Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.

Diaphragm thickness and mobility elicited by two different modalities of inspiratory muscle loading in heart failure participants: A randomized crossover study.

OBJECTIVES: To analyze diaphragmatic thickness, at end-inspiration and end-expiration, diaphragmatic thickening index and mobility via US under two different modalities of inspiratory muscle loading, in two different modalities of inspiratory muscle loading and different load intensities at full-vital capacity maneuvers and the relationship between diaphragmatic thickness with pulmonary function tests in participants with HF. METHODS: This randomized crossover trial, enrolled with 17 HF subjects, evaluated diaphragm thickness (Tdi, mm), fractional thickness (TFdi, %), and mobility (mm) US during low and high intensities (30% and 60% of maximal inspiratory pressure-MIP) with two modalities of inspiratory muscle loading mechanical threshold loading (MTL) and tapered flow-resistive loading (TFRL). RESULTS: Both MTL and TFRL produced a increase in Tdi, but only with high intensity loading compared to baseline-2.21 (0.26) vs. 2.68 (0.33) and 2.73 (0.44) mm; p = .01. TFdi was greater than baseline under all conditions, except during low intensity of TFRL. Diaphragm mobility was greater than baseline under all conditions, and high intensity of TFRL elicited greater mobility compared to all other conditions. Additionally, baseline Tdi was moderately correlated with pulmonary function tests. CONCLUSIONS: MTL and TFRL modalities elicit similar increases in diaphragm thickness at loads, but only during high intensity loading it was greater than baseline. Diaphragm mobility was significantly greater than baseline under both loads and devices, and at high intensity compared to low intensity, although TFRL produced greater mobility compared to modalities of inspiratory muscle loading. There is an association between diaphragm thickness and pulmonary function tests.

Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation.

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.

Effect of adding diaphragmatic breathing to corrective exercises on kyphotic angle and diaphragmatic excursion in postmenopausal kyphotic women: A randomized controlled trial.

BACKGROUND: Age-related thoracic kyphosis can impair posture, diaphragmatic excursion, respiratory function, and overall quality of life (QoL). PURPOSE: This randomized controlled trial aimed to compare the effects of corrective exercises alone versus combined with diaphragmatic breathing exercises on thoracic kyphosis, diaphragmatic excursion, thoracic pain, and QoL in postmenopausal kyphotic women. METHODS: Forty postmenopausal women diagnosed with thoracic kyphosis were randomly divided into two groups. Group A received corrective exercises for 12 weeks (n = 20), while Group B received both diaphragmatic breathing exercises and corrective exercises for the same duration (n = 20). Primary outcome measures were thoracic kyphosis angle and diaphragmatic excursion, while secondary outcome measures were thoracic pain and QoL. Both groups were assessed pre- and post-intervention using a flexible curve ruler for the thoracic kyphosis angle, ultrasonography for the diaphragmatic excursion, the visual analog scale for thoracic pain, and the Arabic version of the QoL Questionnaire of the European Foundation for Osteoporosis for QoL. RESULTS: Both groups showed significant within-group improvements in all measures post-intervention (p < 0.05). Between-group comparisons post-intervention revealed no significant differences (p > 0.05) except for diaphragmatic excursion, where Group B showed significantly greater improvement (p < 0.05). CONCLUSIONS: A 12-week program of corrective exercises alone or combined with diaphragmatic breathing exercises significantly improved kyphosis angle, thoracic pain, and QoL in postmenopausal kyphotic women. The addition of diaphragmatic breathing exercises provided further benefits by increasing diaphragmatic excursion to a greater degree compared with corrective exercises alone.

Comparative Effect of High-Frequency Nasal Cannula and Noninvasive Ventilation on the Work of Breathing and Postoperative Pulmonary Complication after Pediatric Congenital Cardiac Surgery: A Prospective Randomized Controlled Trial.

BACKGROUND: Various forms of commonly used noninvasive respiratory support strategies have considerable effect on diaphragmatic contractile function which can be evaluated using sonographic diaphragm activity parameters. OBJECTIVE: To compare the magnitude of respiratory workload decreased as assessed by thickening fraction of the diaphragm and longitudinal diaphragmatic strain while using high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) modes [nasal intermittent positive pressure ventilation (NIPPV) and bilevel positive airway pressure (BiPAP)] in pediatric patients after cardiothoracic surgery. METHODOLOGY: This prospective randomized controlled trial was performed at a tertiary care surgical intensive care unit in postcardiac surgery patients aged between 1 and 48 months, who were randomly allocated into three groups: 1) HFNC (with flows at 2 L/kg/min), 2) NIPPV via RAMS cannula in PSV mode (pressure support 8 cmH2O, PEEP 5 cmH2O), and 3) BiPAP in nCPAP mode (CPAP of 5 cmH2O). Measurements were recorded at baseline after extubation (R0) and subsequently every 12 hourly (R1, R2, R3, R4, R5) at 12, 24, 36, 48, and 60 hours respectively until therapy was discontinued. RESULTS: Sixty patients were included, with 20 patients each in the NIPPV group, HFNC group, and BiPAP group. Longitudinal strain at crura of diaphragm was lower in the BiPAP group as compared to HFNC group at R2-R4 [R2 (-4.27± -2.73 vs - 8.40± -6.40, P = 0.031), R3 (-5.32± -2.28 vs -8.44± -5.6, P = 0.015), and R4 (-3.8± -3.42 vs -12.4± -7.12, P = 0.040)]. PFR was higher in HFNC than NIPPV group at baseline and R1-R3[R0 (323 ± 114 vs 264 ± 80, P = 0.008), R1 (311 ± 114 vs 233 ± 66, P = 0.022), R2 (328 ± 116 vs 237 ± 4, P = 0.002), R3 (346 ± 112 vs 238 ± 54, P = 0.001)]. DTF and clinical parameters of increased work of breathing remain comparable between three groups. The rate of reintubation (within 48 hours of extubation or at ICU discharge) was 0.06% (1 in NIPPV, 1 in BiPAP, 2 in HFNC) and remain comparable between groups (P = 1.0). CONCLUSION: BiPAP may provide better decrease in work of breathing compared to HFNC as reflected by lower crural diaphragmatic strain pattern. HFNC may provide better oxygenation compared to NIPPV group, as reflected by higher PFR ratio. Failure rate and safety profile are similar among different methods used.

[Quality of life in patients with postoperative unilateral diaphragm relaxation]. / Kachestvo zhizni patsientov s odnostoronnei relaksatsiei diafragmy posle khirurgicheskogo lecheniya.

OBJECTIVE: To evaluate the quality of life before and after video-assisted thoracoscopic plication of relaxed dome of diaphragm. MATERIAL AND METHODS: The study included 17 patients operated on for unilateral relaxation of diaphragm. We analyzed quality of life in preoperative period, 1, 3, 6 and 12 months after surgery using the SF-36 and EuroQ-5D-5L questionnaires. To assess the impact of abnormality on respiratory function, we estimated diaphragm position, spirometry data and SGRQ scores. RESULTS: FVC increased by 16.5% after 1 month, 19.5% after 6 months and 20.1% after 12 months. In addition, FEV1 significantly increased (by 12.6% after 1 month, 10.1% after 6 months and 12.7% after 12 months). Mean values of diaphragm elevation in postoperative period decreased by 25.5-25.6%. According to the SF-36 and EuroQ-5D-5L questionnaires, physical and psychological health components significantly increased within a month after surgical treatment. According to the SGRQ questionnaire, influence of disease on overall status decreased a month after surgery as evidences by lower total score (p<0.05). CONCLUSION: Objective and survey data revealed significant improvement in quality of life after surgery. A trend towards higher quality of life was demonstrated by all questionnaires in a month after surgery.

The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility.

BACKGROUNDS: Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. METHODS: We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. RESULTS: Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively). CONCLUSIONS: EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

Ampakines increase diaphragm activation following mid-cervical contusion injury in rats.

Ampakines are positive allosteric modulators of AMPA receptors. We hypothesized that low-dose ampakine treatment increases diaphragm electromyogram (EMG) activity after mid-cervical contusion injury in rats. Adult male and female Sprague Dawley rats were implanted with in-dwelling bilateral diaphragm EMG electrodes. Rats received a 150 kDyn C4 unilateral contusion (C4Ct). At 4- and 14-days following C4Ct, rats were given an intravenous bolus of ampakine CX717 (5 mg/kg, n = 10) or vehicle (2-hydroxypropyl-beta-cyclodextrin; HPCD; n = 10). Diaphragm EMG was recorded while breathing was assessed using whole-body plethysmography. At 4-days, ampakine administration caused an immediate and sustained increase in bilateral peak inspiratory diaphragm EMG bursting and ventilation. The vehicle had no impact on EMG bursting. CX717 treated rats were able to increase EMG activity during a respiratory challenge to a greater extent vs. vehicle treated. Rats showed a considerable degree of spontaneous recovery of EMG bursting by 14 days, and the impact of CX717 delivery was blunted as compared to 4-days. Direct recordings from the phrenic nerve at 21-24 days following C4Ct confirmed that ampakines stimulated bilateral phrenic neural output in injured rats. We conclude that low-dose intravenous treatment with a low-impact ampakine can enhance diaphragm activation shortly following mid-cervical contusion injury, when deficits in diaphragm activation are prominent.

Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration.

BACKGROUND: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. MATERIAL AND METHODS: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. RESULTS: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. CONCLUSIONS: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.

Aminophylline Improves Ventilator-Induced Diaphragmatic Dysfunction by Targeting IGF-1-FOXO1-MURF1 Pathway.

BACKGROUND: The usage of life-saving mechanical ventilation (MV) could cause ventilator-induced diaphragmatic dysfunction (VIDD), increasing both mortality and morbidity. Aminophylline (AP) has the potential to enhance the contractility of animal skeletal muscle fibers and improve the activity of human respiratory muscles, and the insulin-like growth factor-1 (IGF-1)- forkhead box protein O1 (FOXO1)-muscle RING finger-1 (MURF1) pathway plays a crucial role in skeletal muscle dysfunction. This study aimed to investigate the impact of AP on VIDD and to elucidate the role of the IGF-1-FOXO1-MURF1 pathway as an underlying mechanism. METHODS: Rat models of VIDD were established through MV treatment. IGF-1 lentiviral (LV) interference (LV-IGF-1-shRNA; controlled by lentiviral negative control LV-NC) was employed to inhibit IGF-1 expression and thereby block the IGF-1-FOXO1-MURF1 pathway. Protein and mRNA levels of IGF-1, FOXO1, and MURF1 were assessed using western blot and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), respectively. Diaphragm contractility and morphometry were examined through measurement of compound muscle action potentials (CMAPs) and hematoxylin and eosin (H&E) staining. Oxidative stress was evaluated by levels of hydrogen peroxide (H2O2), superoxide dismutase (SOD), antioxidant glutathione (GSH), and carbonylated protein. Mitochondrial stability was assessed by measuring the mitochondrial membrane potential (MMP), and mitochondrial fission and mitophagy were examined through protein levels of dynamin-related protein 1 (DRP1), mitofusin 2 protein (MFN2), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), and Parkin (western blot). Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate (UTP) nick-end labeling (TUNEL) assay and levels of Bax, B-cell lymphoma 2 (BCL-2), and Caspase-3. Levels of Atrogin-1, neuronally expressed developmentally downregulated 4 (NEDD4), and muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1) mRNA, as well as ubiquitinated protein, were utilized to determine protein degradation. Furthermore, the SUnSET (surface sensing of translation) method was employed to determine rates of protein synthesis. RESULTS: MV treatment upregulated IGF-1 while downregulated FOXO1 and MURF1 (p < 0.05). AP administration reversed IGF-1, FOXO1 and MURF1 (p < 0.05), which was suppressed again by IGF-1 inhibition (p < 0.05), demonstrating the blockage of the IGF-1-FOXO1-MURF1 pathway. MV treatment caused decreased CMAP and cross-sectional areas of diaphragm muscle fibers, and increased time course of CMAP (p < 0.05). Additionally, oxidative stress, cell apoptosis, and protein degradation were increased and mitochondrial stability was decreased by MV treatment (p < 0.05). Conversely, AP administration reversed all these changes induced by MV, but this reversal was disrupted by the blockage of the IGF-1-FOXO1-MURF1 pathway. CONCLUSIONS: In this study, MV treatment induced symptoms of VIDD in rats, which were all effectively reversed by AP regulating the IGF-1-FOXO1-MURF1 pathway, demonstrating the potential of AP in ameliorating VIDD.

Obesity-related reduced spirometry and altered breathing pattern are associated with mechanical disadvantage of the diaphragm.

The aim of this study was to characterize the breathing patterns of individuals with obesity during routine activities such as sitting and standing, and to identify potential contributors to alterations in these patterns. Measurements performed in 20 male subjects with obesity (BMI, 31.8±1.5 kg/m2) and 20 controls (BMI, 23.5±1.4 kg/m2) included anthropometric parameters, breathing-patterns in sitting and standing positions, spirometry, maximal respiratory pressures, and diaphragm B-mode ultrasonography. Individuals with obesity exhibited lower tidal volume and increased respiratory rate to maintain a similar minute-ventilation (p<0.05). Subjects with obesity demonstrated impaired spirometry and respiratory muscle strength, with inspiratory functions being notably compromised (p<0.05). Individuals with obesity had a greater diaphragm thickness at end inspiration but lower thickening-fraction at end quiet and forced breathings and reduced diaphragmatic displacement and excursion during maximal breaths (p<0.05). BMI was negatively associated with all respiratory function markers (p<0.05). Individuals with obesity exhibit a higher respiratory rate but lower tidal volume, likely to accommodate decreased compliance and excess thoracic and abdominal fat, further hindering inspiratory function. Moreover, increased adiposity is associated with a thicker but weaker diaphragm, primarily due to the diaphragm's mechanical disadvantage rather than its intrinsic inability to generate force.

Inter-rater reliability of the dynamic neuromuscular stabilization diaphragm tests among individuals with non-specific low back pain and neck pain.

BACKGROUND: The Dynamic Neuromuscular Stabilization (DNS) diaphragm test and intra-abdominal pressure regulation test (IAPRT) are qualitative clinical tests that assess postural stability provided by the diaphragm. OBJECTIVE: Evaluate the inter-rater reliability of the diaphragm test and IAPRT between an experienced and novice DNS clinician among individuals with non-specific low back pain (LBP) and neck pain. METHODS: Forty-five participants with non-specific LBP and/or neck pain were assessed by an experienced and novice DNS physiotherapist in the diaphragm test and IAPRT, and scored on a visual analog scale (VAS) according to five different criteria. RESULTS: Moderate reliability was noted when assessing LBP and neck pain patients in the diaphragm test and IAPRT (p < 0.001). Moderate reliability also existed when assessing only LBP (p < 0.001) or neck pain (p = 0.002, p = 0.009) independently. Patients with lower pain (NPRS score of 5 or < ) demonstrated lower intra-class correlation coefficients, yet still moderate reliability in the diaphragm test (p = 0.004) and IAPRT (p = 0.001). Patients with higher pain (NPRS score of 6 or > ) demonstrated greater intra-class correlation coefficients, with the diaphragm test resulting in good reliability (p < 0.001). CONCLUSIONS: The diaphragm test and IAPRT demonstrate moderate reliability between an experienced and novice DNS clinician when evaluating LBP and neck pain patients, with a greater degree of reliability noted in patients suffering from higher reported pain.

Association between nutritional risk status and both diaphragmatic dysfunction and diaphragm atrophy in medical intensive care unit patients.

Introduction: Aim: critical illness often leads to malnutrition and diaphragmatic dysfunction (DD), common in intensive care units (ICU). Ultrasonography (US) is a potent tool for detecting DD. This study examines the connection between malnutrition risk and DD in ICU patients using ultrasonographic diaphragm measurements in medical ICU patients. Methods: we assessed nutritional risk using risk screening tools and mid-upper arm circumference measurements (MUAC). Diaphragm atrophy (DA) and DD were evaluated by measuring diaphragmatic excursion (DE), thickness, and thickening fraction (TF) by US. We then compared these diaphragmatic measurements in patients based on their nutritional risk scores. Results: of the fifty patients studied, 54 % to 78 % were at risk of malnutrition, 28 % exhibited diaphragm atrophy (DA), and 24 % showed DD upon ICU admission. Malnutrition risk diagnosed by all nutritional risk screening tools was significantly more frequent in patients with DD, while diagnosed by MUAC was considerably higher in patients with DA. A total of 16 patients (32 %) died during their ICU stay, with DD, DA, and malnutrition risks (as identified by the mNUTRIC Score) being more prevalent among non-survivors (p < 0.05). Malnutrition risk (as determined by the mNUTRIC Score) was an independent risk factor for DD [OR (95 % CI): 6.6 (1.3-34), p = 0.03]. Conclusion: malnutrition risk may be significantly associated with DD and DA in medical ICU patients upon ICU admission.

Introducción: Objetivo: las enfermedades graves a menudo conducen a desnutrición y disfunción diafragmática (DD), comunes en las unidades de cuidados intensivos (UCI). La ultrasonografía (US) es una herramienta poderosa para detectar la DD. Este estudio examina la conexión entre riesgo de desnutrición y DD en pacientes de UCI utilizando mediciones ultrasonográficas del diafragma. Métodos: evaluamos el riesgo nutricional utilizando herramientas de evaluación de riesgos y mediciones de la circunferencia del brazo en su punto medio superior (MUAC). La atrofia del diafragma (DA) y la DD se evaluaron midiendo la excursión diafragmática (DE), el grosor y la fracción de engrosamiento (TF) por ecografía. Luego, comparamos estas mediciones diafragmáticas en pacientes según sus puntuaciones de riesgo nutricional. Resultados: de los cincuenta pacientes estudiados, entre el 54 % y el 78 % estaban en riesgo de desnutrición, el 28 % presentaban atrofia del diafragma (DA) y el 24 % mostraban DD al ingreso en la UCI. El riesgo de desnutrición diagnosticado por todas las herramientas de evaluación del riesgo nutricional fue significativamente más frecuente en los pacientes con DD, mientras que el diagnosticado por el MUAC fue considerablemente mayor en los pacientes con DA. Un total de 16 pacientes (32 %) fallecieron durante su estancia en la UCI, siendo la DD, la DA y los riesgos de desnutrición (según lo identificado por la puntuación mNUTRIC) más prevalentes entre los no sobrevivientes (p < 0,05). El riesgo de desnutrición (según lo determinado por la puntuación mNUTRIC) fue un factor de riesgo independiente de la DD [OR (95 % CI): 6,6 (1,3-34), p = 0,03]. Conclusión: en este estudio se encontró una asociación significativa entre el riesgo de desnutrición y la disfunción diafragmática, así como con la atrofia diafragmática al ingreso en la UCI.

Ruxolitinib: A new hope for ventilator-induced diaphragm dysfunction.

AIM: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. METHODS: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. RESULTS: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two-fold P-STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post-translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P-STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. CONCLUSION: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator-induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD.

Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort.

BACKGROUND: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. METHODS: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea-hypopnea index ⩾ 15. RESULTS: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. CONCLUSION: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.

Mucopolysaccharidosis (MPS IIIA) mice have increased lung compliance and airway resistance, decreased diaphragm strength, and no change in alveolar structure.

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease.NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.

Ultrasonographic evaluation of diaphragm thickness and excursion: correlation with weaning success in trauma patients: prospective cohort study.

PURPOSE: Prolonged mechanical ventilation (MV) subjects multiple trauma patients to ventilator-induced diaphragmatic dysfunction. There is limited evidence on the predictive role of diaphragm ultrasound (DUS) for weaning success in multiple trauma patients. Therefore, we evaluated Ultrasound of the diaphragm as a valuable indicator of weaning outcomes, in trauma patients. MATERIAL AND METHODS: This prospective cohort study included 50 trauma patients from September 2018 to February 2019. DUS was performed twice: upon ICU admission and the first weaning attempt. The diagnostic accuracy of indexes was evaluated by ROC curves. RESULTS: The study included patients with a mean age of 35.4 ± 17.37, and 78% being male. The median injury severity score was 75 (42-75). The failure group exhibited significantly lower right diaphragmatic excursion (DE) compared to the success group (P = 0.006). In addition, the failure group experienced a significant decrease in both right and left DE from admission to the first attempt of weaning from MV (P < 0.001). Both groups showed a significant decrease in inspiratory and expiratory thickness on both sides during weaning from MV compared to the admission time (P < 0.001). The findings from the ROC analysis indicated that the Rapid shallow breathing index (RSBI) (Sensitivity = 91.67, Specificity = 100), respiratory rate (RR)/DE (Right: Sensitivity = 87.5, Specificity = 92.31), and RR/TF (Thickening Fraction) (Right: Sensitivity = 83.33, Specificity = 80.77) demonstrated high sensitivity and specificity in predicting weaning outcome. CONCLUSION: In the context of patients with multiple trauma, employing DUC and assessing diaphragmatic excursion, thickness, RR/DE index, RR/TF index, and RSBI can aid in determining successful ventilator weaning.

Diaphragmatic dysfunction is associated with postoperative pulmonary complications and phrenic nerve paresis in patients undergoing thoracic surgery.

PURPOSE: We aimed to quantify perioperative changes in diaphragmatic function and phrenic nerve conduction in patients undergoing routine thoracic surgery. METHODS: A prospective observational study was performed in patients undergoing esophageal resection or pulmonary lobectomy. Examinations were carried out the day prior to surgery, 3 days and 10-14 days after surgery. Endpoints for diaphragmatic function included ultrasonographic measurements of diaphragmatic excursion and thickening fraction. Endpoints for phrenic nerve conduction included baseline-to-peak amplitude, peak-to-peak amplitude, and transmission delay. Measurements were assessed on both the surgical side and the non-surgical side of the thorax. RESULTS: Forty patients were included in the study. Significant reductions in diaphragmatic excursion were seen on the surgical side of the thorax for all excursion measures (posterior part of the right hemidiaphragm, p < 0.001; hemidiaphragmatic top point, p < 0.001; change in intrathoracic area, p < 0.001). Significant changes were seen for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.041) on the surgical side. However, significant changes were also seen on the non-surgical side for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.022). A postoperative reduction in posterior diaphragmatic excursion of more than 50% was significantly associated with postoperative pulmonary complications (coefficient: 2.69 (95% CI [1.38, 4.01], p < 0.001). CONCLUSION: Thoracic surgery caused a significant unilateral reduction in diaphragmatic excursion on the surgical side of the thorax, which was accompanied by significant changes in phrenic nerve conduction. However, phrenic nerve conduction was also significantly affected on the non-surgical side to a lesser extent, which was not mirrored in diaphragmatic excursion. Our findings suggest that phrenic nerve paresis plays a role in postoperative diaphragmatic dysfunction, which may be a contributing factor in the pathogenesis of postoperative pulmonary complications. CLINICAL TRIALS REGISTRATION NUMBER: NCT04507594.