A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. We demonstrate that simultaneous Chk1- and MK2 inhibition leads to mitotic catastrophe in KRAS-mutant cells. This actionable synergistic interaction is validated using xenograft models, as well as distinct Kras- or Braf-driven autochthonous murine cancer models. Lastly, we show that combined checkpoint inhibition induces apoptotic cell death in KRAS- or BRAF-mutant tumor cells directly isolated from patients. These results strongly recommend simultaneous Chk1- and MK2 inhibition as a therapeutic strategy for the treatment of KRAS- or BRAF-driven cancers.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-ß (Aß) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aß. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

Inspiratory Muscle Dysfunction Mediates and Predicts a Disease Continuum of Hypercapnic Failure in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Advanced chronic obstructive pulmonary disease (COPD) is associated with chronic hypercapnic failure. The present work aimed to comprehensively investigate inspiratory muscle function as a potential key determinant of hypercapnic respiratory failure in patients with COPD. METHODS: Prospective patient recruitment encompassed 61 stable subjects with COPD across different stages of respiratory failure, ranging from normocapnia to isolated nighttime hypercapnia and daytime hypercapnia. Arterialized blood gas analyses and overnight transcutaneous capnometry were used for patient stratification. Assessment of respiratory muscle function encompassed body plethysmography, maximum inspiratory pressure (MIP), diaphragm ultrasound, and transdiaphragmatic pressure recordings following cervical magnetic stimulation of the phrenic nerves (twPdi) and a maximum sniff manoeuvre (Sniff Pdi). RESULTS: Twenty patients showed no hypercapnia, 10 had isolated nocturnal hypercapnia, and 31 had daytime hypercapnia. Body plethysmography clearly distinguished patients with and without hypercapnia but did not discriminate patients with isolated nocturnal hypercapnia from those with daytime hypercapnia. In contrast to ultrasound parameters and transdiaphragmatic pressures, only MIP reflected the extent of hypercapnia across all three stages. MIP values below -48 cmH2O predicted nocturnal hypercapnia (area under the curve = 0.733, p = 0.052). CONCLUSION: In COPD, inspiratory muscle dysfunction contributes to progressive hypercapnic failure. In contrast to invasive tests of diaphragm strength only MIP fully reflects the pathophysiological continuum of hypercapnic failure and predicts isolated nocturnal hypercapnia.

[Task Force Dyspnoe unit (DU)]. / Task Force Dyspnoe Unit (DU).

Acute dyspnoea is one of the most common internal medicine symptoms in the emergency department. It arises from an acute illness or from the exacerbation of a chronic illness. Symptom-related emergency structures and corresponding structural guidelines already exist in the stroke and chest pain units for dealing with the leading symptoms of acute stroke and acute chest pain. These are lacking in Germany for the key symptom of dyspnoea, although the benefits of these structures have already been proven in other countries. The German Society for Pneumology and Respiratory Medicine (DGP) has now set up a task force together with the Association of Pneumology Clinics (VPK), in order to deal with the topic and develop appropriate structural guidelines for such "dyspnoea units" in Germany. At the end of the process, the certification of such units at German hospitals is optional.

[Prognostic factors in an individualised approach to non-pharmacological therapy of COVID-19: from oxygen and mechanical ventilation to extracorporeal membrane oxygenation]. / Prognostische Faktoren bei einem schrittweisen Ansatz zur nicht-pharmakologischen Therapie von Sauerstoff und mechanischer Beatmung bis hin zur extrakorporalen Membranoxygenierung bei COVID-19.

BACKGROUND: Our centre followed a stepwise approach in the nonpharmacological treatment of respiratory failure in COVID-19 in accordance with German national guidelines, escalating non-invasive measures before invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyse this individualized approach to non-pharmacologic therapy in terms of patient characteristics and clinical features that may help predict more severe disease, particularly the need for intensive care. METHOD: This retrospective single-centre study of COVID-19 inpatients between March 2020 and December 2021 analysed anthropometric data, non-pharmacological maximum therapy and survival status via a manual medical file review. RESULTS: Of 1052 COVID-19-related admissions, 835 patients were included in the analysis cohort (54% male, median 58 years); 34% (n=284) received no therapy, 40% (n=337) conventional oxygen therapy (COT), 3% (n=22) high flow nasal cannula (NHFC), 9% (n=73) continuous positive airway pressure (CPAP), 7% (n=56) non-invasive ventilation (NIV), 4% (n=34) intermittent mandatory ventilation (IMV), and 3% (n=29) extracorporeal membrane oxygenation (ECMO). Of 551 patients treated with at least COT, 12.3% required intubation. A total of 183 patients required ICU treatment, and 106 (13%) died. 25 (74%) IMV patients and 23 (79%) ECMO patients died. Arterial hypertension, diabetes and dyslipidemia was more prevalent in non-survivors. Binary logistic analysis revealed the following risk factors for increased mortality: an oxygen supplementation of ≥2 L/min at baseline (OR 6.96 [4.01-12.08]), age (OR 1.09 [1.05-1.14]), and male sex (OR 2.23 [0.79-6.31]). CONCLUSION: The physician's immediate clinical decision to provide oxygen therapy, along with other recognized risk factors, plays an important role in predicting the severity of the disease course and thus aiding in the management of COVID-19.

[Outpatient care in pulmonology - a scientific analysis and a position paper of the German Society of Respiratory Medicine (DGP)]. / Ambulantisierung in der Pneumologie ­ eine wissenschaftliche Analyse und ein Positionspapier der DGP.

INTRODUCTION: The ambulantization of patient care that were previously provided as inpatient service is one of the goals of the current reform in the German healthcare system. In pulmonology, this particularly applies to endoscopic procedures. However, the real costs of endoscopic services, which form the basis for the calculation of a future so called hybrid DRG or in the AOP catalog, are unclear. METHODS: After selection of use cases including endoscopic procedures which can be performed on an outpatient basis by a committee of experts the appropriate DRGs were identified from the §â€Š21-KHEntgG data for 2022 published by the Institute for the Hospital Remuneration System (InEK). The costs were calculated from the respective InEK cost matrix added by the calculated material costs. RESULTS: The use cases suitable for outpatient treatment were systematic endobronchial ultrasound (EBUS) with transbronchial needle aspiration (calculated costs €â€Š2,175.60 without or €â€Š3,315.60 including PET/CT), navigation-assisted bronchoscopy for peripheral lesions (depending on the methodology €â€Š2,870.23 to €4,120.23) and diagnostic (flexible) bronchoscopy (€â€Š1,121.02). CONCLUSION: Outpatient treatment of endoscopic procedures that were previously performed inpatient is possible and necessary, and the costs calculated in this publication can form a reliable basis for appropriate reimbursement. Together with a structural quality that has been transformed to outpatient service and cross-sector cooperation, continued high-quality care for pneumological patients can be ensured.

ERS technical standards for using type III devices (limited channel studies) in the diagnosis of sleep disordered breathing in adults and children.

For more than three decades, type III devices have been used in the diagnosis of sleep disordered breathing in supervised as well as unsupervised settings. They have satisfactory positive and negative predictive values for detecting obstructive and central sleep apnoea in populations with moderately high pre-test probability of symptoms associated with these events. However, standardisation of commercially available type III devices has never been undertaken and the technical specifications can vary widely. None have been subjected to the same rigorous processes as most other diagnostic modalities in the medical field. Although type III devices do not include acquisition of electroencephalographic signals overnight, the minimum number of physical sensors required to allow for respiratory event scoring using standards outlined by the American Academy of Sleep Medicine remains debatable. This technical standard summarises data on type III studies published since 2007 from multiple perspectives in both adult and paediatric sleep practice. Most importantly, it aims to provide a framework for considering current type III device limitations in the diagnosis of sleep disordered breathing while raising research- and practice-related questions aimed at improving our use of these devices in the present and future.

Decannulation/Weaning Potential and Success in Home Intensive Care.

BACKGROUND: The number of patients receiving home long-term ventilation has risen considerably in recent decades owing to medical advancements. Experts believe that the potential for ventilator weaning or tracheostoma removal is currently insufficiently exploited. OBJECTIVE: The objective of this study was to investigate the characteristics, prognosis, and decannulation/weaning potential of patients under home intensive care. METHODS: In this retrospective analysis of 607 patients on home intensive care, decannulation/weaning status and survival were documented for a 2-year period after initial assessment. At the time of hospital discharge, when clinicians had deemed the weaning process concluded, an independent expert noninvasively assessed the long-term decannulation/weaning. Comparative analyses based on specific criteria, such as ventilation and decannulation/weaning status, age, and underlying diseases, were performed. Potential predictors of survival were identified via multivariable logistic regression. RESULTS: Eighteen percent of patients were decannulated/weaned within 2 years after hospital discharge and had better mean survival than patients not decannulated/weaned (552 vs. 420 days, p < 0.001). More than half of these patients were identified to have decannulation/weaning potential based on the assessment of the independent expert. Patients with neuromuscular and neurological diseases had the best survival (546 and 501 days), patients with postsurgical conditions and cardiological diseases the worst (346 and 323 days). Underlying disease and decannulation/weaning status were significant predictors of 2-year survival. CONCLUSION: Successful decannulation/weaning of patients on long-term home intensive care is associated with better survival. Even in the absence of decannulation/weaning potential at the time of hospital discharge, patients may develop decannulation/weaning potential over time, which should therefore be assessed repeatedly.

Analysis of an Individualised Stepwise Approach to Non-Pharmacological Therapy in COVID-19.

BACKGROUND: Early intubation versus use of conventional or high-flow nasal cannula oxygen therapy (COT/HFNC), continuous positive airway pressure (CPAP), and non-invasive ventilation (NIV) has been debated throughout the COVID-19 pandemic. Our centre followed a stepwise approach, in concordance with German national guidelines, escalating non-invasive modalities prior to invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO), rather than early or late intubation. OBJECTIVES: The aims of the study were to investigate the real-life usage of these modalities and analyse patient characteristics and survival. METHOD: A retrospective monocentric observation was conducted of all consecutive COVID-19 hospital admissions between March 2020 and December 2021 at a university-affiliated pulmonary centre in Germany. Anthropometric data, therapy, and survival status were descriptively analysed. RESULTS: From 1,052 COVID-19-related admissions, 835 patients were included (54% male, median 58 years). Maximum therapy was as follows: 34% (n = 284) no therapy, 40% (n = 337) COT, 3% (n = 22) HFNC, 9% (n = 73) CPAP, 7% (n = 56) NIV, 4% (n = 34) IMV, and 3% (n = 29) ECMO. Of 551 patients treated with at least COT, 12.3% required intubation. Overall, 183 patients required intensive unit care, and 106 (13%) died. Of the 68 patients who received IMV/ECMO, 48 died (74%). The strategy for non-pharmacological therapy was individual but remained consistent throughout the studied period. CONCLUSIONS: This study provides valuable insight into COVID-19 care in Germany and shows how the majority of patients could be treated with the maximum treatment required according to disease severity following the national algorithm. Escalation of therapy modality is interlinked with disease severity and thus associated with mortality.

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Adaptive servo-ventilation and mortality in patients with systolic heart failure and central sleep apnea: a single-center experience.

BACKGROUND: Central sleep apnea (CSA) is associated with increased mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Treatment of CSA with a certain type of adaptive servo-ventilation (ASV) device that targets minute ventilation (ASVmv) was found to be harmful in these patients. A newer generation of ASV devices that target peak flow (ASVpf) is presumed to have different effects on ventilation and airway patency. We analyzed our registry of patients with HFrEF-CSA to examine the effect of exposure to ASV and role of each type of ASV device on mortality. METHODS: This is a retrospective cohort study in patients with HFrEF and CSA who were treated with ASV devices between 2008 and 2015 at a single institution. Mortality data were collected through the institutional data honest broker. Usage data were obtained from vendors' and manufacturers' servers. Median follow-up was 64 months. RESULTS: The registry included 90 patients with HFrEF-CSA who were prescribed ASV devices. Applying a 3-h-per-night usage cutoff, we found a survival advantage at 64 months for those who used the ASV device above the cutoff (n = 59; survival 76%) compared to those who did not (n = 31; survival 49%; hazard ratio 0.44; CI 95%, 0.20 to 0.97; P = 0.04). The majority (n = 77) of patients received ASVpf devices with automatically adjusting end-expiratory pressure (EPAP) and the remainder (n = 13) received ASVmv devices mostly with fixed EPAP (n = 12). There was a trend towards a negative correlation between ASVmv with fixed EPAP and survival. CONCLUSION: In this population of patients with HFrEF and CSA, there was no evidence that usage of ASV devices was associated with increased mortality. However, there was evidence of differential effects of type of ASV technology on mortality.

Sleep-related breathing disorders in idiopathic pulmonary fibrosis are frequent and may be associated with pulmonary vascular involvement.

PURPOSE: Sleep-related breathing disorders (SRBD) may be associated with a worse prognosis in idiopathic pulmonary fibrosis (IPF). However, the prevalence of sleep disorders in IPF and the pathophysiological link between SRBD and IPF is unclear. PATIENTS AND METHODS: In this prospective trial, consecutive patients with stable IPF underwent polysomnography and cardiopulmonary exercise testing. Epworth sleepiness scale, Regensburg insomnia scale, and Pittsburgh sleep quality index were evaluated. Exclusion criteria were oxygen supplementation therapy, lung emphysema, and heart failure. For pairwise comparison of categorical data, the two-proportion z-test was applied. Correlation between continuous variables was assessed via the Pearson correlation coefficient. Patients without and with SRBD were compared. To find predictors for SRBD in IPF, multivariable logistic regression was applied. RESULTS: A total of 74 IPF patients were evaluated and 45 patients (11 female, median age 74 years, forced vital capacity 71.3%, DLCO 53.9%) were analyzed. Any kind of sleep disorder was found in 89% of patients. SRBD was present in 49% (81% obstructive sleep apnea, 19% central sleep apnea), insomnia in 40%, and periodic leg movements in 47% of subjects. The SRBD subgroup presented with a significantly lower performance (workload(peak)%pred 86.5 vs. 101.0 (p = 0.036); V'O2(AT) 618.5 ml/min vs. 774.0 ml/min (p = 0.043)) and exhibited a significantly higher V'E/V'CO2(peak) of 43.0 l/l vs. 38.5 l/l (p = 0.037). In search of predictors for SRBD by logistic regression, workload(peak)%pred was identified as a significant variable (p = 0.033). CONCLUSIONS: SRBD is frequent in IPF. Pulmonary vascular limitations may represent the pathophysiological link between IPF and SRBD. Workload(peak)%pred may be an independent risk factor for the occurrence of SRBD.

Clinical and financial impact of sleep disordered breathing on heart failure admissions.

BACKGROUND: The impact of sleep disordered breathing (SDB) on heart failure (HF) is increasingly recognized. However, limited data exist in support of quantification of the clinical and financial impact of SDB on HF hospitalizations. METHODS: A sleep-heart registry included all patients who underwent inpatient sleep testing during hospitalization for HF at a single cardiac center. Readmission data and actual costs of readmissions were obtained from the institutional honest broker. Patients were classified based on the inpatient sleep study as having no SDB, obstructive sleep apnea (OSA), or central sleep apnea (CSA). Cumulative cardiac readmission rates and costs through 3 and 6 months post-discharge were calculated. Unadjusted and adjusted (age, sex, body mass index, and left ventricular ejection fraction) modeling of cost was performed. RESULTS: The cohort consisted of 1547 patients, 393 (25%) had no SDB, 438 (28%) had CSA, and 716 (46%) had OSA. Within 6 months of discharge, 195 CSA patients (45%), 264 OSA patients (37%), and 109 no SDB patients (28%) required cardiovascular readmissions. Similarly, 3- and 6-month mortality rates were higher in both SDB groups than those with no SDB. Both unadjusted and adjusted readmission costs were higher in the OSA and CSA groups compared to no SDB group at 3 and 6 months post-discharge with the CSA and OSA group costs nearly double (~ $16,000) the no SDB group (~ $9000) through 6 months. INTERPRETATION: Previously undiagnosed OSA and CSA are common in patients hospitalized with HF and are associated with increased readmissions rate and mortality.

Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing.

Rationale: Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. Objectives: Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. Methods: From five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs. Measurements and Main Results: A total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93]. Conclusions: Using nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea.

Research Priorities for Patients with Heart Failure and Central Sleep Apnea. An Official American Thoracic Society Research Statement.

Background: Central sleep apnea (CSA) is common among patients with heart failure and has been strongly linked to adverse outcomes. However, progress toward improving outcomes for such patients has been limited. The purpose of this official statement from the American Thoracic Society is to identify key areas to prioritize for future research regarding CSA in heart failure.Methods: An international multidisciplinary group with expertise in sleep medicine, pulmonary medicine, heart failure, clinical research, and health outcomes was convened. The group met at the American Thoracic Society 2019 International Conference to determine research priority areas. A statement summarizing the findings of the group was subsequently authored using input from all members.Results: The workgroup identified 11 specific research priorities in several key areas: 1) control of breathing and pathophysiology leading to CSA, 2) variability across individuals and over time, 3) techniques to examine CSA pathogenesis and outcomes, 4) impact of device and pharmacological treatment, and 5) implementing CSA treatment for all individualsConclusions: Advancing care for patients with CSA in the context of heart failure will require progress in the arenas of translational (basic through clinical), epidemiological, and patient-centered outcome research. Given the increasing prevalence of heart failure and its associated substantial burden to individuals, society, and the healthcare system, targeted research to improve knowledge of CSA pathogenesis and treatment is a priority.

Hypoglossal nerve stimulation for obstructive sleep apnea: updated position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery.

Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize the complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions, whereat, minimal reporting standards to document outcome and usage are recommended.

[Latest news on RA-ILD]. / Aktuelles zur RA-ILD.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is of high clinical relevance. It not only affects the quality of life but also makes a significant contribution to the mortality rate of patients with rheumatoid arthritis. RA-ILD can present with all known radiological and histopathological patterns seen in other interstitial pneumonias. Among these pneumonias, diffuse alveolar damage (DAD), followed by usual interstitial pneumonia (UIP) has the worst prognosis. In addition, acute exacerbation of RA-ILD, which can occur at any time during the disease, is highly lethal. An algorithm for the diagnosis and treatment of RA-ILD is pending and will be addressed in the following article. In addition to immunosuppressants and disease-modifying antirheumatic drugs (DMARD), antifibrotics have recently gained importance in the therapy of RA-ILD.

Sleep laboratories reopening and COVID-19: a European perspective.

Clinical activities regarding sleep disordered breathing (SDB) have been sharply interrupted during the initial phase of the coronavirus disease 2019 (COVID-19) epidemic throughout Europe. In the past months, activities have gradually restarted, according to epidemiological phase of COVID-19 and national recommendations. The recent increase in cases throughout Europe demands a reconsideration of management strategies of SDB accordingly. Diagnosis of SDB and initiation of treatment pose some specific problems to be addressed to preserve the safety of patients and health personnel. This perspective document by a group of European sleep experts aims to summarise some different approaches followed in Europe and United States, which reflect national recommendations according to the epidemiological phase of the COVID-19 infection. Respiratory sleep medicine is likely to change in the near future, and use of telemedicine will grow to avoid unnecessary risks and continue to provide optimal care to patients. In addition, the document covers paediatric sleep studies and indications for titration of noninvasive ventilation, as well as precautions to be followed by patients who are already on positive airway pressure treatment. A single consensus document developed by the European Respiratory Society and national societies would be desirable to harmonise SDB management throughout Europe.

European Respiratory Society statement on sleep apnoea, sleepiness and driving risk.

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.

Beyond the AHI-pulse wave analysis during sleep for recognition of cardiovascular risk in sleep apnea patients.

Recent evidence supports the use of pulse wave analysis during sleep for assessing functional aspects of the cardiovascular system. The current study compared the influence of pulse wave and sleep study-derived parameters on cardiovascular risk assessment. In a multi-centric study design, 358 sleep apnea patients (age 55 ± 13 years, 64% male, body mass index 30 ± 6 kg m-2 , apnea-hypopnea index 13 [5-26] events per hr) underwent a standard overnight sleep recording. A novel cardiac risk index was computed based on pulse wave signals derived from pulse oximetry, reflecting vascular stiffness, cardiac variability, vascular autonomic tone and nocturnal hypoxia. Cardiovascular risk was determined using the ESC/ESH cardiovascular risk matrix, and categorized to high/low added cardiovascular risk. Comparisons between cardiac risk index and sleep parameters were performed for cardiovascular risk prediction. Apnea-hypopnea index, oxygen desaturation index and cardiac risk index were associated with high cardiovascular risk after adjustment for confounders (p = .002, .001, < .001, respectively). In a nested reference model consisting of age, gender and body mass index, adding cardiac risk index but not apnea-hypopnea index or oxygen desaturation index significantly increased the area under the receiver operating characteristic curve (p = .012, .22 and .16, respectively). In a direct comparison of oxygen desaturation index and cardiac risk index, only the novel risk index had an independent effect on cardiovascular risk prediction (pCRI  < .001, pODI  = .71). These results emphasize the association between nocturnal pulse wave and overall cardiovascular risk determined by an established risk matrix. Thus, pulse wave analysis during sleep provides a powerful approach for cardiovascular risk assessment in addition to conventional sleep study parameters.