Histological analysis of thrombi retrieved after acute ischemic stroke from large vessel occlusion: from research to clinical practice

Emergent reperfusion therapies have improved acute ischemic stroke prognosis, but many patients are still bound to bad clinical outcome, probably because of our incomplete knowledge of its pathophysiology. Thanks to mechanical thrombectomy, occluding material is available for histological analysis. Several studies investigated the possible relationship between thrombus composition and clinical, procedural, and radiological variables of acute ischemic stroke. The potential value of thrombus analysis as a tool for clinical practice and research is still not defined, as data from the literature are heterogeneous and sometimes conflicting. We propose a review of the existing literature regarding histological analysis of thrombi in acute ischemic stroke. We classified articles on clot composition according to the clinical variable explored in each study. We first distinguished articles about etiology, procedural, and radiological variables, and then we performed a subclassification for each group. This review could help both in the interpretation of thrombus analysis in clinical practice and in its usage for future research.

Prediction Algorithms for Blood Pressure Based on Pulse Wave Velocity Using Health Checkup Data in Healthy Korean Men: Algorithm Development and Validation

Background Pulse transit time and pulse wave velocity (PWV) are related to blood pressure (BP), and there were continuous attempts to use these to predict BP through wearable devices. However, previous studies were conducted on a small scale and could not confirm the relative importance of each variable in predicting BP. Objective This study aims to predict systolic blood pressure and diastolic blood pressure based on PWV and to evaluate the relative importance of each clinical variable used in BP prediction models. Methods This study was conducted on 1362 healthy men older than 18 years who visited the Samsung Medical Center. The systolic blood pressure and diastolic blood pressure were estimated using the multiple linear regression method. Models were divided into two groups based on age: younger than 60 years and 60 years or older; 200 seeds were repeated in consideration of partition bias. Mean of error, absolute error, and root mean square error were used as performance metrics. Results The model divided into two age groups (younger than 60 years and 60 years and older) performed better than the model without division. The performance difference between the model using only three variables (PWV, BMI, age) and the model using 17 variables was not significant. Our final model using PWV, BMI, and age met the criteria presented by the American Association for the Advancement of Medical Instrumentation. The prediction errors were within the range of about 9 to 12 mmHg that can occur with a gold standard mercury sphygmomanometer. Conclusions Dividing age based on the age of 60 years showed better BP prediction performance, and it could show good performance even if only PWV, BMI, and age variables were included. Our final model with the minimal number of variables (PWB, BMI, age) would be efficient and feasible for predicting BP.

Association between the serum estrone-to-estradiol ratio and parameters related to glucose metabolism and insulin resistance in women with polycystic ovary syndrome

Objective: We aimed to evaluate associations between the ratio of serum estrone (E1) to estradiol (E2) and parameters related to serum glucose metabolism and insulin resistance in women with polycystic ovary syndrome (PCOS). Methods: In total, 133 women between the ages of 18 and 33 diagnosed with PCOS were enrolled in this study. All participants with PCOS underwent blood tests to determine hormonal and biochemical metabolic parameters and a standard 2-hour 75-g oral glucose tolerance test. They were divided into two groups according to the serum E1-to-E2 ratio: group 1 (E1/E2 ratio <2.0) and group 2 (E1/E2 ratio ≥2.0). Results: In the comparative analysis, the waist-to-hip ratio (WHR) was the only clinical variable that was significantly different between the two groups. Patients with a higher E1/E2 ratio showed higher fasting insulin levels, homeostasis model for insulin resistance, and postprandial glucose levels at 2 hours (PPG2). In a correlation analysis, only PPG2 was significantly related to the serum E1/E2 ratio. However, after controlling for the confounding effects of body mass index (BMI) and WHR, fasting glucose was also significantly correlated with the serum E1/E2 ratio. Conclusion: Women with PCOS with a higher serum E1/E2 ratio were found to be more likely to show higher fasting insulin and postprandial glucose levels. Significant correlations were found between the serum E1/E2 ratio and both fasting and postprandial serum glucose levels after adjusting for BMI and WHR in women with PCOS.

Machine Learning Based Algorithms to Impute PaO 2 from SpO2 Values and Development of an Online Calculator

We created an online calculator using machine learning algorithms to impute the partial pressure of oxygen (PaO2)/fraction of delivered oxygen (FiO2) ratio using the non-invasive peripheral saturation of oxygen (SpO2) and compared the accuracy of the machine learning models we developed to previously published equations. We generated three machine learning algorithms (neural network, regression, and kernel-based methods) using 7 clinical variable features (N=9,900 ICU events) and subsequently 3 features (N=20,198 ICU events) as input into the models. Data from mechanically ventilated ICU patients were obtained from the publicly available Medical Information Mart for Intensive Care (MIMIC III) database and used for analysis. Compared to seven features, three features (SpO2, FiO2 and PEEP) were sufficient to impute PaO2 from the SpO2. Any of the tested machine learning models enabled imputation of PaO2 from the SpO2 with lower error and showed greater accuracy in predicting PaO2/FiO2 < 150 compared to the previously published log-linear and non-linear equations. Imputation using data from an independent validation cohort of ICU patients (N = 133) from 2 hospitals within the University of Pittsburgh Medical Center (UPMC) showed greater accuracy with the neural network and kernel-based machine learning models compared to the previously published non-linear equation.

Development and Validation of a Ferroptosis-Related Gene Signature and Nomogram for Predicting the Prognosis of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor with high mortality and poor prognosis. Ferroptosis is a newly discovered form of cell death induced by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs). However, the prognostic value of ferroptosis-related genes (FRGs) for ESCC remains unclear. Based on the ESCC dataset from the Gene Expression Omnibus (GEO) database, we identified 39 prognostic FRGs through univariate Cox regression analysis. After LASSO regression and multivariate Cox regression analyses, a multigene signature based on 10 prognostic FRGs was constructed and successfully divided ESCC patients into two risk groups. Patients in the low-risk group showed a significantly better prognosis than patients in the high-risk group. In addition, we combined the risk score with clinical predictors to construct a nomogram for ESCC. The predictive ability of the nomogram was further verified by ROC curves and calibration plots in both the training and validation sets. The predictive power of the nomogram was demonstrated to be better than that of either the risk score or clinical variable alone. Furthermore, functional analysis revealed that the 10-FRG signature was mainly associated with ferroptosis, differentiation and immune response. Connectivity map analysis identified potential compounds capable of targeting FRGs in ESCC. Finally, we demonstrated the prognostic value of SRC gene in ESCC using the clinical samples and found that SRC inhibition sensitized ESCC cells to ferroptosis inducers by in vitro experiments. In conclusion, we identified and verified a 10-FRG prognostic signature and a nomogram, which provide individualized prognosis prediction and provide insight into potential therapeutic targets for ESCC.

A Study to Assess the Effectiveness of Vitis vinifera soaks on Hemoglobin Level among Anemic Students in a Selected Colleges at Vellore

An experimental study was conducted to assess the effectiveness of vitis vinifera soak on hemoglobin level among anemic students in selected colleges at Vellore. Quantitative evaluative approach was used for this study and the researcher adopted a true experimental research design. The sample was conducted among 60 anemic students in selected colleges at Vellore, in which 30 were in experimental group and 30 were in control group. The sample was selected by using Probability simple random sampling technique with lottery method. The researcher adopted Kristen M. Swanson theory as a conceptual framework. There are six different hypothesis were tested in this study. The Structured interview schedule was used to collect the demographic and clinical variable. Sahli’s hemoglobinometer was used to assess the hemoglobin level. Experimental group received intervention of vitis vinifera soak for 21 days in the morning and control group advised to follow daily routine and no intervention is given. In both groups, on 22nd day the researcher was conducted post test by using same tool. The data were analyzed using both descriptive and inferential statistics. The study revealed that the mean post test score in control group was 9.29 where as in experimental group the mean post test score was 9.82, the mean difference was 0.53. The obtained ‘t’ value was 2.24 which was statistically significant (P<0.01). These findings revealed that the students in experimental group had increased hemoglobin level after administering vitis vinifera soak compared to the control group.

Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib

Introduction: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)—clinically benign pulmonary opacities that resolve despite continued osimertinib treatment—and are not associated with the clinical manifestations of typical TKI-associated ILDs. Methods: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients’ clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. Results: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6–80) and median duration time 14 weeks (range 8–37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. Conclusions: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases.

OS05.4.A Do neurocognitive deficits explain the differences between brain tumour patients and their proxies assessing the patient’s I-ADL?

BACKGROUND Neurocognitive deficits are common among brain tumour patients, and may impact on patient awareness of deficits in instrumental activities in daily life (IADL). This study aimed to examine differences between patient-reported and proxy-reported assessments of the patient’s performance of IADL, and whether the level of (dis)agreement is associated with neurocognitive deficits. MATERIAL AND METHODS A phase III EORTC questionnaire measuring IADL in brain tumour patients (EORTC IADL-BN32) and six neurocognitive test measures were administered as part of a larger multicentre international study designed to develop a brain tumour specific IADL questionnaire. Bland-Altman plots and Mann-Whitney U tests were used to evaluated patient- and proxy-reported IADL on a group level. Subsequently, Mann-Whitney U tests were performed to compare patient-proxy difference scores (patient IADL score - their proxy IADL score) between patients who were considered clearly neurocognitively impaired (≥2 neurocognitive test measures; ≤2.0 SD below healthy controls) and patients who were not. Furthermore, multinomial logistic regression analyses were performed to examined which sociodemgraphic, clinical, and particularly neurocognitive variables were independently associated with patients and proxies differing in their evaluation of patient’s IADL. RESULTS Patients (N=81) and proxies (N=81), on group level, did not significantly differ on either the IADL individual item or scale scores. However, significant differences were found on patient-proxy difference scores between patients who were (N=37) and were not (N=44) considered clearly neurocognitively impaired for 10/32 individual items and one of the scales (i.e. Scale 4: Administrative tasks), all showing that the proxies of clearly neurocognitively impaired patients reported more problems relative to the patients themselves, compared to proxies of patients not clearly neurocognitively impaired. Furthermore, for each scale, a neurocognitive variable, either impaired information processing speed, cognitive flexibility, verbal fluency or the number of neurocognitive test measures impaired, was found to be independently associated with proxies reporting more problems. For 4/5 scales, a clinical variable was additionally independently associated with proxies reporting more problems. Only one variable was independently associated with patient reporting more problems, namely being in active treatment was found to be associated with patients reporting more problems on Scale 4: Administrative tasks. CONCLUSION Results imply a consistent trend of clearly neurocognitively impaired patients underreporting problems with IADL compared to their proxies. It would therefore be advised to administer both the patient- and proxy-version of the EORTC IADL-BN32, particularly if neurocognitive deficits are presumed.

Network analyses reveal negative link between changes in adipose tissue GDF15 and BMI during dietary induced weight loss

Context Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. Objective To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during three steps of a two-phase dietary intervention (DI). Design AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low calorie diet (LCD) at 800 kcal/d) followed with a 6-month ad libitum randomized DI. Methods Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. RT-qPCR was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. Results During LCD, five modules were found, of which three included at least one bio-clinical variable. Change in BMI connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated to changes in expression of genes encoding secreted protein (GDF15, CCL3 and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. Conclusion Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.