Impact of time intervals on drug efficacy and phenotypic outcomes in acute respiratory distress syndrome in mice.

Acute respiratory distress syndrome is a severe lung condition resulting from various causes, with life-threatening consequences that necessitate intensive care. The phenomenon can be modeled in preclinical models, notably through the use of lipopolysaccharide (LPS) instillation in mice. The phenotype induced closely recapitulates the human syndrome, including pulmonary edema, leukocyte infiltration, acute inflammation, impaired pulmonary function, and histological damage. However, the experimental designs using LPS instillations are extremely diverse in the literature. This highly complicates the interpretation of the induced phenotype chronology for future study design and hinders the proper identification of the optimal time frame to assess different readouts. Therefore, the definition of the treatment window in relation to the beginning of the disease onset also presents a significant challenge to address questions or test compound efficacy. In this context, the temporality of the different readouts usually measured in the model was evaluated in both normal and neutrophil-depleted male C57bl/6 mice using LPS-induction to assess the best window for proper readout evaluation with an optimal dynamic response range. Ventilation parameters were evaluated by whole-body plethysmography and neutrophil recruitment were evaluated in bronchoalveolar lavage fluids and in lung tissues directly. Imaging evaluation of myeloperoxidase along with activity in lung lysates and fluids were compared, along with inflammatory cytokines and lung extravasation by enzyme-linked immunoassays. Moreover, dexamethasone, the gold standard positive control in this model, was also administered at different times before and after phenotype induction to assess how kinetics affected each parameter. Overall, our data demonstrate that each readout evaluated in this study has a singular kinetic and highlights the key importance of the timing between ARDS phenotype and treatment administration and/or analysis. These findings also strongly suggest that analyzes, both in-life and post-mortem should be conducted at multiple time points to properly capture the dynamic phenotype of the LPS-ARDS model and response to treatment.

Overview of BMI and Other Ways of Measuring and Screening for Obesity in Pediatric Patients.

Despite a long history of advances in measuring body size and composition, body mass index (BMI) has remained the most commonly used clinical measure. We explore the advantages and disadvantages of using BMI and other measures to estimate adipose tissue, recognizing that no measure of body size or adiposity has fulfilled the goal of differentiating health from disease. BMI and waist circumference remain widely-used clinical screening measures for appropriate risk stratification as it relates to obesity.

Effect of positive allosteric modulation and orthosteric agonism of dopamine D2-like receptors on respiration in mouse models of Rett syndrome.

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the methyl-CPG-binding protein 2 (Mecp2) gene. Frequent apneas and irregular breathing are prevalent in RTT, and also occur in rodent models of the disorder, including Mecp2Bird and Mecp2R168X mice. Sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT (Abdala et al., 2014). Targeting the 5HT1a receptor alone also improves respiration in RTT mice (Levitt et al., 2013). However, the contribution of D2-like receptors in correcting these respiratory disturbances remains untested. PAOPA, a dopamine D2-like receptor positive allosteric modulator, and quinpirole, a dopamine D2-like receptor orthosteric agonist, were used in conjunction with whole-body plethysmography to evaluate whether activation of D2-like receptors is sufficient to improve breathing disturbances in female heterozygous Mecp2Bird/+ and Mecp2R168X/+ mice. PAOPA did not significantly change apnea incidence or irregularity score in RTT mice. PAOPA also had no effect on the ventilatory response to hypercapnia (7 % CO2). In contrast, quinpirole reduced apnea incidence and irregularity scores and improved the hypercapnic ventilatory response in Mecp2R168X/+ and Mecp2Bird/+ mice, while also reducing respiratory rate. These results suggest that D2-like receptors could contribute to the positive effects of sarizotan in the correction of respiratory abnormalities in Rett syndrome. However, positive allosteric modulation of D2-like receptors alone was not sufficient to evoke these effects.

Cerebral blood flow in sleep: A systematic review and meta-analysis.

Sleep plays an essential role in physiology, allowing the brain and body to restore itself. Despite its critical role, our understanding of the underlying processes in the sleeping human brain is still limited. Sleep comprises several distinct stages with varying depths and temporal compositions. Cerebral blood flow (CBF), which delivers essential nutrients and oxygen to the brain, varies across brain regions throughout these sleep stages, reflecting changes in neuronal function and regulation. This systematic review and meta-analysis assesses global and regional CBF across sleep stages. We included, appraised, and summarized all 38 published sleep studies on CBF in healthy humans that were not or only slightly (<24 h) sleep deprived. Our main findings are that CBF varies with sleep stage and depth, being generally lowest in NREM sleep and highest in REM sleep. These changes appear to stem from sleep stage-specific regional brain activities that serve particular functions, such as alterations in consciousness and emotional processing.

Body Composition Analysis of the Clinical Routine Using Air Displacement Plethysmography: Age-Group-Specific Feasibility Analysis among Preterm Infants.

Body composition assessments using air displacement plethysmography (ADP, PEAPOD®) have been introduced into clinical practice at a few neonatal units. To allow accurate body composition assessments in term and preterm infants, a workflow for routine testing is needed. The aim of this study was to analyze the feasibility of weekly routine ADP testing. We analyzed (1) postnatal ages at first ADP assessment, (2) the number of weekly routine in-hospital assessments, and (3) the workload of body composition measurements using ADP in clinical practice on the basis of an retrospective analysis of our own clinical operating procedures. The retrospective analysis of weekly routine ADP testing proved feasible at Nuremberg Children's Hospital. The analysis of postnatal age at the first ADP test revealed differences across groups, with extremely preterm infants starting at a mean postmenstrual age of 36.6 weeks, very preterm infants starting at 34.2 weeks, and moderate to late preterm infants starting at 35.3 weeks. The mean number of tests before discharge was significantly greater in the extremely preterm group (n = 3.0) than in the very preterm (n = 2.4) and moderate to late preterm groups (n = 1.7). The workload of the procedure is reasonable, at 8-13 min per test cycle. The study proved that weekly routine ADP assessments in preterm infants are feasible. However, the initiation of routine testing in extremely preterm infants starts at a significantly greater postnatal age than in the more mature population. ADP assessments can be safely and easily integrated into clinical practice and may be valuable tools for providing additional information on nutritional status and infant growth. A standardized routine protocol allowing identical measurement conditions across healthcare institutions and a standardized interpretation tool for age-adapted body composition data, however, would improve comparability and usability.

Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization.

The emergence of new synthetic opioids (NSOs) has added complexity to recreational opioid markets worldwide. While NSOs with diverse chemical structures have emerged, brorphine currently remains the only NSO with a piperidine benzimidazolone scaffold. However, the emergence of new generations of NSOs, including brorphine analogues, can be anticipated. This study explored the pharmaco-toxicological, opioid-like effect profile of brorphine alongside its non-brominated analogue (orphine) and three other halogenated analogues (fluorphine, chlorphine, iodorphine). In vitro, radioligand binding assays in rat brain tissue indicated that all analogues bind to the µ-opioid receptor (MOR) with nM affinity. While analogues with smaller-sized substituents showed the highest MOR affinity, further in vitro characterization via two cell-based (HEK 293T) MOR activation (ß-arrestin 2 and mini-Gαi recruitment) assays indicated that chlorphine, brorphine, and iodorphine were generally the most active MOR agonists. None of the compounds showed significant in vitro biased agonism compared to hydromorphone. In vivo, we investigated the effects of intraperitoneal (IP) administration of the benzimidazolones (0.01-15 mg/kg) on mechanical and thermal antinociception in male CD-1 mice. Chlorphine and brorphine overall induced the highest levels of antinociception. Furthermore, the effects on respiratory changes induced by a fixed dose (15 mg/kg IP) of the compounds were investigated using non-invasive plethysmography. Fluorphine-, chlorphine-, and brorphine-induced respiratory depressant effects were the most pronounced. For some compounds, pretreatment with naloxone (6 mg/kg IP) could not reverse respiratory depression. Taken together, brorphine-like piperidine benzimidazolones are opioid agonists that have the potential to cause substantial harm to users should they emerge as NSOs. This article is part of the Special Issue on "Novel Synthetic Opioids (NSOs)".

Assessment and monitoring of lung disease in patients with severe alpha 1 antitrypsin deficiency: a european delphi consensus of the EARCO group.

BACKGROUND: Currently, there is conflicting information and guidance on the effective management of Alpha 1 Antitrypsin Deficiency (AATD). Establishing a consensus of assessment and disease management specific to AATD is important for achieving a standardized treatment pathway and for improving patient outcomes. Here, we aim to utilize the Delphi method to establish a European consensus for the assessment and management of patients with severe AATD. METHODS: Two rounds of a Delphi survey were completed online by members of the European Alpha-1 Research Collaboration (EARCO). Respondents were asked to indicate their agreement with proposed statements for patients with no respiratory symptoms, stable respiratory disease, and worsening respiratory disease using a Likert scale of 1-7. Levels of agreement between respondents were calculated using a weighted average. RESULTS: Round 1 of the Delphi survey was sent to 103 members of EARCO and 38/103 (36.9%) pulmonologists from across 15 countries completed all 109 questions. Round 2 was sent to all who completed Round 1 and 36/38 (94.7%) completed all 79 questions. Responses regarding spirometry, body plethysmography, high-resolution computed tomography, and the initiation of augmentation therapy showed little variability among physicians, but there was discordance among other aspects, such as the use of low-dose computed tomography in both a research setting and routine clinical care. CONCLUSIONS: These results provide expert opinions for the assessment and monitoring of patients with severe AATD, which could be used to provide updated recommendations and standardized treatment pathways for patients across Europe.

Advancing cough research: Methodological insights into cough challenge in guinea pig models using double chamber vs whole-body plethysmography.

OBJECTIVE: This study compares two methods of citric acid-induced cough in guinea pigs in whole-body plethysmography (WBP) and double chamber plethysmography (DCP) to evaluate their efficacy. METHODS: Sixteen specific pathogen-free (SPF) and sixteen conventionally-bred (CON) animals were exposed to 0.4 M citric acid aerosol. They underwent cough provocation using both DCP and WBP methods. The number of coughs and latency to the first cough were recorded and analysed using statistical methods to determine significant differences between the two techniques. RESULTS: WBP resulted in significantly higher cough counts (WBP vs. DCP: 13±9 vs 2±3 for SPF; 14±8 vs 5±5 for CON; p<0.0001) and shorter latency (WBP vs. DCP: 59±6 s vs 159±14 s for SPF; 77±4 s vs 112±12 s for CON; p<0.0001) compared to DCP in both groups. CONCLUSION: Methodological differences substantially impact cough responses. WBP provides a more reliable and physiologically relevant methodology for cough assessment, suggesting the need for standardized protocols in cough research to enhance translational relevance.

Three-dimensional geometric morphometric shape analysis of chest wall kinematics in different breathing conditions.

Breathing motion is based on the differential activity of the thoracic, diaphragmatic and abdominal muscles. Muscle contributions differ between rest and exercise conditions and depend on posture and other factors. Traditionally, these changes are investigated on volumetric data using optoelectronic plethysmography (OEP). OEP offers insight into size variations of different chest wall (CW) compartments but does not provide three-dimensional visualization methods of CW breathing kinematics. Here we explore the use of three-dimensional geometric morphometrics to analyse size and shape changes caused by spontaneous breathing motion during quiet (QB), and recovery breathing (REC, immediately after heavy exercise) in two different postures (SIT, sitting on cycle ergometer; STA, standing position). Our findings show that size and shape differ significantly between inspiration and expiration and that differences are greater in REC than in QB. However, this is achieved by stronger expiration in SIT but by greater expiratory and inspiratory movements in STA. Shape analysis suggests that these differences may be attributed to constrained mobility of the shoulder girdle and a minor thoracic spine extension during inspiration owing to position on the ergometer. Breathing motion in STA seems biomechanically less constrained. Geometric morphometrics analyses can provide additional insights into data obtained by OEP.

Comparison of lung volumes measured with computed tomography and whole-body plethysmography - a systematic review.

Introduction: Whole-body plethysmography is the preferred method for measuring the static lung volumes: total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV), as it also incorporates trapped gas - a common finding in chronic obstructive pulmonary disease (COPD). Quantitative computed tomography (CT) is a promising alternative to plethysmography, which can be challenging to perform for patients with severely impaired lung function. The present systematic review explores the agreement between lung volumes measured by plethysmography and CT, as well as the attempts being made to optimize alignment between these two methods. Methods: A literature search was performed on the PubMed database using the block search strategy. Articles were included if they provided both CT based and plethysmography based TLC. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist. Results: 22 articles were included. On average, CT-derived TLC (CT-TLC) was 709 mL lower compared to plethysmography TLC (p-TLC) with a 12.1% deviation from the reference standard, p-TLC. This discrepancy (ΔTLC) appeared slightly larger in obstructive patients (obstructive: 781 mL, non-obstructive: 609 mL), whereas percent deviation was slightly smaller (obstructive: 11.4%, non-obstructive: 13.5%). CT-based RV analyses primarily based on COPD patients measured 603 mL higher than plethysmography (p-RV) with 17.8% deviation from p-RV. Studies utilizing spirometry-gating for CT acquisition reported good agreement between modalities (ΔTLC: 70-280 mL), and one study demonstrated noticeable improvements compared to conventional breath-hold instructions in an otherwise identical study setting. Conclusion: CT quantifications routinely underestimate TLC and overestimate RV in comparison to plethysmography. Spirometry gating reduces the level of disagreement and can be of assistance when patients are already undergoing CT. However, further studies are needed to confirm these results.

How does organophosphorus chemical warfare agent exposure affect respiratory physiology in mice?

In the absence of appropriate medical care, exposure to organophosphorus nerve agents, such as VX, can lead to respiratory failure, and potentially death by asphyxiation. Despite the critical role of respiratory disturbances in organophosphorus-induced toxicity, the nature and underlying mechanisms of respiratory failure remain poorly understood. This study aimed to characterize respiratory alterations by determining their type and duration in mice exposed to a subcutaneous sublethal dose of VX. Respiratory ventilation in Swiss mice was monitored using dual-chamber plethysmography for up to 7 days post-exposure. Cholinesterase activity was assessed via spectrophotometry, and levels of inflammatory biomarkers were quantified using Luminex technology in blood and tissues involved in respiration (diaphragm, lung, and medulla oblongata). Additionally, a histological study was conducted on these tissues to ensure their structural integrity. Ventilatory alterations appeared 20-25 minutes after the injection of 0.9 LD50 VX and increased until the end of the recording, i.e., 40 minutes after intoxication. Concurrent with the occurrence of apnea, increased inspiratory and expiratory times resulted in a significant decrease in respiratory rate in exposed mice compared to controls. Ventilatory amplitude and, consequently, minute volume were reduced, while specific airway resistance significantly increased, indicating bronchoconstriction. These ventilatory effects persisted up to 24 or even 72 hours post-intoxication, resolving on the 7th day. They were correlated with a decrease in acetylcholinesterase activity in the diaphragm, which persisted for up to 72 hours, and with the triggering of an inflammatory reaction in the same tissue. No significant histologic lesions were observed in the examined tissues. The ventilatory alterations observed up to 72 hours post-VX exposure appear to result from a functional failure of the respiratory system rather than tissue damage. This comprehensive characterization contributes to a better understanding of the respiratory effects induced by VX exposure, which is crucial for developing specific medical countermeasures.

Estimation of the prevalence of isolated inter-scalene compression from simultaneous arterial and venous photoplethysmography in patients referred for suspected thoracic outlet syndrome.

Objective.In patients with suspected thoracic outlet syndrome (TOS), diagnosing inter-scalene compression could lead to minimally invasive treatments. During photo-plethysmography, completing a 30 s 90° abduction, external rotation ('surrender' position) by addition of a 15 s 90° antepulsion 'prayer' position, allows quantitative bilateral analysis of both arterial (A-PPG) and venous (V-PPG) results. We aimed at determining the proportion of isolated arterial compression with photo-plethysmography in TOS-suspected patients.Approach.We studied 116 subjects recruited over 4 months (43.3 ± 11.8 years old, 69% females). Fingertip A-PPG and forearm V-PPG were recorded on both sides at 125 Hz and 4 Hz respectively. A-PPG was converted to PPG amplitude and expressed as percentage of resting amplitude (% rest). V-PPG was expressed as percentage of the maximal value (% max) observed during the 'Surrender-Prayer' maneuver. Impairment of arterial inflow during the surrender (As+) or prayer (Ap+) phases were defined as a pulse-amplitude either <5% rest, or <25% rest. Incomplete venous emptying during the surrender (Vs+) or prayer (Vp+) phases were defined as V-PPG values either <70% max, or <87% max.Main results.Of the 16 possible associations of encodings, As - Vs - Ap - Vp- was the most frequent observation assumed to be a normal response. Isolated arterial inflow without venous outflow (As + Vs-) impairment in the surrender position was observed in 10.3% (95%CI: 6.7%-15.0%) to 15.1% (95%CI: 10.7%-20.4%) of limbs.Significance.Simultaneous A-PPG and V-PPG can discriminate arterial from venous compression and then potentially inter-scalene from other levels of compressions. As such, it opens new perspectives in evaluation and treatment of TOS.

Oxygen saturation and work of breathing indices in preterm infants with bronchopulmonary dysplasia compared to healthy preterm infants at discharge.

BACKGROUND: Thoracoabdominal asynchrony (TAA) is commonly seen in preterm infants. Respiratory inductive plethysmography (RIP) is a noninvasive way to objectively assess work of breathing (WOB) indices. The impact of bronchopulmonary dysplasia (BPD) on TAA at discharge has not been established. The aim of this study is to compare WOB indices in premature infants with a diagnosis of BPD to premature infants without a diagnosis of BPD at discharge. METHODS: A prospective, observational study of premature infants (<32 weeks gestation) at discharge during quiet breathing in the supine position. RIP noninvasively measured WOB indices. A high-resolution pulse oximeter collected oxygen saturation and heart rate data. RESULTS: This study included thirty-one infants with BPD and thirty-four infants without BPD. Infants diagnosed with BPD had increased phase angle [BPD Φ = 73 . 90 (8.2) vs NoBPD Φ = 52.6 (8.2), p = 0.039]. Infants diagnosed with BPD had decreased saturations [BPD SpO2 = 96% (0.4) vs NoBPD Sp02 98% (0.3), p=<0.001], increased time with saturations less than 85% [BPD % =2.74 (0.7) vs NoBPD % =0.91 (0.4), p = .018], and increased time with saturations less than 80% [BPD % =1.57 (0.5) vs NoBPD % =0.52 (0.3), p = 0.045]. There was no difference in heart rate or breaths per minute for infants with BPD versus controls. CONCLUSION: Premature infants with BPD demonstrated increased TAA and had lower saturations compared to infants without BPD at discharge despite being chronologically older and being discharged at an older corrected gestational age. The impact of BPD on breathing patterns persists at discharge and suggests these patients may have residual lung and/or respiratory muscle dysfunction.

Advances in Pediatric Lung Function Testing Techniques.

For decades spirometry has been the benchmark test for capturing lung function in children but its recognized limitations required the development of other techniques. This article introduces novel techniques in lung function assessment for pediatric patients, including multiple breath washout, impulse oscillometry, structured light plethysmography, and electrical impedance tomography, and common themes in interpreting the results. Challenges include standardization, reference data, and clinical integration of these innovative tools. Further research is ongoing to optimize these tests for clinical use, especially in diverse populations and pediatric settings.

Characterisation of sleep apneas and respiratory circuitry in mice lacking CDKL5.

CDKL5 deficiency disorder is a rare genetic disease caused by mutations in the CDKL5 gene. Central apneas during wakefulness have been reported in patients with CDKL5 deficiency disorder. Studies on CDKL5-knockout mice, a CDKL5 deficiency disorder model, reported sleep apneas, but it is still unclear whether these events are central (central sleep apnea) or obstructive (obstructive sleep apnea) and may be related to alterations of brain circuits that modulate breathing rhythm. This study aimed to discriminate central sleep apnea and obstructive sleep apnea in CDKL5-knockout mice, and explore changes in the somatostatin neurons expressing high levels of neurokinin-1 receptors within the preBötzinger complex. Ten adult male wild-type and 12 CDKL5-knockout mice underwent electrode implantation for sleep stage discrimination and diaphragmatic activity recording, and were studied using whole-body plethysmography for 7 hr during the light (resting) period. Sleep apneas were categorised as central sleep apnea or obstructive sleep apnea based on the recorded signals. The number of somatostatin neurons in the preBötzinger complex and their neurokinin-1 receptors expression were assessed through immunohistochemistry in a sub-group of animals. CDKL5-knockout mice exhibited a higher apnea occurrence rate and a greater prevalence of obstructive sleep apnea during rapid eye movement sleep, compared with wild-type, whereas no significant difference was observed for central sleep apnea. Moreover, CDKL5-knockout mice showed a reduced number of somatostatin neurons in the preBötzinger complex, and these neurons expressed a lower level of neurokinin-1 receptors compared with wild-type controls. These findings underscore the pivotal role of CDKL5 in regulating normal breathing, suggesting its potential involvement in shaping preBötzinger complex neural circuitry and controlling respiratory muscles during sleep.

Can plethysmographic capillary refill time predict lactate during sepsis? An observational study from Morocco.

Introduction: Blood lactate is a marker of tissue hypoxia while capillary refill time (CRT) is a surrogate of tissue perfusion. Measuring these parameters is recommended for assessing circulatory status and guiding resuscitation. However, blood lactate is not widely available in African emergency departments. Additionally, CRT assessment faces challenges related to its precision and reproducibility. This study aims to evaluate the accuracy of visual CRT(V-CRT) compared to plethysmographic CRT (P-CRT) in predicting lactate levels among septic patients. Methods: This prospective observational study enrolled consecutive patients with sepsis or septic shock over a 6-month period from a tertiary hospital in Marrakech, Morroco. V-CRT and P-CRT were evaluated upon admission, and simultaneous measurements of arterial lactate levels were obtained. The precision of V-CRT and P-CRT in predicting arterial lactate was assessed using ROC curve analysis. Results: Forty-three patients aged of 64±15 years, of whom 70 % were male, were included in the study. Of these, 23 patients (53 %) had sepsis, and 20 patients (47 %) experienced septic shock. Both V-CRT and P-CRT demonstrated statistically significant correlations with arterial lactate, with correlation coefficients of 0.529 (p < 0.0001) and 0.517 (p = 0.001), respectively. ROC curve analysis revealed that V-CRT exhibited satisfactory accuracy in predicting arterial lactate levels >2 mmol/l, with an area under the curve (AUC) of 0.8 (95 % CI=0.65 - 0.93; p < 0.0001). The prediction ability of P-CRT was lower than V-CRT with an AUC of 0.73 (95 % CI: 0.57-0.89; p = 0.043). The optimal thresholds were determined as 3.4 s for V-CRT (sensitivity = 90 %, specificity = 58 %) and 4.1 s for P-CRT (sensitivity = 85 %, specificity = 62 %). Conclusion: These findings suggest that the plethysmographic evaluation did not improve the accuracy of CRT for predicting lactate level. However, V-CRT may still serve as a viable surrogate for lactate in septic patients in low-income settings.

Adapting Real-Time Lung Function Measurements for SARS-CoV-2 Infection Studies in Syrian Hamsters.

Pulmonary function examinations are critical to assess respiratory disease severity in patients. In preclinical rodent models of viral respiratory infections, however, disease is frequently evaluated based on virological, pathological and/or surrogate clinical parameters, which are not directly associated with lung function. To bridge the gap between preclinical and clinical readouts, we aimed to apply unrestrained whole-body plethysmography (WBP) measurements in a SARS-CoV-2 Syrian hamster challenge model. While WBP measurements are frequently used for preclinical research in mice and rats, results from studies in hamsters are still limited. During unrestrained WBP measurements, we obtained highly variable breathing frequency values outside of the normal physiological range for hamsters. Importantly, we observed that animal movements were recorded as breaths during WBP measurements. By limiting animal movement through either mechanical or chemical restraint, we improved the reliability of the lung function readout and obtained breathing frequencies that correlated with clinical signs when comparing two different variants of SARS-CoV-2 post-inoculation. Simultaneously, however, new sources of experimental variation were introduced by the method of restraint, which demands further optimalization of WBP measurements in Syrian hamsters. We concluded that WBP measurements are a valuable refinement either in combination with video recordings or if average values of measurements lasting several hours are analyzed.

Arteriovenous Oscillometric Plethysmography for Fistula Functional Testing.

INTRODUCTION: The aim of the presented prospective observational study was to evaluate the effect of fistula flow on peripheral wave morphology and pulse wave velocity by means of the oscillometric Vicorder®-device with the purpose of fistula surveillance. METHODS: Digitized and normalized curves of 53 haemodialysis patients at the fistula and non-fistula arm were analysed. Slope parameters and the areas under the curve of characteristic sections of pulse waves as well as the power spectrum of the pulse waves and their first and second derivatives were computed. Furthermore, the amplitude of volumetric change (AMP) was assessed. Duplex sonography served as a reference method. RESULTS: In the comprehensive set of novel pulse wave parameters significant inter-arm differences were demonstrated and a significant delay of the systolic maximum at the fistula arm in comparison to the non-fistula arm (204 ± 3.4 vs. 162 ± 5.3 ms, p < 0.001) was proven. Unexpectedly, pulse wave velocity apparently did not differ between both arms (7.85 vs. 8.05 m/s at the fistula/non-fistula side, p = 0.942). The inter-arm differences of the slope parameters were more pronounced in forearm than in upper arm fistulas. Finally, we showed that the inter-arm difference of AMP correlated with volume flow (r = 0.326 with p = 0.017). CONCLUSION: Pulse waves as assessed by oscillometric pulse wave analysis have distinct features at fistula and non-fistula arms. This is due to enhanced arteriovenous flow, i.e. in both the brachial artery and the fistula vein. The analysis of those alterations has the potential to assess fistula function.

In Vivo Measurement of Tidal Volume During Non-invasive Respiratory Support by Continuous-Flow Helmet CPAP.

Recently, the interest in the Helmet interface during non-invasive respiratory support (NIRS) has increased due to the COVID-19 pandemic. During NIRS, positive end-expiratory pressure (PEEP) can be given as continuous positive airway pressure (CPAP), which maintains a positive airway pressure throughout the whole respiratory cycle with Helmet as an interface (H-CPAP). The main disadvantage of the H-CPAP is the inability to measure tidal volume (VT). Opto-electronic plethysmography (OEP) is a non-invasive technique that is not sensitive to gas compression/expansion inside the helmet. OEP acquisitions were performed on 28 healthy volunteers (14 females and 14 males) at baseline and during Helmet CPAP. The effect of posture (semi-recumbent vs. prone), flow (50 vs. 60 L/min), and PEEP (0 vs. 5 vs. 10 cmH2O) on the ventilatory and thoracic-abdominal pattern and the operational volumes were investigated. Prone position limited vital capacity, abdominal expansion and chest wall recruitment. A constant flow of 60 L/min reduced the need for the subject to ventilate while having a slight recruitment effect (100 mL) in the semi-recumbent position. A progressive increasing recruitment was found with higher PEEP but limited by the prone position. It is possible to accurately measure tidal volume during H-CPAP to deliver non-invasive ventilatory support using opto-electronic plethysmography during different clinical settings.

Reproducibility of Air Displacement Plethysmography in Term and Preterm Infants-A Study to Enhance Body Composition Analysis in Clinical Routine.

The quality-initiative analysis of weekly duplicate PEAPOD® body composition measurements was conducted from clinical practice (January to September 2021) on preterm and term infants without respiratory support. Statistical analysis, including regression analysis, Bland-Altman plots and cv-root-mean-square tests, was performed. A total of 188 duplicate (376 individual) measurements were collected from 119 infants (88 preterm, 31 term). The median absolute difference between duplicates was 31.5 g for fat-free mass (FFM). Linear correlation analysis showed R2 = 0.97 for FFM. The absolute differences in FFM and fat mass did not significantly correlate with increasing age. The %FFM differed (p = 0.02) across body weight groups of 1 kg < BW ≤ 2 kg (1.8%; IQR: 0.8, 3.6) and BW > 3 kg (0.9%; IQR: 0.3, 2.1). The median absolute differences were 1 g (IQR: 0.4, 3.1) for body weight and 5.6 mL (IQR: 2.1, 11.8) for body volume. Body volume estimation is charged with a constant absolute error, which is the main factor for differences between repeated body composition assessments. This error becomes more prominent in infants with lower body weights. Nevertheless, reproducibility of weekly PEAPOD testing is sufficient to monitor body compartment changes, offering a foundation for nutritional decisions in both preterm and term infants.