardization of autoantibodies. Anti-Mi-2β antibodies measured by PMAT tend be more highly associated with the clinical phenotype of DM.

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Hyperuricemia as a prognostic marker for long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries

Nutrition & Metabolism ◽

10.1186/s12986-021-00636-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Wenjian Ma ◽

Side Gao ◽

Sizhuang Huang ◽

Jiansong Yuan ◽

Mengyue Yu

Keyword(s):

Myocardial Infarction ◽

Coronary Arteries ◽

Cox Regression ◽

Serum Uric Acid Level ◽

Area Under The Curve ◽

Study Endpoint ◽

Major Adverse Cardiovascular Events ◽

Primary Study ◽

Propensity Score Matching Analysis ◽

Increased Risk

Abstract Background Hyperuricemia (HUA) has been proved as a predictor of worse outcomes in patients with coronary artery disease. Here, we investigated the prognostic value of HUA in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA). Methods A total of 1179 MINOCA patients were enrolled and divided into HUA and non-HUA groups. HUA was defined as a serum uric acid level ≥ 420 μmol/L in men or ≥ 357 μmol/L in women. The primary study endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan–Meier, Cox regression, and receiver-operating characteristic analyses were performed. Results Patients with HUA (prevalence of 23.5%) had a significantly higher incidence of MACE (18.7% vs. 12.8%; p = 0.015) than patients without during the median follow-up of 41.7 months. HUA was closely associated with an increased risk of MACE even after multivariable adjustment (hazard ratio 1.498, 95% confidence interval: 1.080 to 2.077; p = 0.016). HUA remained a robust risk factor of MACE after propensity score matching analysis. Moreover, HUA showed an area under the curve (AUC) of 0.59 for predicting MACE. Incorporation of HUA to the thrombolysis in myocardial infarction (TIMI) score yielded a significant improvement in discrimination for MACE. Conclusions HUA was independently associated with poor prognosis after MINOCA. Routine assessment of HUA may facilitate risk stratification in this specific population.

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Functional assessment of myocardial ischaemia by intracoronary ECG

Open Heart ◽

10.1136/openhrt-2020-001447 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001447

Author(s):

Marius Reto Bigler ◽

Michael Stoller ◽

Fabien Praz ◽

George C M Siontis ◽

Raphael Grossenbacher ◽

...

Keyword(s):

Study Endpoint ◽

Primary Study ◽

Structural Parameter ◽

Coronary Perfusion ◽

Maximal Heart Rate ◽

Operating Characteristics ◽

Fractional Flow ◽

Coronary Syndrome ◽

Flow Reserve ◽

St Segment

IntroductionIn patients with chronic coronary syndrome, percutaneous coronary intervention targets haemodynamically significant stenoses, that is, those thought to cause ischaemia. Intracoronary ECG (icECG) detects ischaemia directly where it occurs. Thus, the goal of this study was to test the accuracy of icECG during pharmacological inotropic stress to determine functional coronary lesion severity in comparison to the structural parameter of quantitative angiographic per cent diameter stenosis (%S), as well as to the haemodynamic indices of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR).MethodThe primary study endpoint of this prospective trial was the maximal change in icECG ST-segment shift during pharmacological inotropic stress induced by dobutamine plus atropine obtained within 1 min after reaching maximal heart rate(=220 - age). IcECG was acquired by attaching an alligator clamp to the angioplasty guidewire positioned downstream of the stenosis. For the pressure-derived stenosis severity ratios, coronary perfusion pressure and simultaneous aortic pressure were continuously recorded.ResultsThere was a direct linear relation between icECG ST-segment shift and %S: icECG=−0.8+0.03*%S (r2=0.164; p<0.0001). There were inverse linear correlations between FFR and %S: FFR=1.1–6.1*10–3*%S (r2=0.494; p<0.0001), and between iFR and %S: iFR=1.27–8.6*10–3*%S (r2=0.461; p<0.0001). Using a %S-threshold of ≥50% as the reference for structural stenosis relevance, receiver operating characteristics-analysis of absolute icECG ST-segment shift during hyperemia showed an area under the curve (AUC) of 0.678±0.054 (p=0.002; sensitivity=85%, specificity=50% at 0.34 mV). AUC for FFR was 0.854±0.037 (p<0.0001; sensitivity=64%, specificity=96% at 0.78), and for iFR it was 0.816±0.043 (p<0.0001;sensitivity=62%, specificity=96% at 0.83).ConclusionsHyperaemic icECG ST-segment shift detects structurally relevant coronary stenotic lesions with high sensitivity, while they are identified highly specific by FFR and iFR.

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