[Curriculum "Tracheostomy management in dysphagia therapy"]. / Curriculum "Trachealkanülenmanagement in der Dysphagietherapie".

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.

[Curriculum "Tracheostomy management in dysphagia therapy"]. / Curriculum "Trachealkanülenmanagement in der Dysphagietherapie".

The number of tracheotomized patients with dysphagia and their need for treatment are continuously increasing in clinical and community settings. The revised version of the directive on home care and community-based intensive care of the Federal Joint Committee (G-BA) requires that tracheotomized patients are regularly evaluated with the aim of identifying and promoting the therapeutic potential after hospital discharge. Dysphagia treatment plays a crucial role as without improvement of severe dysphagia there is practically no possibility for decannulation. Tracheotomized patients with dysphagia are treated by speech and language therapists (SLT); however, the contents of tracheostomy management (TM) are not obligatory in the speech and language therapeutic training curricula, so that there is a need for further education and treatment standards must be secured. Therefore, the German Interdisciplinary Society for Dysphagia (DGD) in cooperation with the participating German medical and therapeutic societies developed a postgraduate curriculum for TM. This should serve as the basis for contents in TM and qualification of therapists within the framework of the delegation of medical services. The goals of the TM curriculum are the definition of theoretical and practical contents of TM, the qualification to perform TM according to current standards of care and quality assurance. The curriculum defines two qualification levels (user and trainer), entry requirements, curricular contents, examination and qualification criteria as well as transitional regulations for SLTs already experienced in TM.

Alveolar gradients in breath analysis. A pilot study with comparison of room air and inhaled air by simultaneous measurements using ion mobility spectrometry.

Analyzing exhaled breath samples, especially using a highly sensitive method such as MCC/IMS (multi-capillary column/ion mobility spectrometry), may also detect analytes that are derived from exogenous production. In this regard, there is a discussion about the optimal interpretation of exhaled breath, either by considering volatile organic compounds (VOCs) only in exhaled breath or by additionally considering the composition of room air and calculating the alveolar gradients. However, there are no data on whether the composition and concentration of VOCs in room air are identical to those in truly inhaled air directly before analyzing the exhaled breath. The current study aimed to determine whether the VOCs in room air, which are usually used for the calculation of alveolar gradients, are identical to the VOCs in truly inhaled air. For the measurement of inhaled air and room air, two IMS, each coupled with an MCC that provided a pre-separation of the VOCs, were used in parallel. One device was used for sampling room air and the other for sampling inhaled air. Each device was coupled with a newly invented system that cleaned room air and provided a clean carrier gas, whereas formerly synthetic air had to be used as a carrier gas. In this pilot study, a healthy volunteer underwent three subsequent runs of sampling of inhaled air and simultaneous sampling and analysis of room air. Three of the selected 11 peaks (P4-unknown, P5-1-Butanol, and P9-Furan, 2-methyl-) had significantly higher intensities during inspiration than in room air, and four peaks (P1-1-Propanamine, N-(phenylmethylene), P2-2-Nonanone, P3-Benzene, 1,2,4-trimethyl-, and P11-Acetyl valeryl) had higher intensities in room air. Furthermore, four peaks (P6-Benzaldehyde, P7-Pentane, 2-methyl-, P8-Acetone, and P10-2-Propanamine) showed inconsistent differences in peak intensities between inhaled air and room air. To the best of our knowledge, this is the first study to compare simultaneous sampling of room air and inhaled air using MCC/IMS. The simultaneous measurement of inhaled air and room air showed that using room air for the calculation of alveolar gradients in breath analysis resulted in different alveolar gradient values than those obtained by measuring truly inhaled air.

Successful simultaneous stenting of a pulmonary artery and vein in pulmonary vascular stenosis due to silicosis. Case report and literature review.

A 58-year-old patient was admitted to the emergency department due to severe respiratory insufficiency. Anamnesis revealed that the patient had experienced increasing stress dyspnea for a few months. Upon imaging, an acute pulmonary embolism was excluded, but peribronchial and hilar soft tissue proliferation with compression of central parts of the pulmonary circulation was found. The patient had a history of silicosis. The histology report showed tumor-free lymph node particles with prominent anthracotic pigment and dust depositions without evidence of IgG4-associated disease. The patient was administered steroid therapy and underwent simultaneous stenting of the left interlobular pulmonary artery and the upper right pulmonary vein. As a result, a significant improvement in symptoms and physical performance was achieved. The diagnosis of inflammatory or, in particular, fibrosing mediastinal processes can be challenging and important clinical symptoms must be taken into account, especially if the pulmonary vasculature is involved. In such cases, the possibility of interventional procedures should be examined in addition to drug therapy options.

[S2k Guideline - Recommendations for Inpatient Therapy of Patients with COVID-19]. / S2k-Leitlinie ­ Empfehlungen zur stationären Therapie von Patienten mit COVID-19.

Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

[Weaning in a Pandemic Situation - A Position Paper]. / Weaning in der Situation einer Pandemie ­ Ein Positionspapier.

The logistical and infectious peculiarities and requirements challenge the intensive care treatment teams aiming at a successful liberation of patients from long-term mechanical ventilation. Especially in the pandemic, it is therefore important to use all potentials for weaning and decannulation, respectively, in patients with prolonged weaning.Weaning centers represent units of intensive medical care with a particular specialization in prolonged weaning. They are an integral part of a continuous care concept for these patients. A systematic weaning concept in the pandemic includes structural, personnel, equipment, infectiological and hygienic issues. In addition to the S2k guideline "Prolonged weaning" this position paper hightlights a new classification in prolonged weaning and organizational structures required in the future for the challenging pandemic situation. Category A patients with high weaning potential require a structured respiratory weaning in specialized weaning units, so as to get the greatest possible chance to realize successful weaning. Patients in category B with low or currently nonexistent weaning potential should receive a weaning attempt after an intermediate phase of further stabilization in an out-of-hospital ventilator unit. Category C patients with no weaning potential require a permanent out-of-hospital care, alternatively finishing mechanical ventilation with palliative support.Finally, under perspective in the position paper the following conceivable networks and registers in the future are presented: 1. locally organized regional networks of certified weaning centers, 2. a central, nationwide register of weaning capacities accordingly the already existing DIVI register and 3. registration of patients in difficult or prolonged weaning.

[Responsibilities of Weaning Centers during the COVID-19 Pandemic Outbreak - Recommendations for the Assignment of ICU Capacities in COVID-19 Patients as shown by the Berlin-Brandenburg POST-SAVE-Model]. / Aufgaben der Weaning-Zentren im Pandemiefall COVID-19.

The enormous increase in patients with severe respiratory distress due to the COVID-19 pandemic outbreak requires a systematic approach to optimize ventilated patient at risk flow. A standardised algorithm called "SAVE" was developed to distribute patients with COVID-19 respiratory distress syndrome requiring invasive ventilation. This program is established by now in Berlin. An instrumental bottleneck of this approach is the vacant slot assignment in the intensive care unit to guarantee constant patient flow. The transfer of the patients after acute care treatment is needed urgently to facilitate the weaning process. In a next step we developed a triage algorithm to identify patients at SAVE intensive care units with potential to wean and transfer to weaning institutions - we called POST SAVE. This manuscript highlights the algorithms including the use of a standardised digital evaluation tool, the use of trained navigators to facilitate the communication between SAVE intensive care units and weaning institutions and the establishment of a prospective data registry for patient assignment and reevaluation of the weaning potential in the future.

[Position Paper for the State of the Art Application of Respiratory Support in Patients with COVID-19 - German Respiratory Society]. / Positionspapier zur praktischen Umsetzung der apparativen Differenzialtherapie der akuten respiratorischen Insuffizienz bei COVID-19.

Against the background of the pandemic caused by infection with the SARS-CoV-2, the German Society for Pneumology and Respiratory Medicine (DGP e.V.), in cooperation with other associations, has designated a team of experts in order to answer the currently pressing questions about therapy strategies in dealing with COVID-19 patients suffering from acute respiratory insufficiency (ARI).The position paper is based on the current knowledge that is evolving daily. Many of the published and cited studies require further review, also because many of them did not undergo standard review processes.Therefore, this position paper is also subject to a continuous review process and will be further developed in cooperation with the other professional societies.This position paper is structured into the following five topics:1. Pathophysiology of acute respiratory insufficiency in patients without immunity infected with SARS-CoV-22. Temporal course and prognosis of acute respiratory insufficiency during the course of the disease3. Oxygen insufflation, high-flow oxygen, non-invasive ventilation and invasive ventilation with special consideration of infectious aerosol formation4. Non-invasive ventilation in ARI5. Supply continuum for the treatment of ARIKey points have been highlighted as core statements and significant observations. Regarding the pathophysiological aspects of acute respiratory insufficiency (ARI), the pulmonary infection with SARS-CoV-2 COVID-19 runs through three phases: early infection, pulmonary manifestation and severe hyperinflammatory phase.There are differences between advanced COVID-19-induced lung damage and those changes seen in Acute Respiratory Distress Syndromes (ARDS) as defined by the Berlin criteria. In a pathophysiologically plausible - but currently not yet histopathologically substantiated - model, two types (L-type and H-type) are distinguished, which correspond to an early and late phase. This distinction can be taken into consideration in the differential instrumentation in the therapy of ARI.The assessment of the extent of ARI should be carried out by an arterial or capillary blood gas analysis under room air conditions and must include the calculation of the oxygen supply (measured from the variables of oxygen saturation, the Hb value, the corrected values of the Hüfner number and the cardiac output). In principle, aerosols can cause transmission of infectious viral particles. Open systems or leakage systems (so-called vented masks) can prevent the release of respirable particles. Procedures in which the invasive ventilation system must be opened, and endotracheal intubation must be carried out are associated with an increased risk of infection.The protection of personnel with personal protective equipment should have very high priority because fear of contagion must not be a primary reason for intubation. If the specifications for protective equipment (eye protection, FFP2 or FFP-3 mask, gown) are adhered to, inhalation therapy, nasal high-flow (NHF) therapy, CPAP therapy or NIV can be carried out according to the current state of knowledge without increased risk of infection to the staff. A significant proportion of patients with respiratory failure presents with relevant hypoxemia, often also caused by a high inspiratory oxygen fraction (FiO2) including NHF, and this hypoxemia cannot be not completely corrected. In this situation, CPAP/NIV therapy can be administered under use of a mouth and nose mask or a respiratory helmet as therapy escalation, as long as the criteria for endotracheal intubation are not fulfilled.In acute hypoxemic respiratory insufficiency, NIV should be performed in an intensive care unit or in a comparable unit by personnel with appropriate expertise. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring with readiness to carry out intubation must be ensured at all times. If CPAP/NIV leads to further progression of ARI, intubation and subsequent invasive ventilation should be carried out without delay if no DNI order is in place.In the case of patients in whom invasive ventilation, after exhausting all guideline-based measures, is not sufficient, extracorporeal membrane oxygenation procedure (ECMO) should be considered to ensure sufficient oxygen supply and to remove CO2.

[Prolonged Weaning - S2k-Guideline Published by the German Respiratory Society]. / Prolongiertes Weaning.

Mechanical ventilation (MV) is an essential part of modern intensive care medicine. MV is performed in patients with severe respiratory failure caused by insufficiency of respiratory muscles and/or lung parenchymal disease when/after other treatments, (i. e. medication, oxygen, secretion management, continuous positive airway pressure or nasal highflow) have failed.MV is required to maintain gas exchange and to buy time for curative therapy of the underlying cause of respiratory failure. In the majority of patients weaning from MV is routine and causes no special problems. However, about 20 % of patients need ongoing MV despite resolution of the conditions which precipitated the need for MV. Approximately 40 - 50 % of time spent on MV is required to liberate the patient from the ventilator, a process called "weaning."There are numberous factors besides the acute respiratory failure that have an impact on duration and success rate of the weaning process such as age, comorbidities and conditions and complications acquired in the ICU. According to an international consensus conference "prolonged weaning" is defined as weaning process of patients who have failed at least three weaning attempts or require more than 7 days of weaning after the first spontaneous breathing trial (SBT). Prolonged weaning is a challenge, therefore, an inter- and multi-disciplinary approach is essential for a weaning success.In specialised weaning centers about 50 % of patients with initial weaning failure can be liberated from MV after prolonged weaning. However, heterogeneity of patients with prolonged weaning precludes direct comparisons of individual centers. Patients with persistant weaning failure either die during the weaning process or are discharged home or to a long term care facility with ongoing MV.Urged by the growing importance of prolonged weaning, this Sk2-guideline was first published in 2014 on the initiative of the German Respiratory Society (DGP) together with other scientific societies involved in prolonged weaning. Current research and study results, registry data and experience in daily practice made the revision of this guideline necessary.The following topics are dealt with in the guideline: Definitions, epidemiology, weaning categories, the underlying pathophysiology, prevention of prolonged weaning, treatment strategies in prolonged weaning, the weaning unit, discharge from hospital on MV and recommendations for end of life decisions.Special emphasis in the revision of the guideline was laid on the following topics:- A new classification of subgroups of patients in prolonged weaning- Important aspects of pneumological rehabilitation and neurorehabilitation in prolonged weaning- Infrastructure and process organization in the care of patients in prolonged weaning in the sense of a continuous treatment concept- Therapeutic goal change and communication with relativesAspects of pediatric weaning are given separately within the individual chapters.The main aim of the revised guideline is to summarize current evidence and also expert based- knowledge on the topic of "prolonged weaning" and, based on the evidence and the experience of experts, make recommendations with regard to "prolonged weaning" not only in the field of acute medicine but also for chronic critical care.Important addressees of this guideline are Intensivists, Pneumologists, Anesthesiologists, Internists, Cardiologists, Surgeons, Neurologists, Pediatricians, Geriatricians, Palliative care clinicians, Rehabilitation physicians, Nurses in intensive and chronic care, Physiotherapists, Respiratory therapists, Speech therapists, Medical service of health insurance and associated ventilator manufacturers.

[Exercise Testing in Respiratory Medicine - DGP Recommendations]. / Belastungsuntersuchungen in der Pneumologie ­ Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V.

This document replaces the DGP recommendations published in 1998 and 2013. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method and its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for blood gas analysis and right heart catheterization during exercise, walk tests, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, obesity, monitoring of rehabilitation or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.

[Survey of Specialist Pulmonary Medicine Health Care Structures for Patients with Interstitial Lung Disease in Nordrhein-Westfalen, Germany - A Pilot Project of the Western German Respiratory Society (WdGP)]. / Erfassung der pneumologisch-fachärztlichen Versorgungsstrukturen für Patienten mit interstitiellen Lungenerkrankungen in Nordrhein-Westfalen.

AIM OF THE STUDY: Survey of specialist pulmonary medicine health care structures for patients with interstitial lung disease (ILD) in Nordrhein-Westfalen, Germany. METHODS: The Western German Respiratory Society initiated a voluntary registration of ILD expert centers. Structural quality and processes were evaluated by questionnaire. RESULTS: 49 centers were registered, 46 allowed analysis of their center data (15 pulmonology specialist practices, 34 hospital pulmonology departments). Specialist practices saw a median of 360 ILD patients per year (26 % first diagnosis), hospital departments a median of 105 ILD patients per year (63 % first diagnosis). 10 centers diagnose more than 100 new ILD cases per year. Specialist practices report median 50 bronchoscopies per year, hospital departments median 1396. 78 % of the centers participate in a multidisciplinary ILD case conference. CONCLUSION: Several ILD expert centers were identified in Nordrhein-Westfalen. Outpatient care mainly involves the monitoring of ILD patients, inpatient services focus on complex initial diagnostics or cases with unusual disease behaviour. ILD centers meeting regional health care needs should be supported in their development.

Targeting intrinsic apoptosis and other forms of cell death by BH3-mimetics in glioblastoma.

INTRODUCTION: Novel approaches to treat malignant brain tumors are necessary since these neoplasms still display an unfavorable prognosis. Areas covered: In this review, the authors summarize and analyze recent preclinical data that suggest that targeting intrinsic apoptosis may be a suitable strategy for the treatment of malignant gliomas. They focus on the anti-apoptotic Bcl-2 family members of proteins and the recent drug developments in that field with a special focus on BH3-mimetics. With the discovery of BH3-mimetics that interfere with anti-apoptotic Bcl-2 family members in the low nanomolar range significant excitement has been generated towards these class of inhibitors, such as ABT-737, ABT-263 and the most recent successor, ABT-199 which is most advanced with respect to clinical application. The authors discuss the more recent selective inhibitors of Bcl-xL and Mcl-1. Concerning Mcl-1, these novel classes of inhibitors have the potential to impact malignant gliomas since these tumors reveal increased levels of Mcl-1. Expert opinion: The recent development of certain small molecules raises significant hope that intrinsic apoptosis might soon be efficiently targetable for malignancies of the central nervous system. That being said, additional studies are necessary to determine which of the BH3-mimetics might be most suitable.

BH3-mimetics and BET-inhibitors elicit enhanced lethality in malignant glioma.

Drug combination therapies remain pivotal for the treatment of heterogeneous malignancies, such as glioblastomas. Here, we show a novel lethal interaction between Bcl-xL and c-myc inhibition accomplished by bromodomain protein inhibitors. Established, patient-derived xenograft and stem cell-like glioma cells were treated with the novel bromodomain protein inhibitors, JQ1 and OTX015, along with BH3-mimetics, ABT263 or Obatoclax. Synergy was assessed by calculation of CI values. Small interfering RNAs (siRNAs) were used for gene silencing and mechanistic studies. In vivo experiments were performed in a glioblastoma xenograft model. Single treatments with JQ1 and OTX015 had only moderate effects on the reduction of cellular viability. However, the combination treatment of BH3-mimetics along with JQ1 or OTX015 resulted in a highly synergistic reduction of cellular viability in a broad range of different model systems of malignant glioma. Similarly, knockdown of c-myc sensitized glioma cells for ABT263 mediated cell death. The enhanced loss of cellular viability in the combination treatment was mediated by activation of apoptosis with dissipation of mitochondrial membrane potential and caspase cleavage. The combination treatment led to a modulation of anti- and pro-apoptotic Bcl-2 family members with an increase in pro-apoptotic Noxa mediated by ATF4. Small interfering RNA mediated knockdown of Bak and Noxa protected glioma cells from ABT263/JQ1 mediated apoptosis. Finally, the combination treatment of ABT263 and OTX015 resulted in a regression of tumors and a significantly smaller tumor size as compared to single or vehicle treated tumors. Thus, these results warrant clinical testing for the drug combination of BH3-mimetics along with bromodain protein inhibitors.

Simultaneous Interference with HER1/EGFR and RAC1 Signaling Drives Cytostasis and Suppression of Survivin in Human Glioma Cells in Vitro.

We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succinimidyl ester was performed in order to determine the induction of apoptosis, necrosis or cytostasis in established and primary cultured glioblastoma cells. Moreover, expression of Ki-67 was determined by immunofluorescence, and the expression of cell cycle proteins was analysed by Western blot. Our data show that combined treatment with erlotinib and NSC23766 resulted in a reduced number of cell divisions, a significantly decreased Ki-67 expression, increased apoptosis and autophagy when compared to single agent treatments. On the molecular level, concomitant treatment with both agents resulted in a pronounced downregulation of cyclin D1, cyclin-dependent kinases 2, 4 and 6, as well as of survivin when compared to treatments with either agent alone. In conclusion, we demonstrate that combined treatment of human glioma cell lines in vitro with erlotinib and NSC23766 markedly inhibits cell division, induces apoptosis independent of caspase-3 activation and induces autophagy concomitant with suppression of survivin.