Search Results (64)

Cervical spinal cord injury directly impacts the phrenic motor neuron pool, resulting in impaired ventilation and diaphragm muscle dysfunction. Previously, we demonstrated that hyperbaric oxygen (HBO) therapy, delivered during the acute phase following SCI, can attenuate diaphragm dysfunction. However, despite the demonstrated efficacy of HBO to improve muscle function, the molecular signaling pathways regulating this effect remain unclear. These experiments test the hypothesis that the protective effects of HBO therapy are associated with upregulation of the endogenous antioxidants SOD1, SOD2 and GPX1. Adult male Sprague-Dawley rats underwent a lateral spinal contusion injury at C4 followed by 10 consecutive days of HBO (3 ATA, 100% O₂, 1 h/day). Room air-treated spinal intact and injured rats were placed in a non-pressurized chamber for equal durations. To prevent the HBO-induced increase in antioxidant expression, antisense oligonucleotides directed towards each gene of interest were administered by intraperitoneal injection daily immediately following completion of HBO exposure (10 mg/kg/day). Saline was used as both the vehicle and placebo. Our results reveal that prevention of the HBO-induced upregulation of SOD1, SOD2 and GPX1 reduces diaphragm-specific force production compared to the control, injured HBO-treated rats. This effect occurred concomitantly with increased gene expression of the inflammatory cytokines IL-6, IL-1β and TNF-α and altered redox balance in the diaphragm. Thus, these data provide evidence that the HBO-induced increase in SOD1, SOD2 and GPX1 antioxidant expression contributes, at least in part, to the therapeutic effect of HBO to preserve diaphragm function following cervical spinal cord injury. Full article

Background/Objectives: Spinal cord injury (SCI) frequently leads to impaired respiratory function and increased pneumonia risk due to reduced respiratory muscle strength, altered thoracic compliance, autonomic dysregulation, and diaphragm displacement. This guideline aims to ensure appropriate, high-quality, and quality-assured care for individuals requiring respiratory support. Methods: This work represents a consensus-based S2k guideline developed by the “BeAtmung” working group of the German-speaking Medical Society for Paraplegiology (DMGP), in collaboration with experts from Germany and Switzerland, and endorsed by eight professional societies. Development followed the German Association of the Scientific Medical Societies (AWMF) guidance manual. Topics were defined in editorial meetings, supported by targeted literature searches and existing guidelines. Drafts were revised regularly with written feedback and final approval was granted after a consensus conference on 18 January 2022. Results: The guideline includes 11 specific recommendations addressing ventilation, monitoring, care structures, and discharge planning. Recommendations were graded using a three-level scheme (“need,” “should,” and “can be considered”) and consensus strength was classified as strong (>95%), consensus (>75–95%), majority (>50–75%), or no consensus (<50%). These recommendations support clinical decision-making and promote standardised, high-quality respiratory care for people with SCI. Conclusions: This guideline provides consensus-based recommendations for the comprehensive respiratory management of individuals with acute and chronic SCI, integrating diagnostic, therapeutic, and long-term care strategies to support high-quality, coordinated care across settings and healthcare systems. Full article

Background: Weaning from mechanical ventilation remains a complex and failure-prone process, with extubation failure rates reaching up to 30%. Conventional indices inadequately capture the multifactorial physiology underlying weaning failure. This study aimed to evaluate whether a multimodal ultrasound approach could improve the identification of mechanisms and prediction of extubation outcomes. Methods: In this prospective pilot observational study, adult mechanically ventilated patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) undergoing spontaneous breathing trials (SBT) were included. Multimodal ultrasound assessment—including transthoracic echocardiography (TTE), lung ultrasound (LUS), diaphragmatic ultrasound (DUS), and venous excess ultrasound (VExUS)—was performed at two predefined time points. Conventional respiratory mechanics parameters were recorded concurrently. The primary outcome was a composite of SBT failure (permanent weaning failure) or reintubation within 48 h. Results: A total of 27 patients were included, of whom 8 (29.6%) experienced extubation failure (5 permanent SBT failure, 3 post-extubation reintubation). Respiratory system compliance showed consistent associations with extubation failure across both ROC and regression analyses (AUC 0.806, 95% CI 0.611–1.000; cutoff ≤ 45 mL/cmH₂O; sensitivity 88%; specificity 74%; NPV 93%). Diaphragm excursion was significantly lower in the failure group (p = 0.042) and showed useful predictive performance (AUC 0.750, 95% CI 0.565–0.935; cutoff ≤ 24 mm; sensitivity 100%; specificity 58%; NPV 100%). Lung ultrasound, VExUS, and echocardiographic parameters did not demonstrate significant predictive value. Given the limited number of outcome events (n = 8) and events-per-variable ratio of 4.0 (EPV = 4.0), all multivariable findings are hypothesis-generating. Conclusions: In this prospective pilot study, respiratory system compliance and diaphragm excursion were associated with extubation failure in patients with preserved left ventricular function, while echocardiographic indices, LUS, and VExUS grading did not demonstrate significant predictive value. These hypothesis-generating findings suggest that impaired diaphragmatic function and reduced compliance may be more closely associated with weaning failure than cardiopulmonary congestion parameters. However, given the small sample size, low EPV, and single-centre design, all findings require validation in larger multicentre studies including patients with impaired systolic function. Full article

Background: Systemic sclerosis (SSc) is an autoimmune disease with interstitial lung disease (ILD) representing the leading cause of mortality. Diaphragmatic muscle impairment, which may contribute to respiratory dysfunction, is underexplored in SSc. Objective: This study aimed to assess diaphragmatic thickness using HRCT in patients with SSc-ILD and to investigate whether this parameter correlates with disease severity and clinical outcomes. Methods: We conducted a multicentric retrospective observational study that included 161 participants: 69 with SSc-ILD and 92 matched controls without pulmonary disease. Preliminary findings from this cohort were previously communicated as a conference abstract at EULAR 2024. Diaphragmatic thickness was measured on axial and coronal CT images at the celiac axis level by two independent radiologists. Clinical and functional parameters were collected, including forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), echocardiographic findings, and 6 min walking test performance. Results: The left hemidiaphragm was significantly thinner in patients with SSc-ILD compared with controls (2.98 ± 1.04 mm vs. 3.44 ± 0.97 mm; p = 0.004), while the right hemidiaphragm showed a non-significant trend toward reduction (3.21 ± 1.09 mm vs. 3.52 ± 1.05 mm; p = 0.072). Thinning of the right hemidiaphragm correlated significantly with lower FVC (p < 0.05). ROC analysis identified an optimal left diaphragm cut-off of ≤3.115 mm (AUC = 0.635, 95% CI: 0.556–0.709, sensitivity = 66.7%, specificity = 60.9%). No associations were found with the autoantibody profile, disease duration, or treatment. Interobserver reliability was excellent (Bland–Altman mean difference −0.002 mm, p = 0.95). Conclusions: HRCT-measured left hemidiaphragm thickness is significantly reduced in patients with SSc-ILD compared with controls, and right hemidiaphragm thickness correlates with impaired lung function. Although its discriminative performance is modest (AUC 0.635), this parameter may serve as a supplementary zero-burden addition to routine HRCT evaluation alongside pulmonary function tests. The retrospective cross-sectional design precludes conclusions about causality or prognosis; prospective studies incorporating concurrent functional diaphragm assessment are warranted. Full article

Background/Objectives: Dysfunctional breathing interacts with common impairments in patients with non-specific chronic neck pain. This study aimed to assess the effect of combining manual therapy with breathing re-education. Methods: A randomized controlled trial with concealed allocation and intention-to-treat analysis, including ninety patients with non-specific chronic neck pain, was employed. Participants were allocated to undertake 10 sessions of either cervical spine and diaphragmatic MT (specifically, Mulligan concept techniques and diaphragmatic doming/release) combined with breathing re-education (experimental group 1, EG1) or cervical spine MT alongside sham diaphragmatic MT (experimental group 2, EG2) or conventional physiotherapy (control group—CG). Interventions lasted 1 month. Primary outcomes were the pain intensity assessed on a 0-to-10 numeric rating scale and the Neck Disability Index percentage. Data were collected at baseline, 1 month, and 4 months post randomization. Results: Pain intensity improved more in the EG1 compared to the CG (mean difference −2.15, 95% CI −2.50 to −1.79) and to a lesser extent relative to the EG2 (mean difference −0.42, 95% CI −0.78 to −0.07) at 1 month. Neck disability equally improved in the EG1 (mean difference −14.72, 95% CI −17.55 to −11.89) and the EG2 (mean difference −13.06, 95% CI −15.93 to −10.19) compared to the CG at 1 month. All significant differences for pain and disability noted at one month remained significant at 4 months. EG1 significantly improved in all respiratory-related secondary outcomes compared to EG2 and the CG, both at 1 and 4 months. Conclusions: Combining diaphragm manual therapy with breathing re-education led to superior improvements in pain and dysfunctional breathing-related outcomes. Trial Registration: NCT05229393. Full article

Background: Skeletal myopathy is a common complication of heart failure (HF), contributing to exercise intolerance and impaired physical function. This study explores the relationship between practical skeletal muscle measurements and key biomarkers in HF patients undergoing cardiac rehabilitation. Methods: Sixty-nine stable chronic HF patients participated in a 3-month phase II cardiac rehabilitation program. Physical examinations, including the 6-Minute Walk Test (6MWT), chest expansion, inspiratory diaphragm thickness, and handgrip strength, were conducted. Blood samples were analyzed for myostatin and miRNA-133a. Data were analyzed using paired t-tests, Wilcoxon tests, Chi-square/Fisher’s exact tests, and correlation analyses. Results: Significant improvements were observed in 6MWT distance, chest expansion, and inspiratory diaphragm thickness following rehabilitation (p < 0.001). Handgrip strength also significantly improved post-rehabilitation. Myostatin and miRNA-133a levels did not change significantly post-rehabilitation. However, exploratory cross-sectional analysis revealed trends suggesting that lower myostatin levels correlated with better endurance (p = 0.036), while higher myostatin levels were also observed in patients with better 6MWT performance (p = 0.014). Higher miRNA-133a levels were potentially associated with better overall fitness, including endurance and respiratory function (p < 0.05). Conclusions: Readily performed physical assessments can serve as clinical indicators of the systemic impact of HF on skeletal muscle. The study highlights the importance of evaluating extracardiac function in HF patients, demonstrating potential exploratory associations between physical function and key biomarkers. Full article

Diaphragm dysfunction that leads to respiratory failure is a significant clinical consequence of sepsis-induced critical illness. Diaphragm muscle weakness contributes to morbidity and mortality in these individuals in part due to impaired mitochondrial function. Restoring normal mitochondrial biogenesis is associated with improved survival and physical function. Therefore, identifying reliable biomarkers of mitochondrial dysfunction in diaphragm muscle will allow for more focused and targeted interventions designed to improve the morbidity of critically ill patients. We used a rodent cecal-ligation and puncture (CLP) model to mimic a moderate grade of sepsis. The diaphragm muscle was harvested from adult mice 48 h following CLP (n = 6) or a sham CLP procedure (n = 6). Our primary finding was that moderate grade CLP increases expression of mitochondria-associated microRNA in the diaphragm. Correspondingly, genes associated with mitochondrial biogenesis decreased. Our study provides evidence for sepsis-mediated dysregulation of mitochondrial homeostasis. This may play a role in diaphragm muscle dysfunction, respiratory failure, and difficult weaning from mechanical ventilation in sepsis-induced critical illness. Full article

Background/Objectives: Sepsis-induced systemic inflammation often leads to diaphragmatic dysfunction and muscle atrophy, contributing to impaired respiratory function. Phosphoglycerate mutase 2 (PGAM2), a key enzyme in glycolysis, plays a significant role in muscle energy metabolism but has not been previously linked to sepsis-induced diaphragmatic dysfunction. This study aims to investigate the role of PGAM2 in sepsis-induced diaphragmatic atrophy and its underlying mechanisms. Methods: A murine sepsis model was established using cecal ligation and puncture (CLP) in C57BL/6 mice. Body and diaphragm weights, along with muscle fiber cross-sectional areas, were measured. PGAM2 expression was evaluated using immunofluorescence, Western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR). In vitro, C₂C₁₂ myotubes were treated with tumor necrosis factor alpha (TNF-α), and PGAM2 expression was manipulated via small interfering RNA (siRNA) knockdown and plasmid overexpression. Atrophy markers (MuRF1, MAFbx/atrogin-1) and JAK2/STAT3 pathway activation were assessed. Results: CLP induced significant diaphragmatic atrophy, as reflected by an approximately 38% reduction in diaphragm weight and an approximately 37% decrease in muscle fiber cross-sectional area compared with the sham group. In contrast, PGAM2 protein expression was increased by approximately 105% in septic diaphragms. PGAM2 expression was also significantly elevated in TNF-α-treated myotubes. PGAM2 knockdown resulted in reduced MuRF1 and MAFbx expression, attenuating myotube atrophy, while PGAM2 overexpression exacerbated atrophy. Moreover, PGAM2 knockdown suppressed activation of the JAK2/STAT3 signaling pathway. Conclusions: These findings demonstrate that PGAM2 contributes to sepsis-induced diaphragmatic atrophy through the activation of the JAK2/STAT3 signaling pathway. PGAM2 may therefore serve as a potential therapeutic target for sepsis-associated diaphragmatic dysfunction. Full article

Background: Smoking adversely affects pulmonary function and systemic health; however, its impact on diaphragm muscle morphology and its relationship with functional capacity and psychosocial outcomes in individuals without clinically diagnosed respiratory disease remain unclear. This study aimed to evaluate diaphragm muscle thickness in smokers and to investigate its associations with pulmonary function, functional capacity, sleep quality, and depression. Methods: This cross-sectional observational study included 20 smokers and 20 age-matched never-smokers. Pulmonary function was assessed using spirometry. Functional capacity was evaluated with the 6-Minute Walk Test (6 MWT) and the 30 s sit-to-stand test (30 s STST). Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Beck Depression Inventory (BDI). Inspiratory and expiratory diaphragm muscle thicknesses were measured by ultrasonography. Between-group comparisons and correlation analyses were performed. Results: Smokers exhibited significant impairments in all assessed parameters except expiratory diaphragm thickness compared with controls (p < 0.05). Large to very large effect sizes were observed for FEV₁, FEF_25–75%, functional capacity, and inspiratory diaphragm thickness. Inspiratory diaphragm thickness showed moderate to strong positive correlations with pulmonary function parameters and a very strong positive correlation with functional capacity, while strong negative correlations were observed with sleep quality and depression (p < 0.05). Smoking duration was strongly associated with poorer functional and psychosocial outcomes. Conclusions: Smoking is associated with early and multidimensional impairments in diaphragm muscle morphology, pulmonary function, functional capacity, and psychosocial status, even in individuals without overt respiratory disease. Reduced inspiratory diaphragm thickness may represent an early and clinically meaningful marker of smoking-related respiratory muscle dysfunction. Full article

In acute respiratory distress syndrome (ARDS), spontaneous breathing is often encouraged to preserve lung function, yet excessive patient-generated inspiratory effort can paradoxically worsen injury, a phenomenon termed patient self-inflicted lung injury (P-SILI). In mechanically heterogeneous lungs, uncontrolled effort amplifies regional stress, strain, and mechanical power, driving alveolar overdistension, cyclic recruitment–derecruitment, pendelluft, and inflammation. Cardiovascular consequences include elevated right ventricular afterload, impaired left ventricular filling, and exacerbation of pulmonary edema. While moderate spontaneous breathing may improve aeration in mild injury, evidence shows that vigorous effort in severe ARDS accelerates histological damage and regional lung stress. Early bedside assessment of respiratory drive and inspiratory effort identifies patients at highest risk, enabling targeted interventions. Strategies to preserve protective spontaneous breathing while limiting injurious effort include individualized positive end-expiratory pressure, titrated sedation, prone positioning, and short-term neuromuscular blockade. By integrating continuous physiological monitoring with personalized ventilatory management, clinicians can mitigate P-SILI, protect the diaphragm, and optimize outcomes. Future studies are needed to test physiology-guided interventions and establish evidence-based approaches to safely harness the benefits of spontaneous breathing in ARDS. Full article

Background: Age-related declines in respiratory muscle strength and ventilatory efficiency can impair functional capacity and metabolic health in older adults. Inspiratory muscle training (IMT) has been proposed as a practical intervention to counteract these changes, yet its systemic effects remain unclear. This study aimed to examine the effects of short-term IMT on functional capacity, diaphragm thickness, and liver tissue characteristics in healthy elderly men. Methods: Thirty community-dwelling men aged 60–80 years were randomly assigned to an IMT or control group. The IMT group performed four weeks of breathing exercises using a POWERbreathe^® device at 40% of maximal inspiratory pressure, with a weekly 10% increase in pressure. Pre- and post-intervention assessments included the six-minute walk test (6MWT), diaphragm thickness and liver density via computed tomography, and quality of life (QoL; SF-12). Results: Four weeks of inspiratory muscle training significantly improved diaphragm thickness (11.7%), fatty liver density (FLD) (+16.7%), and six-minute walk performance (+5.3%), with large time × group effects favoring the IMT group. While the physical quality of life showed modest, comparable improvements, mental health outcomes demonstrated a moderate, time-dependent improvement without a significant group-by-time interaction. Conclusions: Short-term IMT improved diaphragmatic function and functional capacity in older men and was associated with favorable changes in a liver-related biomarker; however, given that only a single liver-related metric was assessed, these findings should not be interpreted as evidence of overall improvements in liver health. Full article

Background and Clinical Significanc: Congenital duodenal diaphragm (CDD) is a rare congenital condition causing partial or complete obstruction of the duodenum, most frequently located in the second part of the duodenum. It is a rare but important cause of intestinal obstruction in infants and young children. Clinically, it often presents with persistent vomiting and failure to thrive. Diagnosis can be made through abdominal X-ray showing the characteristic “double bubble” sign, upper gastrointestinal (GI) series, or gastroscopy. Case Presentation: A 17-month-old female infant with known psychomotor retardation was admitted for evaluation of inadequate weight gain and intermittent postprandial vomiting, both present since birth. Laboratory investigations, including metabolic and electrolyte panels, were within normal limits. Given the persistent clinical symptoms, an upper gastrointestinal series was performed to assess for possible anatomical abnormalities. Imaging revealed a significant delay in the passage of contrast into the second portion of the duodenum, with marked prestenotic dilatation. Subsequent gastroscopy identified a duodenal diaphragm nearly occluding the duodenal lumen at the same site, impeding the passage of the endoscope. Associated findings included gastritis and the presence of food debris in the stomach and proximal duodenum, indicating impaired gastric emptying. The patient underwent successful surgical management via duodenotomy with resection of the septum. Postoperative recovery was uneventful. Conclusions: In infants or young children with persistent postprandial vomiting and inadequate weight gain, anatomical causes such as duodenal diaphragm/web should be considered in the differential diagnosis. Once identified, treatment should be initiated promptly, either endoscopically or surgically, depending on the severity and anatomical characteristics of the obstruction. Full article

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are pathologies that impact mortality and morbidity worldwide. These chronic diseases have multiple causes, and they share some common clinical symptoms, such as diaphragm dysfunction (DD) and cognitive decline (CD), which, in turn, increase the mortality and morbidity rates in patients with COPD and CHF. One of the causes of CD is impaired glymphatic system function, with an accumulation of proteins and metabolites in the central nervous system. The glymphatic system is a structure that has not yet been widely considered by researchers and clinicians. Three key factors stimulate the ongoing physiological function of the glymphatic system: autonomic balance, heart rate, and, most importantly, the diaphragm. All these factors are altered in patients with COPD and CHF. This article reviews the relationship between the importance of the diaphragm, the glymphatic system, and CD, focusing on inspiratory rehabilitation training (IMT). Based on the data reported in this narrative review, we can strongly speculate that a consistent regimen of IMT in patients can improve cognitive status, reducing the cascade of symptoms that follow the diagnosis of CD. Further research is needed to understand whether targeting the glymphatic system with IMT is an effective option for helping patients delay the onset of CD. Full article

Wavefront aberrations caused by thermal flows or arising from the quality of optical components can significantly impair wireless communication links. Such aberrations may result in an increased error rate in the received signal, leading to data loss in laser communication applications. In this study, we explored a newly developed combined stochastic gradient descent optimization algorithm aimed at compensating for optical distortions. The algorithm we developed exhibits linear time and space complexity and demonstrates low sensitivity to variations in input parameters. Furthermore, its implementation is relatively straightforward and does not necessitate an in-depth understanding of the underlying system, in contrast to the Stochastic Parallel Gradient Descent (SPGD) method. In addition, a developed switch-mode approach allows us to use a stochastic component of the algorithm as a rapid, rough-tuning mechanism, while the gradient descent component is used as a slower, more precise fine-tuning method. This dual-mode operation proves particularly advantageous in scenarios where there are no rapid dynamic wavefront distortions. The results demonstrated that the proposed algorithm significantly enhanced the total collected power of the beam passing through the 10 μm diaphragm that simulated a 10 μm fiber core, increasing it from 0.33 mW to 2.3 mW. Furthermore, the residual root mean square (RMS) aberration was reduced from 0.63 μm to 0.12 μm, which suggests a potential improvement in coupling efficiency from 0.1 to 0.6. Full article

Silicon-based MEMS devices are essential in extreme radiation environments but suffer progressive reliability degradation from irradiation-induced defects. Here, the generation, aggregation, and clustering of defects in single-crystal silicon were systematically investigated through molecular dynamics (MD) simulations via employing a hybrid Tersoff–ZBL potential that was validated by nanoindentation and transmission electron microscopy. The influences of the primary knock-on atom energy, temperature, and pre-strain state on defect evolution were quantified in detail. Frenkel defects were found to cause a linear reduction in the Young’s modulus and a nonlinear decline in thermal conductivity via enhanced phonon scattering. To link atomic-scale damage with device-level performance, MD-predicted modulus degradation was incorporated into finite element (FE) models of a sensing diaphragm. The FE analysis revealed that modulus reductions result in nonlinear increases in deflection and stress concentration, potentially impairing sensing accuracy. This integrated MD–FE framework establishes a robust, physics-based approach for predicting and mitigating irradiation damage in silicon-based MEMS operating in extreme environments. Full article