Left ventricular synchrony,torsion, and recoil mechanics in Ebstein’s anomaly: insights from cardiovascular magnetic resonance

Background

Disease progression and heart failure development in Ebstein’s Anomaly (EA) of the tricuspid valve is characterized by both right and left ventricular (LV) deterioration. The mechanisms underlying LV dysfunction and their role in heart failure development are incompletely understood. We hypothesized that LV dyssynchrony and impaired torsion and recoil mechanics induced by paradoxical movement of the basal septum may play a role in heart failure development.

Methods

31 EA patients and 31 matched controls underwent prospective cardiovascular magnetic resonance (CMR). CMR feature tracking (CMR-FT) was performed on apical, midventricular and basal short-axis and 4D–volume analysis was performed using three long-axis views and a short axis cine stack employing dedicated software. Circumferential uniformity ratio estimates (CURE) time-to-peak-based circumferential systolic dyssynchrony index (C-SDI), 4D volume analysis derived SDI (4D–SDI), torsion (Tor) and systolic (sysTR) and diastolic torsion rate (diasTR) were calculated for the LV. QRS duration, brain natriuretic peptide, NYHA and Total R/L-Volume Index (R/L Index) were obtained.

Results

EA patients (31.5 years; controls 31.4 years) had significantly longer QRS duration (123.35 ms?±?26.36 vs. 97.33 ms ±?11.89 p <?0.01) and showed more LV dyssynchrony (4D–SDI 7.60%?±?4.58 vs. 2.54%?±?0.62, p <?0.001; CURE 0.77?±?0.05 vs. 0.86?±?0.03, p?<?0.001; C-SDI 7.70?±?3.38 vs. 3.80?±?0.91, p =?0.001). There were significant associations of LV dyssynchrony with heart failure parameters and QRS duration. Although torsion and recoil mechanics did not differ significantly (p >?0.05) there was an association of torsion and recoil mechanics with dyssynchrony parameters CURE (sysTR r =??0.426; p =?0.017, diasTR r =?0.419; p =?0.019), 4D–SDI (sysTR r =?0.383; p =?0.044) and C-SDI (diasTR r =??0.364; p?=?0.044).

Conclusions

EA is characterized by LV intra-ventricular dyssynchrony, which is associated with heart failure and disease severity parameters. Markers of dyssynchrony can easily be quantified from CMR-FT, and may have a role in the assessment of altered cardiac function, carrying potential management implications for EA patients.

     

Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study

Objective

To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.

Design and setting

Prospective crossover interventional study in an intensive care unit of a university hospital.

Patients

Twenty patients.

Interventions

After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.

Measurements and results

During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO₂ decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.

Conclusions

The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Real-time assessment of right and left ventricular volumes and function in children using high spatiotemporal resolution spiral bSSFP with compressed sensing

Background

Real-time cardiovascular magnetic resonance (CMR) assessment of ventricular volumes and function enables data acquisition during free-breathing. The requirement for high spatiotemporal resolution in children necessitates the use of highly accelerated imaging techniques.

Methods

A novel real-time balanced steady state free precession (bSSFP) spiral sequence reconstructed using Compressed Sensing (CS) was prospectively validated against the breath-hold clinical standard for assessment of ventricular volumes in 60 children with congenital heart disease. Qualitative image scoring, quantitative image quality, as well as evaluation of biventricular volumes was performed. Standard BH and real-time measures were compared using the paired t-test and agreement for volumetric measures were evaluated using Bland Altman analysis.

Results

Acquisition time for the entire short axis stack (~?13 slices) using the spiral real-time technique was ~?20 s, compared to ~?348 s for the standard breath hold technique. Qualitative scores reflected more residual aliasing artefact (p?<?0.001) and lower edge definition (p?<?0.001) in spiral real-time images than standard breath hold images, with lower quantitative edge sharpness and estimates of image contrast (p?<?0.001).There was a small but statistically significant (p?<?0.05) overestimation of left ventricular (LV) end-systolic volume (1.0?±?3.5 mL), and underestimation of LV end-diastolic volume (??1.7?±?4.6 mL), LV stroke volume (??2.6?±?4.8 mL) and LV ejection fraction (??1.5?±?3.0%) using the real-time technique. We also observed a small underestimation of right ventricular stroke volume (??1.8?±?4.9 mL) and ejection fraction (??1.4?±?3.7%) using the real-time imaging technique. No difference in inter-observer or intra-observer variability were observed between the BH and real-time sequences.

Conclusions

Real-time bSSFP imaging using spiral trajectories combined with a compressed sensing reconstruction showed good agreement for quantification of biventricular metrics in children with heart disease, despite slightly lower image quality. This technique holds the potential for free breathing data acquisition, with significantly shorter scan times in children.

     

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

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.

     

Determination of functional residual capacity by oxygen washin-washout: a validation study

Objective

To validate a new system for functional residual capacity (FRC) measurements using oxygen washin/washout in spontaneously breathing humans. The system (LUFU, Drägerwerk AG, Lübeck, Germany) consists of an unmodified EVITA 4 ventilator, a side-stream paramagnetic oxygen sensor and a dedicated software.

Design

Laboratory study and measurements in spontaneously breathing volunteers.

Setting

Pulmonary function laboratory of a university hospital.

Participants

20 healthy and 15 lung diseased volunteers.

Interventions

FRC was measured by LUFU (LUFU-FRC) and by helium dilution (He-FRC); intra-thoracic gas volume (ITGV) was determined by body plethysmography. Each measurement cycle consisted of four independent LUFU-FRC determinations (step change of FiO₂ from 0.21 to 0.5 and back and from 0.21 to 1.0 and back), two helium-dilution runs and two body box measurements. Repeatability and agreement between methods were determined by comparing different measurements of one technique and by comparing different techniques among each other.

Measurements and results

Repeatability of LUFU-FRC was estimated by comparing washin to washout and the different FiO₂steps. The difference of the means was 3.7% at the most. Agreement between methods resulted in the following differences (mean?±?standard deviation of differences) for healthy and lung-diseased volunteers, respectively: LUFU-FRC vs. He-FRC –0.40?±?0.50?L (0.02?±?0.95?L), LUFU-FRC vs. ITGV –0.43?±?0.54?L (–0.18?±?0.61?L) and He-FRC vs. ITGV –0.03?±?0.43?L (–0.20?±?0.98?L).

Conclusions

LUFU is a non-invasive method for the determination of FRC that requires only minor additional equipment and no modification to the ventilator. It can be used in difficult conditions such as breathing patterns with variations from breath to breath. The results of this study show that LUFU is sufficiently reliable and repeatable to warrant its clinical application.

     

Prone equals prone? Impact of positioning techniques on respiratory function in anesthetized and paralyzed healthy children

Objectives

Although the prone position is effectively used to improve oxygenation, its impact on functional residual capacity is controversial. Different techniques of body positioning might be an important confounding factor. The aim of this study was to determine the impact of two different prone positioning techniques on functional residual capacity and ventilation distribution in anesthetized, preschool-aged children.

Design

Functional residual capacity and lung clearance index, a measure of ventilation homogeneity, were calculated using a sulfur-hexafluoride multibreath washout technique. After intubation, measurements were taken in the supine position and, in random order, in the flat prone position and the augmented prone position (gel pads supporting the pelvis and the upper thorax).

Setting

Pediatric anesthesia unit of university hospital.

Patients and participants

Thirty preschool children without cardiopulmonary disease undergoing elective surgery.

Measurements and results

Mean (range) age was 48.5 (24–80) months, weight 17.2 (10.5–26.9)?kg, functional residual capacity (mean ±?SD) 22.9?±?6.2?ml.kg ^?1 in the supine position and 23.3?±?5.6?ml.kg ^?1 in the flat prone position, while lung clearance indices were 8.1?±?2.3 vs. 7.9?±?2.3, respectively. In contrast, functional residual capacity increased to 27.6 ± 6.5 ml.kg ^?1 (pp

Conclusions

Functional residual capacity and ventilation distribution were similar in the supine and flat prone positions, while these parameters improved significantly in the augmented prone position, suggesting that the technique of prone positioning has major implications for pulmonary function.

     

Chagas’ Disease: Update on Current Diagnosis

Purpose of Review

Chagas’ disease has become an emerging health problem due to increased migration. In the present review, we have summarized the usefulness of non-invasive imaging tools for the diagnosis of cardiac involvement in Chagas’ disease, with emphasis on modern technologies. M-mode, bidimensional (2-D), and three-dimensional (3-D) echocardiographies may allow the evaluation of left ventricular (LV) regional and global contractile function, right ventricle (RV) impairment, evidence of aneurysms and thrombi, and assessment of diastolic function in any stage of the disease.

Recent Findings

New modalities such as strain and speckle-tracking imaging have brought non-invasive indices to the understanding of the mechanisms of cardiac dyssynchrony. The assessment of cardiac autonomic denervation using ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG), LV, and RV systolic function and the study of LV mechanical dyssynchrony by gated cardiac blood pool are available in current nuclear imaging for patients with Chagas’ disease. The findings of myocardial fibrosis by cardiac magnetic resonance (CMR), mainly in inferolateral regions, are a marker of subclinical involvement and worse prognosis in Chagas’ disease, even in patients with preserved ventricular function.

Summary

The detection and quantification of early signs of heart involvement by new technologies should be useful for risk stratification and in the clinical decision process for new therapeutic methods and could improve the natural history of the disease.

     

Cardiovascular magnetic resonance left ventricular strain in end-stage renal disease patients after kidney transplantation

Background

Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function.

Methods

We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12?months after KT.

Results

Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p?=?0.007) and global radial strain (GRS) (p?=?0.003), but a decline in global longitudinal strain (GLS) over 12?months (p?=?0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4?±?6.4% at baseline, 60.6%?±?6.9% at 12?months; p?=?0.001). For entire cohort, over 12?months, change in LVEF was significantly correlated with change in GCS (Spearman’s r?=???0.42, p?<?0.001), GRS (Spearman’s r?=?0.64, p?<?0.001), and GLS (Spearman’s r?=???0.34, p?=?0.002). Improvements in GCS and GRS over 12?months were significantly correlated with reductions in LV end-diastolic volume index and LV end-systolic volume index (all p?<?0.05), but not with change in blood pressure (all p?>?0.10).

Conclusions

Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12?months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings.

     

Advanced Cardiovascular Magnetic Resonance Techniques in Grown-Up Congenital Heart Disease

Purpose

Congenital heart diseases comprise a complex population in which functional and anatomic evaluation with cardiac magnetic resonance (CMR) acquires utmost importance in the decision-making process. The use of new CMR technologies can help us understand the physiopathology and improve risk stratification.

Recent Findings

Efforts towards a better understanding of the processes that underlie the occurrence of adverse events in these patients, mainly heart failure and arrhythmia, have been made in the last years. Early identification of subclinical myocardial involvement by means of detection of changes at the cellular level (fibrosis and extracellular expansion) or impaired ventricular mechanics (deformation techniques) is now possible thanks to late gadolinium enhancement/T1 mapping and strain respectively.

Summary

Preliminary studies suggest that the presence of fibrosis, either replacement or diffuse fibrosis, and the detection of impaired deformation parameters or significant dyssynchrony are related to outcomes. Assessment of intracardiac and great vessels flow with 4D flow imaging is an attractive research tool that offers a comprehensive evaluation of hemodynamic status and the possibility of obtaining new promising functional parameters.

     

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.

     

Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI

Purpose

An integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner with time of flight (TOF) technology is now available for clinical use. The aim of this study is to evaluate the potential of TOF PET in PET/MRI to reduce artifacts in PET images when compared to non-TOF PET/MRI, TOF PET/X-ray computed tomography (CT), and non-TOF PET/CT.

Procedures

All patients underwent a single 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) injection, followed first by PET/CT, and subsequently by PET/MRI. PET/CT exams were requested as standard-of-care for oncological indications. Using the PET acquisitions datasets, 4 series of images (TOF PET/CT, non-TOF PET/CT, TOF PET/MRI, and non-TOF PET/MRI) were reconstructed. These image series were visually evaluated for: (1) dental metal artifacts, (2) breathing artifacts, and (3) pelvic artifacts due to scatter correction errors from high bladder [¹⁸F]FDG concentration. PET image quality was assessed by a 3-point scale (1—clinically significant artifact, 2—non clinically significant artifact, and 3—no artifact).

Results

Twenty-five patients (mean?±?SD age: 56?±?13 years old; female: 10, male: 15) were enrolled. TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT scores 2.8, 2.5, 2.4, and 2.3, respectively for the presence of dental artifacts, 2.8, 2.5, 2.2, and 1.9, respectively, for the presence of breathing artifacts, and 2.7, 1.7, 2.0, and 1.3, respectively, for the presence of pelvic artifacts TOF PET/MRI images showed the highest image quality scores among the 4 datasets of PET images.

Conclusion

The superior timing resolution and resulting TOF capability of the new PET/MRI scanner improved PET image quality in this cohort by reducing artifacts compared to non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT.

     

Assessment of Remote Myocardium Heterogeneity in Patients with Ventricular Tachycardia Using Texture Analysis of Late Iodine Enhancement (LIE) Cardiac Computed Tomography (cCT) Images

Purpose

Diffuse remodeling of myocardial extra-cellular matrix is largely responsible for left ventricle (LV) dysfunction and arrhythmias. Our hypothesis is that the texture analysis of late iodine enhancement (LIE) cardiac computed tomography (cCT) images may improve characterization of the diffuse extra-cellular matrix changes. Our aim was to extract volumetric extracellular volume (ECV) and LIE texture features of non-scarred (remote) myocardium from cCT of patients with recurrent ventricular tachycardia (rVT), and to compare these radiomic features with LV-function, LV-remodeling, and underlying cardiac disease.

Procedures

Forty-eight patients suffering from rVT were prospectively enrolled: 5/48 with idiopathic VT (IVT), 23/48 with post-ischemic dilated cardiomyopathy (ICM), 9/48 with idiopathic dilated cardiomyopathy (IDCM), and 11/48 with scars from a previous healed myocarditis (MYO). All patients underwent echocardiography to assess LV systolic and diastolic function and cCT with pre-contrast, angiographic, and LIE scan to obtain end-diastolic volume (EDV), ECV, and first-order texture parameters of Hounsfield Unit (HU) of remote myocardium in LIE [energy, entropy, HU-mean, HU-median, standard deviation (SD), and mean absolute deviation (MAD)].

Results

Energy, HU mean, and HU median by cCT texture analysis correlated with ECV (rho?=?0.5650, rho?=?0.5741, rho?=?0.5068; p?<?0.0005). cCT-derived ECV, HU-mean, HU-median, SD, and MAD correlated directly to EDV by cCT and inversely to ejection fraction by echocardiography (p?<?0.05). SD and MAD correlated with diastolic function by echocardiography (rho?=?0.3837, p?=?0.0071; rho?=?0.3330, p?=?0.0208). MYO and IVT patients were characterized by significantly lower values of SD and MAD when compared with ICM and IDCM patients, independently of LV-volume systolic and diastolic function.

Conclusions

Texture analysis of LIE may expand cCT capability of myocardial characterization. Myocardial heterogeneity (SD and MAD) was associated with LV dilatation, systolic and diastolic function, and is able to potentially identify the different patterns of structural remodeling characterizing patients with rVT of different etiology.

     

Increased nitroglycerin-mediated vasodilation in migraineurs without aura in the interictal period

Purpose

Migraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found.

Methods

A total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography.

Results

There was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39?±?0.68 vs 3.89?±?0.67 mm, respectively; p?=?0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94?±?5.72 vs 6.08?±?2.98%, respectively; p?=?0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56?±?7.36 vs 14.23?±?7.41%, respectively; p?=?0.024).

Conclusion

We think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity.

     

Applying Reflective Multicriteria Decision Analysis (MCDA) to Patient–Clinician Shared Decision-Making on the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the Spanish Context

Introduction

Unresectable, well-differentiated nonfunctioning gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be monitored (watchful waiting, WW) or treated with systemic therapy such as somatostatin analogues (SSAs) to delay progression. We applied a reflective multicriteria decision analysis (MCDA) shared-decision framework (previously developed for the USA) to explore what matters to Spanish patients and clinicians considering GEP-NET treatment options.

Methods

The EVIDEM-derived framework was updated and adapted to the Spanish context. During a Chatham House session, five patients and six physicians assigned criteria weights using hierarchical point allocation and direct rating scale (alternative analysis). Informed by synthesized evidence embedded in the framework, participants scored how each criterion favored SSA treatment (reference case lanreotide) or WW and shared insights and knowledge. Weights and scores were combined into value contributions (norm. weight?×?score/5), which were added across criteria to derive the relative benefit–risk balance (RBRB, scale ??1 to +?1). Exploratory comparisons to US study findings were performed.

Results

Focusing on intervention outcomes (effectiveness, patient-reported, and safety), the mean RBRB favored treatment over WW (+?0.32?±?0.24), with the largest contributions from progression-free survival (+?0.11?±?SD 0.07), fatal adverse events (+?0.06?±?SD 0.08), and impact on HRQoL (+?0.04?±?SD 0.04). Consideration of modulating criteria (type of benefit, need, costs, evidence, and feasibility) increased the RBRB to +?0.50?±?0.14, with type of therapeutic benefit (+?0.10?±?SD 0.08) and quality of evidence (+?0.08?±?SD 0.06) contributing most towards treatment. Alternative weighting yielded similar results. Results were broadly comparable to those derived from the US study.

Conclusion

The multicriteria framework helped Spanish patients and clinicians identify and express what matters to them. The approach is transferable across decision-making contexts.

Funding

IPSEN Pharma.

     

Phase 1 Evaluation of [<Superscript>64</Superscript>Cu]DOTA-Patritumab to Assess Dosimetry,Apparent Receptor Occupancy,and Safety in Subjects with Advanced Solid Tumors

Purpose

The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [⁶⁴Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors.

Procedures

Dosimetry subjects (n?=?5) received [⁶⁴Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n?=?3 out of 6) received [⁶⁴Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy.

Results

The tumor SUV_max (±?SD) was 5.6?±?4.5, 3.3?±?1.7, and 3.0?±?1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044?±?0.008 mSv/MBq and 0.46?±?0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00?±?0.32 at baseline to 0.57?±?0.17 after stable patritumab, corresponding to a RO of 42.1?±?3.

Conclusions

[⁶⁴Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

     

Regional lung derecruitment after endotracheal suction during volume- or pressure-controlled ventilation: a study using electric impedance tomography

Objective

To assess lung volume and compliance changes during open- and closed-system suctioning using electric impedance tomography (EIT) during volume- or pressure-controlled ventilation.

Design and setting

Experimental study in a university research laboratory.

Subjects

Nine bronchoalveolar saline-lavaged pigs.

Interventions

Open and closed suctioning using a 14-F catheter in volume- or pressure-controlled ventilation at tidal volume 10?ml/kg, respiratory rate 20?breaths/min, and positive end-expiratory pressure 10?cmH₂O.

Measurements and results

Lung volume was monitored by EIT and a modified N₂ washout/-in technique. Airway pressure was measured via a pressure line in the endotracheal tube. In four ventral-to-dorsal regions of interest regional ventilation and compliance were calculated at baseline and 30?s and 1, 2, and 10?min after suctioning. Blood gases were followed. At disconnection functional residual capacity (FRC) decreased by 58?±?24% of baseline and by a further 22?±?10% during open suctioning. Arterial oxygen tension decreased to 59?±?14% of baseline value 1?min after open suctioning. Regional compliance deteriorated most in the dorsal parts of the lung. Restitution of lung volume and compliance was significantly slower during pressure-controlled than volume-controlled ventilation.

Conclusions

EIT can be used to monitor rapid lung volume changes. The two dorsal regions of the lavaged lungs are most affected by disconnection and suctioning with marked decreases in compliance. Volume-controlled ventilation can be used to rapidly restitute lung aeration and oxygenation after lung collapse induced by open suctioning.

     

Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria

Purpose

Breath stacking dyssynchrony generates higher tidal volumes than intended, potentially increasing lung injury risk in acute respiratory distress syndrome (ARDS). Lack of validated criteria to quantify breath stacking dyssynchrony contributes to its under-recognition. This study evaluates performance of novel, objective criteria for quantifying breath stacking dyssynchrony (BREATHE criteria) compared to existing definitions and tests if neuromuscular blockade eliminates high-volume breath stacking dyssynchrony in ARDS.

Methods

Airway flow and pressure were recorded continuously for up to 72 h in 33 patients with ARDS receiving volume-preset assist-control ventilation. The flow–time waveform was integrated to calculate tidal volume breath-by-breath. The BREATHE criteria considered five domains in evaluating for breath stacking dyssynchrony: ventilator cycling, interval expiratory volume, cumulative inspiratory volume, expiratory time, and inspiratory time.

Results

The observed tidal volume of BREATHE stacked breaths was 11.3 (9.7–13.3) mL/kg predicted body weight, significantly higher than the preset volume [6.3 (6.0–6.8) mL/kg; p < 0.001]. BREATHE identified more high-volume breaths (≥2 mL/kg above intended volume) than the other existing objective criteria for breath stacking [27 (7–59) vs 19 (5–46) breaths/h; p < 0.001]. Agreement between BREATHE and visual waveform inspection was high (raw agreement 96.4–98.1 %; phi 0.80–0.92). Breath stacking dyssynchrony was near-completely eliminated during neuromuscular blockade [0 (0–1) breaths/h; p < 0.001].

Conclusions

The BREATHE criteria provide an objective definition of breath stacking dyssynchrony emphasizing occult exposure to high tidal volumes. BREATHE identified high-volume breaths missed by other methods for quantifying this dyssynchrony. Neuromuscular blockade prevented breath stacking dyssynchrony, assuring provision of the intended lung-protective strategy.

     

Relationship between gait kinematics and walking energy expenditure during pregnancy in South African women

Background

Various musculoskeletal changes occurring during pregnancy may lead to the change in gait and contribute to the increase in walking energy expenditure. Previous research indicates that changes in gait mechanics may lead to the increase in mechanical work required during walking. However, there is little information to indicate if changes in gait mechanics during pregnancy have impact on active or total energy expenditure. Therefore, the primary aim of this study was to investigate the relationship between changes in gait kinematics and walking energy expenditure in pregnant women.

Methods

Thirty-five women (mean age?=?27.5?±?6.1 years) volunteered for the study during various stages of pregnancy (1st trimester average?=?12.1?±?2.2 weeks; 2nd trimester?=?22.3?±?2.6 weeks; 3rd trimester?=?31.4?±?2.6 weeks). 3D motion analysis was used to assess changes in kinematic parameters during walking at self-selected pace. Resting metabolic rate, and walking energy expenditure expressed in terms of rate and cost of O₂ were analysed with portable metabolic analyser.

Results

Only medio-lateral deviation of centre of gravity (COG_ML) increased 13.6% between the 1st and 2nd, and 39.3% between 2nd and 3rd trimester (p?≤?0.001). However, self-selected walking speed depicted strong significant positive linear relationship with net O₂ rate (r?=?0.70; p?≤?0.001), and was strongly associated with the vertical excursion of the COG (r?=?0.75, p?≤?0.001).

Conclusions

Changes in gait mechanics during pregnancy may lead to an increase in walking energy expenditure. However, the consequent increase in walking energy cost may not be sufficient to offset the natural energy sparing mechanism.