The usefulness of a computer-aided diagnosis scheme for improving the performance of clinicians to diagnose non-mass lesions on breast ultrasonographic images

Purpose

The purpose of this study was to evaluate the usefulness of a computer-aided diagnosis (CAD) scheme for improving the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images.

Methods

The database included 97 ultrasonographic images with hypoechoic areas: 48 benign cases [benign lesion with benign mammary tissue or fibrocystic disease (n = 20), fibroadenoma (n = 11), and intraductal papilloma (n = 17)] and 49 malignant cases [ductal carcinoma in situ (n = 17) and invasive ductal carcinoma (n = 32)]. Seven clinicians, three expert breast surgeons, and four general surgeons participated in the observer study. They were asked their confidence level concerning the possibility of malignancy in all 97 cases with and without the use of the CAD scheme. Receiver operating characteristic (ROC) analysis was performed to evaluate the usefulness of the CAD scheme.

Results

The areas under the ROC curve (AUC) improved for all observers when they used the CAD scheme and increased from 0.649 to 0.783 (P = 0.0167). Notably, the AUC for the general surgeon group increased from 0.625 to 0.793 (P = 0.045).

Conclusions

This study showed that the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images was improved by the use of a CAD scheme.

     

Does severe obstructive sleep apnea syndrome alter retrobulbar blood flow? A color Doppler ultrasound study

Purpose

To evaluate extraocular orbital vessels with color Doppler ultrasound (CDU) and investigate the effects of severe obstructive sleep apnea (OSA) on retrobulbar blood flow.

Methods

Between February 2014 and September 2015, 30 patients with severe OSA (apnea–hypopnea index (AHI) > 30) and 28 controls were prospectively included in this study. Intraocular pressure (IOP) was measured with a Goldmann applanation tonometer, and CDU was used to evaluate the retrobulbar vessels.

Results

The mean AHI score for the OSA group was 63.2 ± 21.5 per hour. The IOP values were significantly higher in the severe OSA group (p < 0.05). The central retinal artery peak systolic velocity (PSV) (p < 0.05) and end-diastolic velocity (EDV) (p < 0.02), and the ophthalmic artery (OA) PSV and EDV, were found to be significantly lower in the OSA group (p < 0.05).

Conclusion

Severe OSA causes an increase in IOP and a decrease in flow velocity in the retrobulbar circulation.

     

Left Atrial structure and function in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy

Background

Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH).

Method

Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n =?34), preclinical mutation carriers without HCM (n =?24) and healthy, familial controls (n =?15).

Results

LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was evidence of impaired LA function with decreased LA total emptying function in both preclinical (64?±?8%) and overt HCM (59?±?10%), compared with controls (70?±?7%; p =?0.002 and p =?0.005, respectively). LA passive emptying function was also decreased in overt HCM (35?±?11%) compared with controls (47?±?10%; p =?0.006). Both LAtotal emptying function and LA passive emptying function were inversely correlated with the extent of late gadolinium enhancement (LGE; p?=?0.005 and p <?0.05, respectively), LV mass (p =?0.02 and p <?0.001) and interventricular septal thickness (p?<?0.001 for both) and serum NT-proBNP levels (p?<?0.001 for both).

Conclusion

LA dysfunction is detectable by CMR in preclinical HCM mutation carriers despite non-distinguishable LV wall thickness and LA volume. LA function appears most impaired in subjects with overt HCM and a greater extent of LV fibrosis.

     

Changes in Healthcare Spending After Diagnosis of Comorbidities Among Endometriosis Patients: A Difference-in-Differences Analysis

Introduction

We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities.

Methods

Women aged 18–49 years with endometriosis (N = 180,278) were extracted from 2006–2015 de-identified Clinformatics^® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient’s index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre–post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis.

Results

The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren’s/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p < 0.001 except for headache (p = 0.045)]. Spending decreased significantly for fatigue, cystitis/UTI, and eczema [p < 0.001 except for fatigue (p = 0.048)] and was not statistically different for the other 11 comorbidities. Difference-in-differences estimates were significantly higher for comorbidity patients for all comorbidities except eczema (p ≤ 0.003). Mean 5-year total cumulative spending was $58,191 per endometriosis patient, of which between 11% and 23% was attributable to comorbidity-related medical claims.

Conclusion

For all but one of the 22 comorbidities associated with endometriosis, comorbidity onset was associated with a relative increase in total healthcare spending.

Funding

AbbVie Inc.

     

Correlation between the combination of apparent integrated backscatter–spectral centroid shift and bone mineral density

Purpose

To introduce a new diagnostic parameter: the linear combination of apparent integrated backscatter and spectral centroid shift.

Methods

Ultrasonic backscatter measurements were performed at the calcanei of 1262 volunteers in vivo. The hip and spine bone mineral densities of the volunteers were measured using dual X-ray absorptiometry. The apparent integrated backscatter and spectral centroid shift were calculated. A new diagnostic parameter, i.e., the linear combination of apparent integrated backscatter and spectral centroid shift, was introduced and its correlation to bone mineral density was analyzed.

Results

The results show that the combination of apparent integrated backscatter and spectral centroid shift is significantly correlated to bone mineral density (R = 0.73–0.84, n = 1262, p < 0.05), and that this correlation is more significant than the correlation between the apparent integrated backscatter and bone mineral density or the correlation between spectral centroid shift and bone mineral density (R = 0.48–0.69, p < 0.05).

Conclusion

The combination of apparent integrated backscatter and spectral centroid shift can provide the complementary information of attenuation of the two parameters and predict more information about cancellous bone, and may be employed to assess cancellous bone status.

     

Ist Kinesiophobie während eines anhaltenden Schmerzzustands mit Lateralitäts- und Emotionserkennungsveränderungen assoziiert?

Background

The aim of this study is to investigate the effects of kinesiophobia on emotion recognition and left/right judgement.

Materials and methods

A total of 67 patients with chronic musculoskeletal pain were tested. In all, 24 patients achieved a score >37 on the Tampa Scale of Kinesiophobia and were included in the study. The ability to recognize basic emotions coded through facial expression was assessed using the Facially Expressed Emotion Labeling (FEEL) test. Left/right judgement was evaluated using a special Face-mirroring Assessment and Treatment program. The Toronto Alexithymia Scale-26 (TAS-26) was used to assess if the patients showed signs of alexithymia.

Results

The FEEL score of patients with kinesiophobia was significantly lower (p = 0.019). The recognition of the basic emotions fear (p = 0.026), anger (p = 0.027), and surprise (p = 0.014) showed significant differences in comparison to unaffected subjects. The basic emotion surprise was recognized more often by patients with kinesiophobia (p = 0.014). Only Scale 1 of the TAS-26 (identification problems of emotions) showed a significant difference between patients with kinesiophobia (p = 0.008) and healthy subjects.

Conclusion

The results show that kinesiophobic patients have altered recognition of emotions, problems in left/right judgement, and show signs of alexithymia.

     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

Histogram Analysis of T1-Weighted,T2-Weighted,and Postcontrast T1-Weighted Images in Primary CNS Lymphoma: Correlations with Histopathological Findings—a Preliminary Study

Purpose

Previously, some reports mentioned that magnetic resonance imaging (MRI) can predict histopathological features in primary CNS lymphoma (PCNSL). The reported data analyzed diffusion-weighted imaging findings. The aim of this study was to investigate possible associations between histopathological findings, such as tumor cellularity, nucleic areas and proliferation index Ki-67, and signal intensity on T1-weighted and T2-weighted images in PCNSL.

Procedures

For this study, 18 patients with PCNSL were retrospectively investigated by histogram analysis on precontrast and postcontrast T1-weighted and fluid-attenuated inversion recovery (FLAIR) images. For every patient, histopathology parameters, nucleic count, total nucleic area, and average nucleic area, as well as Ki-67 index, were estimated.

Results

Correlation analysis identified several statistically significant associations. Skewness derived from precontrast T1-weighted images correlated with Ki-67 index (p = ? 0.55, P = 0.028). Furthermore, entropy derived from precontrast T1-weighted images correlated with average nucleic area (p = 0.53, P = 0.04). Several parameters from postcontrast T1-weighted images correlated with nucleic count: maximum signal intensity (p = 0.59, P = 0.017), P75 (p = 0.56, P = 0.02), and P90 (p = 0.52, P = 0.04) as well as SD (p = 0.58, P = 0.02). Maximum signal intensity derived from FLAIR sequence correlated with nucleic count (p = 0.50, P = 0.03).

Conclusion

Histogram-derived parameters of conventional MRI sequences can reflect different histopathological features in PSNCL.

     

Impact of hysterectomy on three-dimensional rectosigmoid morphology and endoscopy performance: a pilot study

Objectives

Assess differences in three-dimensional colonic metrics on CTC in women with or without hysterectomy following incomplete endoscopy to determine if there is a correlation between colonic morphology and incomplete colonoscopy after hysterectomy.

Methods

Quantitative rectosigmoid metrics were derived from CTC datasets of 37 women with hysterectomy and 36 women without hysterectomy who underwent CTC for incomplete endoscopy. Evaluated metrics included colonic length, volume, tortuosity, and compactness and sigmoid apex height relative to the lumbosacral junction. Differences were measured using the Student’s t test, and intra-reader reliability was assessed using ICC. The relative risk of incomplete rectosigmoid visualization was determined by reviewing the endoscopy reports.

Results

Women with hysterectomy had a lower sigmoid apex height (p = 0.002), as well as increased tortuosity (p = 0.012) and compactness (p = 0.001) and decreased length (p = 0.026) and volume (p = 0.016) of the rectosigmoid. Intra-reader reliability was high for centerline length (ICC = 0.9940) and sigmoid apex height (ICC = 0.9851). The relative risk of incomplete visualization of the rectosigmoid on endoscopy in women with hysterectomy was 2.068 (p = 0.043) compared to women without hysterectomy.

Conclusion

Our pilot data show reproducible quantitative differences in three-dimensional metrics of the rectosigmoid in women with or without hysterectomy who underwent CTC for incomplete endoscopy and increased relative risk of incomplete endoscopic visualization of the rectosigmoid after hysterectomy. Our findings suggest that women with hysterectomy may benefit from CTC rather than endoscopy as the initial diagnostic test for evaluating the colon.

     

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

Introduction

Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients’ satisfaction and adherence.

Methods

ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.

Results

A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p?<?0.001) decrease in angina attack frequency (from 4.7?±?3.5 to 0.9?±?1.3/week) and SAN use (from 4.5?±?3.9 to 0.7?±?1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p?<?0.0001) and non-adherence by 3% (vs. 36% at baseline, p?<?0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p?<?0.01), slight limitation (46% vs. 5% at baseline, p?<?0.001) or moderate limitation (30% vs. 23%, p?<?0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p?<?0.001) or very marked reduction (1% vs. 19% at baseline, p?<?0.01) at month 3.

Conclusion

In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.

Trial Registration

ISRCTN registry Identifier, ISRCTN97780949.

Funding

Servier.

Plain Language Summary

Plain language summary available for this article.

     

Effects of Tiotropium Combined with Theophylline on Stable COPD Patients of Group B,D and its Impact on Small Airway Function: A Randomized Controlled Trial

Introduction

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.

Methods

Eligible participants (n?=?170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.

Results

After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41?±?3.56 and 11.08?±?3.05, p?<?0.0001). The changes of CAT (p?=?0.028) and mMRC scores (p?=?0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF₂₅% pred) was significantly improved after 3 months (4.84?±?8.73%, p?<?0.0001) and 6 months (6.21?±?8.65%, p?<?0.0001). There was a significant difference in small airway function tests (MEF₅₀% pred, MEF₂₅% pred, and MMEF% pred) between the two groups after 6 month of treatment (p?=?0.003, p?<?0.0001, and p?=?0.021, respectively).

Conclusions

Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function.

Trial Registration

Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).

     

A recovery program to improve quality of life,sense of coherence and psychological health in ICU survivors: a multicenter randomized controlled trial,the RAPIT study

Purpose

The aim of this randomized controlled trial (RCT) was to test the effectiveness of a post-ICU recovery program compared to standard care during the first year after ICU discharge.

Methods

A pragmatic, non-blinded, multicenter, parallel-group RCT was conducted between December 2012 and December 2015, at ten intensive care units (ICUs) in Denmark. We randomly assigned 386 adult patients (≥18 years) after receiving mechanical ventilation (≥48 h) to standard care (SC) plus a nurse-led intensive care recovery program or standard care alone after ICU discharge (190 intervention, 196 SC). Primary outcome was health-related quality of life (HRQOL) at 12 months. Secondary outcomes were sense of coherence (SOC), anxiety, depression, and post-traumatic stress disorder (PTSD) assessed at 3 and 12 months after ICU discharge including utilization of healthcare services at 12 months.

Results

At 12 months, we found no differences in HRQOL between groups (mean difference in the Physical Component Summary score, 1.41 [95 % CI, ?1.53 to 4.35; p = 0.35] (n = 235); and in the Mental Component Summary score, 1.92 [95 % CI, ?1.06 to 4.90; p = 0.11] (n = 235). No differences were found on self-reported SOC (p = 0.63), anxiety (p = 0.68), depression (p = 0.67), PTSD (p = 0.27), or the utilization of healthcare services including rehabilitation. We found a difference on anxiety, when a cut-off point ≥11 was applied, in per protocol analysis of complete cases at 3 months favoring the intervention (8.8 % vs. 16.2 %, p = 0.04).

Conclusions

The tested recovery program was not superior to standard care during the first 12 months post-ICU.

Trial registration

The trial is registered at Clinicaltrials.gov, identification no. NCT01721239.

     

Comparing Entropy and the Bispectral Index with the Ramsay Score in Sedated ICU Patients

Objective

ENTROPY? is a new anesthetic depth monitor based on the analysis of the EEG signal. Our aim has been to evaluate sedation of intubated surgical critically ill patients by means of the Ramsay sedation score, the Bispectral index and ENTROPY?, and to analyse the correlation between these variables.

Methods

Sedation was evaluated every 15 min for a 1 h period in 50 non-paralysed postoperative critically ill, intubated patients, enrolled over a 6 month period. A 5 min steady-state period was allowed before each assessment. Both the Bispectral index and the Entropy parameters Response Entropy (RE) and State Entropy (SE), were collected before assessing the Ramsay scale.

Results

Mean values for SE, RE and BIS were 53 ± 27, 60 ± 30, and 62 ± 24 respectively. The median value for the Ramsay was 6 (range 1–6). Significant correlation was found between the four variables (SE-BIS: r = 0.79, p < 0.001; RE-BIS: r = 0.80, p < 0.001; SE-Ramsay: ρ = ?0.71, p < 0.001, RE-Ramsay: ρ = ?0.72, p < 0.001; BIS-Ramsay: ρ = ?0.78, p < 0.001; RE-SE: r = 0.98, p < 0.001). An overlap of BIS and Entropy values for every Ramsay score value between 4–6 was found.

Conclusions

ENTROPY?, BIS and Ramsay score values correlate significantly in sedated postoperative ICU patients. ENTROPY? does not appear superior to BIS for the assessment of sedation in this context.

     

Real-time ultrasound elastography of the Achilles tendon in patients with cerebral palsy: is there a correlation between strain ratio and biomechanical indicators?

Purpose

Our aim was to comparatively investigate the strain ratio and thickness of the Achilles tendon in children with cerebral palsy (CP), and to elucidate whether there is a correlation between biomechanical features of the Achilles tendon and strain ratio.

Methods

A total of 155 participants (72 CP patients and 83 healthy controls) who underwent real-time elastography of both Achilles tendons were studied. A linear transducer (4.8–11.0 MHz) was used to obtain the images. Correlation analysis between age, length, and thickness of the Achilles tendon, and strain ratio (SR) was performed by means of Pearson correlation and Spearman’s rho tests.

Results

Comparison of results obtained from CP patients and controls showed that the length of the Achilles tendon was shorter (p < 0.001) and SR was higher (p < 0.001) in CP patients. In CP patients, there was a positive correlation between SR and age and between SR and the thickness and length of the Achilles tendon (p < 0.001 for all). Furthermore, the length of the tendon and age were positively associated (p < 0.001). ROC analysis revealed that the cut-off value for SR was 1.89.

Conclusion

The results of the present study demonstrated that real-time elastography can constitute a simple, practical, and noninvasive method for evaluation of the elasticity of the Achilles tendon in children with CP.

     

Effect of steatosis on liver signal and enhancement on multiphasic contrast-enhanced magnetic resonance imaging

Purpose

To investigate the effect of steatosis on liver signal and enhancement in multiphasic contrast-enhanced (MCE) MRI.

Materials and methods

In this IRB-approved, HIPAA-compliant, retrospective, observational study, 1217 MCE abdominal MRIs performed during 2014 at a single institution were reviewed. Of these, 1085 were excluded, due to potential factors other than steatosis that may affect liver signal intensity and/or enhancement. In the remaining 132, liver fat fraction (FF) was calculated from the in- and opposed-phase 2D T1-weighted images. Liver signal intensity, absolute enhancement, and relative enhancement on fat-suppressed (Dixon method) 3D T1-weighted images before and after injection of gadobutrol (arterial, portal venous, and equilibrium phases) were plotted against co-localized FF values and the linear trend was evaluated by Pearson correlation coefficient (r). P values <0.05 were considered statistically significant.

Results

Liver signal intensity negatively correlated with FF for all phases (r = ?0.388 to ?0.544, p < 0.001). Absolute enhancement negatively correlated with FF for the portal venous and equilibrium phases (r = ?0.286 and ?0.289, respectively, p < 0.001), but not for the arterial phase (r = ?0.042, p = 0.632). Relative enhancement did not significantly correlate with FF for any phase (p ≥ 0.125).

Conclusion

Steatosis reduces liver signal intensity in MCE MRI. This effect of steatosis was reduced in calculated absolute enhancement and eliminated in calculated relative enhancement.

     

Efficacy of Ivabradine in Combination with Beta-Blockers Versus Uptitration of Beta-Blockers in Patients with Stable Angina (CONTROL-2 Study)

Introduction

Heart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina.

Methods

This multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio.

Results

At the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001).

Conclusion

In patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration.

Trial Registration

ISRCTN30654443.

Funding

Servier.

     

Randomized controlled pilot trial of mindfulness-based stress reduction compared to psychoeducational support for persistently fatigued breast and colorectal cancer survivors

Purpose

Cancer-related fatigue (CRF) is a disruptive symptom for many survivors. Despite promising evidence for efficacy of mindfulness-based stress reduction (MBSR) in reducing CRF, no trials comparing it to an active comparator for fatigued survivors have been published. The purpose of this trial was to compare MBSR to psychoeducation for CRF and associated symptoms.

Methods

Breast (n = 60) and colorectal (n = 11) cancer survivors (stage 0–III) with clinically significant CRF after completing chemotherapy and/or radiation therapy an average of 28 months prior to enrollment were randomized to MBSR or psychoeducation/support groups (PES). MBSR focused on mindfulness training; PES focused on CRF self-management. Outcomes included CRF interference (primary), CRF severity and global improvement, vitality, depression, anxiety, sleep disturbance, and pain. Outcomes were assessed at baseline (T1), post-intervention (T2), and 6-month follow-up (T3) using intent-to-treat analysis.

Results

Between-group differences in CRF interference were not significant at any time point; however, there was a trend favoring MBSR (d = ?0.46, p = 0.073) at T2. MBSR participants reported significantly greater improvement in vitality (d = 0.53, p = 0.003) and were more likely to report CRF as moderately to completely improved compared to the PES group (χ2 (1) = 4.1765, p = 0.041) at T2. MBSR participants also reported significantly greater reductions in pain at T2 (d = 0.53, p = 0.014). In addition, both MBSR and PES produced moderate-to-large and significant within-group improvements in all fatigue outcomes, depression, anxiety, and sleep at T2 and T3 compared to T1.

Conclusion

MBSR and PES appear efficacious for CRF and related symptoms. Larger trials including a usual care arm are warranted.

Trial Registration

ClinicalTrials.gov Identifier: NCT01724333.

     

Histogram analysis of noncancerous liver parenchyma on gadoxetic acid-enhanced MRI: predictive value for liver function and pathology

Purpose

To clarify whether the heterogeneity of hepatic parenchyma in the hepatobiliary phase on gadoxetic acid-magnetic resonance (MR) imaging is correlated with liver damage.

Materials and methods

We retrospectively examined the cases of 98 patients with or without chronic liver disease who underwent gadoxetic acid-enhanced 3T MR imaging before a hepatectomy between December 2010 and October 2014. For the evaluation of the heterogeneity of the signal intensity in the hepatobiliary phase, we placed the region of interest on the hepatic parenchyma, and the skewness and kurtosis were calculated using ImageJ software. A discriminant analysis was performed to examine the routine preoperative laboratory test results including indocyanine green retention at 15 min (ICG-R15), necro-inflammation grade, and liver fibrosis stage according to the METAVIR system: A0/1 (n = 69) and A2 (n = 29); F0/1 (n = 47), F2/3 (n = 31), and F4 (n = 20).

Results

The combination of skewness and kurtosis could discriminate the high ICG-R15 (>20) and low (<20) groups (lambda; 0.925, p = 0.025), necro-inflammatory grade (lambda; 0.926, p = 0.026), and fibrosis stage (lambda; 0.752, p < 0.0001) with statistical significance. The difference between the patients with normal values and those with an abnormal platelet count or aspartate transaminase level was also detectable (lambda; 0.901, p < 0.007, and lambda; 0.864, p = 0.001, respectively).

Conclusion

Histogram analyses of the hepatobiliary phase of gadoxetic acid-enhanced MR imaging have potential as a biomarker for the assessment of liver function, liver fibrosis, and necro-inflammation.

     

Early-stage clear cell tubulopapillary renal cell carcinoma: imaging features and distinction from clear cell and papillary subtypes

Purpose

Clear cell tubulopapillary renal cell carcinoma (CCTPRCC) is a recently described, low-grade subtype of renal cancer. We determined if imaging features could be used to distinguish early-stage CCTPRCC from stage-matched clear cell RCC (ccRCC) and papillary RCC (pRCC).

Methods

This IRB-approved retrospective study included 54 stage T1a patients with pathologically confirmed CCTPRCC (n = 18), ccRCC (n = 18), and pRCC (n = 18). CT (n = 48) and MRI (n = 27) exams were reviewed and imaging features compared. Continuous variables were evaluated using ANOVA and Tukey’s multiple comparison tests. Categorical variables were compared using Chi-square test or Fisher’s exact test.

Results

Compared to pRCC, CCTPRCC had a lower mean attenuation value on unenhanced CT (p < 0.017), was more often hyperintense on T2-weighted images (p < 0.0001), showed an ill-defined margin (p = 0.003), and demonstrated nonenhancing areas (p = 0.0003). The presence of all three of these statistically significant features [hypoattenuation (unenhanced attenuation ≤25 HU), ill-defined margin, nonenhancing areas] yielded an area under the receiver operator curve (ROC) of 0.92 (95% CI 0.83–0.99) for differentiating CCTPRCC from pRCC. There were no significant differences in the imaging features of CCTPRCC and ccRCC.

Conclusions

Early-stage clear cell tubulopapillary renal cell carcinoma can be distinguished from papillary RCC based on low attenuation on unenhanced CT, high intensity on T2-weighted images, an ill-defined margin, and presence of nonenhancing areas, but cannot be distinguished from clear cell RCC.