Predictive role of PI-RADSv2 and ADC parameters in differentiating Gleason pattern 3 + 4 and 4 + 3 prostate cancer

Purpose

To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard.

Methods

We retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as “low risk,” a PI-RADSv2 score ≥ 4 as “high risk” for clinically significant PCa. Mean tumor ADC (ADC_T), ADC of adjacent normal tissue (ADC_N), and ADC_ratio (ADC_T/ADC_N) were calculated. Stepwise regression analysis using tumor location, ADC_T and ADC_ratio, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3.

Results

119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADC_ratio was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score (“low” vs. “high”) was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADC_T (p = 0.03) and ADC_ratio (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively.

Conclusions

ADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.

     

Placebo analgesia and reward processing: Integrating genetics,personality, and intrinsic brain activity

Our expectations about an event can strongly shape our subjective evaluation and actual experience of events. This ability, applied to the modulation of pain, has the potential to affect therapeutic analgesia substantially and constitutes a foundation for non‐pharmacological pain relief. A typical example of such modulation is the placebo effect. Studies indicate that placebo may be regarded as a reward, and brain activity in the reward system is involved in this modulation process. In the present study, we combined resting‐state functional magnetic resonance imaging (rs‐fMRI) measures, genotype at a functional COMT polymorphism (Val158Met), and personality measures in a model to predict the magnitude of placebo conditioning effect indicated by subjective pain rating reduction to calibrated noxious stimuli. We found that the regional homogeneity (ReHo), an index of local neural coherence, in the ventral striatum, was significantly associated with conditioning effects on pain rating changes. We also found that the number of Met alleles at the COMT polymorphism was linearly correlated to the suppression of pain. In a fitted regression model, we found the ReHo in the ventral striatum, COMT genotype, and Openness scores accounted for 59% of the variance in the change in pain ratings. The model was further tested using a separate data set from the same study. Our findings demonstrate the potential of combining resting‐state connectivity, genetic information, and personality to predict placebo effect. Hum Brain Mapp 35:4583–4593, 2014. © 2014 Wiley Periodicals, Inc.     

Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease

OBJECTIVES: To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. METHODS: Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only 1 of levels 4 or 7 was compared with that of patients with N1 disease originating in the same lobe. RESULTS: The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P =.01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P =.63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both N1 and N2 metastases (P =.001). CONCLUSIONS: Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system.     

Certification of standard reference material 970, ascorbic acid in serum,and analysis of associated interlaboratory bias in the measurement process

BACKGROUND: The accurate and reproducible measurement of ascorbic acid is essential in delineating the role of ascorbic acid as a diagnostic tool for human disease and for the comparison of data acquired by different laboratories. A stabilized pair of standards of ascorbic acid in human serum, which is compatible with most analytical methods, have been prepared. METHODS: The certification was based on the gravimetric addition of ascorbic acid to metaphosphoric acid-stabilized, ascorbic acid-depleted serum and NIST liquid chromatography-electrochemical measurements. The NIST results were analyzed statistically for homogeneity, and the expanded uncertainty of each SRM was calculated using all of the NIST data. An interlaboratory comparison exercise was also performed. RESULTS: These materials, Standard Reference Material (SRM) 970 Ascorbic Acid in Serum, Level I and Level II, are homogeneous and are certified to contain (10.07 +/- 0.21) and (30.57 +/- 0.28) mmol ascorbic acid/L of solution (expanded uncertainty), respectively. In the interlaboratory comparison (n = 17), the relative SDs for the two materials were 22% and 19%. CONCLUSIONS: Two lots of serum, each containing different amounts of ascorbic acid stabilized in metaphosphoric acid, have been prepared and characterized. Many laboratories provide inaccurate results.     

Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS

To develop a brief ataxia rating scale (BARS) for use by movement disorder specialists and general neurologists. Current ataxia rating scales are cumbersome and not designed for clinical practice. We first modified the International Cooperative Ataxia Rating Scale (ICARS) by adding seven ataxia tests (modified ICARS, or MICARS), and observed only minimally increased scores. We then used the statistics package R to find a five‐test subset in MICARS that would correlate best with the total MICARS score. This was accomplished first without constraints and then with the clinical constraint requiring one test each of Gait, Kinetic Function‐Arm, Kinetic Function‐Leg, Speech, and Eye Movements. We validated these clinical constraints by factor analysis. We then validated the results in a second cohort of patients; evaluated inter‐rater reliability in a third cohort; and used the same data set to compare BARS with the Scale for the Assessment and Rating of Ataxia (SARA). Correlation of ICARS with the seven additional tests that when added to ICARS form MICARS was 0.88. There were 31,481 five‐test subtests (48% of possible combinations) that had a correlation with total MICARS score of ≥0.90. The strongest correlation of an unconstrained five‐test subset was 0.963. The clinically constrained subtest validated by factor analysis, BARS, had a correlation with MICARS‐minus‐BARS of 0.952. Cronbach alpha for BARS and SARA was 0.90 and 0.92 respectively; and inter‐rater reliability (intraclass correlation coefficient) was 0.91 and 0.93 respectively. BARS is valid, reliable, and sufficiently fast and accurate for clinical purposes. © 2009 Movement Disorder Society     

Functional neuroanatomical investigation of vision-related acupuncture point specificity--a multisession fMRI study

The concept that specific acupuncture points have salubrious effects on distant target organ systems is a salient feature of Traditional Chinese Medicine (TCM). In this study, we used a multiple-session experiment to test whether electroacupuncture stimulation at two TCM vision-related acupoints, UB 60 and GB 37, located on the leg, could produce fMRI signal changes in the occipital regions of the brain, and the specificity of this effect when compared with stimulation at an adjacent non-acupoint (NAP). Six normal, acupuncture naive subjects completed the study. Each subject participated in six identical scanning sessions. Voxelwise group analysis showed that electroacupuncture stimulation at both vision-related acupoints and the NAP produced modest, comparable fMRI signal decreases in the occipital cortex, including the bilateral cuneus, calcarine fissure and surrounding areas, lingual gyrus, and lateral occipital gyrus. Further analysis of fMRI signal changes in occipital cortex showed no significant difference among the three points, UB 60, GB 37, and NAP. Our results thus do not support the view that acupuncture stimulation at vision-related acupoints induces specific fMRI blood oxygen level dependent (BOLD) signal changes in the occipital cortex. We speculate that cross modal inhibition, produced by needling-evoked somatosensory stimulation, may account for our finding of BOLD signal decreases in the occipital cortex. Given the complexity of acupuncture systems and brain activity, additional work is required to determine whether functional neuroanatomical correlates of acupoint specificity can be validated by means of brain imaging tools.     

Caregiving appraisal after traumatic brain injury: The effects of functional status, coping style, social support and family functioning

Perception of caregiving after traumatic brain injury (TBI) has been shown to be an important part of both survivor and family adjustment. The roles of coping style, family functioning, perceived social support and the TBI survivor's functional status have not been fully examined with respect to appraisal of caregiving. This study examined these factors with respect to both positive and negative appraisals of caregiving in four main areas: perceived burden, caregiving relationship satisfaction, beliefs about caregiving, and mastery with caregiving. Sixty primary caregivers of individuals who sustained a TBI within the last 6 months to 15 years were administered the Caregiver Appraisal Scale, as well as the Coping Inventory for Stressful Situations, a 21-item version of the Family Assessment Device, and the Social Provision Scale. These findings were examined in relation to the TBI survivor's scores on the Disability Rating Scale and the Functional Independence Measure at the same time points post-injury. Results revealed that the majority of caregivers in those with moderate to severe brain injuries experienced dissatisfaction with many aspects of caregiving, especially with respect to feelings of burden and mastery. Additionally, emotionally-focused coping, behavioral control issues with respect to family functioning, and perceived social support appear to be most highly related to perceptions of burden, whereas perceived social support alone was the strongest factor in one's perception of caregiving mastery and satisfaction with the caregiving relationship. Interestingly, caregiving ideology was most closely related to avoidance-oriented coping. These results have direct implications for the development of interventions for caregivers of persons with TBI, especially with respect for the need to assess coping style and the development of social support networks.     

Test-retest and between-site reliability in a multicenter fMRI study

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.     

fMRI of sensitization to angry faces

This study examined what is communicated by facial expressions of anger and mapped the neural substrates, evaluating the motivational salience of these stimuli. During functional magnetic resonance imaging, angry and neutral faces were presented to human subjects. Across experimental runs, signal adaptation was observed. Whereas fearful faces have reproducibly evoked response habituation in amygdala and prefrontal cortex, angry faces evoked sensitization in the insula, cingulate, thalamus, basal ganglia, and hippocampus. Complementary offline rating and keypress experiments determined an aversive rank ordering of angry, fearful, neutral, and happy faces and revealed behavioral sensitization to the angry faces. Subjects rated angry faces, in contrast to other face categories such as fear, as significantly more likely to directly inflict harm. Furthermore, they rated angry faces as significantly less likely to produce positive emotional outcomes than the other face categories. Together these data argue that angry faces, a directly aversive stimulus, produce a sensitization response.