The prospective associations between autonomy support, basic psychological needs, motivation and well-being among people with a mild to borderline intellectual disability: a two-wave study.

BACKGROUND: This study, grounded in self-determination theory, examined how satisfaction of the needs for autonomy, relatedness and competence in people with mild to borderline intellectual disability (MBID) changed over a 4.5-year period. Additionally, it explored the association between life events across various domains (i.e. health, support and living situation, crime, relationships and freedom and finance) and these changes and explored the prospective associations between these needs, perceptions of support from direct support staff and the well-being and ill-being of people with MBID. METHODS: Based on a sample of 117 adults with MBID, multiple regression analyses were conducted to determine correlations between constructs at both time points and the impact of autonomy support on need satisfaction and motivation, taking into account life events. RESULTS: The analyses showed that, at both time points, most constructs were statistically significantly correlated and remained so despite a time lag of 4.5 years. Autonomy support emerged as a significant positive predictor, of medium size, for satisfying autonomy and relatedness needs. Its association with competence need satisfaction was not statistically significant after Bonferroni correction. For type of motivation, autonomy support statistically predicted increased autonomous motivation, irrespective of life events. CONCLUSIONS: Findings underline the potential of autonomy supportive direct support in the lives of individuals with MBID. Some unexpected null findings underscore the need for further study into the interplay between autonomy support, life events and the well-being of people with MBID.

Assessment of left ventricular function in horses with aortic regurgitation by 2D speckle tracking.

BACKGROUND: Aortic regurgitation (AR) may lead to left ventricular (LV) dilatation, cardiac arrhythmias and heart failure. Close follow-up of horses with AR is therefore paramount to detect onset of cardiac decompensation. The aim of this study was to examine whether two-dimensional speckle tracking (2DST) can be used to detect altered myocardial function in horses with chronic AR compared to control horses. Speckle tracking was performed on short axis and long axis images of the LV in 29 healthy Warmblood horses and 57 Warmblood horses with AR. Radial, circumferential and longitudinal strain, strain rate and displacement were measured for each segment separately and the average was calculated over all segments. Data generated from the apical segments were not included in the analysis. RESULTS: Radial (SR) and circumferential (SC) strain were significantly higher in horses with moderate AR (average SR 75.5 ± 24.3%, SC 19.3 ± 3.2%) but not in horses with severe AR (SR 65.5 ± 26.2%, SC 16.3 ± 3.5%), compared to control horses (SR 54.5 ± 18.0%, SC 16.8 ± 3.0%). Longitudinal strain did not show significant differences, but longitudinal displacement (DL) was larger in horses with moderate (average DL 29.5 ± 4.1 cm) and severe AR (DL 32.4 ± 6.1 cm) compared to control horses (DL 25.7 ± 4.0 cm), especially in the interventricular septum. Diastolic longitudinal strain rate was lower in early diastole in horses with severe AR (0.93 ± 0.18/s) compared to controls (1.13 ± 0.13/s). CONCLUSIONS: 2DST is able to detect altered myocardial motion in horses with AR, which showed significantly higher radial and circumferential strain. Further research is needed to determine whether these findings contribute to a more accurate diagnosis and prognosis in clinical cases.

Can heart rate variability parameters derived by a heart rate monitor differentiate between atrial fibrillation and sinus rhythm?

BACKGROUND: Heart rate variability (HRV) parameters, and especially RMSSD (root mean squared successive differences in RR interval), could distinguish atrial fibrillation (AF) from sinus rhythm(SR) in horses, as was demonstrated in a previous study. If heart rate monitors (HRM) automatically calculating RMSSD could also distinguish AF from SR, they would be useful for the monitoring of AF recurrence. The objective of the study was to assess whether RMSSD values obtained from a HRM can differentiate AF from SR in horses. Furthermore, the impact of artifact correction algorithms, integrated in the analyses software for HRV analyses was evaluated. Fourteen horses presented for AF treatment were simultaneously equipped with a HRM and an electrocardiogram (ECG). A two-minute recording at rest, walk and trot, before and after cardioversion, was obtained. RR intervals used were those determined automatically by the HRM and by the equine ECG analysis software, and those obtained after manual correction of QRS detection within the ECG software. RMSSD was calculated by the HRM software and by dedicated HRV software, using six different artifact filters. Statistical analysis was performed using the Wilcoxon signed-rank test and receiver operating curves. RESULTS: The HRM, which applies a low level filter, produced high area under the curve (AUC) (> 0.9) and cut off values with high sensitivity and specificity. Similar results were obtained for the ECG, when low level artifact filtering was applied. When no artifact correction was used during trotting, an important decrease in AUC (0.75) occurred. CONCLUSION: In horses treated for AF, HRMs with automatic RMSSD calculations distinguish between AF and SR. Such devices might be a useful aid to monitor for AF recurrence in horses.

Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

BACKGROUND: The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. PATIENTS AND METHODS: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. RESULTS: Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. CONCLUSIONS: Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

Clinical implementation and feasibility of long-course fractionated MR-guided chemoradiotherapy for patients with esophageal cancer: An R-IDEAL stage 1b/2a evaluation of technical innovation.

Purpose: This R-Ideal stage 1b/2a study describes the workflow and feasibility of long-course fractionated online adaptive MR-guided chemoradiotherapy with reduced CTV-to-PTV margins on the 1.5T MR-Linac for patients with esophageal cancer. Methods: Patients with esophageal cancer scheduled to undergo chemoradiation were treated on a 1.5T MR-Linac. Daily MR-images were acquired for online contour adaptation and replanning. Contours were manually adapted to match the daily anatomy and an isotropic CTV-to-PTV margin of 6 mm was applied. Time was recorded for all individual steps in the workflow. Feasibility and patient tolerability were defined as on-table time of ≤60 min and completion of >95% of the fractions on the MR-Linac, respectively. Positioning verification and post-treatment MRIs were retrospectively analyzed and dosimetric parameters were compared to standard non-adaptive conventional treatment plans. Results: Nine patients with esophageal cancer were treated with chemoradiation; eight patients received 41.4 Gy in 23 fractions and one received 50.4 Gy in 28 fractions. Four patients received all planned fractions on the MR-Linac, whereas for two patients >5% of fractions were rescheduled to a conventional linac for reasons of discomfort. A total of 183 (86%) of 212 scheduled fractions were successfully delivered on the MR-Linac. Three fractions ended prematurely due to technical issues and 26 fractions were rescheduled on a conventional linac due to MR-Linac downtime (n = 10), logistical reasons (n = 3) or discomfort (n = 13).The median time per fraction was 53 min (IQR = 3 min). Daily adapted MR-Linac plans had similar target coverage, whereas dose to the organs-at-risk was significantly reduced compared to conventional treatment (26% and 12% reduction in mean lung and heart dose, respectively). Conclusion: Daily online adaptive fractionated chemoradiotherapy with reduced PTV margins is moderately feasible for esophageal cancer and results in better sparing of heart and lungs. Future studies should focus on further optimization and acceleration of the current workflow.

Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia: Endoscopic Findings and Long-Term Mortality.

INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Detection of subclinical left ventricular dysfunction by tissue Doppler imaging in horses with aortic regurgitation.

BACKGROUND: Aortic regurgitation (AR) can have an important clinical impact and in some cases leads to left ventricular (LV) failure. Tissue Doppler imaging (TDI) is an echocardiographic technique that has been used in horses to detect LV dysfunction. OBJECTIVES: To examine whether TDI detects changes in radial myocardial wall motion in horses with AR compared with control horses. STUDY DESIGN: Case-control study. METHODS: Echocardiography was performed in 30 healthy Warmblood horses and 34 Warmblood horses with AR, subdivided in groups with mild, moderate or severe AR. TDI measurements were performed on six segments of the short-axis images of the LV myocardial wall. Myocardial wall motion was evaluated by measuring velocity and deformation during isovolumetric contraction, systole, early and late diastole. Timing of different events was also measured. RESULTS: In most segments, a significantly higher systolic myocardial velocity was found in horses with AR compared with controls. Horses with AR also had higher late diastolic velocity, although the difference was not significant in all segments. TDI measurement of timing intervals demonstrated less difference between groups. MAIN LIMITATIONS: There was a significant difference in age between the control group and horses with AR, which may confound the results. The assessment of AR severity was based on subjective criteria as there is no gold standard. CONCLUSIONS: TDI showed significant differences in radial systolic and late diastolic myocardial velocity in horses with AR. This could indicate an altered LV function in these horses, but further research is needed to investigate the prognostic value of these measurements.

Right ventricular function during pharmacological and exercise stress testing in horses.

The disproportionate rise of pulmonary artery pressure compared to systemic blood pressure during exercise can lead to detrimental right ventricular remodelling in endurance athletes. Horses may act as an extreme model of these athletic cardiovascular adaptations, as they show a three fold increase in pulmonary pressures during exercise. Right ventricular function was examined in ten healthy horses using post-exercise and pharmacological stress echocardiography in a randomised cross-over design. Exercise testing was performed on a treadmill while pharmacological testing was performed using an atropine-dobutamine infusion. Heart rate, systemic blood pressure and cardiac output during echocardiography were similar post-exercise compared to maximal pharmacological stress. Systolic pulmonary artery pressure was significantly higher during the exercise test (121±15mmHg) and during immediate post-exercise echocardiography (93±10mmHg) compared to maximal pharmacological stress (69±12mmHg). Right ventricular diameters as well as the ratio of systolic right to left ventricular area were higher post-exercise. Right ventricular fractional area change was significantly decreased post-exercise (40.5±6.2%) compared to a significant increase during pharmacological stress echocardiography (72.6±7.3%). Serum cardiac troponin I concentration was significantly higher 2h after the pharmacological test compared to baseline values and post-exercise, although the highest value was found post-exercise in the horse with the highest systolic pulmonary artery pressure and lowest right ventricular fractional area change. Pharmacological stress testing is not recommended in further studies on right ventricular adaptations in athletic horses, as this does not reproduce the effects of exercise.

Heart rate variability parameters in horses distinguish atrial fibrillation from sinus rhythm before and after successful electrical cardioversion.

BACKGROUND: Atrial fibrillation (AF) is the most common pathological arrhythmia in horses. After successful treatment, recurrence is common. Heart rate monitors are easily applicable in horses and some devices offer basic heart rate variability (HRV) calculations. If HRV can be used to distinguish between AF and sinus rhythm (SR), this could become a monitoring tool for horses at risk for recurrence of AF. OBJECTIVES: The purpose of this study was to assess whether in horses AF (before cardioversion) and SR (after cardioversion) can be differentiated based upon HRV parameters. STUDY DESIGN: Cohort study with internal controls. METHODS: Six HRV parameters were determined in 20 horses, both in AF and in SR, at rest (2- and 5-min and 1- and 4-h recordings) and during exercise (walk and trot, 2-min recordings). Time-domain (standard deviation of the NN intervals, root mean squared successive differences in NN intervals and triangular index), frequency domain (low/high frequency ratio) and nonlinear parameters (standard deviation of the Poincaré plot [SD]1 and SD2) were used. Statistical analysis was done using paired Wilcoxon signed rank tests and receiver operating characteristic curves. RESULTS: HRV was higher during AF compared to SR. Results for the detection of AF were good (area under the receiver operating characteristic curve [AUC] 0.8-1) for most HRV parameters. Root mean squared successive differences in NN intervals and SD1 yielded the best results (AUC 0.9-1). Sensitivity and specificity were high for all parameters at all recordings, but highest during exercise. Although AUCs improved with longer recordings, short recordings were also good (AUC 0.8-1) for the detection of AF. In horses with frequent second degree atrioventricular block, HRV at rest is increased and recordings at walk or trot are recommended. MAIN LIMITATIONS: Animals served as their own controls and there was no long-term follow-up to identify AF recurrence. CONCLUSIONS: AF (before cardioversion) and SR (after cardioversion) could be distinguished with HRV. This technique has promise as a monitoring tool in horses at risk for AF development.

Assessing aortic regurgitation severity from 2D, M-mode and pulsed wave Doppler echocardiographic measurements in horses.

Aortic regurgitation (AR) in horses can lead to left ventricular (LV) eccentric hypertrophy, ventricular arrhythmia and heart failure. Objective quantification of the severity of regurgitation is difficult. The aim of this study was to evaluate dimensional measurements, systolic time intervals and blood flow velocities, acquired by standard 2D, M-mode and pulsed wave Doppler echocardiography, for quantification of AR. Echocardiography was performed in 32 healthy horses and 35 horses with AR that were subdivided in three groups (mild, moderate or severe AR). From the recorded images LV, left atrial and aortic dimensions, systolic time intervals and aortic blood flow velocities were measured. Diastolic run-off in the aorta (AoDiastDecr) was calculated as the difference in aortic diameter between early diastole and late diastole. Stroke volume (SV) was calculated from pulsed wave Doppler measurements, by the bullet method (SVbullet) and by the area-length method. Pre-ejection period (PEP) and ejection time (LVET) were determined from the M-mode images. Horses with AR showed enlargement of the LV, left atrium and aorta compared to the control group. The SV, the AoDiastDecr and the rate of AoDiastDecr were significantly larger than controls. PEP decreased significantly in horses with AR, whereas LVET did not change. PEP and the newly defined variable AoDiastDecr proved to be easy to measure parameters that provided a good indication of AR severity. There was increased SV in horses with AR using all three methods, but SVbullet was superior for the detection of increased AR severity.

Influence of detomidine on atrial fibrillation cycle length measured by intracardiac electrogram recording and by colour tissue Doppler imaging in horses.

REASONS FOR PERFORMING STUDY: Shortening of atrial fibrillation cycle length (AFCL) is a marker of atrial electrical remodelling due to atrial fibrillation (AF). OBJECTIVES: To investigate the effect of administration of detomidine on AFCL measured invasively from an intra-atrial electrogram (AFCLEGM) and noninvasively by tissue Doppler imaging (AFCLTDI). We hypothesised that detomidine would have no effect on AFCL but would improve the ease of TDI measurements and facilitate noninvasive AFCL determination. STUDY DESIGN: Prospective clinical study. METHODS: Measurements were performed before and after i.v. administration of 7.5 µg/kg bwt detomidine in 33 episodes of AF in 32 horses (582 ± 64 kg bwt, 10 ± 3 years old) referred for electrical cardioversion. The AFCLEGM was measured from a right atrial intracardiac electrogram. The AFCLTDI was measured from atrial colour tissue velocity curves in 5 atrial wall regions. Mean AFCLEGM and AFCLTDI without and with sedation were compared using a repeated-measures linear mixed model with Bonferroni correction for multiple comparisons and calculation of the Bland-Altman mean bias and limits of agreement between AFCLEGM and AFCLTDI. RESULTS: The mean AFCL was significantly increased after sedation, but this increase was very small (mean difference +4 ms). For AFCLTDI measurements, sedation significantly improved the quality of the atrial myocardial velocity curves and the number of AF cycles that could be measured per cardiac cycle. The Bland-Altman bias between AFCLEGM without sedation and AFCLTDI with sedation ranged from -18 to +15 ms depending on wall region. Bland-Altman limits of agreement were similar between AFCLEGM without sedation and AFCLTDI without and with sedation. Therefore, noninvasive AFCLTDI measurements with sedation can be used to estimate the atrial fibrillatory rate. CONCLUSIONS: Sedation facilitates noninvasive AFCL measurements but causes a slight increase in AFCL. Noninvasive AFCL measurements can be used as an indicator of atrial electrical remodelling, to study AF pathophysiology and to investigate the effect of anti-arrhythmic drugs.

Right atrial and right ventricular ultrasound-guided biopsy technique in standing horses.

REASONS FOR PERFORMING STUDY: Endomyocardial biopsies could be a valuable tool in equine cardiology for diagnosing myocardial disease, which is probably underdiagnosed in horses because of lack of specific diagnostic measures and limitations of currently available diagnostic methods. OBJECTIVES: To describe a technique for serial right atrial and right ventricular endomyocardial biopsy in standing horses using a percutaneous approach through the jugular vein. STUDY DESIGN: Prospective study. METHODS: Biopsy was performed in 10 healthy standing horses sedated with detomidine, under continuous electrocardiography monitoring. A 10 cm (n = 6), 45 cm (n = 1) or 98 cm (n = 3) introducer sheath was inserted into the right jugular vein. Under echocardiographic guidance, a biopsy forceps was introduced through the sheath into the right ventricle and right atrium and endomyocardial biopsies were acquired. RESULTS: In all horses, 3 right ventricular biopsies were obtained from the right ventricular apex and 3 right atrial biopsies were obtained from the dorsal right atrial wall near the tuberculum intervenosum. The presence of myocardial tissue was confirmed by histology. All horses showed atrial and ventricular premature depolarisations associated with acquisition of the biopsies. In 9 horses, the arrhythmia disappeared after retraction of the forceps and introducer sheath. In one horse, ventricular premature depolarisations disappeared only after 8 h. No other complications were observed. CONCLUSIONS: Endomyocardial biopsy of the right atrium and right ventricle could be performed in standing horses using a percutaneous approach through the jugular vein and was not associated with complications other than temporary arrhythmias. This technique may be useful for research purposes or as a diagnostic tool, although further research is needed to establish the safety of the technique in clinical patients with myocardial disease.

Atrial natriuretic peptide vs. N-terminal-pro-atrial natriuretic peptide for the detection of left atrial dilatation in horses.

REASONS FOR PERFORMING STUDY: Studies on the use of atrial natriuretic peptide (ANP) as a biomarker for left atrial dilatation in horses have produced variable results. Few have been performed, and the results may have been influenced by ANP instability, differences in sampling protocol and changes in the assay over time. N-Terminal proANP (NT-proANP) is a more stable molecule and might be a good alternative for clinical use. OBJECTIVES: To compare ANP and NT-proANP in terms of the detection of left atrial dilatation and to determine the influence of sample storage at temperatures of -80 and -20°C. STUDY DESIGN: Prospective clinical study. METHODS: Atrial natriuretic peptide and NT-proANP concentrations were compared between healthy horses (Group 1, n = 20), horses with mitral valve regurgitation and a normal atrial size (Group 2, n = 11) and horses with mitral valve regurgitation associated with left atrial dilatation (Group 3, n = 16). The ANP concentration was measured with an equine enzyme-linked immunosorbent assay and the NT-proANP concentration with an enzyme-linked immunosorbent assay developed for use in human patients. Samples were stored at -20 and -80°C and analysed within 7 months. RESULTS: The NT-proANP concentrations were not significantly different between the groups. Horses in Group 3 had a significantly higher ANP concentration (median 366 pg/ml; interquartile range [IQR] 74-2000 pg/ml) compared with horses in Group 1 (median 31 pg/ml; IQR 31-333 pg/ml) or Group 2 (median 31 pg/ml; IQR 31-1152 pg/ml; P = 0.02). The ANP cut-off value for detection of left atrial dilatation was 52 pg/ml (sensitivity 81%; specificity 84%) for sample storage at -80°C, and 44 pg/ml (sensitivity 69%; specificity 84%) for storage at -20°C. A larger decrease in ANP (45 ± 126 pg/ml) than in NT-proANP (10 ± 31 pg/ml) was found associated with sample storage at -20 instead of -80°C. CONCLUSIONS: Atrial natriuretic peptide, but not NT-proANP, can be used to detect left atrial dilatation in horses. Atrial natriuretic peptide is less stable than NT-proANP when samples are stored at -20°C. Atrial natriuretic peptide is a more suitable biomarker of left atrial dilatation in horses than NT-proANP.

Atrial Premature Depolarization-Induced Changes in QRS and T Wave Morphology on Resting Electrocardiograms in Horses.

BACKGROUND: The electrocardiographic differentiation between atrial (APDs) and ventricular (VPDs) premature depolarizations is important. P wave prematurity and normal QRS and T wave morphology generally are used as discriminating criteria for APDs. HYPOTHESIS/OBJECTIVES: The aim of this study was to determine whether P, Q, R, S, and T wave amplitude, PQ interval, QRS and P wave duration and P and T wave morphology differ between APDs and sinus beats. To determine the relationship between the RR coupling interval and the change in S wave amplitude between sinus beats and APDs. METHODS: Case-control study. From a modified base-apex configuration of 30 horses with APDs at rest, sinus beat and APD associated preceding RR interval, P, PQ and QRS duration and P, R, S, and T wave amplitudes were measured. Linear mixed models and logistic regression were used to determine the effect of APDs on the ECG variables studied. RESULTS: In comparison to sinus beats, APDs were associated with a significant (P < .001) change in P amplitude (-0.03 ± 0.01 mV) and increase in S (0.20 ± 0.02 mV) and T (0.08 ± 0.03 mV) amplitude. PQ (-20.3 ± 5.2 ms) and RR (-519 ± 14 ms) interval and P duration (-21.1 ± 3.0 ms) decreased (P < .001). APDs were significantly associated with a singular positive P wave (OR: 11.0, P < .001) and were more likely to have a monophasic positive T wave (OR: 9.2, P < .001). A smaller RR coupling interval was associated with an increased relative difference in S amplitude (P < .01). CONCLUSIONS: Atrial premature depolarizations may lead to changes in QRS and T wave morphology. Knowledge of these changes is important to avoid interpreting certain APDs as VPDs.

Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function.

Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration. Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias.

Evaluation of assays for troponin I in healthy horses and horses with cardiac disease.

Cardiac troponin I (cTnI) is a marker for detection of myocardial damage in horses. Many cTnI assays exist and medical studies have shown that the clinical performance of assays differs. The aim of this study was to compare two different cTnI assays in horses. Serum samples were taken from 23 healthy horses (group 1) and 72 horses with cardiac disease (group 2). Cardiac troponin I was determined using assay 1 in laboratory A (limit of detection, LOD, 0.03 ng/mL) and assay 2 in laboratories B and C (LOD 0.01 ng/mL). In group 1, a median cTnI concentration of <0.03 (<0.03-0.04) ng/mL and <0.01 (<0.01-0.15) ng/mL was found with assays 1 and 2, respectively. A higher median value was demonstrated in group 2 for both assays (assay 1: 0.11 ng/mL, range 0.03-58.27 ng/mL, P < 0.001; assay 2: 0.02 ng/mL, range 0.01-22.87 ng/mL, P = 0.044). Although a significant correlation between assays existed, large mean differences that could be important for clinical interpretation of test results were found. A small mean difference was found between laboratories B and C. A significant optimal (P < 0.001) cut-off value for detection of cardiac disease could only be determined for assay 1 (0.035 ng/mL, sensitivity 70%, specificity 91%). Assay 1 performed better for detection of cardiac disease in horses in this study.

Cardiac troponin I as compared to troponin T for the detection of myocardial damage in horses.

BACKGROUND: Different cardiac troponin I (cTnI) assays give different results. Only 1 manufacturer has marketed troponin T (cTnT) assays. Therefore, cTnT often is preferred for detection of myocardial infarction in human patients. Studies of cTnT in horses are limited. OBJECTIVES: To compare a cTnI and a high-sensitive cTnT assay (hs-cTnT) in horses. ANIMALS: Cardiac troponin I and cTnT were determined in 35 healthy horses (group 1), 23 horses suspected to have primary myocardial damage (group 2a), and 41 horses with secondary myocardial damage caused by structural heart disease (group 2b). METHODS: All cTnI samples were analyzed at laboratory A (limit of detection [LOD]: 0.03 ng/mL), whereas cTnT samples were analyzed at 2 laboratories with the same hs-cTnT assay (laboratory B, LOD: 10.0 pg/mL; laboratory C, LOD: 4.0 pg/mL). RESULTS: The median cTnI concentration in group 2a (0.90 ng/mL; range, 0.03-58.27 ng/mL) was significantly higher (P < .001) than in group 1 (0.03 ng/mL; range, 0.03-0.09 ng/mL) or group 2b (0.05 ng/mL; range, 0.03-30.92 ng/mL), and the optimal cut-off for detection of primary myocardial damage was 0.095 ng/mL (sensitivity: 90.5%, specificity: 100%). Using an LOD of 10.0 pg/mL for all cTnT samples, a cut-off value of 10.5 pg/mL was found, but sensitivity was low (42.9%). When only samples analyzed at laboratory C (n = 58) were included, a cut-off of 6.6 pg/mL was found (sensitivity: 81%, specificity: 100%). CONCLUSIONS AND CLINICAL IMPORTANCE: Despite large quantitative differences, cTnI and cTnT are both useful for detection of myocardial damage in horses.

Light in and sound out: emerging translational strategies for photoacoustic imaging.

Photoacoustic imaging (PAI) has the potential for real-time molecular imaging at high resolution and deep inside the tissue, using nonionizing radiation and not necessarily depending on exogenous imaging agents, making this technique very promising for a range of clinical applications. The fact that PAI systems can be made portable and compatible with existing imaging technologies favors clinical translation even more. The breadth of clinical applications in which photoacoustics could play a valuable role include: noninvasive imaging of the breast, sentinel lymph nodes, skin, thyroid, eye, prostate (transrectal), and ovaries (transvaginal); minimally invasive endoscopic imaging of gastrointestinal tract, bladder, and circulating tumor cells (in vivo flow cytometry); and intraoperative imaging for assessment of tumor margins and (lymph node) metastases. In this review, we describe the basics of PAI and its recent advances in biomedical research, followed by a discussion of strategies for clinical translation of the technique.

Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer.

Neoadjuvant chemotherapy (NAC) for breast cancer is evolving and subsequent adjuvant systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and Human Epidermal growth factor Receptor 2 (HER2) status on the core needle biopsy prior to treatment. It is not well known whether these biomarkers change after NAC, requiring a change in further adjuvant systemic treatment. A review of the literature (PubMed search) revealed 32 relevant studies that investigated the concordance of the hormone receptors (ER and/or PR) and HER2 after NAC with or without trastuzumab. Discordance of the hormone receptor status was reported in four out of eight studies in 8-33% of the patients. About half of the studies that tested the ER and PR receptor status separately reported discordances of 2.5-17% and 5.9-51.7% respectively. Studies that concluded that ER and/or PR receptor remained stable after NAC were performed with evidently lower number of patients compared to studies that reported a change. Good concordance of the HER2 amplification tested with FISH was reported, although the HER2 expression measured with immunohistochemistry was more discordant. A switch to a negative HER2 receptor in up to 43% of the patients was reported when NAC was combined with trastuzumab. Until more comparable studies are being published, retesting the receptor status of the residual tumor after NAC should be considered in order to improve future tailored adjuvant therapies.

The diagnostic value of nipple discharge cytology in 618 consecutive patients.

AIM: Preoperative stratification of patients presenting with nipple discharge (ND) according to malignancy risk has proven difficult. Nevertheless, cytological examination is considered to be a diagnostic aid. The aim of this study was to determine its complementary value in clinical decision-making in patients presenting with ND. METHODS: We retrospectively collected data on macroscopic ND colour, ND cytology, physical examination, mammography, ultrasound and fine-needle aspiration cytology results. On ND cytology, benign diagnoses were considered negative, whereas suspicious and malignant diagnoses were considered positive for malignancy. RESULTS: From 1992 to 2006, 618 patients had an ND smear, of those 163 patients had a biopsy. Sensitivity and specificity were 16.7% and 66.1%, respectively. These values were lower when ND was bloody than when ND was non-bloody (p=0.66 and p<0.05 for sensitivity and specificity, respectively). When macroscopically defining bloody ND as positive and non-bloody ND as negative, macroscopic ND colour examination had a remarkably higher sensitivity (60.6 vs. 18.2%, p<0.001) and only a slightly lower specificity (53.6 vs. 65.0%, p=0.07) when compared to cytological ND examination. Only 1 malignant lesion was designated positive solely by ND cytology (unique sensitivity (95% CI), 2.8% (0.0-8.4%)) and 3 lesions were correctly classified as negative by ND cytology (unique specificity (95% CI), 1.6%, 0.0-3.7%)). CONCLUSION: Nipple discharge cytology has little complementary diagnostic value. Therefore, its routine use for detection of ND-related breast pathology should be reconsidered carefully. Nipple discharge cytology may redirect patient management well in some cases, but it may confuse work-up in the majority.