Chronic Neuromuscular Disease Research Articles

Management of Chronic Neuromuscular Respiratory Failure in the Intensive Care Unit.

In this seminar we describe the critical care management of patients with chronic neuromuscular diseases (cNMD). Determination of the acuity of the critical illness and trajectory of illness in the setting of cNMD is necessary to guide decision making. Systemic complications of critical illness, cardiac support needs, and peri-intubation considerations may be affected by underlying diagnosis. Mechanical ventilatory support, whether noninvasive or invasive, requires redefinition of the goals of ventilation on a patient-by-patient basis. Mode and approach to invasive ventilation and liberation to noninvasive ventilation versus tracheostomy have limited evidence, but potential clinical approaches are reviewed.

Diagnoses of muscular dystrophy in a veterans health system.

Early diagnosis of a chronic neuromuscular disease such as muscular dystrophy (MD) generally excludes an individual from active-duty military service. However, it is not known whether veterans are sometimes diagnosed with milder forms of MD at a later timepoint. We aimed to determine the prevalence of MD in a veterans health system. We abstracted clinical and genetic test data on patients who received care for a diagnosis of MD at the North Florida/South Georgia Veterans Health System between 2008 and 2021. We then determined which of these individuals would meet criteria for a definite diagnosis of MD, based on electrodiagnostic testing, muscle biopsy, and genetic testing of the individual or an affected first degree relative. We identified 12 patients with definite MD and 36 with possible or probable MD. The definite cases included myotonic dystrophy type 1 (4), myotonic dystrophy type 2 (3), oculopharyngeal MD (2), Becker MD (1), distal MD (1), and facioscapulohumeral MD (1). At least five of the cases classified as definite developed symptoms after discharge from active duty. Clinicians who care for veterans should be knowledgeable about, and have access to, diagnostic testing and treatment options for MD. When conducting MD surveillance, it is important to include veterans health systems as a data source. Mild cases of MD and those of later onset appear to be compatible in some cases with successful completion of military service.

Epidemiology, Patient Characteristics, and Treatment Patterns of Myasthenia Gravis in Taiwan: A Population-Based Study.

Myasthenia gravis (MG) is a chronic neuromuscular disease leading to significant disease burden. This study aimed to investigate the epidemiology of MG in Taiwan. A retrospective study was conducted using the Taiwan National Health Insurance Research Database. Prevalent patients with MG diagnosis (either ocular or generalized MG) from 2013 to 2019 were identified, and 2813 patients with initial MG diagnosis from 2014 to 2019 were further defined as the incident cohort. Patient characteristics, treatment patterns, and the occurrence of MG-related events were analyzed. The number of prevalent patients with MG increased from 4476 in 2013 to 5752 in 2019, with the prevalence rate increasing from 19 to 24 per 100,000 population. The incidence rate also slightly increased from 1.9 to 2.3 per 100,000 population during the study period. Almost all incident patients (99%, n = 2791) received MG-related treatment during the follow-up period. Among 1876 patients who received monotherapy as their initial treatment in the outpatient setting, the mean time from the index date to initial treatment was 48.8 (standard deviation 164.3) days, and most patients received acetylcholinesterase inhibitors (88.5%, n = 1661) as their initial treatment. During the first year after the index date, 133 (4.7%) incident patients experienced their first myasthenic crisis, and 96.2% of these events occurred within 3months. The prevalence of MG increased steadily in Taiwan, and the treatment of patients with MG was consistent with guidelines. Despite a high treatment rate, patients still experienced MG-related events, highlighting the limitation of current treatments and emphasizing the need for early intervention and novel treatment approaches.

Long-Term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-Based Study

Introduction: Healthcare costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease, are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and preexisting (PE) MG in Sweden. Methods: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥24-month follow-up during the period January 1, 2010, to December 31, 2017, were included. Results: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years, and 52.3% were female. In the first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs. 83.9%), corticosteroids (59.6% vs. 45.8%), thymectomy (12.1% vs. 0.7%), and plasma exchange (3.8% vs. 0.6%); had higher all-cause (70.9% vs. 35.8%) and MG-related (62.5% vs. 18.4%) hospitalization rates with 11 more hospitalization days (all p < 0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred EUR 7,302 (p < 0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p < 0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ∼55% for ND MG from year 1 and were comparable with PE MG. Conclusion: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies, and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

Comparison of volume-controlled ventilation and pressure-limited ventilation in laparoscopic appendicectomy - a randomized controlled clinical trial

Background: Laparoscopic appendicectomy is a widely performed surgery globally, offering notable benefits such as reduced postoperative pain, quicker mobility, and shorter hospital stays. Aims and Objectives: The study aimed to assess the changes in respiratory mechanics and compare the outcomes of volume-controlled and pressure-limited ventilation (PLV) in patients undergoing laparoscopic appendectomy. Materials and Methods: This randomized, prospective, single-blinded control study was conducted at K.A.P.V. Government Medical College, Tiruchirapalli, on 60 ASA I and II patients scheduled to undergo laparoscopic appendicectomy under general anesthesia. The patients were randomly divided into two groups (volume-controlled ventilation [VCV] group and the PLV group) of 30 patients. A patient’s history includes age, sex, history of diabetes, hypertension, or any cardiovascular disease, respiratory tract infection, wheezing or chronic chest infections, seizures, neuromuscular disease or weakness, etc. Results: There was no significant difference in gender, age, or body mass index between groups. There is no significant difference in the mean arterial pressure or ETCO2 between groups at various intervals. There was a significant difference in the mean heart rate between the VCV and the PLV groups at 5 and 20 min after induction. There was a significant difference in the peak airway pressure, dynamic compliance, and airway resistance between the VCV group and the PLV group at 10 min after induction (T1), 5 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum (T3), and immediately after Trendelenburg position (T4). Conclusion: The airway resistance and peak airway pressure do not increase, and the dynamic compliance was improved in the PLV during laparoscopic appendicectomy.

Acute neuromuscular disorders in critically ill children

Acute neuromuscular disorders are a group of neurological emergencies characterized by rapid onset of motor weakness commonly involving the respiratory and bulbar muscles. These can be acute or an exacerbation of the chronic neuromuscular disease. An accurate and timely diagnosis allows for the timely institution of specific therapies, improving long-term functional outcomes. Landry–Guillain–Barre syndrome (LGBS), acute transverse myelitis, compressive myelopathy, traumatic spinal lesions, and anterior horn cell myelitis (due to viral infections) are some of the common causes of acute motor weakness in children. LGBS is the most common among all. The diagnosis relies on clinical presentation, signs, cerebrospinal fluid analysis, electrophysiological studies, and neuroimaging of the spine. Once compressive or traumatic spinal lesions are suspected, immediate neuroimaging of the spine is essential to plan early neurosurgical intervention. Pediatric intensive care unit (PICU) admission is often required for supportive management and immunomodulation. Supportive management typically includes endotracheal intubation to protect the airway, mechanical ventilation (MV) to support breathing, monitoring, management of autonomic dysfunction, control of pain, physiotherapy, adequate nutrition, prevention of pressure sores, bladder–bowel care, psychological support, and planning of long-term care. Autonomic dysfunction can cause hemodynamic instability, arrhythmias, sudden cardiac arrest, and death, requiring close monitoring and management in PICU. Tracheostomy is often needed in children who continue to have respiratory paralysis and are predicted to require long-term term mechanical ventilation. The outcome generally depends on the primary disease and long-term care.

A history of home mechanical ventilation: The past, present and future.

This state-of-the-art review provides an overview of the history of home mechanical ventilation (HMV), including early descriptions of mechanical ventilation from ancient and Renaissance perspectives and the mass development of ventilators designed for long-term use during the poliomyelitis epidemic. Seminal data from key clinical trials supports the application of HMV in certain patients with chronic obstructive pulmonary disease, neuromuscular disease and obesity-related respiratory failure. Innovative engineering coupled with refined physiological understanding now permits widespread delivery of home mechanical ventilation to a global population, using portable devices with advanced ventilatory modes and telemonitoring capabilities. Exponential growth in digital technology continues, and ongoing research is needed to understand how to harness clinical and physiological data to benefit patients and healthcare services in a clinically- and cost-effective manner.

Frequency and satisfaction of conventional and complementary or alternative therapies for neuromuscular disorders

BackgroundCausal therapies are not yet available for most neuromuscular diseases. Additionally, data on the use of complementary or alternative therapies (CAM) in patients groups with a variety of different neuromuscular diseases are rare. This retrospective cross-sectional study aims to record the frequency of use and satisfaction of conventional therapies and complementary or alternative medicine (CAM) in patients with neuromuscular disorders in order to compare them afterwards.MethodsPatients from the University of Leipzig (Department and Outpatient Department of Neurology), the Friedrich-Baur-Institute (Department of Neurology), the Hoher Meißner Clinic (Department of Neurology) and the German Society for Muscular Diseases (DGM e.V.) were included. The focus of this study has been on patients with chronic neuromuscular diseases. Our data are based on standardised questionnaires in analogue form from three German neuromuscular centres and in digital form from the official website of the German Society for Muscular Diseases. Therapy satisfaction was assessed with the Patient Evaluation of Global Response (PEGR) ranking scale (very satisfactory + 2 to very unsatisfactory − 2).ResultsOf 192 questionnaires analysed, the most common diagnoses were spinal muscular atrophy (n = 42; 21.9%), muscular dystrophies (n = 41; 21.4%) and myotonic dystrophies (n = 38; 19.8%). More than half (n = 112; 58.3%) used both conventional and CAM treatments. Physiotherapy (n = 165) was used most frequently within all treatments with conventional manual (PEGR 1.25, p = 0.013; CI 95%) and aquatic therapy (PEGR 1.3, p = 0.038) showing significantly higher satisfaction compared to therapy on training equipment. Less-used therapies such as psychotherapy (n = 53; PEGR 1.2) were also satisfactory. Within CAM, massages (n = 96) were the most reported and meditation (PEGR 1.5) was best rated. Massage therapy was significantly more satisfactory than progressive muscle relaxation (p = 0.003) and chiropractic treatment (p = 0.036). Chiropractic treatment (PEGR − 0.1) was rated most negatively. No significant differences were found between the group of conventional therapies and CAM users regarding social and disease-dependent factors.ConclusionsTreatment with conventional therapy (manual, aquatic therapy) and some CAM therapies can be recommended if adequately indicated.

Clinically defined aspiration pneumonia is an independent risk factor associated with long-term hospital stay: a prospective cohort study

BackgroundLong-term hospital stay is associated with functional decline in patients with pneumonia, especially in the elderly. Among elderly patients with pneumonia, aspiration pneumonia is a major category. Clinical definition is usually used because it can occur without apparent aspiration episodes. It is still not clear whether a long-term hospital stay is due to aspiration pneumonia itself caused by underlying oropharyngeal dysfunction or simply due to functional decline in elderly patients with multiple comorbidities during acute infection. The aim of this study is to identify whether clinically defined aspiration pneumonia itself was associated with a long-term hospital stay.MethodsA prospective observational study on community-acquired (CAP) or healthcare-associated pneumonia (HCAP) was conducted from January 2012 through January 2014. Aspiration pneumonia was clinically defined as pneumonia not only occurring in patients after documented aspiration episodes, but also occurring in those with underlying oropharyngeal dysfunction: chronic disturbances of consciousness and/or chronic neuromuscular diseases. We defined thirty-day hospital stay as a long-term hospital stay and compared it with logistic regression analysis. Potential confounders included age, sex, HCAP, body mass index (BMI), long-term bed-ridden state, heart failure, cerebrovascular disorders, dementia, antipsychotics use, hypnotics use, and CURB score which is a clinical prediction tool used to assess the severity, standing for; C (presence of Confusion), U (high blood Urea nitrogen level), R (high Respiratory rate), and B (low Blood pressure). In a sub-analysis, we also explored factors associated with long-term hospital stay in patients with aspiration pneumonia.ResultsOf 2,795 patients, 878 (31.4%) had aspiration pneumonia. After adjusting potential confounders, the aspiration pneumonia itself was significantly associated with long-term hospital stay (adjusted odds ratio 1.44; 95% confidence interval 1.09—1.89, p < 0.01), as were higher age, male sex, high CURB score, HCAP, low BMI, heart failure, cerebrovascular disease, and antipsychotics use. Sub-analysis revealed factors associated with long-term hospital stay in the aspiration pneumonia, which included male sex, and multi-lobar chest X-ray involvement.ConclusionsClinically defined aspiration pneumonia itself was independently associated with long-term hospital stay. This result could potentially lead to specific rehabilitation strategies for pneumonia patients with underlying oropharyngeal dysfunction.

PCR70 Patient and Physician Concordance in Treatment Satisfaction and Symptom Severity Among Male and Female Myasthenia Gravis Patients in the United States and Five European Countries

Myasthenia Gravis (MG) is a chronic neuromuscular disease manifesting as muscle weakness and fatigue. Quantifying the severity of symptoms and satisfaction with MG treatment can differ between patient and treating physician.

BioDigit MG: A Pilot Study Examining a Digital Technology for Quantitative Assessment and Remote Monitoring of Myasthenia Gravis (P7-8.005)

<h3>Objective:</h3> To develop a standardized, clinically-validated digital solution for rigorous, longitudinal assessment of ocular weakness and dysarthria in myasthenia gravis (MG), which can be applied remotely. <h3>Background:</h3> MG is a chronic autoimmune neuromuscular disease characterized by fluctuating weakness of skeletal muscle, which frequent affects ocular muscles and speech. Current assessments of myasthenic weakness require neurologic expertise, are time-consuming and can still be subjective. Additionally, measured at one point in time, assessments provide a snapshot of a patient’s MG, which may not adequately reflect the spectrum of fluctuating weakness. Ratings of ocular weakness and dysarthria are particularly subjective. These shortcomings of current outcome measures limit performance of clinical trials and provide a limited view of the patient’s clinical status. <h3>Design/Methods:</h3> We developed a tablet-based digital health solution that captures video data collected by patients and MG-specific patient-reported outcome measures. Ptosis and dysarthria are rated asynchronously. The tablet provides text instruction and audio prompts to the patient and data are uploaded to a cloud. Predetermined measures of success have been defined. <h3>Results:</h3> A pilot study with a target sample size of 20 individuals with MG is ongoing to determine the feasibility of using the proposed solution as a health monitoring platform for MG. Two MG experts will rate speech and video data for dysarthria and ptosis based on the Quantitative Myasthenia Gravis (QMG) scale. Association between the extracted speech and facial characteristics to clinical scores of dysarthria and ptosis will be investigated. <h3>Conclusions:</h3> Despite considerable recent advances in treatments for MG, rigorous, longitudinal tools for monitoring of its characteristic fluctuating weakness remain limited and represent an unmet need. The feasibility, validity and acceptability of the proposed digital solution will be determined for 20 patients with MG. If successful, this technology will be further developed and studied in a larger observational study. <b>Disclosure:</b> An immediate family member of Dr. Guidon has received personal compensation for serving as an employee of GE Healthcare. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Momenta. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Guidon has received research support from MGFA. The institution of Dr. Guidon has received research support from Project Data Sphere. The institution of Dr. Guidon has received research support from MGNet. The institution of Dr. Guidon has received research support from MGNet. Dr. Guidon has received publishing royalties from a publication relating to health care. Dr. Mishra has received personal compensation for serving as an employee of Biosensics. Miss Lindsay has nothing to disclose. Mr. Mulukutla has received personal compensation for serving as an employee of BioSensics LLC. Dr. Vaziri has received personal compensation for serving as an employee of Biosensics.

The Impact of Generalized Myasthenia Gravis Severity on Work and Daily Activities: A Real World Study (P7-8.006)

<h3>Objective:</h3> To explore the relationship between generalised myasthenia gravis (gMG) severity and the ability to work and perform normal daily activities. <h3>Background:</h3> GMG is a rare and chronic autoantibody neuromuscular disease which manifests as muscle weakness and fatigue. The symptoms of gMG may affect patients’ ability to work and perform daily activities. <h3>Design/Methods:</h3> Data came from the Adelphi gMG Disease Specific Programme (DSP), a cross-sectional survey of MG treating physicians and their consulting MG patients, administered in 5 European countries and the US between March and September 2020. Patient data included demographics, severity based on Myasthenia Gravis Foundation of America (MGFA) classification (class I least severe, class V most severe) and the Charlson Comorbidity Index (CCI). Patients completed the Work, Productivity and Activity Impairment (WPAI) questionnaire. Linear regressions assessed the relationship between MGFA class and WPAI while controlling for age and CCI. <h3>Results:</h3> A total of 257 people with MGFA class II-IV (gMG) completed at least one of the WPAI questions: 40% were employed full/part-time, 41% were on long-term sick leave or retired. Mean age was 54.7 years; 52.9% were male. There was no significant association between MGFA class II or III-IV on the percentage of work time missed (n=90, <i>p</i>=0.44). MGFA class III-IV gMG were associated with a 14.3% higher impairment while working vs class II (n=94, <i>p</i>=0.01) and were associated with 14.8% higher overall work impairment due to gMG (n=84; <i>p</i>=0.04). Respondents with class III-IV gMG reported 15.5% higher impairment in normal daily activities than the less severe class II respondents (n=257, <i>p</i>&lt;0.01). <h3>Conclusions:</h3> Generalized Myasthenia Gravis impacts the ability to work and perform daily activities with more severe disease associated with greater impairment. Treatments that control symptoms resulting in less severe disease could have a positive impact on work and daily activities of patients living with gMG. <b>Disclosure:</b> Dr. Pesa has received personal compensation for serving as an employee of Janssen. Dr. Pesa has stock in J&amp;J. Dr. Chaudhry has received personal compensation for serving as an employee of Johnson &amp; Johnson. Dr. Chaudhry has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Jonathan de Courcy has nothing to disclose. Miss Barlow has nothing to disclose. Miss Chatterton has nothing to disclose. Mr. Thomas has nothing to disclose. Mr. Gibson has nothing to disclose. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MT pharma. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Dr. Govindarajan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MT pharma . Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Catalyst. The institution of Dr. Govindarajan has received research support from Band of Hope . The institution of Dr. Govindarajan has received research support from Alexion. Dr. Govindarajan has received publishing royalties from a publication relating to health care.

Respiratory Musculature Evaluated by Computed Tomography in the Setting of Prolonged Mechanical Ventilation.

Diaphragm atrophy has been observed in subjects who undergo invasive mechanical ventilation. We propose a new method to assess for respiratory muscle (RM) changes in subjects who undergo invasive mechanical ventilation by assessing for changes in respiratory muscles through computed tomography (CT). A retrospective case series study was conducted on subjects who underwent invasive mechanical ventilation and received at least 2 chest CT scans during admission. Exclusion criteria included history of chronic mechanical ventilation dependence and neuromuscular disease. Respiratory muscle cross-sectional area (CSA) was measured at the T6 vertebrae. Fourteen subjects were included: mean (± SD) age, BMI, and admission APACHE II scores were 54.0 y (± 14.9), 32.6 kg/m2 (± 10.9), and 23.5 (± 6.0), respectively. Ten (71%) subjects were male. Mean length of time between CT chest scans was 7.5 d (± 3.3). Mean duration of invasive mechanical ventilation was 4.5 d (± 3.4). The percentage change in TM CSA among those who underwent invasive mechanical ventilation was 10.5% (± 6.1). We demonstrated that serial analysis of respiratory muscle CSA through CT chest scans can be a method to assess for respiratory muscle atrophy in subjects undergoing mechanical ventilation. Future prospective studies involving larger populations are needed to better understand how this method can be used to predict outcomes in mechanically ventilated patients.

Practical Guide to Management of Long-Term Noninvasive Ventilation for Adults With Chronic Neuromuscular Disease.

Recent technological advances in respiratory support and monitoring have dramatically enhanced the utility of long-term noninvasive ventilation (NIV). Improved quality of life and prolonged survival have been demonstrated for several common chronic neuromuscular diseases. Many adults with progressive neuromuscular respiratory disease can now comfortably maintain normal ventilation at home to near total respiratory muscle paralysis without needing a tracheostomy. However, current practice in many communities falls short of that potential. Mastery of the new technology calls for detailed awareness of the respiratory cycle; expert knowledge of mechanical devices, facial interfaces, and quantitative monitoring tools for home ventilation; and a willingness to stay current in a rapidly expanding body of clinical research. The depth and breadth of the expertise required to manage home assisted ventilation has given rise to a new focused medical subspecialty in chronic respiratory failure at the interface between pulmonology, critical care, and sleep medicine. For clinicians seeking pragmatic "how to" guidance, this primer presents a comprehensive, physician-directed management approach to long-term NIV of adults with chronic neuromuscular respiratory disease. Bi-level devices, portable ventilators, ventilation modalities, terminology, and monitoring strategies are reviewed in detail. Building on that knowledge base, we present a step-by-step guide to initiation, refinement, and maintenance of home NIV tailored to patient-centered goals of therapy. The quantitative approach recommended incorporates routine monitoring of home ventilation using technologies that have only recently become widely available including cloud-based device telemonitoring and noninvasive measurements of blood gases. Strategies for troubleshooting and problem solving are included.

High Flow Nasal Cannula Therapy in the Pediatric Home Setting.

High flow nasal cannula (HFNC) therapy may be better tolerated than traditional non-invasive ventilation (NIV) and is rapidly gaining acceptance in pediatric acute care. In Israel, HFNC is approved for domestic use. We aim to describe its indications, efficacy, parental satisfaction and safety. Retrospective study of children treated with home HFNC therapy in three pediatric centers. Data included demographic parameters, indication of use, weight and days of hospitalization before and after initiation. Safety, tolerability and parental satisfaction were assessed via standardized telephone questionnaire. Median (IQR) age of initiating home HFNC in 75 children was 8.3 (2.2, 29.6) months. Indications were obstructive sleep apnea (33; 44%), airway malacia (19; 25%), chronic lung disease (15; 20%), neuromuscular disease (4; 5%) and post-extubation support (4; 5%). Weight standard deviation score rose from -2.3 pre HFNC to -1.7 at 6.7 months post HFNC initiation, p<0.001. Hospital admission days during the two months pre vs post HFNC initiation were 22 (5.5, 60) and 5 (0, 14.7) respectively, p<0.008. Median (IQR) parental satisfaction score was 5/5 (4, 5). Fifty of 60 (83%) respondents would recommend home HFNC to other families in a similar situation. There were no serious adverse events. In our population, domestic HFNC appeared safe and well tolerated for a variety of indications. Its introduction was associated with improved weight gain, fewer hospitalization days and high parental satisfaction. Further work is required to characterize groups of children most likely to benefit from HFNC, as opposed to traditional modes of NIV. This article is protected by copyright. All rights reserved.

Utilising pneuRIP device in determining the adequacy of respiratory support when weaning high-flow nasal cannula in paediatric patients with acute respiratory distress: A pilot study.

Recognition of paediatric respiratory distress and timely intervention is critical, especially during the weaning phase of support in paediatric acute respiratory failure, as weaning too aggressively can lead to further setbacks in a patient's recovery. We aimed to determine if pulmonary function measurements obtained with the pneuRIP device, a noninvasive pulmonary function testing device that provides measurements of labored breathing index (LBI), phase angle and %rib cage (%RC) contribution to breathing, will provide predictive values to assess the adequacy of respiratory support while weaning from HFNC. We reviewed patients ages 0-18 years admitted to the PICU for respiratory distress due to respiratory infections receiving HFNC. Patients with history of chronic lung disease and chronic neuromuscular disease with baseline habnormal breathing patterns were excluded. Phase angle, LBI and %RC were obtained every hour and with every wean of HFNC. Nine patients were enroled. Mean LBI range remained 1.27-1.68 when LBI was plotted as a function of the HFNC flow rate. Mean values of %RC contribution to breathing ranged 43.65-57.12 as a function of the HFNC flow rate. No significant deviations existed in either %RC (P=0.16) or LBI (P=0.16) during the weaning of HFNC. Mean phase angle for all subjects was 41.48°-74.12° for the duration of wean and showed significant deviation from baseline during the weaning process (p=0.001). Measurements of LBI and %RC on the pneuRIP device effectively demonstrated tolerance of weaning HFNC during the recovery phase of acute respiratory failure from a respiratory infection.

Influence of cough airflow characteristics on respiratory mucus clearance

A cough is a respiratory reflex for respiratory mucus clearance. The cough airflow dynamics can be characterized by three parameters, which are cough peak flow rate (CPFR), peak velocity time (PVT), and cough expired volume (CEV). In this study, the three-dimensional human respiratory airways from generation 0 to 5 are reconstructed from computerized tomography images. The non-Newtonian property of respiratory mucus is considered. The airflow–mucus interaction phenomenon has been analyzed in time and space based on the Eulerian wall film model. The maximum air velocity and wall shear stress could reach 38 m/s and 14 Pa, respectively, when the CPFR is 6 L/s. In addition, the influence of CPFR, PVT, and CEV on mucus clearance has been studied. The cough efficiency is used to quantify the mucus clearance. The results showed that increasing the cough peak flow rate has no noticeable effect on mucus clearance under normal and low mucus viscosity. Increasing the cough peak flow rate can effectively improve mucus clearance when the mucus viscosity becomes high. Specifically, the CEV has an apparent positive effect on clearing mucus regardless of the viscosity and thickness. This study provides a new research direction to improve mucus clearance by improving the CEV rather than the CPFR for patients with chronic obstructive pulmonary disease, neuromuscular disease, or other pulmonary diseases.

A Subject-Tailored Variability-Based Platform for Overcoming the Plateau Effect in Sports Training: A Narrative Review.

The plateau effect in training is a significant obstacle for professional athletes and average subjects. It evolves from both the muscle-nerve-axis-associated performance and various cardiorespiratory parameters. Compensatory adaptation mechanisms contribute to a lack of continuous improvement with most exercise regimens. Attempts to overcome this plateau in exercise have been only partially successful, and it remains a significant unmet need in both healthy subjects and those suffering from chronic neuromuscular, cardiopulmonary, and metabolic diseases. Variability patterns characterize many biological processes, from cellular to organ levels. The present review discusses the significant obstacles in overcoming the plateau in training and establishes a platform to implement subject-tailored variability patterns to prevent and overcome this plateau in muscle and cardiorespiratory performance.

Multiple Cranial Nerve Palsies in Otolaryngology Consultation: An Atypical Clinical Presentation Revealing Myasthenia Gravis

Introduction: Myasthenia gravis is a chronic autoimmune neuromuscular disease, presents with weakness and fatigability of striated skeletal muscles. It is a rare disease in Cameroon. We report an uncommon case of myasthenia gravis in a patient with feeding difficulties, notion of oronasal reflux and swallowing disorders as first complaints. Observation: We report the case of a 29-year-old woman consulted at our department of Otolaryngology and Cervico-Facial Surgery for dysphagia and swallowing disorders. She also presented with facial diplegia, oculomotor paralysis, nasal voice, and dysarthria which has been evolving for several years now. The clinical examination revealed multiple cranial nerve palsies. The complementary workup showed a decrement of more than 50% in the electroneuromyography and the presence of anti-acetylcholine receptor autoantibodies in the blood workup. A diagnosis of myasthenia confirms clinical presumption. We initially observed a worsening of neuromuscular disorders despite the pyridostigmine treatment and subsequently a clear improvement of the clinical features concerning swallowing and speech disorders, oculomotricity and facial diplegia under a treatment combining prednisone and azathioprine. Conclusion: Myasthenia gravis is a rare and potentially fatal autoimmune neuromuscular disease. We thus highlight the atypical clinical presentation and therapeutic itinerary of our patient and the importance to think about this clinical diagnosis in front of any multiple cranial nerve paralysis in otolaryngology consultation.

A Functional Human-on-a-Chip Autoimmune Disease Model of Myasthenia Gravis for Development of Therapeutics.

Myasthenia gravis (MG) is a chronic and progressive neuromuscular disease where autoantibodies target essential proteins such as the nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction (NMJ) causing muscle fatigue and weakness. Autoantibodies directed against nAChRs are proposed to work by three main pathological mechanisms of receptor disruption: blocking, receptor internalization, and downregulation. Current in vivo models using experimental autoimmune animal models fail to recapitulate the disease pathology and are limited in clinical translatability due to disproportionate disease severity and high animal death rates. The development of a highly sensitive antibody assay that mimics human disease pathology is desirable for clinical advancement and therapeutic development. To address this lack of relevant models, an NMJ platform derived from human iPSC differentiated motoneurons and primary skeletal muscle was used to investigate the ability of an anti-nAChR antibody to induce clinically relevant MG pathology in the serum-free, spatially organized, functionally mature NMJ platform. Treatment of the NMJ model with the anti-nAChR antibody revealed decreasing NMJ stability as measured by the number of NMJs before and after the synchrony stimulation protocol. This decrease in NMJ stability was dose-dependent over a concentration range of 0.01–20 μg/mL. Immunocytochemical (ICC) analysis was used to distinguish between pathological mechanisms of antibody-mediated receptor disruption including blocking, receptor internalization and downregulation. Antibody treatment also activated the complement cascade as indicated by complement protein 3 deposition near the nAChRs. Additionally, complement cascade activation significantly altered other readouts of NMJ function including the NMJ fidelity parameter as measured by the number of muscle contractions missed in response to increasing motoneuron stimulation frequencies. This synchrony readout mimics the clinical phenotype of neurological blocking that results in failure of muscle contractions despite motoneuron stimulations. Taken together, these data indicate the establishment of a relevant disease model of MG that mimics reduction of functional nAChRs at the NMJ, decreased NMJ stability, complement activation and blocking of neuromuscular transmission. This system is the first functional human in vitro model of MG to be used to simulate three potential disease mechanisms as well as to establish a preclinical platform for evaluation of disease modifying treatments (etiology).