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.

     

Prospective,Randomized, Single Masked,Parallel Study Exploring the Effects of a Preservative-Free Ophthalmic Solution Containing Hyaluronic Acid 0.4% and Taurine 0.5% on the Ocular Surface of Glaucoma Patients Under Multiple Long-Term Topical Hypotensive Therapy

Introduction

To compare the effects of a preservative-free (PF) ophthalmic solution containing hyaluronic acid (HA) 0.4% and taurine (TAU) 0.5% with those of a PF ophthalmic solution containing HA 0.2% on ocular surface signs, symptoms, and morphological parameters in glaucoma patients under multiple long-term topical hypotensive therapy.

Methods

Eligible patients underwent evaluation of ocular surface parameters by ocular surface disease index (OSDI) and glaucoma symptom scale (GSS) questionnaires, breakup time test (BUT), Schirmer I test, corneal and conjunctival staining (Oxford scale), and conjunctival in vivo confocal microscopy (Heidelberg Retina Tomograph 3, Heidelberg Engineering GmbH, Heidelberg, Germany). After the baseline visit, patients were randomized to use a PF ophthalmic solution containing HA 0.4% and TAU 0.5%, QID, in both eyes (group 1) or to use a PF ophthalmic solution containing HA 0.2%, QID (group 2) in addition to the ongoing preserved hypotensive treatment. Follow-up visits were scheduled at 30 and 90 days.

Results

Thirty-nine eyes of 39 glaucoma patients were included in the study. At baseline, results of study tests of both groups were similar. After 90 days in group 1 the BUT (p?=?0.01), the Oxford score (p?=?0.03), the conjunctival goblet cells (CGC) density (p?=?0.0005) ,and the two questionnaires score significantly improved (OSDI, p?=?0.003; GSS, p?=?0.003) compared to baseline values, while in group 2 all these parameters did not differ from baseline (BUT, p?=?0.39; Oxford score, p?=?0.54; CGC density, p?=?0.33, OSDI p?=?0.65, GSS, p?=?0.25). The BUT and the CGC density were statistically different between groups both at 30 and 90 days (p?=?0.04 and p?=?0.04, respectively). The Schirmer I test did not statistically change after 90 days in both groups.

Conclusions

The PF ophthalmic solution with HA 0.4% and TAU 0.5% seems to improve CGC density and reduce signs and symptoms of dry eye in glaucoma patients under long-term multiple preserved hypotensive therapy.

Trial registration

ClinicalTrials.gov identifier, NCT03480295.

     

The Impact of a Single Nucleotide Polymorphism in<Emphasis Type="Italic"> SIGMAR1</Emphasis> on Depressive Symptoms in Major Depressive Disorder and Bipolar Disorder

Introduction

Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers.

Methods

A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively.

Results

In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode.

Conclusion

The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.

     

Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery

Purpose

The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.

Procedures

The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)—score and immunohistochemical analysis in normal pancreatic tissue (n?=?9), pancreatic (n?=?137), and periampullary (n?=?28) adenocarcinoma.

Results

Integrin α_vβ₆, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p?<?0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients.

Conclusions

The results of this study show that integrin α_vβ₆, CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

     

Adaptive leadership curriculum for Indian paramedic trainees

Background

Paramedic trainees in developing countries face complex and chaotic clinical environments that demand effective leadership, communication, and teamwork. Providers must rely on non-technical skills (NTS) to manage bystanders and attendees, collaborate with other emergency professionals, and safely and appropriately treat patients. The authors designed a NTS curriculum for paramedic trainees focused on adaptive leadership, teamwork, and communication skills critical to the Indian prehospital environment.

Methods

Forty paramedic trainees in the first academic year of the 2-year Advanced Post-Graduate Degree in Emergency Care (EMT-paramedic equivalent) program at the GVK-Emergency Management and Research Institute campus in Hyderabad, India, participated in the 6-day leadership course. Trainees completed self-assessments and delivered two brief video-recorded presentations before and after completion of the curriculum.

Results

Independent blinded observers scored the pre- and post-intervention presentations delivered by 10 randomly selected paramedic trainees. The third-party judges reported significant improvement in both confidence (25 %, p?<?0.01) and body language of paramedic trainees (13 %, p?<?0.04). Self-reported competency surveys indicated significant increases in leadership (2.6 vs. 4.6, p?<?0.001, d?=?1.8), public speaking (2.9 vs. 4.6, p?<?0.001, d?=?1.4), self-reflection (2.7 vs. 4.6, p?<?0.001, d?=?1.6), and self-confidence (3.0 vs. 4.8, p?<?0.001, d?=?1.5).

Conclusions

Participants in a 1-week leadership curriculum for prehospital providers demonstrated significant improvement in self-reported NTS commonly required of paramedics in the field. The authors recommend integrating focused NTS development curriculum into Indian paramedic education and further evaluation of the long term impacts of this adaptive leadership training.

     

Lack of agreement between thermodilution and electrical velocimetry cardiac output measurements

Objective

The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance—electrical velocimetry (EV^®)—has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV^®-CO measurements reflect intraindividual changes in CO during cardiac surgery.

Design

Prospective, observational study.

Setting

Operating room (OR) and intensive care unit (ICU) of a university hospital.

Patients

Twenty-nine patients undergoing elective cardiac surgery.

Interventions

None.

Measurements

CO was determined simultaneously by PA-TD and EV^® after induction of anesthesia (t1) and 4.9?±?3.5?h after ICU admission (t2).

Results

TD-CO was 3.9?±?1.4 and 5.4?±?1.1 l/min at t1 and t2 (?p?®-CO was 4.3?±?1.1 and 4.9?±?1.5 l/min at t1 and t2 (?p?=?0.013). Bland–Altman analysis showed a bias of ?0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n?=?12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n?=?9 and n?=?8 patients, respectively.

Conclusions

The disagreement between PA-TD and EV^®-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV^®-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.

     

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.

     

Predictive factors for polypharmacy among child and adolescent psychiatry inpatients

Background

Aim was to determine the predictive factors for polypharmacy among inpatient children and adolescents with psychiatric disorders.

Methods

Blinded, case-note review of children and adolescents with ICD 10 diagnosis of psychiatric disorders on psychotropic medication was conducted. Data on demography, illness, and treatment was analyzed with univariate and multivariate techniques.

Results

Proscribing non-pharmacological interventions (OR = 4.7) and pro re nata medication (OR = 3.3), increased the risk of polypharmacy. Prescribing physical restraint reduced the risk of receiving multiple medications (OR = 0.3).

Conclusion

Proscribing non-pharmacological interventions, pro re nata medication and physical restraints increased polypharmacy.

     

Respiratory variations in aortic blood flow predict fluid responsiveness in ventilated children

Objective

To investigate whether respiratory variations in aortic blood flow velocity (ΔVpeak ao), systolic arterial pressure (ΔPS) and pulse pressure (ΔPP) could accurately predict fluid responsiveness in ventilated children.

Design and setting

Prospective study in a 18-bed pediatric intensive care unit.

Patients

Twenty-six children [median age 28.5 (16–44) months] with preserved left ventricular (LV) function.

Intervention

Standardized volume expansion (VE).

Measurements and main results

Analysis of aortic blood flow by transthoracic pulsed-Doppler allowed LV stroke volume measurement and on-line ΔVpeak ao calculation. The VE-induced increase in LV stroke volume was >?15% in 18 patients (responders) and p?=?0.001], whereas ΔPP and ΔPS did not significantly differ between groups. The prediction of fluid responsiveness was higher with ΔVpeak ao [ROC curve area 0.85 (95% IC 0.99–1.8), p?=?0.001] than with ΔPS (0.64) or ΔPP (0.59). The best cut-off for ΔVpeak ao was 12%, with sensitivity, specificity, and positive and negative predictive values of 81.2%, 85.7%, 93% and 66.6%, respectively. A positive linear correlation was found between baseline ΔVpeak ao and VE-induced gain in stroke volume (rho?=?0.68, p?=?0.001).

Conclusions

While respiratory variations in aortic blood flow velocity measured by pulsed Doppler before VE accurately predict the effects of VE, ΔPS and ΔPP are of little value in ventilated children.

     

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.

     

Design and evaluation of the StartingTogether App for home visits in preventive child health care

Background

The StartingTogether program (in Dutch SamenStarten) is a family-centred method for early identification of social-emotional and behavioural problems in young children. Nurses in preventive child health care find it challenging to: determine family issues and need for care; provide education; refer to social services; increase parent empowerment. To mitigate these challenges, we developed and evaluated the StartingTogether App, offering nurses and parents conversational support, tailored education and information on social services.

Methods

A mixed method design, consisting of a qualitative evaluation of the StartingTogether App, with group discussions with nurses (N?=?14) and a pilot test (N?=?5), and a randomized controlled trial, evaluating the effectiveness of the app. Nurses (N?=?33) made home visits to parents (N?=?194), in teams with or without the app. Nurses were surveyed on the challenges experienced during visits. Parents (N?=?166) were surveyed on their satisfaction with health care and app. Nurses were interviewed on the benefits and barriers to use the app.

Results

Parents with the StartingTogether App were more satisfied with the visits than parents without (p?=?.002). Parents with a high educational level were more satisfied with the visits than the parents with a low educational level. With the app, their satisfaction level was similar (p?<?.001). Nurses using the app felt more equipped to communicate with parents (p?=?.012) and experienced that parents were more knowledgeable and skilled (p?=?.001). Parents felt that with the app the nurse was more polite (p?=?.02), listened more carefully (p?=?.03), and had more time (p?=?.02). Nurses with the app gave parents more opportunity to ask questions (p?=?.001) and gave clearer answers (p?<?.001). The qualitative evaluation indicated that some nurses needed extra time to develop the habit of using the app.

Conclusions

The StartingTogether App contributes to parents’ satisfaction with home visits. An interaction effect between parents’ educational level and rating of home visits indicated that the app has an additional value for parents with a lower educational level. Applying mobile applications, such as the StartingTogether App, potentially has a positive effect on communication between nurses and parents about the family situation in relation to parent empowerment and the child’s development.

Trial registration

The study is registered with ISRCTN under the number ISRCTN12491485, on August 23, 2018. Retrospectively registered.

     

Migraine induction with calcitonin gene-related peptide in patients from erenumab trials

Background

Migraine prevention with erenumab and migraine induction by calcitonin gene-related peptide (CGRP) both carry notable individual variance. We wanted to explore a possible association between individual efficacy of anti-CGRP treatment and susceptibility to migraine induction by CGRP.

Methods

Thirteen migraine patients, previously enrolled in erenumab anti-CGRP receptor monoclonal antibody trials, received CGRP in a double-blind, placebo-controlled, randomized cross-over design to investigate their susceptibility to migraine induction. A standardized questionnaire was used to assess the efficacy of previous antibody treatment. The patients were stratified into groups of high responders and poor responders. Primary outcomes were incidence of migraine-like attacks and area under the curve of headache intensity after infusion of CGRP and placebo. All interviews and experiments were performed in laboratories at the Danish Headache Center, Copenhagen, Denmark.

Results

Ten high responders and three poor responders were included. CGRP induced migraine-like attacks in ten (77%) patients, whereof two were poor responders, compared to none after placebo (p?=?0.002). The area under the curve for headache intensity was greater after CGRP, compared to placebo, at 0–90 min (p?=?0.009), and 2–12 h (p?=?0.014). The median peak headache intensity score was 5 (5–9) after CGRP, compared to 2 (0–4) after placebo (p?=?0.004).

Conclusions

Patients with an excellent effect of erenumab are highly susceptible to CGRP provocation. If an association is evident, CGRP provocation could prove a biomarker for predicting antibody treatment efficacy.

Trial registration

Retrospectively registered at clinicaltrials.gov with identifier: NCT03481400.

     

Effects of a self-managed home-based walking intervention on psychosocial health outcomes for breast cancer patients receiving chemotherapy: a randomised controlled trial

Purpose

This study evaluated the effectiveness of a self-managed home-based moderate intensity walking intervention on psychosocial health outcomes among breast cancer patients undergoing chemotherapy.

Methods

The randomised controlled trial compared a self-managed, home-based walking intervention to usual care alone among breast cancer patients receiving chemotherapy. Outcome measures included changes in self-report measures of anxiety, depression, fatigue, self-esteem, mood and physical activity. Fifty participants were randomised to either the intervention group (n?=?25), who received 12 weeks of moderate intensity walking, or the control group (n?=?25) mid-way through chemotherapy. Participants in the intervention group were provided with a pedometer and were asked to set goals and keep weekly diaries outlining the duration, intensity and exertion of their walking. Levels of psychosocial functioning and physical activity were assessed pre- and post-intervention in both groups.

Results

The intervention had positive effects on fatigue (F?=?5.77, p?=?0.02), self-esteem (F?=?8.93, p?≤?0.001), mood (F?=?4.73, p?=?0.03) and levels of physical activity (x ²?=?17.15, p?=?0.0011) but not anxiety (F?=?0.90, p?=?0.35) and depression (F?=?0.26, p?=?0.60) as assessed using the HADS. We found an 80 % adherence rate to completing the 12-week intervention and recording weekly logs.

Conclusion

This self-managed, home-based intervention was beneficial for improving psychosocial well-being and levels of physical activity among breast cancer patients treated with chemotherapy.

Trial registration

Current Controlled Trials ISRCTN50709297.

     

Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation

Purpose

The aim of this work is to develop an efficient and fully automated radiosynthesis of three derivatives of the Pittsburgh compound B labeled with gallium-68 for the detection of amyloid plaques.

Procedures

The radiolabeling of the precursors and purification of the radiolabeled agents by high pressure liquid chromatography has been studied prior to their in vitro and in vivo evaluations.

Results

The complete process led, in 50 min, to pure Ga-68 products in a 12–38 % yield and with appreciable specific radioactivity (SRA, 85–168 GBq/μmol) which enabled us to demonstrate a considerable in vivo stability of the products. Unfortunately, this result was associated with a poor blood–brain barrier (BBB) permeability and a limited uptake of our compounds by amyloid deposits was observed by in vitro autoradiography.

Conclusion

Although we have not yet identified a compound able to significantly mark cerebral amyloidosis, this present investigation will likely contribute to the development of more successful Ga-68 radiotracers.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Bioluminescence Imaging to Monitor the Effects of the Hsp90 Inhibitor NVP-AUY922 on NF-κB Pathway in Endometrial Cancer

Purpose

In this study, we first aimed to evaluate the effects in vitro and in vivo, of the Hsp90 inhibitor NVP-AUY922, in endometrial cancer (EC). We also aimed to track nuclear factor kappa B (NF-κB) signalling, a key pathway involved in endometrial carcinogenesis and to check whether NVP-AUY922 treatment modulates it both in vitro and in vivo.

Procedures

I n vitro effects of NVP-AUY922 on EC cell growth and the signalling pathways were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic assays, Western Blot and luciferase assay. NVP-AUY922 effect on Ishikawa (IK) xenograft growth was evaluated in vivo, and NF-κB activity was monitored using bioluminescence imaging.

Results

NVP-AUY922 inhibited the growth of three endometrial cell lines tested in vitro. In vivo, NVP-AUY922 reduced tumour growth of 47 % (p?=?0.042) compared to control condition. Moreover, the bioluminescence signal of the tumours harbouring IK NF-κB-LUC cells was significantly reduced in NVP-AUY922-treated animals compared to untreated ones.

Conclusions

NVP-AUY922 reduced EC tumour growth and NF-κB signalling both in vitro and in vivo. As therapeutic resistance of EC remains a challenge for oncologists nowadays, we think that NVP-AUY922 represents a valid alternative to conventional chemotherapy, and we believe that this approach for assessing and tracking the activation of NF-κB pathway may be of therapeutic benefit.

     

FLT-PET/CT diagnosis of primary and metastatic nodal lesions of gastric cancer: comparison with FDG-PET/CT

Purpose

To examine the diagnostic performance of ¹⁸F-fluorothymidine (FLT)-PET/CT of primary and metastatic nodal lesions of gastric cancer by comparing with ¹⁸F-fluorodeoxyglucose (FDG)-PET/CT.

Methods

The enrolled study population comprised 17 patients with 17 newly diagnosed gastric cancers who underwent surgery of the primary lesion and regional nodes after both FDG- and FLT-PET/CT scans. Visual detectability of the primary gastric lesions was correlated with pathological factors using the Fisher exact or Mann–Whitney U test. The sensitivity, specificity, and accuracy in detecting nodal lesions were compared between both PET/CT scans using the McNemar exact or χ ² test.

Results

Fourteen of 17 (82.4%) primary cancers were visualized by both FDG- and FLT-PET/CT scans. Although FDG or FLT visibility was not significantly associated with tumor size (p = 0.16) or histological type (p = 1.00), the 3 nonvisible lesions were pathologically early (T1) cancers. The sensitivity, specificity, and accuracy for detecting nodal metastasis were 44.8% (13/29), 98.7% (164/166), and 90.8% (177/195) for FDG-PET/CT, and 31.0% (9/29), 100% (166/166), and 89.7% (175/195) for FLT-PET/CT, respectively. No significant difference was found between the two scans in sensitivity (p = 0.13), specificity (p = 0.48), or accuracy (p = 1.00).

Conclusion

FLT-PET/CT may have the same diagnostic value as FDG-PET/CT for detection of primary and nodal lesions of gastric cancer.

     

Reproducibility of Contrast-Enhanced Ultrasound in Mice with Controlled Injection

Purpose

Sensitivity of contrast-enhanced ultrasound (CEUS) to microvascular flow modifications can be limited by intra-injection variability (injected dose, rate, volume).

Procedures

To evaluate the effect of injection variability on microvascular flow evaluation, CEUS was compared between controlled and manual injections where enhancement was assessed in vitro within a flow phantom, in normal murine kidney (N?=?12) and in murine ectopic tumors (N?=?10).

Results

For both in vitro and in vivo measurements in the renal cortex, controlled injections significantly improved reproducibility of functional parameter estimation. Their coefficient of variation (CV) in the renal cortex ranged from 4 to 19 % for controlled injection vs. 5 to 43 % for manual injections. For measurements in tumors, controlled injection only decreased the CV significantly for the mean transit time. In tumors, multiple injections of contrast agent with a 15-min delay between each were shown to strongly modify contrast uptake by facilitating penetration of microbubbles.

Conclusion

Improved reproducibility of CEUS assessments in murine models should provide more robust quantification of flow parameters and more sensitive evaluation of tumor modifications in therapeutic models.

     

Clear cell renal cell carcinoma: identifying the gain of chromosome 20 on multiphasic MDCT

Purpose

To investigate whether multiphasic multidetector computed tomography (MDCT) enhancement can help identify the gain of chromosome 20 in clear cell renal cell carcinomas (RCCs), a rare prognostically significant cytogenetic abnormality.

Methods

With the Institutional Review Board approval, we queried our institution’s pathology database to derive a cohort of 52 cases of clear cell RCC with preoperative four-phase renal mass protocol MDCT and karyotypes of the resected specimens during a 10-year period. Each lesion was evaluated for absolute and relative (compared to contralateral normal renal cortex) attenuations in each phase. Relative attenuation was calculated as [(lesion attenuation ? cortex attenuation)/cortex attenuation] × 100. The absolute and relative attenuations were compared using t-tests.

Results

Clear cell RCCs with the gain of 20 had significantly less nephrographic and excretory phase enhancement than clear cell RCCs without the gain of 20 (86.4 HU vs. 111.4 HU, p = 0.007; 70.0 HU vs. 89.4 HU, p = 0.003; respectively). Additionally, the relative nephrographic and excretory phase attenuations of clear cell RCCs with the gain of 20 were significantly less than that of clear cell RCCs without the gain of 20 (?52.7 vs. ?34.7, p = 0.002; ?44.9 vs. ?31.1, p = 0.005; respectively).

Conclusion

Multiphasic MDCT enhancement may assist in identifying the gain of chromosome 20 in clear cell RCCs, if validated in a large prospective trial.