Lower Area Under The Curve Values Research Articles

Latent Heat Loss Through Fabrics During an Alternate Simulated Work–Rest Sequence

Humans produce different rates of sweating depending on the intensity level of a given activity. The clothing worn during the activity has a significant effect on the latent heat loss that can occur before, during, and after the activity. The water adsorption and spreading properties of a material yield differences in the amount of heat exchange that can occur between the person and the environment. Current test methods evaluate this using a value known as evaporative resistance, which is used to determine the heat exchange potential of a material. However, this value is only taken once the material has reached “steady state” and does not consider the sweating period before steady state is reached, or the drying period after steady state is reached. Therefore, an area under the curve (AUC) value was derived during these periods to compare the heat exchange properties of different materials. A sweating guarded hot plate was used to simulate different sweat rates, and therefore activity levels, to compare materials constructed of cotton, viscose, polyester, and wool. The overall latent heat loss of the hydrophobic wool was much less compared to the other samples with a gentler slope and lower AUC values than the other samples. It was found that the segment of time analyzed has a significant impact on the conclusion drawn about the latent heat loss of a material, p < 0.0001. Sweat rate also has a significant impact on the heat loss value, p < 0.0001, but is perhaps less useful when comparing samples to each other. It was found that comparing the different periods of the test could yield different conclusions when comparing materials for latent heat loss. Several current test methods do not consider phases outside of the steady state period and therefore miss valuable information pertinent to user comfort during these phases, especially in the post-exercise phase.

Multiparametric MRI-based whole-liver radiomics for predicting early-stage liver fibrosis in rabbits.

To develop and validate a whole-liver radiomic model using multiparametric MRI for predicting early-stage liver fibrosis (LF) in rabbits. A total of 134 rabbits (early-stage LF, n = 91; advanced-stage LF, n = 43) who underwent liver magnetic resonance elastography (MRE), hepatobiliary phase, dynamic contrast enhanced (DCE), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging, and T2* scanning were enrolled and randomly allocated to either the training or validation cohort. Whole-liver radiomic features were extracted and selected to develop a radiomic model and generate quantitative Rad-scores. Then, multivariable logistic regression was utilized to determine the Rad-scores associated with early-stage LF, and effective features were integrated to establish a combined model. The predictive performance was assessed by the area under the curve (AUC). The MRE model achieved superior AUCs of 0.95 in the training cohort and 0.86 in the validation cohort, followed by the DCE-MRI model (0.93 and 0.82), while the IVIM model had lower AUC values of 0.91 and 0.82, respectively. The Rad-scores of MRE, DCE-MRI and IVIM were identified as independent predictors associated with early-stage LF. The combined model demonstrated AUC values of 0.96 and 0.88 for predicting early-stage LF in the training and validation cohorts, respectively. Our study highlights the remarkable performance of a multiparametric MRI-based radiomic model for the individualized diagnosis of early-stage LF. This is the first study to develop a combined model by integrating multiparametric radiomic features to improve the accuracy of LF staging.

Quality assessment of the MRI-radiomics studies for MGMT promoter methylation prediction in glioma: a systematic review and meta-analysis.

To evaluate the methodological quality and diagnostic accuracy of MRI-based radiomic studies predicting O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in gliomas. PubMed Medline, EMBASE, and Web of Science were searched to identify MRI-based radiomic studies on MGMT methylation in gliomas published until December 31, 2022. Three raters evaluated the study methodological quality with Radiomics Quality Score (RQS, 16 components) and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis Or Diagnosis (TRIPOD, 22 items) scales. Risk of bias and applicability concerns were assessed with QUADAS-2 tool. A meta-analysis was performed to estimate the pooled area under the curve (AUC) and to assess inter-study heterogeneity. We included 26 studies, published from 2016. The median RQS total score was 8 out of 36 (22%, range 8-44%). Thirteen studies performed external validation. All studies reported AUC or accuracy, but only 4 (15%) performed calibration and decision curve analysis. No studies performed phantom analysis, cost-effectiveness analysis, and prospective validation. The overall TRIPOD adherence score was between 50% and 70% in 16 studies and below 50% in 10 studies. The pooled AUC was 0.78 (95% CI, 0.73-0.83, I2 = 94.1%) with a high inter-study heterogeneity. Studies with external validation and including only WHO-grade IV gliomas had significantly lower AUC values (0.65; 95% CI, 0.57-0.73, p < 0.01). Study RQS and adherence to TRIPOD guidelines was generally low. Radiomic prediction of MGMT methylation status showed great heterogeneity of results and lower performances in grade IV gliomas, which hinders its current implementation in clinical practice. MGMT promoter methylation status appears to be variably correlated with MRI radiomic features; radiomic models are not sufficiently robust to be integrated into clinical practice to accurately predict MGMT promoter methylation status in patients with glioma before surgery. • Adherence to the indications of TRIPOD guidelines was generally low, as was RQS total score. • MGMT promoter methylation status prediction with MRI radiomic features provided heterogeneous diagnostic accuracy results across studies. • Studies that included grade IV glioma only and performed external validation had significantly lower diagnostic accuracy than others.

Validation and modification of the AFHCHDC7 risk score for predicting the long-term cardiovascular disease risk after the Great East Japan Earthquake: The Fukushima Health Management Survey

ObjectivesThis study aimed to evaluate the predictive performance of the AFHCHDC7 risk score, developed for post-disaster cardiovascular disease (CVD) risk management, for 6-year CVD risk in Fukushima Prefecture after the Great East Japan Earthquake compared to the Suita CVD risk score and to modify the AFHCHDC7 risk score. MethodsThe present study comprised 14,779 individuals aged 30–79 years with no history of CVD at baseline who underwent the comprehensive health checkup and completed the mental health and lifestyle survey in 2011. Its primary outcome was CVD onset (myocardial infarction, stroke). Logistic regression analyses were used to construct a prediction model. The calibration performance and discrimination performance according to area under the curve (AUC) values were evaluated for each model. ResultsThe AFHCHDC7 risk score had lower AUC values than the Suita CVD risk score from baseline for 6 years (AUC: 0.65). The modified AFHCHDC7 risk score (age-stratified, adding sex and smoking) had higher predictive performance than the Suita CVD risk score from baseline for 6 years (AUC: 0.74 vs. 0.73). ConclusionsThe modified AFHCHDC7 score may be useful as a simple tool for identifying individuals’ long-term CVD risk in disaster evacuees. The utility of this score needs to be carefully evaluated in future studies.

The role of single-nucleotide polymorphisms of some candidate genes of carbohydrate and fat metabolism in predicting the risk of type 2 diabetes mellitus

Over the past decade, some progress has been made in identifying and characterizing variants of DNA polymorphisms of genes associated with predisposition to type 2 diabetes mellitus (T2DM). The analysis of gene polymorphisms in combination with socio-demographic, clinical and metabolic parameters can be considered as a promising approach to identify high-risk groups for the development of T2DM. The review includes foreign and domestic studies of predictive models for the risk of developing T2DM comprising single-nucleotide polymorphisms, published in the period from 2006 to 2021. The search for the literature sources was carried out on the PubMed platform. The predictive accuracy of polygenic risk scores was assessed by comparing the area under the curve (AUC). The most commonly used clinical predictors of T2DM risk are sex, age, BMI, family history of diabetes, presence of arterial hypertension, waist circumference, waist-to-hip ratio. All genetic risk models for T2DM had lower AUC values than phenotypic (clinical) risk models. The addition of genetic factors has, in turn, improved AUC compared to purely clinical risk models in many studies, which may be a useful tool for primary prevention of T2DM. However, only those polymorphisms that strongly confirm their association with the risk of developing T2DM in different populations studies should be added to predictive risk scales.

CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest gastrointestinal cancers with a 5-year survival rate of less than 10%. Biomarkers for early PDAC detection are useful in treating patients with PDAC. Extracellular vesicles (EVs) are lipid-bound vesicles that are potential biomarkers of various diseases such as PDAC. In this study, we quantitatively measured the serum levels of EVs (CD63+-EVs) or platelet-derived EVs (CD41+- and CD61+-EVs) and evaluated their potential use as biomarkers of PDAC.MethodsWe measured the serum levels of CD63+-, CD41+-, CD61+-EVs using sandwich enzyme-linked immunosorbent assay based on Tim4 with specificity for phosphatidylserine on EVs in age- and sex-matched healthy controls (HCs, n = 39) and patients with PDAC (n = 39). We also examined the effect of tumor burden on the serum EV levels after surgical resection (n = 28). CA19-9, a clinical PDAC biomarker, was also measured for comparison.ResultsSerum levels of CD63+-EVs, CD41+-EVs, and CD61+-EVs were significantly increased in patients with PDAC compared to HCs. Receiver operating characteristic analysis revealed that CD63+-EVs exhibited the highest diagnostic performance to discriminate patients with PDAC from HCs (area under the curve (AUC): 0.846), which was comparable to CA19-9 (AUC: 0.842). CA19-9 showed lower AUC values in early stages (I–II, AUC: 0.814) than in late stages (III–IV, AUC: 0.883) PDAC. Conversely, CD63+-EVs, CD41+-EVs, and CD61+-EVs showed comparable AUCs between early- and late-stage PDAC. The combined use of CA19-9 and CD63+-EVs showed a higher diagnostic performance for early-stage PDAC (AUC: 0.903) than CA19-9. The serum levels of CD63+-EVs, CD41+-EVs, CD61+-EVs, and CA19-9 decreased significantly after surgical resection, demonstrating that EVs are increased in sera of patients depending on the tumor burden.ConclusionsThe serum levels of CD63+-EVs and platelet-derived EVs (CD41+-EVs, CD61+-EVs) are increased in patients with PDAC than HCs. Since CD63+-EVs showed a high AUC to discriminate patients with PDAC from HCs; they might be useful as potential biomarkers for PDAC.

Abstract 8916: Frequency Analysis of the QRS Differentiates Left Bundle Branch Pacing from RV Septal Pacing

Introduction: Left bundle branch pacing (LBBP) is an increasingly common procedure. The pacing lead is advanced via the RV septum into the myocardium with the goal of directly stimulating the LBB for more effective left ventricular (LV) activation. We have previously found that QRS frequency is useful for assessing successful LV activation in cardiac resynchronization therapy. Hypothesis: We surmised that the QRS complex of patients who underwent LBBP would exhibit significantly different frequency characteristics than simple RV septal pacing. Methods: We analyzed the QRS frequency of 36 patients with normal LV ejection fraction (≥50%) who have undergone LBBP for comparison to 33 patients who underwent RV septal pacing. Time frequency analysis was performed which yields a weighted average frequency (AKA: “center of energy” frequency or Cf) of the QRS. Chest lead V2 yielded the best frequency discrimination. We performed ROC analysis for all significant variables in multivariate analysis to obtain the area under the curve (AUC) predictive value. Results: See table: QRS duration, LVAT: paced LV activation time, AUC: area under the curve. Conclusions: Our data show that the QRS in LBB paced patients is significantly shorter and has a much higher Cf in lead V2 with high predictive value by ROC analysis compared to RV septal pacing. Baseline LVEF and paced LVAT exhibited lower AUC values. Such measurements may be of use during implantation of the pacing lead to ensure capture of the LBB when LV activation times and/or morphologic changes are equivocal.

Development and Assessment of an Otolaryngology-Specific Surgical Priority Scoring System.

ObjectiveTo develop and assess an otolaryngology-specific surgical priority scoring system that incorporates varying levels of mucosal involvement.Study DesignRetrospective cohort.SettingAcademic medical center.MethodsA novel mucosal score was developed based on best available evidence. This mucosal score was incorporated into the Medically Necessary, Time-Sensitive (MeNTS) score to generate a MeNTS-Mucosal (MeNTS-M) score. A retrospective cohort of patients was identified to assess the surgical priority scoring systems. Inclusion criteria included all scheduled surgical procedures between March 23, 2020, and April 17, 2020. Decisions about whether to proceed or cancel were made based on best clinical judgment by surgeons, without use of any surgical priority scores. The predictive value of the surgical priority scoring systems was assessed in this retrospective cohort.ResultsThe median MeNTS score was significantly lower in adult patients whose surgery proceeded compared to those for whom the surgery was cancelled (48 vs 56; P = .004). Mucosal and MeNTS-M scores were not statistically different based on whether surgery proceeded. Among adult patients, the highest area under the curve (AUC) was for the MeNTS scoring system (0.794); both the mucosal and MeNTS-M systems had lower AUC values (which were significantly lower than the AUC for the MeNTS scoring system).ConclusionThis study represents development and assessment of the first otolaryngology-specific surgical priority score and incorporates varying levels of mucosal disruption. The combined MeNTS-M scoring system could be a valuable tool in appropriately triaging otolaryngology–head and neck surgery procedures.

Comparison of the different voxel sizes in the estimation of peri-implant fenestration defects using cone beam computed tomography: an ex vivo study

BackgroundTo examine the influence of voxel sizes to detect of peri-implant fenestration defects on cone beam computed tomography (CBCT) images.Materials and methodsThis study performed with three sheep heads both maxilla and mandible and two types of dental implant type 1 zirconium implant (Zr40) (n = 6) and type 2 titanium implant (Ti22) (n = 10). A total of 14 peri-implant fenestrations (8 buccal surfaces, 6 palatal/lingual surface) were created while 18 surfaces (8 buccal, 10 palatal/lingual) were free of fenestrations. Three observers have evaluated the images of fenestration at each site. Images obtained with 0.75 mm3, 0.100 mm3, 0.150 mm3, 0.200 mm3, and 0.400 mm3 voxel sizes. For intra- and inter-observer agreements for each voxel size, Kappa coefficients were calculated.ResultsIntra- and inter-observer kappa values were the highest for 0.150 mm3, and the lowest in 0.75 mm3 and 0.400 mm3 voxel sizes for all types of implants. The highest area under the curve (AUC) values were found higher for the scan mode of 0.150 mm3, whereas lower AUC values were found for the voxel size for 0.400 mm3. Titanium implants had higher AUC values than zirconium with the statistical significance for all voxel sizes (p ≤ 0.05).ConclusionA voxel size of 0.150 mm3 can be used to detect peri-implant fenestration bone defects. CBCT is the most reliable diagnostic tool for peri-implant fenestration bone defects.

Permeability Measures Predict Hemorrhagic Transformation after Ischemic Stroke.

ObjectiveWe sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measures in ischemic stroke patients receiving alteplase only.MethodsA pixel‐based analysis of pretreatment CT perfusion (CTP) was undertaken to define the optimal CTP permeability thresholds to predict the likelihood of HT. We then compared previously proposed predictors of HT using regression analyses and receiver operating characteristic curve analysis to produce an area under the curve (AUC). We compared AUCs using χ2 analysis.ResultsFrom 5 centers, 1,407 patients were included in this study; of these, 282 had HT. The cohort was split into a derivation cohort (1,025, 70% patients) and a validation cohort (382 patients or 30%). The extraction fraction (E) permeability map at a threshold of 30% relative to contralateral had the highest AUC at predicting any HT (derivation AUC 0.85, 95% confidence interval [CI], 0.79–0.91; validation AUC 0.84, 95% CI 0.77–0.91). The AUC improved when permeability was assessed within the acute perfusion lesion for the E maps at a threshold of 30% (derivation AUC 0.91, 95% CI 0.86–0.95; validation AUC 0.89, 95% CI 0.86–0.95). Previously proposed associations with HT and parenchymal hematoma showed lower AUC values than the permeability measure.InterpretationIn this large multicenter study, we have validated a highly accurate measure of HT prediction. This measure might be useful in clinical practice to predict hemorrhagic transformation in ischemic stroke patients before receiving alteplase alone. ANN NEUROL 2020;88:466–476

Role of dynamic perfusion magnetic resonance imaging in patients with local advanced rectal cancer.

BACKGROUNDThe management of rectal cancer patients is mainly based on the use of the magnetic resonance imaging (MRI) technique as a diagnostic tool for both staging and restaging. After treatment, to date, the evaluation of complete response is based on the histopathology assessment by using different tumor regression grade (TRG) features (e.g., Dworak or Mandard classifications). While from the radiological point of view, the main attention for the prediction of a complete response after chemotherapy treatment focuses on MRI and the potential role of diffusion-weighted images and perfusion imaging represented by dynamic-contrast enhanced MRI. The main aim is to find a reliable tool to predict tumor response in comparison to histopathologic findings.AIMTo investigate the value of dynamic contrast-enhanced perfusion-MRI parameters in the evaluation of the healthy rectal wall and tumor response to chemo-radiation therapy in patients with local advanced rectal cancer with histopathologic correlation.METHODSTwenty-eight patients with biopsy-proven rectal adenocarcinoma who underwent a dynamic contrast-enhanced MR study performed on a 1.5T MRI system (Achieva, Philips), before (MR1) and after chemoradiation therapy (MR2), were enrolled in this study. The protocol included T1 gadolinium enhanced THRIVE sequences acquired on axial planes. A dedicated workstation was used to generate color permeability maps. Region of interest was manually drawn on tumor tissue and normal rectal wall, hence the following parameters were calculated and statistically analyzed: Relative arterial enhancement (RAE), relative venous enhancement (RVE), relative late enhancement (RLE), maximum enhancement (ME), time to peak and area under the curve (AUC). Perfusion parameters were related to pathologic TRG (Mandard's criteria; TRG1 = complete regression, TRG5 = no regression).RESULTSTen tumors (36%) showed complete or subtotal regression (TRG1-2) at histology and classified as responders; 18 tumors (64%) were classified as non-responders (TRG3-5). Perfusion MRI parameters were significantly higher in the tumor tissue than in the healthy tissue in MR1 (P < 0.05). At baseline (MR1), no significant difference in perfusion parameters was found between responders and non-responders. After chemo-radiation therapy, at MR2, responders showed significantly (P < 0.05) lower perfusion values [RAE (%) 54 ± 20; RVE (%) 73 ± 24; RLE (%): 82 ± 29; ME (%): 904 ± 429] compared to non-responders [RAE (%): 129 ± 45; RVE (%): 154 ± 39; RLE (%): 164 ± 35; ME (%): 1714 ± 427]. Moreover, in responders group perfusion values decreased significantly at MR2 [RAE (%): 54 ± 20; RVE (%): 73 ± 24; RLE (%): 82 ± 29; ME (%): 904 ± 429] compared to the corresponding perfusion values at MR1 [RAE (%): 115 ± 21; RVE (%): 119 ± 21; RLE (%): 111 ± 74; ME (%): 1060 ± 325]; (P < 0.05). Concerning the time-intensity curves, the AUC at MR2 showed significant difference (P = 0.03) between responders and non-responders [AUC (mm2 × 10-3) 121 ± 50 vs 258 ± 86], with lower AUC values of the tumor tissue in responders compared to non-responders. In non-responders, there were no significant differences between perfusion values at MR1 and MR2.CONCLUSIONDynamic contrast perfusion-MRI analysis represents a complementary diagnostic tool for identifying vascularity characteristics of tumor tissue in local advanced rectal cancer, useful in the assessment of treatment response.

Evaluation of functionally weighted dose-volume parameters for thoracic stereotactic ablative radiotherapy (SABR) using CT ventilation

For the purpose of reducing radiation pneumontisis (RP), four-dimensional CT (4DCT)-based ventilation can be used to reduce functionally weighted lung dose. This study aimed to evaluate the functionally weighted dose-volume parameters and to investigate an optimal weighting method to realize effective planning optimization in thoracic stereotactic ablative radiotherapy (SABR).Forty patients treated with SABR were analyzed. Ventilation images were obtained from 4DCT using deformable registration and Hounsfield unit-based calculation. Functionally-weighted mean lung dose (fMLD) and functional lung fraction receiving at least x Gy (fVx) were calculated by two weighting methods: thresholding and linear weighting. Various ventilation thresholds (5th-95th, every 5th percentile) were tested. The predictive accuracy for CTCAE grade ≧ 2 pneumonitis was evaluated by area under the curve (AUC) of receiver operating characteristic analysis.AUC values varied from 0.459 to 0.570 in accordance with threshold and dose-volume metrics. A combination of 25th percentile threshold and fV30 showed the best result (AUC: 0.570). AUC values with fMLD, fV10, fV20, and fV40 were 0.541, 0.487, 0.548 and 0.563 using a 25th percentile threshold. Although conventional MLD, V10, V20, V30 and V40 showed lower AUC values (0.516, 0.477, 0.534, 0.552 and 0.527), the differences were not statistically significant.fV30 with 25th percentile threshold was the best predictor of RP. Our results suggested that the appropriate weighting should be used for better treatment outcomes in thoracic SABR.

Acute metabolic responses following different resistance exercise protocols

Resistance exercise (RE) can be an excellent modality for glycemic control. Studies have demonstrated that a single RE session can reduce glycemia in subjects with or without diabetes. Little is known about the dose-response effect of RE on glycemic control. This study aimed to investigate the acute metabolic responses after different RE protocols. Eighty-nine males were separated into six groups that completed RE protocols: 2 sets of 18 repetitions (2 × 18 at 50% of 1-repetition maximum (1RM); n = 19); 3 sets of 12 repetitions (3 × 12 at 70% of 1RM; n = 14); 4 sets of 9 repetitions (4 × 9 at 80% of 1RM; n = 13); 6 sets of 6 repetitions (6 × 6 at 90% of 1RM; n = 19); circuit (2 × 18 at 50% of 1RM; n = 12); and a control session (n = 12). The exercise sequence consisted of 8 exercises. An oral glucose tolerance test was conducted with metabolic measurements immediately after each RE protocol and every 15 min until 120 min of recovery. All groups exhibited significantly lower values (p < 0.05) in the glucose area under the curve (AUC) when compared with control over a 120 min monitoring period. The 6 × 6 group showed a significantly lower glucose AUC versus the 3 × 12 and 4 × 9 groups (p = 0.004; p = 0.001, respectively). As for blood lactate, the control and 6 × 6 groups exhibited lower AUC values versus all other groups (p < 0.05), and AUC for glucose and lactate concentration showed a negative and significant correlation (r = -0.46; p < 0.0001). It appears that a combination of 9-12 repetitions per set and 3-4 sets per muscle group might be optimal for acute postprandial glucose control.

Histologic Factors Associated With Need for Surgery in Patients With Pedunculated T1 Colorectal Carcinomas

Most patients with pedunculated T1 colorectal tumors referred for surgery are not found to have lymph node metastases, and were therefore unnecessarily placed at risk for surgery-associated complications. We aimedto identify histologic factors associated with need for surgery in patients with pedunculated T1 colorectal tumors. We performed a cohort-nested matched case-control study of 708 patients diagnosed with pedunculated T1 colorectal tumors at 13 hospitals in The Netherlands, from January 1, 2000 through December 31, 2014, followed for a median of 44 months (interquartile range, 20-80 months). We identified 37 patients (5.2%) who required surgery (due to lymph node, intramural, or distant metastases). These patients were matched with patients with pedunculated T1 colorectal tumors without a need for surgery (no metastases, controls, n= 111). Blinded pathologists analyzed specimens from eachtumor, stained with H&E. We evaluated associations between histologic factors and patient need for surgery using univariable conditional logistic regression analysis. We used multivariable least absolute shrinkage and selection operator (LASSO; an online version of the LASSO model is available at:http://t1crc.com/calculator/) regression to develop models for identification of patients with tumors requiring surgery, and tested the accuracy of our model by projecting our case-control data toward the entire cohort (708 patients). We compared our model with previously developed strategies to identify high-risk tumors: conventional model 1 (based onpoor differentiation, lymphovascular invasion, or Haggitt level 4) and conventional model 2 (based on poor differentiation, lymphovascular invasion, Haggitt level 4, or tumor budding). We identified 5 histologic factors that differentiated cases from controls: lymphovascular invasion, Haggitt level 4 invasion, muscularis mucosae type B (incompletely or completely disrupted), poorly differentiated clusters and tumor budding, which identified patients who required surgery with an area under the curve (AUC) value of 0.83 (95% confidence interval, 0.76-0.90). When we used a clinically plausible predicted probability threshold of ≥4.0%, 67.5% (478 of 708) of patients were predicted to not need surgery. This threshold identified patients who required surgery with 83.8% sensitivity (95% confidence interval, 68.0%-93.8%) and 70.3% specificity (95% confidence interval, 60.9%-78.6%). Conventional models 1 and 2 identified patients who required surgery with lower AUC values (AUC, 0.67; 95% CI, 0.60-0.74; P= .002 and AUC, 0.64; 95% CI, 0.58-0.70; P < .001, respectively) than our LASSO model. When we applied our LASSO model with a predicted probability threshold of ≥4.0%, the percentage of missed cases (tumors mistakenly assigned as low risk) was comparable (6of 478 [1.3%]) to that of conventional model 1 (4 of 307 [1.3%]) and conventional model 2 (3 of 244 [1.2%]). However, the percentage of patients referred for surgery based on our LASSO model was much lower (32.5%, n= 230) than that for conventional model 1 (56.6%, n= 401) or conventional model2 (65.5%, n= 464). In a cohort-nested matched case-control study of 708 patients with pedunculated T1 colorectal carcinomas, we developed a modelbased on histologic features of tumors that identifies patients who require surgery (due to high risk of metastasis) withgreater accuracy than previous models. Our model might be used to identify patients most likely to benefit from adjuvant surgery.

Assessing the risk of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients by monitoring oxidative-stress markers in plasma.

The level of antioxidants, such as thiol-containing tripeptide glutathione (GSH), in cytomegalovirus (CMV)-infected cells is notably increased. We previously showed that GSH levels in plasma, as measured by untargeted 1H nuclear magnetic resonance, are higher in allogeneic stem cell transplant (allo-SCT) recipients who subsequently develop CMV viraemia. We hypothesized that the net level of oxidative-stress markers present in plasma may be reduced in patients who develop CMV DNAaemia compared to those who do not. We serially monitored the levels of malondialdehyde (MDA) and carbonylated proteins (CPs) early after allo-SCT and assessed whether they could predict the occurrence of CMV DNAaemia. MDA levels were measured in 43 patients (28 had CMV DNAaemia) and CPs were quantified in 53 patients (38 patients developed CMV DNAaemia). The area under the curve (AUC) value for MDA, but not for CPs, was significantly lower in patients who subsequently developed CMV DNAaemia compared to those who remained DNAaemia-free (P=0.043). A trend toward lower MDA AUC values was observed in episodes of CMV DNAaemia with faster CMV replicative kinetics and in those who reached higher peak CMV DNA levels. Moreover, receiver operating characteristic curve analyses indicated that the MDA biomarker had the predictive ability to discriminate between patients with or without subsequent CMV DNAaemia (AUC=0.69, 95 % confidence interval 0.51-0.85, P=0.05). In summary, serial quantitation of MDA may be useful for individualizing antiviral prophylaxis therapies (targeted prophylaxis) in the upcoming era of new antiviral drugs with improved safety profiles.

Intraoperative auditory steady-state monitoring during surgery in the cerebellopontine angle for estimation of postoperative hearing classes.

OBJECTIVE Brainstem auditory evoked potentials (BAEPs) have been used for intraoperative monitoring of the auditory nerve for many years. However, BAEPs yield limited information about the expected postoperative hearing quality and speech perception. The auditory steady-state response (ASSR) enables objective audiograms to be obtained in patients under anesthesia. These ASSRs could be used for intraoperative estimation of hearing classes to improve the postoperative outcome and quality of life. Studies investigating the clinical use of ASSRs during total intravenous anesthesia are currently lacking. The work presented in this article therefore investigates the application of ASSRs for intraoperative estimation of hearing classes. METHODS In 43 patients undergoing surgery for vestibular schwannoma, ASSR measurements were performed at the beginning and end of the surgical procedure. ASSR stimuli consisted of 80-dB hearing level amplitude-modulated tones with 5-minute duration, 90-Hz modulation, and 3 different carrier frequencies: 500, 1000, and 2000 Hz. Stimulation was performed unilaterally with and without contralateral masking, using single and combined carriers. Evoked responses were recorded and analyzed in the frequency domain. ASSRs were compared with extraoperative hearing classes and BAEPs using ANOVA, correlation, and receiver operating characteristic statistics. RESULTS ASSRs yielded high and consistent area under the curve (AUC) values (mean 0.83) and correlation values (mean -0.63), indicating reliable prediction of hearing classes. Analysis of BAEP amplitude changes showed lower AUC (mean 0.79) and correlation values (0.63, 0.37, and 0.50 for Waves I, III, and V, respectively). Latencies showed low AUC values (mean 0.6) and no significant correlation. Combination of several carriers for simultaneous evaluation reduced ASSR amplitudes and respective AUC values. Contralateral masking did not show a significant effect. CONCLUSIONS ASSRs robustly estimate hearing class in patients under total intravenous anesthesia, even when using short measurement durations. The method provides a diagnostic performance that exceeds conventional BAEP monitoring and enables objective and automated evaluation. On the basis of these findings, continuous intraoperative auditory monitoring could become a promising alternative or adjunct to BAEPs.

Specificity of Compensatory Reserve and Tissue Oxygenation as Early Predictors of Tolerance to Progressive Reductions in Central Blood Volume.

We previously reported that measurements of muscle oxygen saturation (SmO2) and the compensatory reserve index (CRI) provided earlier indication of reduced central blood volume than standard vital signs (e.g., blood pressure, heart rate, arterial oxygen saturation). In the present study, we hypothesized that the CRI would provide greater sensitivity and specificity to detect progressive decrease in central circulating blood volume compared with SmO2. Continuous noninvasive measures of CRI (calculated from feature changes in the photoplethysmographic arterial waveforms) were collected from 55 healthy volunteer subjects before and during stepwise lower body negative pressure (LBNP) to the onset of hemodynamic decompensation. Near infrared spectroscopy was used on the forearm to obtain deep SmO2, hydrogen ion concentration ([H]), and hemoglobin volume (HbT; decreases reflect vasoconstriction). CRI decreased by 97% in a linear fashion across progressive blood volume loss, with no clinically significant alterations in vital signs. The receiver operating characteristic (ROC) area under the curve (AUC) for the CRI was 0.91, with a sensitivity of 0.87 and specificity of 0.80, when predicting decompensation at progressive levels of LBNP. In comparison, SmO2, [H], and HbT had significantly lower ROC AUC, sensitivity and specificity values for detecting the same outcome. Consistent with our hypothesis, CRI detected central hypovolemia with significantly greater specificity than measures of tissue metabolism. Single measurement of CRI may enable more accurate triage, while CRI monitoring may allow for earlier detection of casualty deterioration.

Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients

BackgroundIn HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group.MethodsEarly RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4).ResultsEighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC 0-4h (median: 1469 μg*h/L [range 936–3677]) compared with monoinfected patients (2030 μg*h/L [851–7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 μg*h/L [110–425] versus 271 μg*h/L [82–1091], p = 0.001).ConclusionsThese results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC0-4h values observed in the more immunosuppressed coinfected patients.

Ruminal ochratoxin A degradation—Contribution of the different microbial populations and influence of diet

The mycotoxin ochratoxin A (OTA) is degraded extensively in the rumen. In this study, the relative contribution of different rumen microbial populations (MP) and the effect of diet on degradation of OTA were evaluated in a factorial design experiment. Degradation of OTA was quantified by using the Hohenheim gas test (HGT) in vitro fermentation system. Five different HGT diets were used (concentrate:forage proportions (C:F) – 10:90, 30:70, 50:50, 70:30, 90:10), and donor animals were fed diets with the respective ratio. Diets with the highest concentrate content were supplied with and without 10g/kg sodium bicarbonate (70:30 BC and 90:10 BC). The MP included whole rumen fluid, fungi+protozoa, bacteria+protozoa, protozoa and bacteria+fungi. Protozoa numbers were counted after 24h and OTA and ochratoxin alpha (OTα) analysed at 0, 4, 8, 12, 24h. Area under the curve (AUC) and half-life were calculated for the latter two. The short average OTA half-life for whole rumen fluid of 2.6h (1.3–4.5h) demonstrates the high OTA degradation capacity of the rumen MP (i.e., standard HGT inoculum) and corresponds well with published in vivo results. Both MP and diet affected OTA degradation. Interactions among factors occurred (P<0.001), which made it necessary to do further comparisons within factor levels. Among MP, those with bacteria (bacteria+fungi and bacteria+protozoa) had lower AUC values (P<0.001) for OTA (196–673ng/mlh, meaning higher degradation capacity, than those without bacteria (fungi+protozoa and protozoa; 701–1206ng/mlh). Whole rumen fluid had the lowest AUC values (146–249ng/mlh; P<0.05). Diet had a quadratic effect (P=0.001) on protozoal numbers with minimum values for the lowest and highest C:F ratios, for bacteria+protozoa, fungi+protozoa and protozoa, but no corresponding effect was found for OTA degradation parameters. While the generally high capacity to degrade OTA was confirmed, results for the contribution of different microbial groups shed new light on ruminal OTA degradation.

Visfatin Genotypes Influence Glucose And Obesity-related Variables And Their Aerobic Exercise Training Responses

Previous research has linked the proposed adipokine visfatin and its gene (PBEF1) polymorphisms with glucose and obesity-related conditions; however, no one has examined them in connection with aerobic exercise training in generally healthy older individuals. PURPOSE: To determine whether PBEF1 polymorphisms are associated with the response of glucose and obesity-related variables to aerobic exercise training. METHODS: Following the completion of 6 wks of dietary stabilization, 116 healthy, sedentary, middle-aged, Caucasian men and women underwent 24 wks of aerobic exercise training. DEXA was used to assess body composition, and oral glucose tolerance testing was used to determine glucose and insulin response variables, including total area under the curve (AUC) and insulin sensitivity (IS), before and after 6 months of aerobic exercise training. TaqMan and RFLP assays were used to determine PBEF1 genotypes, and ANCOVA was used to test for differences between genotype groups. RESULTS: There were several associations at baseline between glucose and obesity-related variables and the PBEF1 polymorphisms. The -4689 (rs2110385) TT genotype group had lower insulin AUC (p < 0.01) and higher IS (p < 0.02) values than the GG genotype group, whereas PBEF1 -1001 (rs9770242) G allele carriers had lower fasting insulin (p < 0.03), lower body mass index (BMI; p < 0.02), and higher IS values than the TT genotype group (p = 0.04). Additionally, the -948 T allele carriers group had lower glucose AUC (p = 0.03), lower insulin AUC (p < 0.02), and higher IS values than the GG genotype group (p < 0.02). Finally, the SER301SER (rs2302559) TT genotype group had lower fasting insulin (p < 0.02), lower insulin AUC (p < 0.01), and higher IS (p < 0.01) values than the CC genotype group. The SER301SER polymorphism also influenced aerobic exercise training-induced changes in percent body fat (p < 0.02) and BMI (p = 0.03). CONCLUSIONS: Our results suggest that variation at the PBEF1 locus is associated with baseline and aerobic exercise training-induced changes in glucose and obesity-related variables. Future studies need to address the physiological mechanisms and functional significance of visfatin polymorphic variation.