Nasal High-Flow Oxygen Therapy in Chronic Respiratory Failure for Homecare Applications-A Feasibility Study.

Background: While high-flow nasal cannulas (HFNCs) represent the standard of care in the intensive care unit for patients with severe hypoxemia, its use in homecare settings is uncommon despite its potential. The potential benefits and challenges of the high-flow nasal cannula (HFNC) in homecare settings compared to standard long-term oxygen via nasal low-flow therapy are unclear. Methods: We conducted a prospective monocentric feasibility study at the Department of Respiratory Medicine, University Hospital, Goethe University Frankfurt, Germany. Patients with interstitial lung disease or severe bronchiectasis (including cystic fibrosis) were enrolled into the study. The HFNC was introduced during hospitalization. The patients' compliance with home use advice and arterial blood gas results were evaluated at a 4-6-week follow-up. Results: A total of 12 patients were analyzed. HFNC initiation did not result in a significant improvement of the pO2/fiO2 (p/f) ratio. Only 8 out of 12 (66.6%) patients used the HFNC at home after the initial in-hospital initiation. Only 7 of the total 12 patients were using the therapy at a follow-up 3-6 weeks after HFNC onset. Two patients died during the observation, resulting in a surveillance mortality rate of 16.7%. Conclusions: The feasibility data showed low adherence to the HFNC at home. The lack of any positive effect on the p/f ratio may be due to low airflow rates and overall mild hypoxemia compared to patients with severe respiratory failure in the ICU.

Multicenter Real-World Analysis of Combined MET and EGFR Inhibition in Patients With Non-Small Cell Lung Cancer and Acquired MET Amplification or Polysomy After EGFR Inhibition.

PURPOSE: MET amplification is a common resistance mechanism to EGFR inhibition in EGFR-mutant non-small cell lung cancer (NSCLC). Several trials showed encouraging results with combined EGFR and MET inhibition (EGFRi/METi). However, MET amplification has been inconsistently defined and frequently included both polysomy and true amplification. METHODS: This is a multicenter, real-world analysis in patients with disease progression on EGFR inhibition and MET copy number gain (CNG), defined as either true amplification (MET to centromere of chromosome 7 ratio [MET-CEP7] ≥ 2) or polysomy (gene copy number ≥ 5, MET-CEP7 < 2). RESULTS: A total of 43 patients with MET CNG were included, 42 of whom were detected by FISH. Twenty-three, 7, and 14 received EGFRi/METi, METi, and SoC, respectively. Patients in the EGFRi/METi cohort exhibited a superior real-world clinical benefit rate, defined as stable disease or better, of 82% (95% confidence interval [CI], 60-95) compared to METi (29%, 4-71) and SoC (50%, 23-77). Median real-world progression-free survival was longer with EGFRi/METi with 9.8 vs. 4.3 months with METi (hazard ratio [HR], 0.19, 95% CI, 0.06-0.57) and 3.7 months with SoC (0.41, 0.18-0.91), respectively. Overall survival was numerically improved. Interaction analysis with treatment and type of CNG (amplification vs. polysomy) suggests that differences were exclusively driven by MET-amplified patients receiving EGFRi/METi (HR for OS, 0.09, 0.01-0.54). CONCLUSION: In this real-world study, EGFRi/METi showed clinical benefit over METi and SoC. Future studies should focus on the differential impact of the type of MET CNG with a focus on true MET amplification as predictor of response.

Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.

PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

Frequency and clinical significance of Herpes simplex virus type 1/2 reactivation in adult patients with mild to moderately severe community-acquired pneumonia: a multicentre cohort study.

PURPOSE: This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP). METHODS: The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death). RESULTS: Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7-16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0-2 and survived the first 28 day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66 years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS. CONCLUSION: Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course.

The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches.

Comparison of clinical outcomes in hospitalized patients with COVID-19 or non-COVID-19 community-acquired pneumonia in a prospective observational cohort study.

PURPOSE: Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management. METHODS: Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment. RESULTS: Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38-8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31-12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47-2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65-8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27-0.70]). CONCLUSION: Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens.

Resurgence of common respiratory viruses in patients with community-acquired pneumonia (CAP)-A prospective multicenter study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs. OBJECTIVES: The aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18-59 years and ≥60 years. STUDY DESIGN: We analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study. RESULTS: We identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected. CONCLUSIONS: Beginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns.

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019.

INTRODUCTION: Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany. METHODS: Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2 years and adults ≥ 60 years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities). RESULTS: Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60 years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44 year old persons (five to sixfold higher) than in ≥ 75 year old persons (two to threefold higher). CONCLUSIONS: This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60 years and among adults with underlying risk factors.

Mycobacterium avium complex pulmonary disease patients with limited treatment options.

How to identify MAC-PD patients with limited treatment options: an expert consensus https://bit.ly/3QwLQ8T.

Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care. METHODS: We focused on cardiovascular comorbidities, blood high sensitivity troponin (hs-troponin) and lipid profiles in COPD patients with and without AATD. We used clinical data from six German University Medical Centres of the MIRACUM (Medical Informatics Initiative in Research and Medicine) consortium. The codes for the international classification of diseases (ICD) were used for COPD as a main diagnosis and for comorbidities and blood laboratory data were obtained. Data analyses were based on the DataSHIELD framework. RESULTS: Out of 112,852 visits complete information was available for 43,057 COPD patients. According to our findings, 746 patients with AATD (1.73%) showed significantly lower total blood cholesterol levels and less cardiovascular comorbidities than non-AATD COPD patients. Moreover, after adjusting for the confounder factors, such as age, gender, and nicotine abuse, we confirmed that hs-troponin is a suitable predictor of overall mortality in COPD patients. The comorbidities associated with AATD in the current study differ from other studies, which may reflect geographic and population-based differences as well as the heterogeneous characteristics of AATD. CONCLUSION: The concept of MIRACUM is suitable for the analysis of a large healthcare database. This study provided evidence that COPD patients with AATD have a lower cardiovascular risk and revealed that hs-troponin is a predictor for hospital mortality in individuals with COPD.

Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-Cohort.

OBJECTIVES: The objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH. METHODS: Seventy-three (n = 73) PLWH (median CD4 3-6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test. RESULTS: Although the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally. CONCLUSIONS: Our study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations.

RSV vaccination strategies for high-risk patients 2023: a collaborative position paper by leading German medical societies and organizations.

Respiratory syncytial virus (RSV) inflicts severe illness and courses of infections not only in neonates, infants, and young children, but also causes significant morbidity and mortality in older adults and in people with immunosuppression, hemato-oncologic disease, chronic lung disease, or cardiovascular disease. In June and August 2023, effective vaccines against RSV were approved for the first time by the European Medicines Agency (EMA) for the EU. The respective pivotal studies showed a very high efficacy of the vaccine in preventing severe RSV-associated respiratory infections. At this point, use of the respective vaccines is restricted to persons aged 60 years or older, according to the registration studies. We therefore recommend use of the vaccination in persons aged 60 years or older. In addition, we recommend use of the vaccination in adults of any age with severe pulmonary or cardiovascular pre-existing conditions, as well as in adults with significant immune compromise, after individual consultation with the treating physician. Cost coverage can be applied for individually with the responsible health insurance company.

Efficacy and safety of zapnometinib in hospitalised adult patients with COVID-19 (RESPIRE): a randomised, double-blind, placebo-controlled, multicentre, proof-of-concept, phase 2 trial.

Background: Zapnometinib is an oral, non-ATP-competitive, small-molecule inhibitor of MEK1/MEK2 with immunomodulatory and antiviral properties. We aimed to investigate the safety and efficacy of zapnometinib in patients with COVID-19. Methods: In this randomised, double-blind, placebo-controlled, multicentre, proof-of-concept, phase 2 trial, we recruited hospitalised adults with moderate or severe COVID-19 from 18 hospitals in Germany, India, Romania, South Africa, and Spain. Those requiring ICU admission or ventilator support at screening or randomisation were excluded. Patients were randomly assigned (1:1) to receive oral zapnometinib (900 mg on Day 1; 600 mg on Days 2-6) or matching placebo, on top of standard of care. Randomisation, stratified by baseline clinical severity status (CSS 3 or 4, measured on a 7-point ordinal scale), was done using Interactive Response Technology. Patients, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was CSS at Day 15 and was conducted on the full analysis set (FAS: all patients who were randomised to the study, received at least one dose of study medication and had at least one post-dose assessment of CSS, as randomised). Safety analyses were conducted on the safety analysis set (all study participants who received at least one dose of study medication, as treated). This study is registered at ClinicalTrials.gov (NCT04776044) and EudraCT (2020-004206-59). Findings: The trial was terminated early as the emergence of the Omicron variant impacted recruitment. Between 12th April 2021 and 9th August 2022, 104 of the planned 220 patients were enrolled and randomly assigned, 103 were treated, and 101 were included in the FAS (zapnometinib: n = 50; placebo: n = 51). The primary outcome was not significantly different between the two groups, but patients on zapnometinib had higher odds of improved CSS versus placebo (odds ratio [OR] 1.54 [95% CI 0.72-3.33]; p = 0.26). Predefined subgroup analyses identified trends for improved CSS in patients with severe disease at baseline (OR 2.57 [0.76-8.88]; p = 0.13) and non-Omicron variants (OR 2.36 [0.85-6.71]; p = 0.10); the p value of the CSS subgroup by Treatment interaction term in the model was p = 0.28. The frequency and intensity of adverse events was low and similar between arms. Twenty (39.2%) patients treated with zapnometinib experienced adverse events compared with eighteen (34.6%) patients treated with placebo. One patient receiving zapnometinib and two patients receiving placebo died during the study. None of the deaths were considered related to study medication. Interpretation: These results provide proof-of-concept for the innovative approach of targeting the Raf/MEK/ERK pathway in patients with hospitalised moderate/severe COVID-19. Further clinical studies will be required to evaluate the clinical benefit of zapnometinib in this and other indications. Funding: Atriva Therapeutics GmbH and the Federal Ministry of Education and Research, Germany.

Survival benefit with checkpoint inhibitors versus chemotherapy is modified by brain metastases in patients with recurrent small cell lung cancer.

Introduction: Small cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear. Methods: In this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival. Results: Among 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HRadj] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HRadj 0.34, p=0.003; no CRT: HRadj 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HRadj 0.85, p=0.59). Conclusion: CPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM.

Best Practices for the Management of Patients with Non-Tuberculous Mycobacterial Pulmonary Disease According to a German Nationwide Analysis of Expert Centers.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic inflammatory lung disease caused by infection with non-tuberculous mycobacteria (NTM). International guidelines provide evidence-based recommendations on appropriate diagnosis and treatment strategies, but there is a need for sharing day-to-day best practice between treatment centers to optimize patient care. This is particularly valuable for rare diseases like NTM-PD. In this cross-sectional analysis of NTM-PD management in Germany, medical and administrative staff from seven treatment centers were interviewed to identify best practice in the diagnosis, treatment, and ongoing management of patients with NTM-PD, including related hospital infrastructure and administration processes. A prioritization led to a collection of best practices for the management of patients with NTM-PD in Germany, which is presented here. Selected current best practices included performance of regular sputum tests for diagnosis, use of medical reports, and regular follow-up visits as well as increased interaction between physicians across different specialties. Future best practices that may be implemented to overcome current barriers comprised disease awareness activities, patient empowerment, and new approaches to enhance physician interaction. Challenges related to their implementation are also discussed and will help to raise disease awareness. The presented best practices may guide and optimize patient management in other centers.

[Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method]. / Maßnahmen und Empfehlungen für die Sicherstellung adäquater stationärer Versorgungskapazitäten für das Pandemiemanagement innerhalb einer Region ­ Ergebnisse eines hybriden Delphi-Verfahrens.

INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.

Characteristics, clinical course and outcome of ventilated patients at a non-surgical intensive care unit in Germany: a single-centre, retrospective observational cohort analysis.

OBJECTIVES: The objective of this study was to evaluate epidemiological characteristics, clinical course and outcome of mechanically ventilated non-surgical intensive care unit (ICU) patients, with the aim of improving the strategic planning of ICU capacities. DESIGN: We conducted a retrospective observational cohort analysis. Data from mechanically ventilated intensive care patients were obtained by investigating electronic health records. The association between clinical parameters and ordinal scale data of clinical course was evaluated using Spearman correlation and Mann-Whitney U test. Relations between clinical parameters and in-hospital mortality rates were examined using binary logistic regression analysis. SETTING: A single-centre study at the non-surgical ICU of the University Hospital of Frankfurt, Germany (tertiary care-level centre). PARTICIPANTS: All cases of critically ill adult patients in need of mechanical ventilation during the years 2013-2015 were included. In total, 932 cases were analysed. RESULTS: From a total of 932 cases, 260 patients (27.9%) were transferred from peripheral ward, 224 patients (24.1%) were hospitalised via emergency rescue services, 211 patients (22.7%) were admitted via emergency room and 236 patients (25.3%) via various transfers. In 266 cases (28.5%), respiratory failure was the reason for ICU admission. The length of stay was higher in non-geriatric patients, patients with immunosuppression and haemato-oncological disease or those in need of renal replacement therapy. 431 patients died, which corresponds to an all-cause in-hospital mortality rate of 46.2%. 92 of 172 patients with presence of immunosuppression (53.5%), 111 of 186 patients (59.7%) with pre-existing haemato-oncological disease, 27 of 36 patients (75.0%) under extracorporeal membrane oxygenation (ECMO) therapy, and 182 of 246 patients (74.0%) undergoing renal replacement therapy died. In logistic regression analysis, these subgroups and older age were significantly associated with higher mortality rates. CONCLUSIONS: Respiratory failure was the main reason for ventilatory support at this non-surgical ICU. Immunosuppression, haemato-oncological diseases, the need for ECMO or renal replacement therapy and older age were associated with higher mortality.

Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure.

Liver cirrhosis is the end stage of all chronic liver diseases and contributes significantly to overall mortality of 2% globally. The age-standardized mortality from liver cirrhosis in Europe is between 10 and 20% and can be explained by not only the development of liver cancer but also the acute deterioration in the patient's overall condition. The development of complications including accumulation of fluid in the abdomen (ascites), bleeding in the gastrointestinal tract (variceal bleeding), bacterial infections, or a decrease in brain function (hepatic encephalopathy) define an acute decompensation that requires therapy and often leads to acute-on-chronic liver failure (ACLF) by different precipitating events. However, due to its complexity and organ-spanning nature, the pathogenesis of ACLF is poorly understood, and the common underlying mechanisms leading to the development of organ dysfunction or failure in ACLF are still elusive. Apart from general intensive care interventions, there are no specific therapy options for ACLF. Liver transplantation is often not possible in these patients due to contraindications and a lack of prioritization. In this review, we describe the framework of the ACLF-I project consortium funded by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) based on existing findings and will provide answers to these open questions.