Pulse Arrival Time and Pulse Interval as Accurate Markers to Detect Mechanical Alternans.
ABSTRACT: Mechanical alternans (MA) is a powerful predictor of adverse prognosis in patients with heart failure and cardiomyopathy, but its use remains limited due to the need of invasive continuous arterial pressure recordings. This study aims to assess novel cardiovascular correlates of MA in the intact human heart to facilitate affordable and non-invasive detection of MA and advance our understanding of the underlying pathophysiology. Arterial pressure, respiration, and ECG were recorded in 12 subjects with healthy ventricles during voluntarily controlled breathing at different respiratory rate, before and after administration of beta-blockers. MA was induced by ventricular pacing. A total of 67 recordings lasting approximately 90 s each were analyzed. Mechanical alternans (MA) was measured in the systolic blood pressure. We studied cardiovascular correlates of MA, including maximum pressure rise during systole (dPdtmax), pulse arrival time (PAT), pulse wave interval (PI), RR interval (RRI), ECG QRS complexes and T-waves. MA was detected in 30% of the analyzed recordings. Beta-blockade significantly reduced MA prevalence (from 50 to 11%, p < 0.05). Binary classification showed that MA was detected by alternans in dPdtmax (100% sens, 96% spec), PAT (100% sens, 81% spec) and PI (80% sens, 81% spec). Alternans in PAT and in PI also showed high degree of temporal synchronization with MA (80 ± 33 and 73 ± 40%, respectively). These data suggest that cardiac contractility is a primary factor in the establishment of MA. Our findings show that MA was highly correlated with invasive measurements of PAT and PI. Since PAT and PI can be estimated using non-invasive technologies, these markers could potentially enable affordable MA detection for risk-prediction.
Project description:The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD). The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC.
Project description:As non-invasive continuous blood pressure monitoring (NCBPM) has gained wide attraction in the recent decades, many pulse arrival time (PAT) or pulse transit time (PTT) based blood pressure (BP) estimation studies have been conducted. However, most of the studies have used small homogeneous subject pools to generate models of BP based on particular interventions for induced hemodynamic change. In this study, a large open biosignal database from a diverse group of 2309 surgical patients was analyzed to assess the efficacy of PAT, PTT, and confounding factors on the estimation of BP. After pre-processing the dataset, a total of 6,777,308 data pairs of BP and temporal features between electrocardiogram (ECG) and photoplethysmogram (PPG) were extracted and analyzed. Correlation analysis revealed that PAT or PTT extracted from the intersecting-tangent (IT) point of PPG showed the highest mean correlation to BP. The mean correlation between PAT and systolic blood pressure (SBP) was -0.37 and the mean correlation between PAT and diastolic blood pressure (DBP) was -0.30, outperforming the correlation between BP and PTT at -0.12 for SBP and -0.11 for DBP. A linear model of BP with a simple calibration method using PAT as a predictor was developed which satisfied international standards for automatic oscillometric BP monitors in the case of DBP, however, SBP could not be predicted to a satisfactory level due to higher errors. Furthermore, multivariate regression analyses showed that many confounding factors considered in previous studies had inconsistent effects on the degree of correlation between PAT and BP.
Project description:Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction.The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization.Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined.Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals.The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization.
Project description:BACKGROUND:Frequent somatic mutations of BRAF and CTNNB1 were identified in both histological subtypes of craniopharyngioma (adamantinomatous and papillary) which shed light on target therapy to cure this oncogenic disease. The aim of this study was to investigate the noninvasive MRI-based radiomics diagnosis to detect BRAF and CTNNB1 mutations in craniopharyngioma patients. METHODS:Forty-four patients pathologically diagnosed as adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) were retrospectively studied. High-throughput features were extracted from manually segmented tumors in MR images of each case. The modifications-robustness in region of interests and Random Forest-based feature selection methods were adopted to select the most significant features. Random forest classifier with 10-fold cross-validation was applied to build our radiomics model. RESULTS:Four features were selected to make pathological diagnosis between ACP and PCP with area under the receiver operating characteristic curve (AUC) of 0.89, accurancy (ACC) of 0.86, sensitivity (SENS) of 0.89 and specificity (SPEC) of 0.85. The other two features were applied to estimate BRAF V600E mutation with AUC of 0.91, ACC of 0.93, SENS of 0.83 and SPEC of 0.97. Accurate predication of CTNNB1 mutation by three selected features was realized with AUC of 0.93, ACC of 0.86, SENS of 0.86 and SPEC of 0.86. CONCLUSIONS:We developed a reliable MRI-based radiomics approach to perform pathological and molecular diagnosis in craniopharyngioma patients with considerably accurate prediction, which could offer potential guidance for clinical decision-making.
Project description:BACKGROUND:Prader-Willi syndrome (PWS) is a rare and poorly characterized disease. Recent genomic and transcriptomic studies contributed to elucidate the molecular bases of the syndrome. In this study, we characterized the expression of circulating miRNAs in patients with PWS compared to those with non-syndromic obesity in association with liver steatosis. METHODS:MiRNAs were studied by qRT-PCR in serum samples from 30 PWS and 30 non-syndromic obese subjects. RESULTS:MiRNA expression was associated with the presence of the syndrome and to the grade of liver steatosis. MiR-122-5p, miR-151a, miR-92a-3p were up-regulated in obese (4.38-fold, p < 0.01; 2.72-fold, p < 0.05; 1.34-fold p < 0.05, respectively) and were able to differentiate obese from PWS (AUC = 0.81, sens/spec 78/71%). When stratifying groups according to the presence of steatosis, the expression of miR-151a-5p, miR-92a-3p, miR-106b-5p, and miR-93-5p were lower in PWS with steatosis grade 1. Within the group with steatosis grade 1, miR-151a-5p was significantly distinguished PWS from obese (AUC = 0.85, sens/spec 80/85%) and the combination of miR-106b-5p and miR-93-5p showed higher performances in discriminating different grades of steatosis in PWS (AUC = 0.84, sens/spec 93/74%). CONCLUSIONS:MiRNAs represent a tool to better classify and characterize PWS, providing new information about the clinical picture and the extent of steatosis.
Project description:STRATIFY is a prediction tool developed for use in for hospital inpatients, using a 0-5 score to predict patients who will fall. It has been widely used as part of hospital fall prevention plans, but it is not clear how good its operational utility is in a variety of settings.(i) to describe the predictive validity of STRATIFY for identifying hospital inpatients who will fall via systematic review and descriptive analysis, based on its use in several prospective cohort studies of hospital inpatients; (ii) to describe the predictive validity of STRATIFY among inpatients in geriatric rehabilitation via meta-analysis and (iii) in turn, to help practitioners and institutions wishing to implement interventions to prevent in-hospital falls.a systematic literature review of prospective validation studies of STRATIFY for falls prediction in hospital inpatients. For inclusion, studies must report prospective validation cohorts, with sufficient data for calculation of sensitivity (SENS), specificity (SPEC), negative and positive predictive value (NPV and PPV), total predictive accuracy (TPA) and 95% confidence intervals (CI). We performed meta-analysis using precision-weighted fixed- and random-effects models using studies that evaluated STRATIFY among geriatric rehabilitation inpatients.key features of the patient population, setting, study design and numbers of falls/fallers were abstracted. SENS, SPEC, PPV, NPV, TPA and 95% CI were reported for each cohort. Pooled values and chi-squared test for homogeneity were reported for a meta-analysis of studies conducted in geriatric rehabilitation settings.forty-one papers were identified by the search, with eight ultimately eligible for inclusion in the systematic review and four for inclusion in the meta-analysis. The predictive validity of STRATIFY, using a random-effects model, for the four studies involving geriatric patients was as follows: SENS 67.2 (95% CI 60.8, 73.6), SPEC 51.2 (95% CI 43.0, 59.3), PPV 23.1 (95% CI 14.9, 31.2), NPV 86.5 (95% CI 78.4, 94.6). The Q((3)) test for homogeneity was not significant for SENS at P = 0.36, but it was significant at P < 0.01 for SPEC, PPV and NPV. TPA across all four studies varied from 43.2 to 60.0.the current study reveals a relatively high NPV and low PPV and TPA for the STRATIFY instrument, suggesting that it may not be optimal for identifying high-risk individuals for fall prevention. Further, the study demonstrates that population and setting affect STRATIFY performance.
Project description:Purpose:Accurate delineation of the prostate gland and intraprostatic lesions (ILs) is essential for prostate cancer dose-escalated radiation therapy. The aim of this study was to develop a sophisticated deep neural network approach to magnetic resonance image analysis that will help IL detection and delineation for clinicians. Methods and Materials:We trained and evaluated mask region-based convolutional neural networks to perform the prostate gland and IL segmentation. There were 2 cohorts in this study: 78 public patients (cohort 1) and 42 private patients from our institution (cohort 2). Prostate gland segmentation was performed using T2-weighted images (T2WIs), although IL segmentation was performed using T2WIs and coregistered apparent diffusion coefficient maps with prostate patches cropped out. The IL segmentation model was extended to select 5 highly suspicious volumetric lesions within the entire prostate. Results:The mask region-based convolutional neural networks model was able to segment the prostate with dice similarity coefficient (DSC) of 0.88 ± 0.04, 0.86 ± 0.04, and 0.82 ± 0.05; sensitivity (Sens.) of 0.93, 0.95, and 0.95; and specificity (Spec.) of 0.98, 0.85, and 0.90. However, ILs were segmented with DSC of 0.62 ± 0.17, 0.59 ± 0.14, and 0.38 ± 0.19; Sens. of 0.55 ± 0.30, 0.63 ± 0.28, and 0.22 ± 0.24; and Spec. of 0.974 ± 0.010, 0.964 ± 0.015, and 0.972 ± 0.015 in public validation/public testing/private testing patients when trained with patients from cohort 1 only. When trained with patients from both cohorts, the values were as follows: DSC of 0.64 ± 0.11, 0.56 ± 0.15, and 0.46 ± 0.15; Sens. of 0.57 ± 0.23, 0.50 ± 0.28, and 0.33 ± 0.17; and Spec. of 0.980 ± 0.009, 0.969 ± 0.016, and 0.977 ± 0.013. Conclusions:Our research framework is able to perform as an end-to-end system that automatically segmented the prostate gland and identified and delineated highly suspicious ILs within the entire prostate. Therefore, this system demonstrated the potential for assisting the clinicians in tumor delineation.
Project description:Background/Objectives:Early detection of fall risk in persons older than 65 is of clinical relevance, but the diagnostic accuracy of currently used functional tests (eg ?short ?physical ?performance ?battery [SPPB] and ?timed ?up and ?go test [TUG]) to assess older persons' fall risks remains moderate. Recent literature highlights the importance of strong hip abductors to prevent falls. We thus aimed to assess the diagnostic accuracy of hip abductor strength measures to assess older persons' fall risks. Methods:Hip abductor maximum voluntary isometric strength (ABD MVIS), rate of force generation (ABD RFG), and the SPPB and TUG functional fall risk assessments were assessed in 60 persons aged over 65 years (82.0 ± 6.1 years). The diagnostic accuracy (area under the curve [AUC], sensitivity [sens], specificity [spec], positive predictive value [PPV], negative predictive value [NPV], and positive and negative likelihood ratios [LR+, LR-]) was evaluated at a clinically important 90% sensitivity level. Cut-off values for clinical use were calculated. Results:In our population, hip ABD MVIS (AUC 0.8, sens 90.6%, spec 57.1%, PPV 70.7%, NPV 84.2%, LR+ 2.1, LR- 0.2, and cut-off value ? 1.1 N/kg) and hip ABD RFG (AUC 0.8, sens 90.6%, spec 46.4%, PPV 65.9%, NPV 81.3%, LR+ 1.7, LR- 0.2, and cut-off ? 8.47 N/kg/s) show diagnostic accuracy comparable to other fall risk assessments (SPPB and TUG) and a high net sensitivity when used in a test battery. Conclusion:Hip ABD MVIS or RFG shows good diagnostic accuracy to differentiate between older fallers and nonfallers compared to the chosen external criterion history of falls. The high net sensitivity when hip ABD MVIS or RFG ?is combined with currently used fall risk assessments shows promise in contributing value to a test battery and should be investigated further in longitudinal studies.
Project description:Background: Constant blood flow despite changes in blood pressure, a phenomenon called autoregulation, has been demonstrated for various organ systems. We hypothesized that by changing hydrostatic pressures in peripheral arteries, we can establish these limits of autoregulation in peripheral arteries based on local pulse wave velocity (PWV). Methods: Electrocardiogram and plethysmograph waveforms were recorded at the left and right index fingers in 18 healthy volunteers. Each subject changed their left arm position, keeping the right arm stationary. Pulse arrival times (PAT) at both fingers were measured and used to calculate PWV. We calculated ?PAT (?PWV), the differences between the left and right PATs (PWVs), and compared them to the respective calculated blood pressure at the left index fingertip to derive the limits of autoregulation. Results: ?PAT decreased and ?PWV increased exponentially at low blood pressures in the fingertip up to a blood pressure of 70 mmHg, after which changes in ?PAT and ?PWV were minimal. The empirically chosen 20 mmHg window (75-95 mmHg) was confirmed to be within the autoregulatory limit (slope = 0.097, p = 0.56). ?PAT and ?PWV within a 20 mmHg moving window were not significantly different from the respective data points within the control 75-95 mmHg window when the pressure at the fingertip was between 56 and 110 mmHg for ?PAT and between 57 and 112 mmHg for ?PWV. Conclusions: Changes in hydrostatic pressure due to changes in arm position significantly affect peripheral arterial stiffness as assessed by ?PAT and ?PWV, allowing us to estimate peripheral autoregulation limits based on PWV.
Project description:BACKGROUND:Preschool screening for developmental difficulties is increasingly becoming part of routine health service provision and yet the scope and validity of tools used within these screening assessments is variable. The aim of this review is to report on the predictive validity of preschool screening tools for language and behaviour difficulties used in a community setting. METHODS:Studies reporting the predictive validity of language or behaviour screening tools in the preschool years were identified through literature searches of Ovid Medline, Embase, EBSCO CINAHL, PsycInfo and ERIC. We selected peer-reviewed journal articles reporting the use of a screening tool for language or behaviour in a population-based sample of children aged 2-6 years of age, including a validated comparison diagnostic assessment and follow-up assessment for calculation of predictive validity. RESULTS:A total of eleven eligible studies was identified. Six studies reported language screening tools, two reported behaviour screening tools and three reported combined language & behaviour screening tools. The Language Development Survey (LDS) administered at age 2 years achieved the best predictive validity performance of the language screening tools (sens 67%, spec 94%, NPV 88% and PPV 80%). The Strengths and Difficulties Questionnaire (SDQ) administered at age 4 years achieved the best predictive validity compared to other behaviour screening tools (Sens 31%, spec 93%, NPV 84% and PPV 52%). The SDQ and Sure Start Language Measure (SSLM) administered at 2.5 years achieved the best predictive validity of the combined language & behaviour assessments (sens 87%, spec 64%, NPV 97% and PPV 31). Predictive validity data and diagnostic odds ratios identified language screening tools as more effective and achieving higher sensitivity and positive predictive value than either behaviour or combined screening tools. Screening tools with combined behaviour and language assessments were more specific and achieved higher negative predictive value than individual language or behaviour screening tools. Parent-report screening tools for language achieved higher sensitivity, specificity and negative predictive value than direct child assessment. CONCLUSIONS:Universal screening tools for language and behaviour concerns in preschool aged children used in a community setting can demonstrate excellent predictive validity, particularly when they utilise a parent-report assessment. Incorporating these tools into routine child health surveillance could improve the rate of early identification of language and behavioural difficulties, enabling more informed referrals to specialist services and facilitating access to early intervention.