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Glycogen storage disease type 1a (GSD 1a) is a metabolic disorder caused by deficiency of an enzyme required for glycogen breakdown, causing hypoglycaemia and lactic acidosis. Metabolic derangements cause disease manifestations affecting the kidneys, liver and platelet function. Physiological changes in pregnancy worsen fasting intolerance and increase reliance on exogenous glucose to avoid lactic acidosis. Fetal macrosomia and declining respiratory function result in high rates of caesarean sections. We report the multidisciplinary team (MDT) management of a 25-year-old woman with GSD 1a in an unplanned pregnancy. Existing percutaneous endoscopic gastrostomy tube feeding, alongside high-calorie drinks and intravenous dextrose during labour, managed the risks of hypoglycaemia and lactic acidosis. Metabolic parameters were regularly monitored and fortnightly growth scans were assessed for macrosomia. Allopurinol was continued throughout the pregnancy to reduce the risk of hyperuricaemia. MDT management optimised maternal and fetal care throughout pregnancy and labour, resulting in a successful vaginal delivery.

Pulmonary rehabilitation is a cornerstone of management for patients after lung transplantation (LT), but the benefits of inspiratory muscle training (IMT) after LT in children are unclear. Therefore, we examined whether IMT can improve respiratory function and dyspnoea in a paediatric patient after LT.The patient was a 13-year-old boy who underwent double LT. However, mild physical activity such as walking triggered dyspnoea for the patient. The patient underwent IMT with the intensity of approximately 30% of his maximal inspiratory pressure (MIP) for 2 months.The patient’s MIP was increased by approximately 60% after 2 months, and his forced vital capacity as a percent of the predicted normal value increased from 74.6% to 83.4%, with improvement of dyspnoea.IMT may help improve dyspnoea after LT in children with respiratory muscle weakness and a decline in respiratory function.

Background Malignant tumors occurring around both the spinal column and posterior chest wall are uncommon. Surgical resection of chest wall tumors adjacent to the spinal column is still challenging due to the surrounding anatomical structures. The purpose of the present study was to evaluate the long-term outcomes of surgical management in malignant tumors involving the spinal column and posterior chest wall. Methods Between 1999 and 2007, 10 consecutive patients underwent en bloc resection combined with the posterior chest wall in the treatment of malignant tumors around the spinal column. There were 6 males and 4 females with a mean age at the surgery of 40.9 years old (range, 14–62 years old). The mean postoperative follow-up period was 159.7 months (range, 84–245 months). The clinical history, physical examination, laboratory data, radiological findings, and operative findings for each patient were retrospectively reviewed. Results All surgeries were performed via a combined anterior and posterior approach. The mean numbers of partially resected vertebrae and ribs were 3.1 and 4.1, respectively. Lower or upper lobectomy was performed in four patients, and the diaphragm was partially resected in two patients. The surgical margin was wide in seven patients and marginal in two patients. Although five patients had postoperative respiratory problem, all patients improved immediately without life-threatening complications. There were no patients with respiratory insufficiency after surgery. One patient with osteosarcoma died of lung metastases 99 months after surgery. At the final follow-up, only one patient had local recurrence, five had been continuously disease-free, and three were alive with no evidence of disease. Conclusions En bloc resection and reconstruction in selected patients with malignant tumors involving both the spinal column and posterior chest wall demonstrated good long-term results for local control and the respiratory function.

Hepatitis E virus (HEV)-associated neuralgic amyotrophy (NA) is often bilateral and severe, involving structures outside the brachial plexus, such as the phrenic nerves or the lumbosacral plexus. We report a case of an HEV-positive man who had presented with brachial neuritis, with significant phrenic nerve involvement, resulting in diaphragmatic paralysis requiring non-invasive ventilation. Prognosis of HEV-associated NA is often unfavourable and recovery is usually incomplete. Identifying HEV-associated NA early could potentially aid in prognostication and management planning, as clinicians and patients would be expectant of its potential features and severity. Respiratory function should be monitored in patients with HEV who suffer from NA, as diaphragmatic paralysis could potentially lead to severe respiration difficulties requiring ventilatory support.

Introduction: Obstructive sleep apnea syndrome is a common condition in childhood and if left untreated can result in many health problems. An accurate diagnosis of the etiology is crucial for obstructive sleep apnea treatment success. Functional orthodontic appliances that stimulate mandibular growth by forward mandibular positioning are an alternative therapeutic option in growing patients. Objective: To perform a literature review about the effects of functional orthodontic appliances used to correct the mandibular deficiency in obstructive sleep apnea treatment. Methods: The literature search was conducted in June 2020 using Cochrane Library; PubMed, EBSCO (Dentistry & Oral Sciences Source), LILACS Ovid; SciELO Web of Science; EMBASE Bireme and BBO Bireme electronic databases. The search included papers published in English, until June 2020, whose methodology referred to the types and effects of functional orthopedic appliances on obstructive sleep apnea treatment in children. Results: The search strategy identified thirteen articles; only four articles were randomized clinical studies. All studies using the oral appliances or functional orthopedic appliances for obstructive sleep apnea in children resulted in improvements in the apnea-hypopnea index score. The cephalometric (2D) and tomographic (3D) evaluations revealed enlargement of the upper airway and increase in the upper airspace, improving the respiratory function in the short term. Conclusion: Functional appliances may bean alternative treatment for obstructive sleep apnea, but it cannot be concluded that they are effective in treating pediatric obstructive sleep apnea. There are significant deficiencies in the existing evidence, mainly due to absence of control groups, small sample sizes, lack of randomization and no long-term results. Resumo Introdução: A síndrome da apneia obstrutiva do sono é uma condição comum na infância e, se não tratada, pode resultar em muitos problemas de saúde. Um diagnóstico preciso da etiologia é crucial para o sucesso do tratamento dessa condição clínica. Aparelhos ortodônticos funcionais que estimulam o crescimento mandibular através do anteroposicionamento mandibular são uma opção terapêutica para pacientes em crescimento. Objetivo: Fazer uma revisão da literatura sobre os efeitos do aparelho ortodôntico funcional usado para corrigir a deficiência mandibular no tratamento da apneia obstrutiva do sono. Método: A pesquisa bibliográfica foi feita em junho de 2020 nos os bancos de dados eletrônicos da Cochrane Library; PubMed, EBSCO (Dentistry & Oral Sciences Source), Lilacs Ovid; SciELO Web of Science; Embase Bireme e BBO Bireme. A busca incluiu artigos publicados em inglês, até junho de 2020, cuja metodologia referia-se aos tipos e efeitos dos aparelhos ortopédicos funcionais no tratamento da apneia obstrutiva do sono em crianças. Resultados: A estratégia de busca identificou 19 artigos; apenas quatro eram estudos clínicos randomizados. Todos os estudos que usaram aparelhos orais ou aparelhos ortopédicos funcionais para apneia obstrutiva do sono em crianças resultaram em melhorias no índice de apneia-hipopneia. As avaliações cefalométrica (2D) e tomográfica (3D) mostraram alargamento das vias aéreas superiores e aumento do espaço das vias aéreas superiores, que melhoraram a função respiratória em curto prazo. Conclusão: Os aparelhos funcionais podem ser um tratamento opcional para apneia obstrutiva do sono, mas não é possível concluir que sejam eficazes na população pediátrica. Existem deficiências significativas nas evidências existentes, principalmente devido à ausência de grupos de controle, tamanho pequeno das amostras, falta de randomização e ausência de resultados em longo prazo.

Postoperative pulmonary complications and acute respiratory failure are among the leading causes of adverse postoperative outcomes. Noninvasive ventilation may safely and effectively prevent acute respiratory failure in high-risk patients after cardiothoracic surgery and after abdominal surgery. Moreover, noninvasive ventilation can be used to treat postoperative hypoxemia, particularly after abdominal surgery. Noninvasive ventilation also can be helpful to prevent or manage intraoperative acute respiratory failure during non-general anesthesia, primarily in patients with poor respiratory function. Finally, noninvasive ventilation is superior to standard preoxygenation in delaying desaturation during intubation in morbidly obese and in critically ill hypoxemic patients. The few available studies in children suggest that noninvasive ventilation could be safe and valuable in treating hypoxemic or hypercapnic acute respiratory failure after cardiac surgery; on the other hand, it could be dangerous after tracheoesophageal correction.

Summary Background and objective Presbyphonia is an age-related voice disorder characterized by vocal fold atrophy and incomplete glottal closure during phonation. The extent to which the effects of presbyphonia may be compounded by age-related declines in the respiratory system and further impact communication and quality of life remains unknown. Therefore, the objective of this study was to determine how variations in respiratory function impacts voice measures in a sample of participants with presbyphonia. Methods In this pilot study, 21 participants with presbyphonia underwent respiratory assessments (spirometry and respiratory muscle strength testing) and voice assessments (videostroboscopy, acoustic analysis, auditory-perceptual ratings, aerodynamic assessment, and self-assessments). Factor and cluster analyses were conducted to extract voice and respiratory constructs and to identify groups of participants with similar profiles. Correlations and regression analyses were conducted to better describe the relationships between voice and respiratory function. Results Respiratory function was found to impact voice via two main pathways: through its physiological effect on voice and through its impact on general health and impairment. A lower respiratory function was associated with a lower vocal fold pliability and regularity of vibration and with an elevated aerodynamic resistance accompanied by laryngeal hyperfunction. Standardized measures of respiratory function were associated with perceived voice-related handicap. Respiratory function did not associate with voice quality, which was mostly influenced by the severity of vocal fold atrophy. Conclusion Poor respiratory health exacerbates the burden of vocal fold atrophy and, therefore, implementation of respiratory screening prior to starting voice therapy may significantly affect the treatment plan and consequently the outcomes of voice therapy in this patient population.

The impact of concomitant lung resection during esophagectomy on short-term outcomes is not well characterized. This study tests the hypothesis that lung resection at the time of esophagectomy is not associated with increased perioperative morbidity or mortality.Perioperative outcomes for esophageal cancer patients who underwent esophagectomy alone (EA) were compared to patients who had concurrent esophagectomy and lung resection (EL) using the NSQIP database between 2006-2017. Predictors of morbidity and mortality, including combined surgery, were evaluated using multivariable logistic regression.Among the 6,225 study patients, 6,068 (97.5%) underwent EA and 157 (2.5%) underwent EL. There were no differences in baseline characteristics between the two groups. Operating time for EL was longer than EA (median 416 versus 371 minutes, P0.01). Median length of stay was 10 d for both groups. Perioperative mortality was not significantly different between EL and EA patients (5.1% versus 2.8%, P = 0.08). EL patients had higher rates of postoperative pneumonia (22.3% versus 16.2%, P = 0.04) and sepsis (11.5% versus 7.1%, P = 0.03), however major complication rates overall were similar (40.8% versus 35.3%, P = 0.16). Combining lung resection with esophagectomy was not independently associated with increased postoperative morbidity (AOR 1.21 [95% CI 0.87-1.69]) or mortality (AOR 1.63 [95% CI 0.74-3.58]).Concurrent lung resection during esophagectomy is not associated with increased mortality or overall morbidity, but is associated with higher rates of pneumonia beyond esophagectomy alone. Surgeons considering combined lung resection with esophagectomy should carefully evaluate the patient's risk for pulmonary complications and pursue interventions preoperatively to optimize respiratory function.

The effects of untreated obstructive sleep apnea (OSA) on cardiopulmonary function remain unclear. Cardiorespiratory fitness (CRF), commonly reflected by VO(2) max measured during cardiopulmonary exercise testing, has gained popularity in evaluating numerous cardiopulmonary conditions and may provide a novel means of identifying OSA patients with the most clinically significant disease. This emerging testing modality provides simultaneous assessment of respiratory and cardiovascular function with results helping uncover evidence of evolving pathology in either organ system. In this review, we highlight the current state of the literature in regard to OSA and CRF with a specific focus on changes in cardiovascular function that have been previously noted. While OSA does not appear to limit respiratory function during exercise, studies seem to suggest an abnormal cardiovascular exercise response in this population including decreased cardiac output, a blunted heart rate response (ie, chronotropic incompetence), and exaggerated blood pressure response. Surprisingly, despite these observed changes in the cardiovascular response to exercise, results involving VO(2) max in OSA remain inconclusive. This is reflected by VO(2) max studies involving middle-aged OSA patients showing both normal and reduced CRF. As prior studies have not extensively characterized oxygen desaturation burden, we propose that reductions in VO(2) max may exist in OSA patients with only the most significant disease (as reflected by nocturnal hypoxia). Further characterizing this relationship remains important as some research suggests that positive airway pressure therapy or aerobic exercise may improve CRF in patients with OSA. In conclusion, while it likely that severe OSA, via an abnormal cardiovascular response to exercise, is associated with decreased CRF, further study is clearly warranted to include determining if OSA with decreased CRF is associated with increased morbidity or mortality. CITATION: Powell TA, Mysliwiec V, Brock MS, Morris MJ. OSA and cardiorespiratory fitness: a review. J Clin Sleep Med. 2022;18(1):279–288.

© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved., While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period., This project was supported by Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and by Canadian Institutes of Health Research operating grants (327387; 452843; 70797). The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the University College London Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC), and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Alzheimer’s Society grant (AS-PG-16-007), the Bluefield Project and the EU Joint Programme – Neurodegenerative Disease Research (GENFI-PROX grant 2019-02248). M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a- 004-517). M.B.’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). J.B.R. is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). It is also funded by the Ministry of Health, Italy (S.S.). R.V.’s work is supported by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie. R.S.-V.’s work is supported by Instituto de Salud Carlos III (grant number 20/00448), cofunded by the EU. ANR-PRTS PrevdemALS study funding (I.L.B.). Several authors of this publication (J.C.vS., M.S., A.D., M.O., R.V., I.L.B., J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.

Introduction Laryngospasm is an involuntary sustained closure of sphincter musculature that leads to an unpleasant subjective experience of dyspnea and choking. It is an underreported symptom in amyotrophic lateral sclerosis (ALS). This study aimed to better characterize the prevalence and clinical characteristics of laryngospasm in ALS patients. Methods The medical records of 571 patients with ALS followed between 2008-2018 were searched for evidence of laryngospasm. A total of 23 patients with laryngospasm were identified and data related to patient and laryngospasm characteristics were extracted. Results Laryngospasm was reported in 4% of ALS patients. Females comprised 57% of patients and mean age was 63.4 years. Laryngospasm frequently manifested in patients with moderate bulbar dysfunction and seemed independent of respiratory function. Among laryngospasm patients, 26% were cigarette smokers and 13% had a history of gastroesophageal reflux. The most common reported trigger was excessive saliva irritating the vocal cords (35%) followed by eating a meal (17%). There was significant variation in laryngospasm frequency (up to 5 per hour) and duration (seconds to minutes). Most patients could not identify an effective coping mechanism, although 13% reported that drinking water was effective. Discussion Despite its low prevalence in ALS, laryngospasm should be included in the symptom enquiry. This study may improve patient care through increased recognition of the clinical features of laryngospasm in ALS patients, identifying a link between laryngospasm and moderate bulbar dysfunction, and highlighting trigger avoidance as a management strategy. Additional research is required to understand the pathophysiology and optimal treatment.

Background/aim: There is limited information about peripheral blood eosinophilia (PBE) and airway obstruction in sarcoidosis. Since pulmonary sarcoidosis affects the airways, it is often confused with asthma. The aims of the study are to investigate airway obstruction and PBE in sarcoidosis patients and to examine the similarity of clinical presentation with asthma. Materials and methods: The patients matching the ATS/ERS/WASOG diagnosis criteria and were between 18 and 80 years of age were included consecutively between 2018 and 2020. Other diseases causing granulomas were excluded. Results: A total of 84 patients were included of which 26 (31%) had a PBE level of >= 300 mu L with no significant difference seen between sarcoidosis stage and PBE (p > 0.05). A significant (p < 0.05) decrease was only seen in FEV1 as the stage of sarcoidosis progressed. Respectively 31 (36.9%), 12 (14.3%) and 4 (4.8%) patients had an obstructive, restrictive and mixed respiratory function disorder. Twenty-four (28.6%) subjects with sarcoidosis had history of asthma. Spring fever, eczema, and skin/nose allergy were noticed in 17 (20.2%) of the patients. Conclusion: Mild PBE may be seen in sarcoidosis. Patients applying with PBE, airway obstruction, bronchial hyperreactivity along with spring fever, eczema, skin/nose allergy, wheezing, chest tightness, shortness of breath and cough may be also evaluated in terms of sarcoidosis.

Summary Background Pompe disease is a rare disorder characterised by progressive loss of muscle and respiratory function due to acid α-glucosidase deficiency. Enzyme replacement therapy with recombinant human acid α-glucosidase, alglucosidase alfa, is the first approved treatment for the disease, but some patients do not respond, and many do not show a sustained benefit. We aimed to assess the safety and efficacy of an investigational two-component therapy (cipaglucosidase alfa, a novel recombinant human acid α-glucosidase, plus miglustat, an enzyme stabiliser) for late-onset Pompe disease. Methods We did a randomised, double-blind, parallel-group, phase 3 trial at 62 neuromuscular and metabolic medical centres in 24 countries in the Americas, Asia-Pacific, and Europe. Eligible participants were aged 18 years or older with late-onset Pompe disease, and had either been receiving alglucosidase alfa for at least 2 years or were enzyme replacement therapy-naive. Participants were randomly assigned (2:1) using interactive response technology software, stratified by 6-min walk distance and previous enzyme replacement therapy status, to intravenous cipaglucosidase alfa (20 mg/kg) plus oral miglustat or to intravenous alglucosidase alfa (20 mg/kg) plus oral placebo once every 2 weeks for 52 weeks. Patients, investigators, and outcome assessors were masked to treatment assignment. The primary endpoint was change from baseline to week 52 in 6-min walk distance, assessed using a mixed-effect model for repeated measures analysis for comparison of superiority in the intention-to-treat population (all patients who received at least one dose of study drug). This study is now complete and is registered with ClinicalTrials.gov , NCT03729362 . Findings Between Dec 3, 2018, and Nov 26, 2019, 130 patients were screened for eligibility and 125 were enrolled and randomly assigned to receive cipaglucosidase alfa plus miglustat (n=85) or alglucosidase alfa plus placebo (n=40). Two patients in the alglucosidase alfa plus placebo group did not receive any dose due to absence of genotype confirmation of late-onset Pompe disease and were excluded from analysis. Six patients discontinued (one in the alglucosidase alfa plus placebo group, five in the cipaglucosidase alfa plus miglustat group), and 117 completed the study. At week 52, mean change from baseline in 6-min walk distance was 20·8 m (SE 4·6) in the cipaglucosidase alfa plus miglustat group versus 7·2 m (6·6) in the alglucosidase alfa plus placebo group using last observation carried forward (between-group difference 13·6 m [95% CI −2·8 to 29·9]). 118 (96%) of 123 patients experienced at least one treatment-emergent adverse event during the study; the incidence was similar between the cipaglucosidase alfa plus miglustat group (n=81 [95%]) and the alglucosidase alfa plus placebo group (n=37 [97%]). The most frequently reported treatment-emergent adverse events were fall (25 [29%] patients in the cipaglucosidase alfa plus miglustat group vs 15 [39%] in the alglucosidase alfa plus placebo group), headache (20 [24%] vs 9 [24%]), nasopharyngitis (19 [22%] vs 3 [8%]), myalgia (14 [16%] vs 5 [13%]), and arthralgia (13 [15%]) vs 5 [13%]). 12 serious adverse events occurred in eight patients in the cipaglucosidase alfa plus miglustat group; only one event (anaphylaxis) was deemed related to study drug. One serious adverse event (stroke) occurred in the alglucosidase alfa plus placebo group, which was deemed unrelated to study drug. There were no deaths. Interpretation Cipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6-min walk distance in our overall population of patients with late-onset Pompe disease. Further studies should investigate the longer-term safety and efficacy of cipaglucosidase alfa plus miglustat and whether this investigational two-component therapy might provide benefits, particularly in respiratory function and in patients who have been receiving enzyme replacement therapy for more than 2 years, as suggested by our secondary and subgroup analyses. Funding Amicus Therapeutics.

PURPOSE OF REVIEW This review aims to summarize the current literature describing vestibular-autonomic interactions and to describe their putative role in various disorders' clinical presentations, including orthostatic dizziness and motion sensitivity. RECENT FINDINGS The vestibular-autonomic reflexes have long been described as they relate to cardiovascular and respiratory function. Although orthostatic dizziness may be in part related to impaired vestibulo-sympathetic reflex (orthostatic hypotension), there are various conditions that may present similarly. A recent clinical classification aims to improve identification of individuals with hemodynamic orthostatic dizziness so that appropriate recommendations and management can be efficiently addressed. Researchers continue to improve understanding of the underlying vestibular-autonomic reflexes with recent studies noting the insular cortex as a cortical site for vestibular sensation and autonomic integration and modulation. Work has further expanded our understanding of the clinical presentation of abnormal vestibular-autonomic interactions that may occur in various conditions, such as aging, peripheral vestibular hypofunction, traumatic brain injury, and motion sensitivity. SUMMARY The vestibular-autonomic reflexes affect various sympathetic and parasympathetic functions. Understanding these relationships will provide improved identification of underlying etiology and drive improved patient management.

Supplemental Digital Content is available in the text., Background. Uncontrolled donation after circulatory death (DCD) donors are an extraordinary resource to increase the number of lungs available for transplantation. However, the risk of the warm ischemia resulting from cardiac arrest to irreversibly damage the organs is considerable. Moreover, graft preservation issues and organizational problems often worsen the dangerous effects of warm ischemia. Ex vivo lung perfusion (EVLP) enables us to evaluate and recondition lungs whose functionality is doubtful, as well as to overcome the difficulties related to time and logistics. Methods. We report the case of uncontrolled DCD lungs successfully treated with an exceptionally prolonged EVLP. Because the donor’s blood count and liver biopsy showed signs of possible leukemia, EVLP was protracted up to 17 h while waiting for immunohistochemical analyses to rule out this diagnosis; eventually, the results came back negative, and the lungs were judged suitable for transplantation. Results. The recipient was a 32-y-old male individual with cystic fibrosis, colonized by Pandoraea pnomenusa. Bilateral transplantation required central extracorporeal membrane oxygenation. The patient was extubated after 36 h and was discharged 21 d after the operation. Despite early recolonization by Pandoraea pnomenusa and airway complications requiring pneumatic dilatation, he is alive and has a satisfactory respiratory function 15 mo after transplantation. Conclusions. Uncontrolled DCD represents a challenge due to both logistical issues and the complexity of graft evaluation before procurement. EVLP with cellular perfusate could be a valuable tool to overcome these limits. Nonetheless, caution should be exercised when interpreting the effects of this technique on airway healing.

Many coronavirus disease 2019 (Covid-19) survivors show symptoms months after acute illness. The aim of this work is to describe the clinical evolution of Covid-19, one year after discharge. We performed a prospective cohort study on 238 patients previously hospitalized for Covid-19 pneumonia in 2020 who already underwent clinical follow-up 4 months post-Covid-19. 200 consented to participate to a 12-months clinical assessment, including: pulmonary function tests with diffusing lung capacity for carbon monoxide (DLCO); post-traumatic stress (PTS) symptoms evaluation by the Impact of Event Scale (IES); motor function evaluation (by Short Physical Performance Battery and 2 min walking test); chest Computed Tomography (CT). After 366 [363–369] days, 79 patients (39.5%) reported at least one symptom. A DLCO

Recently it was documented that fatiguing, high-intensity exercise resulted in a significant attenuation in maximal skeletal muscle mitochondrial respiratory capacity, potentially due to the intramuscular metabolic perturbation elicited by such intense exercise. With the utilization of intrathecal fentanyl to attenuate afferent feedback from group III/IV muscle afferents, permitting increased muscle activation and greater intramuscular metabolic disturbance, this study aimed to better elucidate the role of metabolic perturbation on mitochondrial respiratory function. Eight young, healthy males performed high-intensity cycle exercise in control (CTRL) and fentanyl-treated (FENT) conditions. Liquid chromatography-mass spectrometry and high-resolution respirometry were used to assess metabolites and mitochondrial respiratory function, respectively, pre- and postexercise in muscle biopsies from the vastus lateralis. Compared with CTRL, FENT yielded a significantly greater exercise-induced metabolic perturbation (PCr: −67% vs. −82%, Pi: 353% vs. 534%, pH: −0.22 vs. −0.31, lactate: 820% vs. 1,160%). Somewhat surprisingly, despite this greater metabolic perturbation in FENT compared with CTRL, with the only exception of respiratory control ratio (RCR) (−3% and −36%) for which the impact of FENT was significantly greater, the degree of attenuated mitochondrial respiratory capacity postexercise was not different between CTRL and FENT, respectively, as assessed by maximal respiratory flux through complex I (−15% and −33%), complex II (−36% and −23%), complex I + II (−31% and −20%), and state 3CI+CII control ratio (−24% and −39%). Although a basement effect cannot be ruled out, this failure of an augmented metabolic perturbation to extensively further attenuate mitochondrial function questions the direct role of high-intensity exercise-induced metabolite accumulation in this postexercise response.

The term "early-onset scoliosis" (EOS) refers to spinal deformities that develop before the age of 10 years. The aim of surgical treatment for EOS is stopping the progression of the curvature, maintaining the correction, ensuring the maximum growth of the vertebrae, and ensuring that the vertebrae remain mobile. Using magnetically controlled growing rods (MCGRs) in the treatment of EOS is intended to protect the patient from the negative effects of repetitive surgeries, increase patient compliance and satisfaction, and increase the speed of return to normal social life. Our aim was to report the early radiological evaluation findings and detect the changes in the quality of life of patients and their parents after the diagnosis of EOS and treatment with MCGRs.We performed a retrospective clinical study (level 4 case series) of 20 patients with a surgical indication for the treatment of EOS. The 20 patients had undergone treatment with MCGRs and lengthening procedures at 3-month intervals from August 2014 to August 2016. The mean patient age at surgery was 7.9 years (range, 4-10 years), and the mean length of follow-up was 14.9 months (range, 6-30 months). The preoperative, early postoperative, and final follow-up radiographs of all patients were obtained. The Cobb angle, thoracic kyphosis, spinal height, thoracic height, sagittal balance, coronal balance, shoulder balance, and pelvic balance were measured from the radiographs. All the patients had undergone preoperative and final follow-up respiratory function tests, and all the patients completed the Early Onset Scoliosis 24-item questionnaire (EOSQ-24). The outcome measures were the Cobb angle, thoracic kyphosis, spinal height, thoracic height, sagittal balance, coronal balance, shoulder balance, and pelvic balance. All the patients had undergone preoperative and final follow-up respiratory function tests, and the parents of every patient completed the Turkish version of the EOSQ-24.The preoperative, early postoperative and final follow-up mean Cobb angles were 56.6° (range, 38°-93°), 30.5° (range, 13°-80°), and 33.5° (range, 14°-86°), respectively. These findings showed statistically significant improvement in the Cobb angle (P0.05). The thoracic height was also significantly increased. The preoperative, early postoperative, and final follow-up mean height was 181 mm (range, 123-224 mm), 200 mm (range, 164-245 mm), and 212 mm (range, 167-248 mm), respectively (P0.05). The measurements for spinal height had also increased significantly, with preoperative, early postoperative, and final follow-up values of 219 mm (range, 213-366 mm), 315 mm (range, 260-402 mm), and 338 mm (range, 261-406 mm), respectively (P0.05). The thoracic kyphosis measurement was 41° (range, 5°-65°) preoperatively, which had decreased significantly to 32.5° (range, 0°-53°) at the final follow-up (P0.05). Our measurements showed no statistically significant differences in the coronal and sagittal balance, pelvic balance, or shoulder balance. No significant differences were found between the preoperative and postoperative respiratory function test results. The assessment of the EOSQ-24 scores had demonstrated significant improvements in the mean scores at the final follow-up (P0.05). When different categories in the EOSQ-24 were evaluated separately, no statistically significant differences were found between the preoperative and final follow-up scores for general health, pain and discomfort, respiratory function, movement capability, physical function, or effects on daily life (P0.05). However, the exhaustion and energy levels, emotional state, effect of the disease on the parents and patient, and parent satisfaction scores had increased significantly from the preoperative assessment to the final follow-up (P0.05). The financial effect had decreased significantly at the final follow-up compared with the preoperative values (P0.05). Four patients had developed complications requiring further treatment, and none of the patients had developed infection that required surgical intervention.Our study showed that insertion of a MCGR is a safe procedure for treatment of EOS to correct the deformity and improve function in daily life. This method reduces the need for repetitive surgery and the likelihood of complications associated with other treatments. Thus, treatment with MCGRs increases patient satisfaction and facilitates patient compliance.

Background Children and adolescents with cerebral palsy often have poor respiratory function, which is often not addressed. Objective To examine if adding inspiratory muscle training to sensorimotor exercises would improve mobility capacity and respiratory function in children and adolescents with cerebral palsy. Methods Forty school-children and adolescents with cerebral palsy aged 8–15 years with Gross Motor Function Classification System I–III, participated in this randomized controlled trial. The experimental group received 45 min of sensorimotor physical therapy in addition to 15 min of inspiratory muscle training for 18 sessions over six weeks. In contrast, the control group received 45 min of sensorimotor training session, three times a week over six weeks. The primary outcome measure was the six-minute walk test. The secondary outcome measures were maximal inspiratory and maximal expiratory pressure, as well as pulmonary function tests. Results Time by group interaction showed no statistical significance between the groups in any outcome measures except for peak expiratory flow. The mean difference of 9.6 cm H2O (95% CI: 3.2, 35.5) in the MIP from baseline to 2-month follow-up supports the experimental intervention. Post-training, the between-group mean difference was 19.8 (95% CI: -18, 57.6) meter in the six-minute walk test. Conclusion Adding inspiratory muscle training to sensorimotor physical therapy did not impact mobility capacity in children and adolescents with cerebral palsy.

Swallowing impairments co-occur with chronic obstructive pulmonary disease (COPD) leading to aspiration, disease exacerbations, and malnutrition. This pilot survey study aimed to identify current clinical practice patterns for swallowing evaluation and treatment in persons with COPD. A 35-question Qualtrics survey was deployed to medical speech-language pathology (SLP) social media sites and professional boards; flyers were distributed at a professional conference. Forty-eight SLPs completed the study. SLPs routinely include a clinical swallow examination (96%), videofluoroscopic swallowing study (79%), adjunctive respiratory measures (respiratory rate [83%], and pulse oximetry [67%], respiratory–swallow pattern [77%]) but less frequently include fiberoptic endoscopic evaluation of swallowing (23%). Self-reported advanced clinical experience and expert respiratory analysis skills were associated with adjunctive respiratory measure (respiratory rate, pulse oximetry) inclusion during assessment. Compensatory strategy training (77%) is a preferred treatment for dysphagia in COPD; however, respiratory–swallow pattern training and expiratory muscle strength training are increasing in use. SLPs self-report a comprehensive, individualized patient-centered care approach with inclusion of adjunctive respiratory-focused methods in dysphagia evaluation and treatment practice in persons with COPD. Advances in the identification of the integral role of respiratory function in swallowing integrity may be translating to clinical practice methods for dysphagia management in persons with COPD.

Objective The aim of this study was to elucidate the relationship between atrial fibrillation (AF) and chronic obstructive pulmonary disease (COPD) classification based on clinical severity determined in current guidelines. AF is the most common chronic arrhythmia that requires treatment. COPD is one of the risk factors for AF, but this relationship was only explored through respiratory function test results. Methods Patients who received inpatient treatment for COPD between November 2019 and January 2017 were screened. Patients with coronary artery disease, heart failure, valvular heart disease, diabetes, chronic kidney disease, hypertension, thyroid dysfunction, and sleep apnea syndrome were excluded. According to the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, patients with COPD were divided into groups A, B, C, and D, and the relationship between AF and these groups was investigated. Results There was no difference between the two groups (depending on the presence of AF) in terms of sex and body mass index. There was a significant difference between the two groups in terms of age, left ventricular ejection fraction (LVEF), left atrium, right atrium, right ventricle, and systolic pulmonary artery pressure. When patients with COPD were classified according to clinical and symptomatic severity, the frequency of AF increased as the clinical severity increased. Conclusion Regardless of the forced expiratory volume - first second (FEV1) value in the respiratory test, the incidence of AF is higher in patients with COPD with a clinically more severe picture.

BACKGROUND Ultrasonography (USG) of the diaphragm is a promising alternative to pulmonary function tests (PFT) for assessing respiratory function in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). METHODS We studied 33 patients fulfilling Awaji criteria (definite = 14; probable = 12; possible = 7) and 33 age and gender-matched controls. Diaphragm thickness was measured using USG at the end of expiration (DTex) and end of inspiration (DTin). The thickness ratio (TR) was calculated as DTin/DTex. The mean age at onset and duration were 49.73 ± 12.7 years and 13.57 ± 9.7 months, respectively. Men = 25 (75.8%); Limb onset ALS/MND = 24 patients (72.7%); bulbar onset = 9 (27.3%). RESULTS Compared to controls, ALS/MND patients had reduced mean DTex (2.22 ± 0.29 mm vs. 2.02 ± 0.32 mm, p = .012) and DTin (4.0 ± 0.71 mm vs. 3.41 ± 0.38 mm, p

Objective Neuroinflammation is an important pathogenic mechanism in amyotrophic lateral sclerosis (ALS), with regulatory T cells (Tregs) mediating a slower rate of disease progression. Dimethyl fumarate enhances Treg levels and suppresses pro-inflammatory T cells. The present study assessed the safety and efficacy of dimethyl fumarate in ALS. Methods Phase-2, double-blind, placebo-controlled randomised clinical trial recruited participants from May 1, 2018 to September 25, 2019, across six Australian sites. Participants were randomised (2:1 ratio) to dimethyl fumarate (480 mg/day) or matching placebo, completing visits at screening, baseline, weeks 12, 24 and 36. The primary efficacy endpoint was a change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) at week 36. Secondary outcome measures included survival, neurophysiological index (NI), respiratory function, urinary neurotrophin-receptor p75 and quality of life. Results A total of 107 participants were randomised to dimethyl fumarate (n = 72) or placebo (n = 35). ALSFRS-R score was not significantly different at week 36 (−1.12 [−3.75 to 1.52, p = 0.41]). Dimethyl fumarate was associated with a reduced NI decline week 36 (differences in the least-squares mean: (0.84 [−0.51 to 2.22, p = 0.22]). There were no significant differences in other secondary outcome measures. Safety profiles were comparable between groups. Interpretation Dimethyl fumarate, in combination with riluzole, was safe and well-tolerated in ALS. There was no significant improvement in the primary endpoint. The trial provides class I evidence for safety and lack of efficacy of dimethyl fumarate in ALS.

Background: The differential effects of PM2.5 fractions on children’s lung function remain inconclusive. This study aimed to examine whether lung function in asthmatic children was associated with increased PM2.5 fractions in urban areas in Nagasaki prefecture, Japan, where the air pollution level is relatively low but influenced by transboundary air pollution. Methods: We conducted a multiyear panel study of 73 asthmatic children (boys, 60.3%; mean age, 8.2 years) spanning spring 2014–2016 in two cities. We collected self-measured peak expiratory flow (PEF) twice a day and daily time-series data for PM2.5 total mass and its chemical species. We fitted a linear mixed effects model to examine short-term associations between PEF and PM2.5, adjusting for individual and time-varying confounders. A generalized linear mixed effects model was also used to estimate the association for worsening asthma defined by severe PEF decline. Back-trajectory and cluster analyses were used to investigate the long-range transboundary PM2.5 in the study areas. Results: We found that morning PEFs were adversely associated with higher levels of sulfate (− 1.61 L/min; 95% CI: − 3.07, − 0.15) in Nagasaki city and organic carbon (OC) (− 1.02 L/min; 95% CI: − 1.94, − 0.09) in Isahaya city, per interquartile range (IQR) increase at lag1. In addition, we observed consistent findings for worsening asthma, with higher odds of severe PEF decline in the morning for sulfate (odds ratio (OR) = 2.31; 95% CI: 1.12, 4.77) and ammonium (OR = 1.73; 95% CI: 1.06, 2.84) in Nagasaki city and OC (OR = 1.51; 95% CI: 1.06, 2.15) in Isahaya city, per IQR increase at lag1. The significant chemical species were higher on days that could be largely attributed to the path of Northeast China origin (for sulfate and ammonium) or both the same path and local sources (for OC) than by other clusters. Conclusions: This study provides evidence of the differential effects of PM2.5 fractions on lung function among asthmatic children in urban areas, where the Japanese national standards of air quality have been nearly met. Continuous efforts to promote mitigation actions and public awareness of hazardous transboundary air pollution are needed to protect susceptible children with asthma., Environmental Health, 20, art. no. 110; 2021

Summary Background There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function. Methods The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60–90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178 ) has also been completed, but will be reported separately. Findings Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50·1 (IQR 37·5–51·1) weeks. The median duration of treatment was 47·9 (IQR 26·4–48·1) weeks. Change from baseline in supine SVC at 12 weeks was –6·73% with levosimendan and –6·99% with placebo, with no significant difference between the treatments (estimated treatment difference 0·26%, 95% CI –2·03 to 2·55, p=0·83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10·69, 95% CI –15·74 to 37·12; nominal p value=0·43). The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%]). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis. Interpretation Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation. Funding Orion Corporation.

Introduction/aims In this study, researchers evaluated the effects of lung volume recruitment treatment (LVR) - a low-tech, low-cost, manual 'breath stacking' technique used to help people cough with enough force to clear their airways, thereby reducing the risk of aspiration and choking - on five volitional airway clearance and protection behaviors used by people living with amyotrophic lateral sclerosis (PwALS). Methods Using a repeated-measures cross-over design, 29 PwALS performed five volitional airway clearance and protection behaviors in LVR treatment and in no-treatment, control conditions. Peak cough flow (PCF) was used to measure maximum expiratory rate during forced expiration, throat clearing, hawking, post-swallow coughing and the supraglottic swallowing maneuver. Comparisons were made as a function of condition (treatment or control) and three time-points (pre-treatment, and 15- and 30-minutes post-treatment). Results LVR treatment had a significant positive effect on maximum expiratory rates during all tested airway clearance and protection behaviors. Increased PCF values lasted for up to 30 minutes post-LVR for all tested behaviors in the treatment condition. Discussion Findings demonstrate that LVR treatment can increase control over airway clearance in PwALS, as well as provide improved airway protection for up to 30 minutes, the duration of a typical meal. This study has implications for patient care. These include offering patients control over some of the most feared symptoms of ALS, particularly choking during activities of daily living, and enhanced ALS respiratory care in low-resource settings. Findings may have implications for other neurodegenerative disorders in which dysphagia occurs with retained sensory function. This article is protected by copyright. All rights reserved.

Objective. Examining the effects of a pulmonary rehabilitation (PR) program applied to patients undergoing coronary artery bypass grafting (CABG) surgery with open heart technique on respiratory functions, functional capacity, and quality of life (QoL). Design. This randomised controlled study applied the Consolidated Standards of Reporting Trials statement. Methods. The study was conducted with two groups: the intervention group ( n = 25 ) and the control group ( n = 25 ). The control group received standard care after coronary artery bypass grafting. On the contrary, the experimental group participated in a PR program created by the researchers in addition to standard care. After coronary artery bypass grafting, the respiratory functions (on the 4th day of clinical care) and QoL (at the 6th week) of both groups were evaluated. The primary outcome measure was the respiratory function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC). The secondary outcome measure of this study was the QoL. Results. When the average pulmonary function test values of the patients were examined, the mean FVC and FEV1 values of the patients in the intervention group on the 4th day of clinical care were significantly higher with a medium level size effect than the control group ( p = 0.027 ; effect size d = 0.643 ; p < 0.024 ; effect size d = 0.658 , respectively). At the postoperative 6th week measurement of QoL, a decrease was observed in all subdimensions of the scale, albeit less in the intervention group ( p < 0.05 ). There was a decrease in both the mental and physical component summary of QoL ( p < 0.05 ). Conclusion. The results of this study revealed that pulmonary rehabilitation applied to patients who have undergone coronary artery bypass graft recover their functional capacity faster.

In amyotrophic lateral sclerosis (ALS) lower plasma creatinine level has been associated with shorter survival and faster functional decline. It has not been clear if creatinine is associated with respiratory outcome. We analyzed retrospectively a population of unselected ALS patients. Multiple-regression and Cox-regression analyses were performed. We included 233 patients, mean age 62.8, mean disease duration of 18.6 months. At baseline, creatinine was significantly associated with ALSFRS-R, but not with its decline rate. No predictive value was disclosed for FVC, its decline rate, or with survival. We did not confirm that creatinine is a marker of respiratory outcome.

AIMS: Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19. METHODS: We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209). RESULTS: After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P 

Background The brainstem has the critical role of regulating cardiac and respiratory function and it also provides motor and sensory function to the face via the cranial nerves. Despite the observation of a brainstem lesion in a radiological examination, it is difficult to obtain tissues for a pathological diagnosis because of the location and small volume of the brainstem. Thus, we aimed to share our 6‐year experience with stereotactic biopsies from brainstem lesions and confirm the value and safety of stereotactic biopsy on this highly eloquent area in this study. Methods We retrospectively reviewed the medical records of 42 adult patients who underwent stereotactic biopsy on brainstem lesions from 2015 to 2020. The radiological findings, surgical records, pathological diagnosis, and postoperative complications of all patients were analyzed. Results Histopathological diagnoses were made in 40 (95.2%) patients. Astrocytic tumors were diagnosed in 29 (69.0%) patients, diffuse large B cell lymphoma in 5 (11.9%) patients, demyelinating disease in 4 (9.5%) patients, germinoma in 1 (2.4%) patient, and radiation necrosis in 1 (2.4%) patient. In the 40 patients with successful stereotactic biopsy, 10 (25.0%) patients had inconsistent preoperative radiological diagnosis and postoperative pathological diagnosis. In addition, there was a difference between the treatments prescribed by the radiological and pathological diagnoses in 8 out of 10 patients whose diagnoses changed after biopsy. There was no operative mortality among the 42 patients. Conclusions A pathological diagnosis can be made safely and efficiently in brainstem lesions using stereotactic biopsy. This pathological diagnosis will enable patients to receive appropriate treatment., Three approaches to stereotactic biopsy for brainstem and a Venn diagram showing the location of 42 brainstem lesion that performed stereotactic biopsy.

Pregnancy is associated with a number of pathophysiological changes (including modification of vascular resistance, increased vascular permeability, and coagulative disorders) that can lead to specific (eclampsia, preeclampsia) or not specific (intracranial hemorrhage) neurological complications. In addition to these disorders, pregnancy can affect numerous preexisting neurologic conditions, including epilepsy, brain tumors, and intracerebral bleeding from cerebral aneurysm or arteriovenous malformations. Intracranial complications related to pregnancy can expose patients to a high risk of intracranial hypertension (IHT). Unfortunately, at present, the therapeutic measures that are generally adopted for the control of elevated intracranial pressure (ICP) in the general population have not been examined in pregnant patients, and their efficacy and safety for the mother and the fetus is still unknown. In addition, no specific guidelines for the application of the staircase approach, including escalating treatments with increasing intensity of level, for the management of IHT exist for this population. Although some of basic measures can be considered safe even in pregnant patients (management of stable hemodynamic and respiratory function, optimization of systemic physiology), some other interventions, such as hyperventilation, osmotic therapy, hypothermia, barbiturates, and decompressive craniectomy, can lead to specific concerns for the safety of both mother and fetus. The aim of this review is to summarize the neurological pathophysiological changes occurring during pregnancy and explore the effects of the possible therapeutic interventions applied to the general population for the management of IHT during pregnancy, taking into consideration ethical and clinical concerns as well as the decision for the timing of treatment and delivery.

Introduction/aims Spinal muscular atrophy (SMA) type III is a relatively mild form of SMA. Few studies have investigated the changes in both respiratory and upper limb function within this population after loss of ambulation. The aim of this study was to assess change in percentage of predicted forced vital capacity (FVC% predicted) and change in the Revised Upper Limb Module (RULM) score in these patients throughout a 24-month period after loss of ambulation. Effect of scoliosis and its surgical correction, disease duration since loss of ambulation, weight, and height were also investigated. Methods Retrospective analyses were performed on 24 nonambulant SMA III patients from data collected at two centers in the United Kingdom. Results The FVC% predicted score showed a significant progressive deterioration of 17% over the 24-month period. Respiratory deterioration correlated significantly with age, weight, disease duration since loss of ambulation, and spinal correctional surgery. Longitudinal RULM data were available for 16 patients; a significant deterioration was observed with a mean decrease in score of 3 over 24 months. Age correlated negatively with RULM score, as did height and time since loss of ambulation. A significant positive correlation between FVC% predicted and RULM was demonstrated. Discussion This study highlights how SMA type III patients have progressive deterioration of respiratory and upper limb function after loss of ambulation. Combining data from these assessments could provide insight into clinical progression, inform clinical trials, and provide assistance in managing disease progression expectations for patients.

Objectives: To investigate the effect of trunk training on trunk control, arm, and pulmonary function in children with Duchenne muscular dystrophy. Design: A randomised controlled trial. Settings: Neuromuscular diseases clinic of university hospital. Subjects: Twenty-six children with Duchenne muscular dystrophy aged 5–16 were included in the study. Intervention: Participants were randomly allocated into two groups. The study group ( N = 13) exercised with the trunk-oriented exercise program and the conventional exercise program, whereas the control group ( N = 13) underwent the conventional exercise program for eight weeks. Main measures: The primary outcomes were trunk control was assessed using the Trunk Control Measurement Scale, the arm function was assessed using Performance of Upper Limb, and respiratory function using the pulmonary function test. Data collection was conducted at baseline, and eighth week. The differences in trunk control scores, arm function scores, and respiratory function values before and after the training were calculated for the intergroup comparison. Results: The mean age of the participants was 11.6 (2.6) in the study group and 10.6 (3.4) in the control group. The changes between trunk control score, arm function score (total and distal level score), and respiratory function value (Forced Vital Capacity, Forced Expiratory Volume in one second, and Peak Expiratory Flow Volume percentage values) were compared and significant differences were found after eight week periods in the study and control groups. Conclusions: Trunk-oriented exercise program in Duchenne muscular dystrophy might be effective for trunk control, arm, and respiratory function.

Shinsuke Kitazawa, Ashoka Indranatha Wijesinghe, Naoki Maki, Takahiro Yanagihara, Yusuke Saeki, Naohiro Kobayashi, Shinji Kikuchi, Yukinobu Goto, Hideo Ichimura, Yukio Sato Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, JapanCorrespondence: Yukio SatoDepartment of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, JapanTel +81 29 853 3210Fax +81 29 853 7991Email ysato@md.tsukuba.ac.jpPurpose: In performing surgery for lung cancer, emphysema is a risk factor related to postoperative respiratory complications (PRC). However, few studies have addressed the risk of radiological emphysematous volume affecting PRC. The aim of this study was to investigate the relationship between emphysematous volume as measured on 3-dimensional computed tomography and PRC.Patients and Methods: We reviewed 342 lung cancer patients undergoing lobectomy between 2013 and 2018. The percentage of low attenuation area (LAA%) was defined as the percentage of the lung area showing attenuation of − 950 Hounsfield units or lower. Preoperative factors including age, sex, body mass index, smoking index, respiratory function, tumour histology, and LAA% were evaluated. PRC included pneumonia, atelectasis, prolonged air leakage, empyema, hypoxia, ischemic bronchitis, bronchopleural fistula, and exacerbation of interstitial pneumonia. Uni- and multivariable analyses were performed to investigate the relationship between independent clinical variables and postoperative adverse events.Results: Median LAA% was 5.0% (range, 0– 40%) and PRC was observed in 50 patients (14.6%). Patients who presented with PRC showed significantly high LAA% compared to those without complications (median: 8.1% vs 3.8%; p < 0.001). Based on univariable analysis, age, sex, smoking index, percentage of forced expiratory volume in 1 s (FEV1.0%), histology, and LAA% were significant predictors for PRC. Multivariable analysis revealed higher LAA% as a significant risk factor for PRC (odds ratio = 1.040; 95% confidence interval, 1.001– 1.080; p = 0.046).Conclusion: In addition to respiratory function with spirometry, LAA% can be used as a predictor of PRC.Keywords: lung cancer, emphysema, radiology and other imaging, respiratory function tests, thoracic surgery

Background In 1992, a landmark study demonstrated clinical deterioration in respiratory function and nutritional status prior to the onset of cystic fibrosis-related diabetes (CFRD). We re-evaluated this outcome. Methods The Montreal Cystic Fibrosis Cohort is a prospective CFRD screening study. We performed a 6-year retrospective analysis of nutritional parameters and FEV1 (%) in subjects who developed incident CFRD and in controls who maintained normoglycemia (NG). In the former group, data was collected over 6 years prior to diabetes onset. Results Subjects (n = 86) had a mean age of 31.7 ± 8.1 years, BMI of 23.0 ± 4.0 kg/m2, and FEV1% of 70.1 ± 24.2%. Eighty-one percent had pancreatic insufficiency (PI). Patients were grouped as follows: NG+PS (pancreatic sufficient) (n = 16), NG+PI (pancreatic insufficient) (n = 21), CFRD+PS (n = 3) and CFRD+PI (n = 46). At their most recent screen NG+PS subjects had significantly greater BMI, as compared to NG+PI and CFRD+PI groups (26.2 ± 3.6 kg/m2 vs 22.6 ± 4.2 kg/m2 vs 22.1 ± 3.5 kg/m2, p = 0.0016). FEV1 was significantly greater in the NG+PS group (91.5 ± 16.8% vs 67.8 ± 25.3% vs 63.5 ± 22.2%, p = 0.0002). The rates of change in weight, BMI, fat mass (%), and FEV1 prior to the most recent visit (NG+PS, NG+PI groups) or to the diagnosis of de novo CFRD were similar between groups. Conclusion In a contemporary context, CFRD onset is not preceded by deterioration in BMI, fat mass, or pulmonary function. Low BMI and FEV1 are more closely associated with PI than a pre-diabetic state.

Background Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting. Objectives The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19–associated ARDS. Methods A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography. Results Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17). Conclusions In this pilot trial, intravenous metoprolol administration to patients with COVID-19–associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19–associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic., Central Illustration

Professional voice users form an increasing part of our population. Physical fitness instructors listed as professional voice users are at risk for voice problem as they perform vigorous exercises, instruct at the same time and compete vocally with loud background music. Hence, there is a dire need to study the voice problems in this population. The current study was aimed at investigating the phonatory and respiratory functions in physical fitness instructors in comparison to a control group.Cross-sectional study design MATERIALS AND METHODS: Fifty physical fitness instructors (48 males and two females) and 50 controls (45 males and five females) with the age range of 18-40 years were initially enrolled in the study. The phonatory function measures (perceptual, physiological, and acoustic) and respiratory function measures (aerodynamics) were obtained.Following the data analysis only for male participants, the majority of the perceptual parameters such as grade, roughness, breathiness, and strain showed significant increase in the clinical group compared to controls (P0.05). Similarly, few acoustic parameters such as fundamental frequency (FFew perceptual and acoustic parameters are sensitive in differentiating the voice problems in physical fitness instructors from the controls. The significant perceptual and acoustic parameters implied that they are at risk for developing voice problems. Hence, early identification and prevention of voice problems in this population is warranted.

biSignificance:/i/bThe metabolic disorder, diabetes mellitus, results in microvascular complications, including diabetic kidney disease (DKD), which is partly believe to involve disrupted energy generation in the kidney, leading to injury that is characterized by inflammation and fibrosis. An increasing body of evidence indicates that the innate immune complement system is involved in the pathogenesis of DKD; however, the precise mechanisms remain unclear.biRecent Advances:/i/bComplement, traditionally thought of as the prime line of defense against microbial intrusion, has recently been recognized to regulate immunometabolism. Studies have shown that the complement activation products, Complement C5a and C3a, which are potent pro-inflammatory mediators, can mediate an array of metabolic responses in the kidney in the diabetic setting, including altered fuel utilization, disrupted mitochondrial respiratory function, and reactive oxygen species generation. In diabetes, the lectin pathway is activated via autoreactivity toward altered self-surfaces known as danger-associated molecular patterns, or via sensing altered carbohydrate and acetylation signatures. In addition, endogenous complement inhibitors can be glycated, whereas diet-derived glycated proteins can themselves promote complement activation, worsening DKD, and lending support for environmental influences as an additional avenue for propagating complement-induced inflammation and kidney injury.biCritical Issues:/i/bRecent evidence indicates that conventional renoprotective agents used in DKD do not target the complement, leaving this web of inflammatory stimuli intact.biFuture Directions:/i/bFuture studies should focus on the development of novel pharmacological agents that target the complement pathway to alleviate inflammation, oxidative stress, and kidney fibrosis, thereby reducing the burden of microvascular diseases in diabetes.iAntioxid. Redox Signal/i. 37, 781-801.

Summary Background Asthma and chronic obstructive pulmonary diseases are conditions characterized by a variable progression. Some individuals experience longer asymptomatic periods while others acute worsening periods and/or exacerbations triggered by symptom multiplication factors. Medications are adjusted to the patients’ respiratory function, self-assessment of health and emerging certain physical changes. A more effective treatment may be applied by real-time data registered during the patient’s everyday life. Aim and methods Introducing new modern digital technology in pulmonary rehabilitation (PR) to help tracking the patients’ medication, thus we systematically reviewed the latest publications on telemedicine and pulmonary telerehabilitation. Conclusion The use of the latest digital technologies in PR is very exciting and offers great opportunities while treating patients affected by specific conditions. On the one hand, adherence to medication can be improved in patients with chronic respiratory diseases by using these new state of the art devices; on the other hand, digital devices will also be able to monitor various physiological parameters of patients during their usual everyday activities. Data can be stored on a smartphone and shared with the provider. Relying on this information, physicians will be able to tailor medications and dosage to the specific needs of individual patients. Telerehabilitation may be a sustainable solution to the growing burden of chronic respiratory disease worldwide. However, PR must keep its cornerstones, such as education and motivations, which are most successful when conducted in person. Many issues remain to be resolved in the future, e.g. cybersecurity while using smart devices since they offer unique opportunities for PR.

OBJECTIVES Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality. DESIGN Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators. SETTING Eight academic and community hospitals in Sweden and Canada. PATIENTS Adult patients with suspected infection episodes. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The main cohort included 19,396 episodes (median age, 67.0 [53.0-77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0-76.0; women 42.1-50.2%; mortality 2.3-13.3%). Peripheral oxygen saturation levels 96-95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10-2.23) in the main cohort and 1.36 (95% CI, 1.00-1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94-91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74-0.77) to 0.78 (95% CI, 0.77-0.80; p < 0.001). Peripheral oxygen saturation/FIO2 ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor. CONCLUSIONS These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings.

A roundtable convened in July 2020 examined issues concerning respiratory support in amyotrophic lateral sclerosis (ALS), with reference to the potential for an early-phase orally administered medication that might either postpone the introduction of noninvasive ventilation (NIV) and/or enhance the benefits to be gained from it. Attention was also given to the impact of the COVID-19 pandemic on usual practice in the assessment and management of ALS-related respiratory difficulties. Implementation of NIV marks a step-change in clinical status for patients and a major increase in burden for caregivers. All means to ease this transition should be explored: an oral therapy that supported respiratory function and patients' independence and sense of well-being would aid discussions to facilitate the eventual successful introduction of NIV. Assessment of a candidate oral therapy that might support respiratory function in ALS patients would be aided by the development of improved patient-reported outcome measures for robust quantification of treatment effect and quality of life. Such instruments could also be used to monitor patients' status during the COVID-19 pandemic, averting some of the risks of face-to-face assessment plus the patient burden and costs of traditional methods. Several oral candidate therapies have recently failed to meet their primary endpoints in clinical trials. However, understanding of the underlying physiology and appropriate trial design have grown and will inform future developments in this field.

The sleep disruption experienced by patients admitted to hospital may have a negative effect on health but the nature and magnitude of the effect has not been conclusively outlined. The review was designed to examine the impact of sleep disruption associated with being a hospital inpatient, on short-term physical health outcomes in adult patients. Searches comprised journal databases, gray literature sources, and backward and forward citation searching. Two reviewers independently screened the records. Original studies of adult hospitalized patients' sleep were included if physical outcomes were also measured. Interventional studies were excluded. The methodological quality was assessed independently by 2 reviewers using CASP checklists. Sleep assessment measures and results, physical outcomes and contextual data were extracted. Results were synthesized according to frequently reported outcomes: delirium, pain intensity, physical strength, and respiratory function. A meta-analysis was not performed; studies were heterogeneous and reporting was limited. Of 9919 retrieved records, 26 published studies were included (published: 2001-2020). Risk of bias was moderately high. Confounding factors were poorly reported. Total sleep time was either normal or reduced. Sleep was disrupted: arousal indices were high (mean: 0 5-21/h); slow wave sleep proportions were limited. Subjective sleep quality was poor. The association between sleep reduction or disruption and short-term health outcomes was negative, mixed or equivocal and included increased delirium, higher pain intensity, poorer strength, and adverse respiratory function. The impact of sleep disruption on outcomes for hospitalized patients is not well defined.

Background: Clinical characteristics of patients with congenital myopathies (CM) are well known but there is a lack of knowledge about the natural history and course of disease of the different genetic subtypes. In 2010 we assessed the national cohort of Danish patients with CM to decide genetic diagnosing and describe genotype- phenotype relationships. AIM of this follow-up study was to evaluate the course of disease since the initial study and to evaluate the applicability of standard assessment methods to reflect change over time and patients own opinion on the course of disease. Methods: All available genetically diagnosed patients studied by us in 2010 (n = 41) were invited to the follow-up study; assessment of motor function (MFM-32), muscle strength (MRC %)and respiratory function (FVC %) and prime assessor were the same as in the initial study. Patients were asked whether the course of disease had progresses, was stable or had improved. Results: 23 patients (15–61 y) accepted the invitation. Mean follow-up time was 7.7 years. Loss of muscle strength was more prominent in patients with mutations in DNM2, RYR1 and TPM2/3 genes and deterioration in FVC % was more evident in patients carrying NEB and ACTA1 gene mutations. MFM-sum score was less sensitive to change compared to MRC-sum score. In general, agreement between the patient’s own opinion of the course of disease and results of assessments was good. Conclusion: The number of patients in the study is too small to be conclusive, but the results indicate that CM can be stable or slowly progressive depending on the genetic subtype.

Duchenne muscular dystrophy (DMD) is a progressive and lethal disease, caused by X‐linked mutations of the dystrophin encoding gene. The lack of dystrophin leads to muscle weakness, degeneration, fibrosis, and progressive loss of skeletal, cardiac, and respiratory muscle function resulting in premature death due to the cardiac and respiratory failure. There is no cure for DMD and current therapies neither cure nor arrest disease progression. Thus, there is an urgent need to develop new approaches and safer therapies for DMD patients. We have previously reported functional improvements which correlated with increased dystrophin expression following transplantation of dystrophin expressing chimeric (DEC) cells of myoblast origin to the mdx mouse models of DMD. In this study, we demonstrated that systemic‐intraosseous transplantation of DEC human cells derived from myoblasts of normal and DMD‐affected donors, increased dystrophin expression in cardiac, respiratory, and skeletal muscles of the mdx/scid mouse model of DMD. DEC transplant correlated with preservation of ejection fraction and fractional shortening on echocardiography, improved respiratory function on plethysmography, and improved strength and function of the limb skeletal muscles. Enhanced function was associated with improved muscle histopathology, revealing reduced mdx pathology, fibrosis, decreased inflammation, and preserved muscle morphology and architecture. Our findings confirm that DECs generate a systemic protective effect in DMD‐affected target organs. Therefore, DECs represents a novel therapeutic approach with the potential to preserve or enhance multiorgan function of the skeletal, cardiac, and respiratory muscles critical for the well‐being of DMD patients., Systemic‐intraosseous transplantation of human dystrophin expressing chimeric (DEC) cells (0.5 × 106 and 1 × 106) results in significant increase in dystrophin expression in heart, diaphragm, and gastrocnemius muscle (GM) which correlates with the reduction of centrally nucleated fibers in diaphragm and GM indicating reduced muscle pathology and further confirming beneficial effect of DEC therapy at 90 days after systemic transplant to mdx/scid mouse model of DMD.

Brick-kilns are polluted environments due to the use of low-quality technologies and fuels, which generates black fumes with a large number of pollutants. The objective of this research was to analyze environmental exposure and biomarkers of exposure to polycyclic aromatic hydrocarbons, metals, and respiratory health in brickmakers to assess the baseline state of contamination in a brick-kiln area of San Luis Potosi, Mexico. Lead was quantified in soil and particulate matter of 2.5 μm (PM2.5) and 10 μm (PM10) in brick-kiln areas. In brickmakers, lead was evaluated in whole blood and 10 hydroxylated metabolites of polycyclic aromatic hydrocarbons were determined in urine. Respiratory health was assessed by spirometry, exhaled breath condensate, and a COPD-PS questionnaire. Data association was performed by Spearman correlation. Environmental concentrations and biomarkers of exposure are presented as medians, for lead, it was 60.4 mg/kg, for PM10, it was 2663.1 μg/m3, and for PM2.5, it was 166.6 μg/m3. For blood lead, it was 1.06 μg/dL, and the summed concentration of OH-PAHs in urine was 16.1 μg/L. Spirometry values were 2.8 ± 0.6 L and 2.9 ± 1.3 L/s FEV1 and FEV 25-75 respectively. The correlation results indicate that the older the age of the workers is and the extensive period they have been working, their lung function is affected the most. The health vulnerability present in these occupational activities is high, so it is necessary to make visible, address these economic activities in Mexico, and apply surveillance systems based on the health of the worker.