P-value Range Research Articles

P5719Plasma proteomics identify plaque-related proteins that predict long-term recurrent coronary events in patients with acute coronary syndrome

Abstract Background Coronary plaque burden and composition drive recurrent ischaemic events in coronary artery disease. Purpose We first investigated the association between plasma proteins and coronary plaque characteristics in a cohort of asymptomatic individuals with low-intermediate Framingham Risk Score. Plaque-related proteins were further evaluated in a second cohort of patients with acute coronary syndrome (ACS) to determine their prognostic value for predicting future myocardial infarction (MI). Methods We profiled 1305 plasma proteins using an aptamer-based array (SOMAscan) in asymptomatic individuals who had undergone 384-slice coronary computed tomography angiography. Plaques were categorized by composition as calcified or non-calcified. First, we identified proteins that were different (based on multiple testing adjusted p-values: q-value <0.05) between 250 ACS patients who suffered a recurrent MI event on follow-up compared with another 250 ACS patients who remained event-free using Mann-Whitney U test. Next, protein candidates that also correlated (Pearson's p<0.05) with specific categories of plaque composition were evaluated using a cox proportional hazards model to determine the risk of recurrent MI, adjusting for potential confounders in the second cohort. Results A total of 65 and 120 plasma proteins were significantly associated with calcified and non-calcified plaques respectively in the asymptomatic cohort (N=79). Of these 185 proteins, 23 proteins were differentially expressed (DE) between ACS patients with and without recurrent MI events (median follow-up 1811 days). The top three up-and down-regulated proteins in the recurrent MI group were macrophage-capping protein, trefoil factor 3 and cystatin-SN (median FC 1.22, 1.17 and 1.17; q-value 4.34x10–6, 2.18x10–4, 3.17x10–3 respectively) and fibroblast growth factor 20, lymphotoxin a2/b1 and vascular endothelial growth factor receptor 2 (median FC 0.92, 0.94 and −0.090; q-value 1.31x10–3, 9.45x10–3 and 3.90x10–3) respectively. The quartiles of these protein concentrations were also associated with risk of recurrent MI, (log-rank test p-value range from 2.71x10–7 to 0.04). Of the DE proteins, the adjusted hazards ratio (HR) of cystatin-SN in the highest quartile (Q4) was 1.44 times that of the first quartile (Q1) (adjusted HR: 1.44, 95% CI: 0.93–2.2) and higher plasma concentration of cystatin-SN was associated with increasing risk of recurrent MI events (Trend test p=0.004). On the other hand, the highest quartile of fibroblast growth factor 20 was associated with 44% reduction in risks of recurrent MI adjusted HR: 0.56, 95% CI of HR: 0.35–0.87), with significant trend test (p=0.0096). Conclusions Large-scale plasma proteomics identified novel plaque-related proteins predictive of recurrent coronary events in patients with ACS. Further studies may help unravel the biological underpinnings of these circulating proteins and their potential as novel prognostic biomarkers. Acknowledgement/Funding This work was supported by grant NMRC/CSA-INV/0001/2016 from the National Medical Research Council, Singapore.

Examining patient and visit characteristics associated with the cancer patient experience.

204 Background: Your Voice Matters (YVM) is a 28-item patient experience survey for adult cancer outpatients undergoing treatment in Ontario.The purpose was to examine patient and visit characteristics associated with YVM responses. Methods: YVM was administered to eligible patients (n=8,704) at 14 centres in 2017.Respondents answered items on a five-point Likert scale (4 or 5 = positive response). A multivariable logistic regression (MLR) was undertaken for each YVM item.Variables (reference group) included: disease site (heamatology), age group (65+), sex (female), rurality (urban), last visit type (consult), income quintile(highest) and immigration tercile (lowest). Significant results ( p<.05) vary by MLR model. Therefore a p-value range is provided for all significant variables for all MLR models. Results: Patients were more likely to have a less positive experience if they had central nervous system ( p =.000-.013), gastrointestinal ( p =.004-.026), head and neck ( p =.002-.025), or lung cancer ( p =.017-.049); were between the ages of 18-39 years ( p = <.0001-.048); were female ( p =.0001-.022); received chemotherapy( p =.0001-.047); lived in a rural location ( p =.042); from a mid-( p =.027-.045) and mid-high income quartile ( p =.021); and in the high- ( p =.002-.043) and middle-immigrant terciles ( p =.028-.047), when compared to the reference group. Patient were more likely to have a more positive experience if they had skin cancer ( p =.004-.032); were between the ages of 40-64 years ( p =.003-.033); receiving radiation ( p =.0001-.041) or a minor procedure ( p =.015); and were from the mid-low ( p =.003-.042) and low income quartile ( p =.001-.032), when compared to the reference group. Conclusions: The cancer patient experience varies by patient and visit characteristics. Future initiatives should examine these characteristics to better understand their populations to create a more tailored approaches to cancer care.

P128. The association of preoperative disc height with radiographic and clinical outcomes following ACDF

BACKGROUND CONTEXT Disc space collapse often occurs later in the natural course of cervical degenerative disc disease, and during anterior cervical discectomy and fusion (ACDF), restoration of disc space height and lordosis can assist with decompression and restoration of alignment. It is unclear if the amount of preoperative cervical disc space collapse correlates with outcomes following ACDF. PURPOSE The aim of the present study was to characterize preoperative disc space height in a sample of ACDF patients and to determine the association with postoperative clinical and radiographic outcomes following ACDF. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE Analysis of consecutive patients who underwent a single-level ACDF between 2008-2015 for cervical radiculopathy and/or myelopathy, with more than 6 months of clinical and radiographic follow-up was conducted. Exclusion criteria were patients under 18 years of age at the time of surgery, previous cervical fusion or concomitant posterior cervical surgery, had postoperative follow up less than 6 months, or had an ACDF for cervical spine fracture, tumor, or infection. OUTCOME MEASURES Preoperative disc height was measured in terms of preoperative anterior vertebral distance (pAVD), mid-vertebral distance (pMVD), and posterior vertebral distance (pPVD). Sagittal parameters were also measured, and included change in C2-C7 lordosis, T1 angle, levels fused, sagittal vertical axis (SVA), fusion mass lordosis, proximal and distal adjacent segment lordosis. Visual Analog Scale (VAS) neck, VAS arm, and Neck Disability Index (NDI) scores were collected at each postoperative clinical visit. The rates of adjacent segment disease, reoperation, fusion, and subsidence (postoperative disc space collapse >2mm) were determined for the study period. METHODS Radiographs were reviewed preoperatively and immediately postoperatively, and at final follow up along with patient-reported outcomes. Bivariate and multivariate logistic regressions were subsequently used to compare clinical outcomes between disc height. Multivariate analyses controlled for differences in baseline patient characteristics. RESULTS A total of 120 patients were included. At final follow-up, pAVD was associated with increased lordosis, SVA and proximal lordosis. Additionally, pMVD was associated with increased postoperative SVA (p=0.025), and final SVA (p=0.011). Preoperative PVD was associated with decreased postoperative distal lordosis (p=0.037) and increased final SVA (p=0.032). Notably, greater pAVD was associated with greater final VAS arm scores (p=0.022), greater pMVD was associated with increased final VAS neck (p=0.037) and final VAS arm scores (p=0.040), and greater pPVD was associated with greater final VAS neck (p=0.031) and arm (p=0.023) scores. Greater AVD, MVD, and PVD were all associated with a decreased preoperative to postoperative difference in VAS neck (p-value range 0.034-0.04). CONCLUSIONS Increased anterior, middle and posterior preoperative disc height were all associated with increased final SVA, among other parameters. Patients with well-maintained preoperative disc heights had greater final VAS neck scores, VAS arm scores, and had less postoperative improvement in VAS neck scores compared to patients with preoperative collapsed discs. These results suggest that patients with preoperative cervical disc space collapse may have superior outcomes compared to patients with maintained cervical disc height, and future studies are needed to further explore these differences. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

An evaluation of phase angle, bioelectrical impedance vector analysis and impedance ratio for the assessment of disease status in children with nephrotic syndrome

BackgroundOedema, characterized by accumulation of extracellular water (ECW), is one of the major clinical manifestations in children suffering from nephrotic syndrome (NS).The lack of a simple, inexpensive and harmless method for assessing ECW may be solved by the use of the bioelectrical impedance analysis (BIA) technique.The aims of this study were to examine whether phase angle (PA), bioelectrical impedance vector analysis (BIVA) and the impedance ratio (IR) reflect change in disease status in children with NS.MethodsEight children (age range: 2–10 years) with active NS (ANS group) were enrolled. In five of these (ANS* subgroup), impedance was also measured at remission (NSR group). Thirty-eight healthy children (age range: 2–10 years) were included as healthy controls (HC group). Whole-body impedance was measured with a bioimpedance spectroscopy device (Xitron 4200) with surface electrodes placed on the wrist and ankle.ResultsValues of PA, BIVA and IR were found to be significantly lower (p-value range < 0.001 to < 0.01) in the ANS patients compared to the HC and NSR groups. No significant differences were observed between the NSR and HC groups.ConclusionThe studied parameters can be used to assess change in disease status in NS patients. Data were consistent with NS being associated with expansion of ECW.

Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC].Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire.Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063–.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment.Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.

Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study.

PurposeRoflumilast (Daliresp, Daxas) is a FDA-approved phosphodiesterase 4 (PDE4) inhibitor for the treatment of moderate-to-severe chronic obstructive pulmonary disease. In mice and in limited human studies, this oral medication can cause weight loss and improve insulin sensitivity. We set out to determine the mechanism of its effect on insulin sensitivity.Patients and methodsEight adults with overweight/obesity and prediabetes received roflumilast for 6 weeks. Before and after roflumilast, subjects underwent tests of insulin sensitivity, mixed meal test, body composition, markers of inflammation, and mitochondria function. Dietary intake and physical activity were also assessed. Our primary outcome was the change in peripheral insulin sensitivity, as assessed by the hyper-insulinemic euglycemic clamp.ResultsThis study was underpowered for the primary outcome. Pre- and post-roflumilast mean peripheral insulin sensitivity were 48.7 and 70.0 mg/g fat free mass/minute, respectively, (P-value=0.18), respectively. Among the mixed meal variables, roflumilast altered glucagon-like peptide 1 (GLP-1) hormone the most, although the average effect was not statistically significant (P=0.18). Roflumilast induced a trend toward significance in 1) decreased energy intake (from 11,095 KJ to 8,4555 KJ, P=0.07), 2) decreased fat mass (from 34.53 to 32.97 kg, P=0.06), 3) decreased total and LDL cholesterol (P=0.06 for both variables), and 4) increased plasma free fatty acids (from 0.40 to 0.50 mEq/L, P=0.09) The interval changes in adiposity and free fatty acid were significantly associated with the subject’s age (P-value range= <0.001 to 0.02 for the correlations). Inflammatory and adhesion markers, though unchanged, significantly correlated with one another and with incretin hormones only after roflumilast.ConclusionWe demonstrate, for the first time in humans, increasing percentage of fat mass loss from roflumilast with increasing age in adults with prediabetes and overweight/obesity. We also demonstrate novel associations among roflumilast-induced changes in incretin hormones, inflammatory markers, peripheral insulin sensitivity, and adiposity. We conclude that roflumilast’s early effects on insulin sensitivity is indirect and likely mediated through roflumilast’s prioritization of lipid over glucose handling.Clinical trials registrationNCT01862029.

A Novel Technique of Morcellation Using a Pneumovesicum After Holmium Laser Enucleation of the Prostate in Complicated Situations: Our Initial Experience and Tips.

PurposeTo describe our initial experience with a novel method of adenoma retrieval using a pneumovesicum (PNV) after Holmium laser enucleation of the prostate (HoLEP).MethodsFrom January 2016 to April 2018, a total of 93 consecutive patients treated with HoLEP were enrolled in this study. For tissue morcellation, we used the PNV morcellation technique for an initial series of 21 patients and the conventional technique (Lumenis VersaCut) for a consecutive series of 72 patients. We compared efficiency and safety between the novel technique and the traditional technique. Subgroup analysis was performed to assess the effectiveness of the current technique in the large prostate (>70 mL).ResultsThere were significant differences in mean age and prostate volume between the 2 groups. However, there were no significant differences in the baseline characteristics and preoperative parameters in the subgroup analysis of large prostates (>70 mL). The mean morcellation efficiency was higher (8.50±1.94 minutes vs. 1.76±0.45 minutes, P<0.05) and the time of morcellation (7.81±1.25 minutes vs. 34.04±11.14 minutes, P<0.05) was shorter in the PNV group. Moreover, there were no significant differences between groups in hospitalization period (2.62±1.10 days vs. 2.90±1.26 days, P=0.852) and any other postoperative events, including recatheterization, reoperation, clot retention, and urethral stricture (P-value range, 0.194–0.447). In the PNV group, there were some cases of procedure-related complications, including postoperative extravesical leakage (5th case), clot retention (8th case), and recatheterization (9th case).ConclusionsThis method has a higher tissue retrieval efficacy, with the advantage of excellent visibility compared to conventional morcellation. The current method can be applied when a transurethral morcellator is out of order or cannot be used.

The impact of intratumoral heterogeneity on prognostic biomarkers in localized prostate cancer.

46 Background: Genomic biomarkers can identify patients that harbour aggressive disease. The utility of these biomarkers is uncertain due to genomic variation between prostate biopsy specimens. To quantify the robustness of genomic biomarkers, we performed spatio-genomic characterization of distinct tumor foci. We scored three validated DNA-based biomarkers of early biochemical recurrence: percentage of genome with a copy number aberration (PGA), a 100-loci biomarker, and an optimized 31- loci biomarker derived from the previous. For each biomarker, we determined their robustness to intratumoral heterogeneity in association with predicting early biochemical recurrence (eBCR; ≤18 months) and long term control (LTC; ≥48 months). Methods: We queried a registry of 1054 patients with high-risk prostate cancer who underwent a radical prostatectomy (RP). We developed a cohort (n = 42) risk matched by clinicopathologic prognostic indices. Half of the patients had eBCR, while the other half had LTC. We profiled multiple tumor foci per patient, analyzing 119 tumor foci. For each focus, CNA profiles were generated, and three biomarker scores were calculated. For each patient and biomarker, we calculated the score of the lowest-score region, the highest-score region, or sampling of all foci and use the mean score. Results: All three biomarkers distinguished LTC from eBCR. PGA scores separated the two groups with an area under the receiver operator curves (AUC) ranging from 0.75-0.80. The 100- and 31-loci signatures, had AUCs ranging from 0.76-0.85 and 0.76-0.80 respectively. Using Cox proportional hazards modeling, we found that PGA was associated with LTC (Hazard ratio (HR) range: 2.56-6.22; p &lt; 0.05. This was replicated for the 100-loci signature (HR range: 3.55-5.23; p &lt; 0.05). The 31-loci detected associations with eBCR independent of how different foci were summarized (log-rank p-value range: 5.1 x 10-4- 5.9 x 10-3). Conclusions: Despite divergence in biomarker scores, all three predicted eBCR. Our study suggests that genomic biomarkers can overcome intratumoral heterogeneity, making discrete samples potentially adequate in patients with high-risk disease to determine the risk of eBCR after radical treatment.

Penurunan Derajat Stres Pegawai Di Lembaga “X” Bandung melalui Pelatihan Coping Resources

This research was part of the thesis research and was conducted to find out whether the training of coping resources can reduce the stress level on the employees at organization “X” Bandung. The method used in this research is quasi experimental method with design used in this research is one group design, pre-test and post-test design. Validity test on stress and coping resources questionnaire using construct validity with range of r or rs value for stress questionnaire is 0.418 – 0.874 and for coping resources questionnaire is 0.439 – 0.828 and p-value range for stress questionnaire is 0.000 – 0.047 and for coping resources questionnaire is 0.000 – 0.036. Reliability test on stress and coping resources questionnaire using the formula coefficient reliability alpha cronbach with a value of 0.954 for stress questionnaire and 0.943 for coping resources questionnaire. Based on the results of research shows that training coping resources can reduce the stress level on the employees at Organization “X” Bandung. &#x0D; &#x0D; Keywords: coping resources, stress, and training

Comparison of statistical tests in effective connectivity analysis of ECoG data

BackgroundThe effects of statistical testing on the results of multivariate autoregressive (MVAR)-based effective connectivity analysis have not been adequately investigated, and it is still unclear which statistical test can provide the most accurate results. New methodsUsing simulated and real electrocorticographic (ECoG) data, we investigated the performance of three nonparametric statistical tests – Monte Carlo permutation, bootstrap resampling, and surrogate data method in MVAR-based effective connectivity analysis. Receiver operating characteristic (ROC) analysis and area under the ROC curve (AUC) were used to assess the performance of each statistical test method. In addition, we found optimal p-values for each method based on ROC analysis. Finally, we investigated the application of statistical tests on partial directed coherence analysis of ECoG data collected in a patient with epilepsy. ResultsThe bootstrap statistical test performed more accurately than other methods. The surrogate method slightly outperformed the Monte Carlo permutation method. Optimal p-values of statistical tests depended on signal-to-noise ratio (SNR) of data, and its value increased by reducing SNR of data. By considering the typical SNR range of electrophysiological data, we recommended an optimal p-value range for the application of each statistical test method. Comparison with existing methodsLimited studies have investigated the performance of statistical tests for MVAR-based effective connectivity analysis. For the first time, we have investigated the effects of baseline connections on the various performances of statistical tests. ConclusionsWe recommend utilizing the bootstrap statistical test with p-value between 0.05 and 0.1 for effective connectivity analysis of ECoG data.

A comparison of full-field digital mammograms versus 2D synthesized mammograms for detection of microcalcifications on screening

ObjectivesTo compare the observer agreement of microcalcification detection on synthetic 2D images to full field digital mammography (FFDM) at screening and determine if calcifications can be detected to the same degree and given the same BI-RADS assessment. Material and methodsTwo-experienced radiologists retrospectively reviewed synthetic 2D images and FFDM, in separate sessions, to detect microcalcifications and provide a BIRADS assessment. A third experienced breast radiologist reviewed the cases that were disagreed upon and gave a final assessment.Between March 2016–December 2016, 414 women obtained a screening mammogram with tomosynthesis and acquisition of FFDM. 71 cases had combined FFDM and tomosynthesis images, calcifications visible on FFDM or no calcifications present, which comprised the study group. Synthetic 2D images were constructed from the DBT images. During session 1, all synthetic 2D images for the 71 cases were reviewed. During session 2, all the FFDM images for the 71 cases were reviewed. Tomosynthesis images were not reviewed. The agreement of detection of calcifications and BIRADS assessment between radiologists for FFDM and synthetic 2D images were assessed using Cohen’s kappa test. Fisher’s exact test was used to detect the differences in calcification identification among various breast densities on FFDM and synthetic 2D images. ResultsFor the detection of calcifications between synthetic 2D images and FFDM, there was moderate to substantial agreement (p-values < 0.0001) for the two radiologist. For the BIRADS assessments, the agreement between synthetic 2D imaging and FFDM was moderate (p-values < 0.0001). The inter-reader agreement for detection of calcifications was fair for using synthetic 2D and moderate for using FFDM (p-value < 0.0001). The final inter-reader agreement between FFDM and synthetic 2D images for the detection of calcifications was moderate (p-values < 0.0001) with the addition of the third reader. For the final BI-RADS assessment, there was moderate agreement between synthetic 2D imaging and FFDM (p-value < 0.0001). The two readers did not demonstrate a significant difference in the detection of microcalcifications for those who were dense or non-dense (p-value range 0.076–0.302). ConclusionRadiologist interpreting synthetic 2D imaging and FFDM have similar frequency for detection of calcifications and BIRADS assessment. A synthetic 2D mammogram may be a sufficient replacement for FFDM at screening.

Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis.

Output from biomarker studies involving immunohistochemistry applied to tissue microarrays (TMA) is limited by the lack of an efficient and reproducible scoring methodology. In this study, we examine the functionality and reproducibility of biomarker scoring using the new, open-source, digital image analysis software, QuPath. Three different reviewers, with varying experience of digital pathology and image analysis, applied an agreed QuPath scoring methodology to CD3 and p53 immunohistochemically stained TMAs from a colon cancer cohort (n = 661). Manual assessment was conducted by one reviewer for CD3. Survival analyses were conducted and intra- and interobserver reproducibility assessed. Median raw scores differed significantly between reviewers, but this had little impact on subsequent analyses. Lower CD3 scores were detected in cases who died from colorectal cancer compared to control cases, and this finding was significant for all three reviewers (P-value range = 0.002-0.02). Higher median p53 scores were generated among cases who died from colorectal cancer compared with controls (P-value range = 0.04-0.12). The ability to dichomotise cases into high versus low expression of CD3 and p53 showed excellent agreement between all three reviewers (kappa score range = 0.82-0.93). All three reviewers produced dichotomised expression scores that resulted in very similar hazard ratios for colorectal cancer-specific survival for each biomarker. Results from manual and QuPath methods of CD3 scoring were comparable, but QuPath scoring revealed stronger prognostic stratification. Scoring of immunohistochemically stained tumour TMAs using QuPath is functional and reproducible, even among users of limited experience of digital pathology images, and more accurate than manual scoring.

Relationship between Take-Off Force Profiles and Single Leg Hop Distance

The anterior single leg hop for distance test (SLHOP) is a functional performance task that is often used to assess return to play criteria following ACL reconstruction. Clinicians primarily assess SLHOP distance, but the way an individual completes the task may be important when determining return to play status. Recent research has indicated that non-uniformity in vertical ground reaction force (VGRF) profiles may be related to pathomechanics during a vertical jump, but little research has been done to explore the relationship between force profiles and SLHOP distance. PURPOSE: To determine the correlation between a force profile ratio and SLHOP distance. METHODS: Twenty-three female collegiate soccer players (19.1±1.5 years; 166.9±7.1 cm; 62.6±8.3 kg) performed three SLHOP tests for maximal distance off a tri-axial force plate. The SLHOP was performed on the dominant limb. Ground reaction force (GRF) data were collected during SLHOP take-off phase to produce force-time curves that were used to calculate the ratio between the instantaneous and average force profile between three events. Force profile ratios were calculated between: A) the minimum GRF after initiation of the countermovement and the peak GRF prior to takeoff, and B) the point during the countermovement when body weight is reached and peak GRF. Ratio A and B where calculated in both the vertical (z) and anterior-posterior (y) axes. All forces were normalized to body weight, and SLHOP distances were normalized to leg length (cm/cm). The strength of the association between each of the aforementioned force profile ratios and maximum SLHOP distance were calculated using Pearson correlation coefficients with an alpha level set a priori at p<0.05. RESULTS: There were no significant correlations between any combination of force profile ratios and SLHOP distance (p-value range:0.19 to 0.62, r range: -0.11 to -0.26). CONCLUSION: Force profile ratios between straight-line and trace-line distance are not significantly related to average or maximum SLHOP distance. Further research should explore the relationship between other phases within the force-time curve, pathomechanics, and SLHOP distance.

Reliability and validity of MicroScribe-3DXL system in comparison with radiographic cephalometric system: Angular measurements

The aim of the study was to assess the reliability and validity of cephalometric variables from MicroScribe-3DXL. Seven cephalometric variables (facial angle, ANB, maxillary depth, U1/FH, FMA, IMPA, FMIA) were measured by a dentist in 60 Malay subjects (30 males and 30 females) with class I occlusion and balanced face. Two standard images were taken for each subject with conventional cephalometric radiography and MicroScribe-3DXL. All the images were traced and analysed. SPSS version 2.0 was used for statistical analysis with P-value was set at P<0.05. The results revealed a significant statistic difference in four measurements (U1/FH, FMA, IMPA, FMIA) with P-value range (0.00 to 0.03). The difference in the measurements was considered clinically acceptable. The overall reliability of MicroScribe-3DXL was 92.7% and its validity was 91.8%. The MicroScribe-3DXL is reliable and valid to most of the cephalometric variables with the advantages of saving time and cost. This is a promising device to assist in diverse areas in dental practice and research.

Effect of acute intermittent hypoxia on baroreflex sensitivity to decreasing and increasing blood pressures

ObjectivePatients with sleep apnea exhibit impairments in reflex responses to decreasing, but not increasing, arterial blood pressures (BP). Attenuated BP control may contribute to the increased risk of developing hypertension observed in patients with sleep apnea; however the mechanisms involved are not completely understood. Therefore, we aimed to examine the differential effect of acute intermittent hypoxia (IH) on baroreflex sensitivity during decreasing compared to increasing BP. We hypothesized acute IH would attenuate baroreflex sensitivity to decreasing, but not increasing, BP.MethodsHeart rate (HR, electrocardiography), BP (brachial arterial catheter), and muscle sympathetic nerve activity (MSNA, microneurography of the peroneal nerve) were assessed in 14 healthy adults (8M/6F; 32±1 yrs, 26±1 kg/m2). Baroreflex sensitivity was evaluated during decreasing and increasing BP using the modified Oxford technique before and after 30‐min of IH [25‐s hypoxic (0.10 FiO2) exposures alternating with 120‐s room air breathing]. Data were analyzed from the depressor (nitroprusside) and pressor (phenylephrine) phases of the modified Oxford for measures of cardiovagal and sympathetic baroreflex sensitivity, as well as the T50 (diastolic BP with a 50% likelihood of an MSNA burst).ResultsIH resulted in 15 events where oxygen saturation was reduced (SpO2: 98±1% vs 92±2%, p&lt;0.01). Resting normoxic ventilation, carotid chemosensitivity to hypoxia, and MSNA were increased following IH (all p&lt;0.05). HR, systolic BP, diastolic BP, and the T50 were not altered following 30‐min of IH (p‐value range 0.08 to 0.90). Diastolic BP was greater than T50 at baseline (Decreasing BP: p=0.046); however, after IH, diastolic BP was no longer significantly different than the T50 (p=0.52). Cardiovagal baroreflex sensitivity to decreasing and increasing BP differed at baseline (14.0±1.7 vs 22.0±3.3 ms/mmHg, p=0.02) and following IH (11.3±1.1 vs 19.1±2.0 ms/mmHg, p&lt;0.01). Cardiovagal baroreflex sensitivity to decreasing BP tended to be lower following IH (p=0.09). Sympathetic baroreflex sensitivity to decreasing and increasing BP did not differ at baseline (−2.1±0.3 vs −2.5±0.3 %/mmHg; p=0.28) or following IH (−2.6±0.6 vs −3.0±0.4 %/mmHg, p=0.55) and was unaffected by IH (p‐value range 0.20–0.40).ConclusionsAcute IH has a differential effect on baroreflex sensitivity. Specifically, cardiovagal baroreflex sensitivity to decreasing, but not increasing, BP tends to be lower following IH. In contrast, sympathetic baroreflex sensitivity is unaffected by IH. Prior to IH, diastolic BP is greater than the T50, thus promoting lower MSNA. Despite no change in baroreflex sensitivity after IH, diastolic BP is no longer significantly different than the T50 – consistent with higher MSNA following IH.Support or Funding InformationNIH HL130339, Mayo Clinic Center for Biomedical DiscoveryThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

An exploratory study on differences in cumulative plantar tissue stress between healing and non-healing plantar neuropathic diabetic foot ulcers

BackgroundMechanical stress is important in causing and healing plantar diabetic foot ulcers, but almost always studied as peak pressure only. Measuring cumulative plantar tissue stress combines plantar pressure and ambulatory activity, and better defines the load on ulcers. Our aim was to explore differences in cumulative plantar tissue stress between people with healing and non-healing plantar diabetic foot ulcers. MethodsWe analyzed a subgroup of 31 patients from a randomized clinical trial, treated with a removable offloading device for their plantar diabetic forefoot ulcer. We measured in-device dynamic plantar pressure and daily stride count to calculate cumulative plantar tissue stress at the ulcer location and associated this with ulcer healing and ulcer surface area reduction at four weeks (Student's t and chi-square test for significance, Cohen's d for effect size). FindingsIn 12 weeks, 68% (n = 21) of the ulcers healed and 32% (n = 10) did not. No statistically significant differences were found for cumulative plantar tissue stress, plantar pressure or ambulatory activity between people with healed and not-healed ulcers. Cumulative plantar tissue stress was 25% lower for people with healed ulcers (155 vs. 207 MPa·s/day; P = 0.71; Effect size: d = 0.29). Post-hoc analyses in the 27 patients who self-reported to be adherent to wearing the device showed that cumulative plantar tissue stress was 49% lower for those who reached ≥75% ulcer surface area reduction at four weeks (140 vs. 275 MPa·s/day; P = 0.09; d = 0.76); smaller differences and effect sizes were found for peak pressure (24%), peak pressure-time integral (30%) and ambulatory activity (26%); (P-value range: 0.14–0.97; Cohen's d range: 0.14–0.70). InterpretationMeasuring cumulative plantar tissue stress may provide insight beyond that obtained from plantar pressure or ambulatory activity alone, with regard to diabetic foot ulcer healing using removable offloading devices. These explorative findings provide baseline data for further studies on this relevant topic.

Subgroup analysis by baseline (BL) weight-associated parameters: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based (gem) therapy.

410 Background: We report prognostic evaluation of BL weight-associated parameters (body-mass index [BMI], body surface area [BSA] and weight) in pts with mPDAC after progression following gem-based therapy (NAPOLI-1 trial; NCT01494506). Pts received nal-IRI+5-FU/LV, nal-IRI monotherapy or 5-FU/LV in NAPOLI-1, an international, randomised, phase 3 trial; nal-IRI+5-FU/LV treatment resulted in a 45% increased median OS vs. 5-FU/LV (unstratified HR = 0.67; p = 0.012). Methods: This exploratory subgroup analysis compares outcomes by BL BMI, BSA and weight, using primary survival analysis data from the ITT population for all treatment arms combined (n = 417) and the nal-IRI+5-FU/LV arm on its own (n = 117). Results: OS and PFS were not significantly different between BL BMI, BSA and weight median subgroups in the entire NAPOLI-1 ITT population (HR range 1.06–1.15; log-rank p-value range 0.21–0.60; Table) and in the nal-IRI+5-FU/LV arm (HR range 0.94–1.19; log-rank p-value range 0.43–1.00). Conclusions: This post-hoc subgroup analysis did not detect any prognostic impact on treatment outcome by BL BMI, BSA and weight for mPDAC pts progressed following gem-based therapy. This observation rules out a treatment-independent effect. No evidence of a predictive effect on nal-IRI+5-FU/LV efficacy was found. Clinical trial information: NCT01494506. [Table: see text]

Decrement in Professional Cyclists' Performance After a Grand Tour.

To analyze professional cyclists' performance declines after, and the exercise demands during, a Grand Tour. Seven professional cyclists performed 2 incremental exercise tests, 1 wk before and the day after the Vuelta España. During the race the exercise demands were analyzed on the basis of heart rate (HR). Three intensity zones were established according to reference HR values corresponding to the ventilatory- (VT) and respiratory-compensation (RCT) thresholds determined during the prerace test. In addition, exercise demands for the last weeks of the Vuelta were recalculated using the reference HR determined during the postrace test for the 3rd week and averaging the change observed in the VT and RCT per stage for the 2nd week. The reference HR for the beginning of the 2nd week was estimated. A significant (P-value range, .044-.000) decrement in oxygen uptake, power output, and HR at maximal exercise, VT, and RCT was found after the race. Based on the prerace test, the mean time spent daily above the RCT was 13.8 ± 10.2min. This time decreased -1.2min·day-1 across the race. When the exercise intensity was corrected according to the postrace test, the time above RCT (34.1 ± 9.9min) increased 1.0min·day-1. These data indicate that completing a Grand Tour may result in a significant decrement in maximal and submaximal endurance performance capacity. This may modify reference values used to analyze exercise demands. As a consequence, the high-intensity exercise performed by cyclists may be underestimated.

Donor site morbidity after vascularized fibula free flap: gait analysis during prolonged walk conditions

The aim of this study was to determine the effect of vascularized fibula free flap (VFFF) harvest on gait variables during the six-minute walk test (6MWT). Eleven patients who had undergone VFFF harvest and 11 healthy peers participated in this case–control study. The main evaluation consisted of the collection of gait variables using the GAITRite system during three periods of the 6MWT: beginning (0–1min), middle (2:30–3:30min), and end (5–6min). The 6MWT was significantly shorter in the VFFF group than in the reference group (−31%, P<0.001). Most gait variables differed significantly between the groups for each period (P-value range 0.04–0.0004), including toe in/out on the operated side (P-value range 0.005–0.01). The increase in toe in/out on the operated side suggests a functional modification caused by an imbalance of the agonist–antagonist muscles. On comparison of the different periods, gait velocity decreased between the beginning and middle periods and increased between the middle and end periods in both groups. However, a significantly lower velocity between the beginning and end periods was found only for the VFFF group (P=0.026), suggesting an alteration in physical management. In conclusion, these results suggest that VFFF harvesting could alter gait and joint integrity.

The diameter of single bundle, hamstring autograft does not significantly influence revision rate or clinical outcomes after anterior cruciate ligament reconstruction

BackgroundAnterior cruciate ligament (ACL) graft failure is a complication of ACL reconstruction (ALCR). Smaller autograft diameter may be a contributing factor. Our aim was to determine if hamstring autograft diameter influences graft rupture and patient-reported outcome scores. MethodsThis study included 786 consecutive patients undergoing primary, single bundle, autograft hamstring ACLR. The primary outcome was revision ACLR surgery. Secondary outcomes were patient reported International Knee Documentation Committee (IKDC) score, Knee Injury & Osteoarthritis Outcome Score (KOOS) and Tegner Activity score. Multiple logistic regression and Fischer Exact tests were employed for statistical analysis. ResultsIncreasing autograft diameter did not lead to a reduction in revision ACLR surgery (odds ratio [OR], 1.093; 95% confidence interval [CI], 0.612 to 1.954; P=0.76). Revision ACLR positively correlated with male gender (OR, 3.971; 95% CI 1.109 to 14.214; P=0.03) and negatively correlated with increasing age (OR, 0.919; 95% CI 0.882–0.958, P<0.0001). There was no association between graft rupture rate and dichotomized graft size. At latest follow-up, there was no correlation between graft diameter and IKDC (Pearson's adjusted R2=0.058; P=0.75), Tegner Activity score (Pearson's adjusted R2=0.244; P=0.53), or any component of the KOOS (Pearson's adjusted R2 range: 0.008 to 0.141; P-value range: 0.21 to 0.76). ConclusionIncreased hamstring autograft diameter did not significantly reduce revision ACLR surgery or improve clinical outcomes. Other factors such as gender and age do influence the rate of revision ACL surgery. Study designLevel IV, retrospective case series.