Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

Patient Sex Impacts Volume Phenotypes and Hemodynamics in Chronic Heart Failure: A Multicenter Analysis.

BACKGROUND: Quantitative methods have shown clinically significant heterogeneity in blood volume (BV) profiles in patients with chronic heart failure (HF). How patients' sex might impact this volume heterogeneity and its relationship to cardiac hemodynamics remains to be defined. METHODS: Retrospective analysis of clinical and quantitative BV, plasma volume (PV) and red blood cell (RBC) mass data was undertaken across 3 medical centers. BV was quantitated using nuclear medicine I-131-labeled plasma albumin indicator-dilution methodology with cardiac hemodynamics obtained within 24 hours. RESULTS: In an analysis of 149 males and 106 females, absolute BV was greater, on average, in males (6.9 ± 1.7 vs 5.0 ± 1.2 liters; P < 0.001); however, a wide range in BVs was demonstrated in both sexes (2.9-14.5 liters). Male sex was associated with higher prevalence of large (+ 25% of normal) BV and PV expansions (36% vs 15% and 51% vs 21%, respectively; both P < 0.001). In contrast, female sex was associated with higher prevalence of normal total BV (44% vs 27%; P = 0.005), PV (54% vs 27%; P < 0.001), hypovolemia (23% vs 11%; P = 0.005), and true anemia (42% vs 26%; P < 0.001). Cardiac hemodynamics differed by sex, but only modest associations were demonstrated between volume profiles and cardiac filling pressures. CONCLUSIONS: Findings support unique intravascular volume profiles reflecting sex-specific differences in the prevalence and distributions of total BV, PV and RBC mass profiles in patients with chronic HF. This underscores the importance of recognizing patients' sex as a significant factor influencing volume homeostasis, which needs to be taken into account to individualize volume-management strategies effectively.

Predictive Energy Equations Inaccurately Estimate Metabolic Demands of Older Adult Trauma Patients.

INTRODUCTION: Suboptimal nutrition promotes unfavorable outcomes in trauma patients, particularly among those aged 60 and over. While many institutions employ predictive energy equations to determine patients' energy requirements, mounting evidence shows these equations inaccurately estimate caloric needs. In this pilot randomized controlled trial, we sought to quantify the discrepancy between predictive equations and indirect calorimetry (IC)-the gold standard for determining energy requirements-in the older adult trauma population. METHODS: This is a nested cohort study within a pilot randomized control trial in which 32 older adult trauma patients were randomized 3:1 to receive IC-guided nutrition delivery versus standard of care. IC requirements of patients in the intervention arm were compared to Mifflin St. Jeor (MSJ), Harris-Benedict (HB), and the American Society for Parenteral and Enteral Nutrition-Society of Critical Care Medicine (ASPEN-SCCM) predictive energy equations. RESULTS: Twenty patients underwent IC to assess measured resting energy expenditure (mREE), yielding a mean (standard deviation) mREE of 23.1 ± 4.8 kcal/kg/d. MSJ and HB gave mean predictive resting energy expenditures of 17.5 ± 2.0 and 18.5 ± 2.0 kcal/kg/d in these patients, demonstrating that IC-derived values were 32.1% and 25.0% higher, respectively. When patients were stratified by body mass index (BMI), MSJ, and HB more severely underestimated caloric requirements in individuals with BMI <30 versus BMI 30-50. While the mean mREE fell within the mean predictive resting energy expenditure range prescribed by ASPEN-SCCM equations (21.4 ± 4.1 to 26.2 ± 4.3 kcal/kg/d), individuals' IC-derived values fell within their personal range in 8 of 20 cases. CONCLUSIONS: The MSJ and HB predictive energy equations consistently and significantly underpredict metabolic demands of older adult trauma patients compared to IC and perform worse in lower BMI individuals. ASPEN-SCCM equations frequently overpredict or underpredict resting energy expenditure. While these findings should be confirmed in a larger randomized control trial, this study suggests that institutions should prioritize IC to accurately identify the metabolic demands of older trauma patients.

Reference values of diaphragmatic dimensions in healthy children aged 0-8 years.

Diaphragmatic thickness (Tdi) and diaphragm thickening fraction (dTF) are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children are scarce. We determined reference values of Tdi and dTF using ultrasound in healthy children aged 0-8 years old and assessed their reproducibility. In a prospective, observational cohort, Tdi and dTF were measured on ultrasound images across four age groups comprising at least 30 children per group: group 1 (0-6 months), group 2 (7 months-1 year), group 3 (2-4 years) and group 4 (5-8 years). Ultrasound images of 137 healthy children were included. Mean Tdi at inspiration was 2.07 (SD 0.40), 2.09 (SD 0.40), 1.69 (SD 0.30) and 1.72 (SD 0.30) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at expiration was 1.64 (SD 0.30), 1.67 (SD 0.30), 1.38 (SD 0.20) and 1.42 (SD 0.20) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at inspiration and mean Tdi at expiration for groups 1 and 2 were significantly greater than those for groups 3 and 4 (both p < 0.001). Mean dTF was 25.4% (SD 10.4), 25.2% (SD 8.3), 22.8% (SD 10.9) and 21.3% (SD 7.1) for group 1, 2, 3 and 4, respectively. The intraclass correlation coefficients (ICC) representing the level of inter-rater reliability between two examiners performing the ultrasounds was 0.996 (95% CI 0.982-0.999). ICC of the inter-rater reliability between the raters in 11 paired assessments was 0.989 (95% CI 0.973-0.995).   Conclusion: Ultrasound measurements of Tdi and dTF were highly reproducible in healthy children aged 0-8 years.    Trial registration: ClinicalTrials.gov identifier (NCT number): NCT04589910. What is Known: • Diaphragmatic thickness and diaphragm thickening fraction are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children to compare these with are scarce. What is New: • We determined normal values of diaphragmatic thickness and diaphragm thickening fraction using ultrasound in 137 healthy children aged 0-8 years old. The diaphragmatic thickness of infants up to 1 year old was significantly greater than that of children from 2 to 8 years old. Diaphragmatic thickness decreased with an increase in body surface area. These normal values in healthy children can be used to assess changes in respiratory muscle thickness in mechanically ventilated children.

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes.

BACKGROUND: Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes. METHODS AND RESULTS: We retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm3) and below-median (<219 cm3) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank P = 0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.5%; log-rank P = 0.67). CONCLUSIONS: In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.

Quantitative Blood Volume Analysis and Hemodynamic Measures of Vascular Compliance in Patients With Worsening Heart Failure.

BACKGROUND: The role of blood volume (BV) expansion vs a change in vascular compliance in worsening heart failure (HF) remains under debate. We aimed to assess the relationship between BV and resting and stress hemodynamics in worsening HF and to further elucidate the significance of BV in cardiac decompensation. METHODS AND RESULTS: Patients with worsening HF underwent radiolabeled indicator-dilution BV analysis and cardiac catheterization. Intravascular volumes and resting/stress hemodynamics were recorded. Provocative stress maneuvers included change in systolic blood pressure (ΔSBP) from lying to standing and Valsalva and intracardiac pressure changes with leg raise. Correlation between BV and invasive hemodynamics were assessed by linear regression. Of 27 patients with worsening HF, patients' characteristics included mean age 61 ± 12 years, 70% male, 19% Black, and mean ejection fraction 29% ± 15%. Of the patients, 13 (48%) had hypervolemia as measured by total BV, which weakly correlated with ΔSBP by position (R2 = 0.009) and Valsalva (R2 = 0.003) and with right atrial (R2 = 0.049) and pulmonary capillary wedge (R2 = 0.047) pressure changes during leg raise. CONCLUSIONS: In patients with worsening HF, BV mildly correlated with intracardiac pressures at rest. Provocative maneuvers intended to test vascular compliance did not correlate with BV, indicating that compliance may serve as a stand-alone metric in HF.

Monitoring muscle mass using ultrasound: a key role in critical care.

PURPOSE OF REVIEW: The loss of muscle mass in critically ill patients contributes to morbidity and mortality, and results in impaired recovery of physical functioning. The number of publications on the topic is increasing. However, there is a lack of consistent methodology and the most optimal methodology remains unclear, hampering its broad use in clinical practice. RECENT FINDINGS: There is a large variety of studies recently published on the use of ultrasound for assessment of muscle mass. A selection of studies has been made, focusing on monitoring of muscle mass (repeated measurements), practical aspects, feasibility and possible nutrition and physical therapy interventions. In this review, 14 new small (n = 19-121) studies are categorized and reviewed as individual studies. SUMMARY: The use of ultrasound in clinical practice is feasible for monitoring muscle mass in critically ill patients. Assessment of muscle mass by ultrasound is clinically relevant and adds value for guiding therapeutic interventions, such as nutritional and physical therapy interventions to maintain muscle mass and promote recovery in critically ill patients.

Novel approaches to metabolic assessment and structured exercise to promote recovery in ICU survivors.

PURPOSE OF REVIEW: Survivorship or addressing impaired quality of life (QoL) in ICU survivors has been named 'the defining challenge of critical care' for this century to address this challenge; in addition to optimal nutrition, we must learn to employ targeted metabolic/muscle assessment techniques and utilize structured, progressive ICU rehabilitative strategies. RECENT FINDINGS: Objective measurement tools such as ccardiopulmonary exercise testing (CPET) and muscle-specific ultrasound show great promise to assess/treat post-ICU physical dysfunction. CPET is showing that systemic mitochondrial dysfunction may underlie development and persistence of poor post-ICU functional recovery. Finally, recent data indicate that we are poor at delivering effective, early ICU rehabilitation and that there is limited benefit of currently employed later ICU rehabilitation on ICU-acquired weakness and QoL outcomes. SUMMARY: The combination of nutrition with effective, early rehabilitation is highly likely to be essential to optimize muscle mass/strength and physical function in ICU survivors. Currently, technologies such as muscle-specific ultrasound and CPET testing show great promise to guide ICU muscle/functional recovery. Further, we must evolve improved ICU-rehabilitation strategies, as current methods are not consistently improving outcomes. In conclusion, we must continue to look to other areas of medicine and to athletes if we hope to ultimately improve 'ICU Survivorship'.

Role of anabolic testosterone agents and structured exercise to promote recovery in ICU survivors.

PURPOSE OF REVIEW: ICU survivors frequently suffer significant, prolonged physical disability. 'ICU Survivorship', or addressing quality-of-life impairments post-ICU care, is a defining challenge, and existing standards of care fail to successfully address these disabilities. We suggest addressing persistent catabolism by treatment with testosterone analogues combined with structured exercise is a promising novel intervention to improve 'ICU Survivorship'. RECENT FINDINGS: One explanation for lack of success in addressing post-ICU physical disability is most ICU patients exhibit severe testosterone deficiencies early in ICU that drives persistent catabolism despite rehabilitation efforts. Oxandrolone is an FDA-approved testosterone analogue for treating muscle weakness in ICU patients. A growing number of trials with this agent combined with structured exercise show clinical benefit, including improved physical function and safety in burns and other catabolic states. However, no trials of oxandrolone/testosterone and exercise in nonburn ICU populations have been conducted. SUMMARY: Critical illness leads to a catabolic state, including severe testosterone deficiency that persists throughout hospital stay, and results in persistent muscle weakness and physical dysfunction. The combination of an anabolic agent with adequate nutrition and structured exercise is likely essential to optimize muscle mass/strength and physical function in ICU survivors. Further research in ICU populations is needed.

The malnourished surgery patient: a silent epidemic in perioperative outcomes?

PURPOSE OF REVIEW: As many as two of every three major surgery patients are malnourished preoperatively - a diagnosis rarely made and treated even less frequently. Unfortunately, perioperative malnutrition is perhaps the least often identified surgical risk factor and is among the most treatable to improve outcomes. RECENT FINDINGS: Two important perioperative nutrition guidelines were published recently. Both emphasize nutrition assessment as an essential component of preoperative screening. The recently published perioperative nutrition screen (PONS) readily identifies patients at malnutrition risk, allowing for preoperative nutritional optimization. The use of computerized tomography scan and ultrasound lean body mass (LBM) evaluation to identify sarcopenia associated with surgical risk and guide nutrition intervention is garnering further support. Preoperative nutrition optimization in malnourished patients, use of immunonutrition in all major surgery, avoidance of preoperative fasting, inclusion of postoperative high-protein nutritional supplements, and early postoperative oral intake have all recently been shown to improve outcomes and should be utilized. SUMMARY: The recent publication of new surgical nutrition guidelines, the PONS score, and use of LBM assessments will allow better identification and earlier intervention on perioperative malnutrition. It is essential that in the future no patient undergoes elective surgery without nutrition screening and nutrition intervention when malnutrition risk is identified.

Measuring and monitoring lean body mass in critical illness.

PURPOSE OF REVIEW: To help guide metabolic support in critical care, an understanding of patients' nutritional status and risk is important. Several methods to monitor lean body mass are increasingly used in the ICU and knowledge about their advantages and limitations is essential. RECENT FINDINGS: Computed tomography scan analysis, musculoskeletal ultrasound, and bioelectrical impedance analysis are emerging as powerful clinical tools to monitor lean body mass during ICU stay. Accuracy, expertise, ease of use at the bedside, and costs are important factors which play a role in determining which method is most suitable. Exciting new research provides an insight into not only quantitative measurements, but also qualitative measurements of lean body mass, such as infiltration of adipose tissue and intramuscular glycogen storage. SUMMARY: Methods to monitor lean body mass in the ICU are under constant development, improving upon bedside usability and offering new modalities to measure. This provides clinicians with valuable markers with which to identify patients at high nutritional risk and to evaluate metabolic support during critical illness.

A feasibility study into adenosine triphosphate measurement in exhaled breath condensate: a potential bedside method to monitor alveolar deformation.

Recent research suggested an important role for pulmonary extracellular adenosine triphosphate (ATP) in the development of ventilation-induced lung injury. This injury is induced by mechanical deformation of alveolar epithelial cells, which in turn release ATP to the extracellular space. Measuring extracellular ATP in exhaled breath condensate (EBC) may be a non-invasive biomarker for alveolar deformation. Here, we study the feasibility of bedside ATP measurement in EBC. We measured ATP levels in EBC in ten subjects before and after an exercise test, which increases respiratory parameters and alveolar deformation. EBC lactate concentrations were measured as a dilution marker. We found a significant increase in ATP levels in EBC (before 73 RLU [IQR 50-209] versus after 112 RLU [IQR 86-203]; p value 0.047), and the EBC ATP-to-EBC lactate ratio increased as well (p value 0.037). We present evidence that bedside measurement of ATP in EBC is feasible and that ATP levels in EBC increase after exercise. Future research should measure ATP levels in EBC during mechanical ventilation as a potential biomarker for alveolar deformation.

Identifying Frailty Using Point-of-Care Ultrasonography: Image Acquisition and Assessment.

Frailty is a significant predictor of a range of adverse outcomes in surgical patients, including increased mechanical ventilation time, longer hospital stays, unplanned readmissions, stroke, delirium, and death. However, accessible tools for screening in clinical settings are limited. Computed tomography of the psoas muscle is the current standard imaging device for measuring frailty, but it is expensive, time-consuming, and exposes the patient to ionizing radiation. Recently, the use of point-of-care ultrasound (POCUS) has emerged as a potential tool to determine the presence of frailty and has been shown to accurately predict frailty and postoperative outcomes. In this article, we will describe the image acquisition of the quadriceps muscles and explain how they can be used to determine frailty and predict postoperative adverse events. We will present information on probe selection, patient positioning, and troubleshooting. Images from a demonstration will be used to present the POCUS technique and example results. The article will culminate in a discussion of the use of these images in medical decision-making and potential limitations.

Comparison of Cardiopulmonary Exercise Test Variables to Predict Adverse Events in Patients with Heart Failure.

PURPOSE: Given the rising burden of heart failure (HF), stratification of patients at increased risk for adverse events is critical. We aim to compare the predictive value of various maximal and submaximal cardiopulmonary exercise test (CPET) variables for adverse events in patients with HF. METHODS: 237 patients with HF (66 [58-73] years, 30% women, 70% HF with reduced ejection fraction) completed a CPET and had five years of follow-up. Baseline characteristics and clinical outcomes (all-cause mortality, major adverse cardiovascular events, and cardiovascular-related hospitalization) were extracted from electronic patient files. Receiver operating characteristics curves for maximal (e.g. peak VO2) and submaximal CPET variables (e.g. VE/VCO2 slope, cardiorespiratory optimal point (COP), VO2 at anaerobic threshold) were compared using the Akaike Information Criterion (AIC) method, whereas their calibration was assessed. RESULTS: 103 participants (43%) reached the composite endpoint, and 55 (23%) died. Percent predicted peak VO2 was the best predictor for adverse outcomes (AIC: 302.6) followed by COP (AIC: 304.3), and relative peak VO2 (mL/(kg·min), AIC: 304.4). Relative peak VO2 (AIC: 217.1) and COP (AIC: 224.4) were also among the three best predictors for mortality, together with absolute peak VO2 (ml/min, AIC: 220.5). A good calibration between observed and predicted event rate was observed for these variables. CONCLUSIONS: Percent predicated and relative peak VO2 had the best predictive accuracy for adverse events and mortality, but the submaximal COP had a non-inferior predictive accuracy for adverse events in patients with HF. These findings highlight the potential of submaximal exercise testing in patients with HF.

Feasibility of a Novel Augmented 6-Minute Incremental Step Test: A Simplified Cardiorespiratory Fitness Assessment Tool.

Background: The cardiopulmonary exercise test (CPET) is considered a gold standard in assessing cardiorespiratory fitness (CRF) but has limited accessibility due to competency requirements and cost. Incorporating portable sensor devices into a simple bedside test of CRF could improve diagnostic and prognostic value. Objectives: The authors sought to evaluate the association of an augmented 6-minute incremental step test (6MIST) with standard CPET. Methods: We enrolled patients undergoing clinically indicated supine cycle ergometry CPET with invasive hemodynamics (iCPET) for the same-day 6MIST. CRF-related variables were simultaneously recorded using a signal morphology-based impedance cardiograph (PhysioFlow Enduro) and a portable metabolic analyzer (VO2 Master Pro) during incremental pace stationary stepping. The correlation between CPET and hemodynamic parameters from both tests was assessed using the intraclass correlation coefficient (ICC). Results: Fifteen patients (mean age 60 ± 14 years, 40% female, 27% Black) were included. All patients who agreed to undergo 6MIST completed the study without any test-related adverse events. We observed good to excellent correlation between iCPET- and 6MIST-measured CPET parameters: peak heart rate (ICC = 0.60; 95% CI: 0.15-0.85), absolute peak O2 consumption (VO2) (ICC = 0.77; 95% CI: 0.44-0.92), relative peak VO2 (ICC = 0.64; 95% CI: 0.20-0.86), maximum ventilation (ICC = 0.59; 95% CI: 0.13-0.84), O2 pulse (ICC = 0.71; 95% CI: 0.33-0.89), and cardiorespiratory optimal point (ICC = 0.82; 95% CI: 0.52-0.94). No significant correlation was determined between iCPET and 6MIST in measuring cardiac index at rest (ICC = 0.19; 95% CI: -0.34 to 0.63) or at peak exercise (ICC = 0.36; 95% CI: -0.17 to 0.73). Conclusions: We demonstrate the feasibility of a novel augmented 6MIST with wearable devices for simultaneous CPET and hemodynamic assessment. 6MIST-measured CPET parameters were strongly correlated with the iCPET-derived measurements. Additional studies are needed to confirm the validity of the 6MIST compared to standard upright CPET.

Diagnosing Sarcopenia with AI-Aided Ultrasound (DINOSAUR)-A Pilot Study.

Background: Sarcopenia has been recognized as a determining factor in surgical outcomes and is associated with an increased risk of postoperative complications and readmission. Diagnosis is currently based on clinical guidelines, which includes assessment of skeletal muscle mass but not quality. Ultrasound has been proposed as a useful point-of-care diagnostic tool to assess muscle quality, but no validated cut-offs for sarcopenia have been reported. Using novel automated artificial intelligence (AI) software to interpret ultrasound images may assist in mitigating the operator-dependent nature of the modality. Our study aims to evaluate the fidelity of AI-aided ultrasound as a reliable and reproducible modality to assess muscle quality and diagnose sarcopenia in surgical patients. Methods: Thirty-six adult participants from an outpatient clinic were recruited for this prospective cohort study. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. Ultrasonography of the rectus femoris muscle was performed, and images were analyzed by an AI software (MuscleSound® (Version 5.69.0)) to derive muscle parameters including intramuscular adipose tissue (IMAT) as a proxy of muscle quality. A receiver operative characteristic (ROC) curve was used to assess the predictive capability of IMAT and its derivatives, with area under the curve (AUC) as a measure of overall diagnostic accuracy. To evaluate consistency between ultrasound users of different experience, intra- and inter-rater reliability of muscle ultrasound parameters was analyzed in a separate cohort using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: The median age was 69.5 years (range: 26-87), and the prevalence of sarcopenia in the cohort was 30.6%. The ROC curve plotted with IMAT index (IMAT% divided by muscle area) yielded an AUC of 0.727 (95% CI: 0.551-0.904). An optimal cut-off point of 4.827%/cm2 for IMAT index was determined with a Youden's Index of 0.498. We also demonstrated that IMAT index has excellent intra-rater reliability (ICC = 0.938, CI: 0.905-0.961) and good inter-rater reliability (ICC = 0.776, CI: 0.627-0.866). In Bland-Altman plots, the limits of agreement were from -1.489 to 1.566 and -2.107 to 4.562, respectively. Discussion: IMAT index obtained via ultrasound has the potential to act as a point-of-care evaluation for sarcopenia screening and diagnosis, with good intra- and inter-rater reliability. The proposed IMAT index cut-off maximizes sensitivity for case finding, supporting its use as an easily implementable point-of-care test in the community for sarcopenia screening. Further research incorporating other ultrasound parameters of muscle quality may provide the basis for a more robust diagnostic tool to help predict surgical risk and outcomes.

No association between thickening fraction of the diaphragm and extubation success in ventilated children.

Introduction: In mechanically ventilated adults, thickening fraction of diaphragm (dTF) measured by ultrasound is used to predict extubation success. Whether dTF can also predict extubation success in children is unclear. Aim: To investigate the association between dTF and extubation success in children. Second, to assess diaphragm thickness during ventilation and the correlation between dTF, diaphragm thickness (Tdi), age and body surface. Method: Prospective observational cohort study in children aged 0-18 years old with expected invasive ventilation for >48 h. Ultrasound was performed on day 1 after intubation (baseline), day 4, day 7, day 10, at pre-extubation, and within 24 h after extubation. Primary outcome was the association between dTF pre-extubation and extubation success. Secondary outcome measures were Tdi end-inspiratory and Tdi end-expiratory and atrophy defined as <10% decrease of Tdi end-expiratory versus baseline at pre-extubation. Correlations were calculated with Spearman correlation coefficients. Inter-rater reliability was calculated with intraclass correlation (ICC). Results: Fifty-three patients, with median age 3.0 months (IQR 0.1-66.0) and median duration of invasive ventilation of 114.0 h (IQR 55.5-193.5), were enrolled. Median dTF before extubation with Pressure Support 10 above 5 cmH2O was 15.2% (IQR 9.7-19.3). Extubation failure occurred in six children, three of whom were re-intubated and three then received non-invasive ventilation. There was no significant association between dTF and extubation success; OR 0.33 (95% CI; 0.06-1.86). Diaphragmatic atrophy was observed in 17/53 cases, in three of extubation failure occurred. Children in the extubation failure group were younger: 2.0 months (IQR 0.81-183.0) vs. 3.0 months (IQR 0.10-48.0); p = 0.045. At baseline, pre-extubation and post-extubation there was no significant correlation between age and BSA on the one hand and dTF, Tdi- insp and Tdi-exp on the other hand. The ICC representing the level of inter-rater reliability between the two examiners performing the ultrasounds was 0.994 (95% CI 0.970-0.999). The ICC of the inter-rater reliability between the raters in 36 paired assessments was 0.983 (95% CI 0.974-0.990). Conclusion: There was no significant association between thickening fraction of the diaphragm and extubation success in ventilated children.

The utility of a portable muscle ultrasound in the assessment of muscle alterations in children with acute lymphoblastic leukaemia.

BACKGROUND: During treatment for acute lymphoblastic leukaemia (ALL), children are prone to musculoskeletal deterioration. However, non-invasive tools to measure muscle mass and intramuscular alterations are limited. In this study we explored the feasibility of muscle ultrasound in children with ALL. Additionally, we analysed whether automated ultrasound outcomes of muscle size and intramuscular fat infiltration (IMAT) were associated with appendicular skeletal muscle mass (ASMM), muscle strength and physical performance. METHODS: Children with ALL, aged 3-18 years were included during maintenance therapy. Bilateral images of the rectus femoris muscle were captured using a portable linear array transducer connected to a tablet. Subsequently, an automated image annotation software (MuscleSound) was used to estimate cross-sectional area, muscle thickness and IMAT. Feasibility was assessed using acceptance (percentage of children approached who were enrolled), practicality (percentage of children that completed the ultrasound measurement after enrolment) and implementation (percentage of children that had sufficient imaging to be processed and analysed by the software). Assessments of ASMM by bioimpedance analysis, muscle strength using handheld dynamometry and timed physical performance tests were administered at the same visit. Multivariable linear models were estimated to study the associations between muscle ultrasound outcomes and ASMM, strength and physical performance, adjusted for sex, age, body mass index and ALL treatment week. RESULTS: Muscle ultrasound was performed in 60 out of 73 invited patients (76.9%), of which 37 were boys (61.7%), and median age was 6.1 years (range: 3-18.8 years). The acceptance was 98.7%, practicality 77.9% and implementation was 100%. Patients who refused the examination (n = 13) were younger (median: 3.6, range: 3-11.2 years) compared with the 60 examined children (P = 0.0009). In multivariable models, cross-sectional area was associated with ASMM (ß = 0.49 Z-score, 95% confidence interval [CI]:0.3,2.4), knee-extension strength (ß = 16.9 Newton [N], 95% CI: 4.8, 28.9), walking performance (ß = -0.46 s, 95% CI: -0.75, -0.18) and rising from the floor (ß = -1.07 s, 95% CI: -1.71, -0.42). Muscle thickness was associated with ASMM (ß = 0.14 Z-score, 95% CI: 0.04, 0.24), knee-extension strength (ß = 4.73 N, 95% CI: 0.99, 8.47), walking performance (ß = -0.13 s, 95% CI: -0.22, -0.04) and rising from the floor (ß = -0.28 s, 95% CI: -0.48, -0.08). IMAT was associated with knee-extension strength (ß = -6.84 N, 95% CI: -12.26, -1.41), walking performance (ß = 0.2 s, 95% CI: 0.08, 0.32) and rising from the floor (ß = 0.54 s, 95% CI: 0.27, 0.8). None of the muscle ultrasound outcomes was associated with handgrip strength. CONCLUSIONS: Portable muscle ultrasound appears a feasible and useful tool to measure muscle size and intramuscular alterations in children with ALL. Validation studies using magnetic resonance imaging (gold standard) are necessary to confirm accuracy in paediatric populations.

Clinical Utility of the Cardiorespiratory Optimal Point in Patients with Heart Failure.

INTRODUCTION: We assessed the cardiorespiratory optimal point (COP)-the minimal V̇E /V̇O 2 in a given minute of an incremental cardiopulmonary exercise test-in patients with heart failure (HF) and aimed to determine 1) its association with patient and disease characteristics, 2) changes after an exercise-based cardiac rehabilitation program (CR), and 3) the association with clinical outcomes. METHODS: We studied 277 HF patients (67 (58-74) yr, 30% female, 72% HF with restricted ejection fraction) between 2009 and 2018. Patients participated in a 12- to 24-wk CR program, and COP was assessed pre- and post-CR. Patient and disease characteristics and clinical outcomes (mortality and cardiovascular-related hospitalization) were extracted from patient files. The incidence of clinical outcomes was compared across COP tertiles (low, <26.0; moderate, 26.0-30.7; high, >30.7). RESULTS: Median COP was 28.2 (24.9-32.1) and was reached at 51% ± 15% of V̇O 2peak . Lower age, female sex, higher body mass index, the absence of a pacemaker or the absence of chronic obstructive pulmonary disease, and lower N-terminal prohormone brain natriuretic peptide concentrations were associated with a lower COP. Participation in CR reduced COP (-0.8; 95% confidence interval, -1.3 to -0.3). Low COP had a reduced risk (adjusted hazard ratio, 0.53; 95% confidence interval, 0.33-0.84) for adverse clinical outcomes as compared with high COP. CONCLUSIONS: Classic cardiovascular risk factors are associated with a higher, more unfavorable, COP. CR-based exercise training reduces COP, whereas a lower COP is associated with a better clinical prognosis. As COP can be established during a submaximal exercise test, this may offer novel risk stratification possibilities for HF care programs.