Pt-Black-Modified (Hemi)spherical AFM Sensors: In Situ Imaging of Light-Driven Hydrogen Peroxide Evolution.

In this work, we present (hemi)spherical atomic force microscopy (AFM) sensors for the detection of hydrogen peroxide. Platinum-black (Pt-B) was electrodeposited onto conductive colloidal AFM probes or directly at recessed microelectrodes located at the end of a tipless cantilever, resulting in electrocatalytically active cantilever-based sensors that have a small geometric area but, due to the porosity of the films, exhibit a large electroactive surface area. Focused ion beam-scanning electron microscopy tomography revealed the porous 3D structure of the deposited Pt-B. Given the accurate positioning capability of AFM, these probes are suitable for local in situ sensing of hydrogen peroxide and at the same time can be used for (electrochemical) force spectroscopy measurements. Detection limits for hydrogen peroxide in the nanomolar range (LOD = 68 ± 7 nM) were obtained. Stability test and first in situ proof-of-principle experiments to achieve the electrochemical imaging of hydrogen peroxide generated at a microelectrode and at photocatalytically active structured poly(heptazine imide) films are demonstrated. Force spectroscopic data of the photocatalyst films were recorded in ambient conditions, in solution, and by applying a potential, which demonstrates the versatility of these novel Pt-B-modified spherical AFM probes.

Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with more than 200 entities and relevant differences in disease course and prognosis. Little data is available on hospitalisation patterns in ILD. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for hospitalisations. Reasons for hospitalisation were classified as all cause, ILD-related and respiratory hospitalisations, and patients were analysed for frequency of hospitalisations, time to first non-elective hospitalisation, mortality and progression-free survival. Additionally, the risk for hospitalisation according to GAP index and ILD subtype was calculated by Cox proportional-hazard models as well as influencing factors on prediction of hospitalisation by logistic regression with forward selection. RESULTS: In total, 601 patients were included. 1210 hospitalisations were recorded during the 6 months prior to registry inclusion until the last study visit. 800 (66.1%) were ILD-related, 59.3% of admissions were registered in the first year after inclusion. Mortality was associated with all cause, ILD-related and respiratory-related hospitalisation. Risk factors for hospitalisation were advanced disease (GAP Index stages II and III) and CTD (connective tissue disease)-ILDs. All cause hospitalisations were associated with pulmonary hypertension (OR 2.53, p = 0.005). ILD-related hospitalisations were associated with unclassifiable ILD and concomitant emphysema (OR = 2.133, p = 0.001) as well as with other granulomatous ILDs and a positive smoking status (OR = 3.082, p = 0.005). CONCLUSION: Our results represent a crucial contribution in understanding predisposing factors for hospitalisation in ILD and its major impact on mortality. Further studies to characterize the most vulnerable patient group as well as approaches to prevent hospitalisations are warranted.

Disease trajectories in interstitial lung diseases - data from the EXCITING-ILD registry.

BACKGROUND: Interstitial lung diseases (ILD) comprise a heterogeneous group of mainly chronic lung diseases with different disease trajectories. Progression (PF-ILD) occurs in up to 50% of patients and is associated with increased mortality. METHODS: The EXCITING-ILD (Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases) registry was analysed for disease trajectories in different ILD. The course of disease was classified as significant (absolute forced vital capacity FVC decline > 10%) or moderate progression (FVC decline 5-10%), stable disease (FVC decline or increase < 5%) or improvement (FVC increase ≥ 5%) during time in registry. A second definition for PF-ILD included absolute decline in FVC % predicted ≥ 10% within 24 months or ≥ 1 respiratory-related hospitalisation. Risk factors for progression were determined by Cox proportional-hazard models and by logistic regression with forward selection. Kaplan-Meier curves were utilised to estimate survival time and time to progression. RESULTS: Within the EXCITING-ILD registry 28.5% of the patients died (n = 171), mainly due to ILD (n = 71, 41.5%). Median survival time from date of diagnosis on was 15.5 years (range 0.1 to 34.4 years). From 601 included patients, progression was detected in 50.6% of the patients (n = 304) with shortest median time to progression in idiopathic NSIP (iNSIP; median 14.6 months) and idiopathic pulmonary fibrosis (IPF; median 18.9 months). Reasons for the determination as PF-ILD were mainly deterioration in lung function (PFT; 57.8%) and respiratory hospitalisations (40.6%). In multivariate analyses reduced baseline FVC together with age were significant predictors for progression (OR = 1.00, p < 0.001). Higher GAP indices were a significant risk factor for a shorter survival time (GAP stage III vs. I HR = 9.06, p < 0.001). A significant shorter survival time was found in IPF compared to sarcoidosis (HR = 0.04, p < 0.001), CTD-ILD (HR = 0.33, p < 0.001), and HP (HR = 0.30, p < 0.001). Patients with at least one reported ILD exacerbation as a reason for hospitalisation had a median survival time of 7.3 years (range 0.1 to 34.4 years) compared to 19.6 years (range 0.3 to 19.6 years) in patients without exacerbations (HR = 0.39, p < 0.001). CONCLUSION: Disease progression is common in all ILD and associated with increased mortality. Most important risk factors for progression are impaired baseline forced vital capacity and higher age, as well as acute exacerbations and respiratory hospitalisations for mortality. Early detection of progression remains challenging, further clinical criteria in addition to PFT might be helpful.

[Proposals for the Prevention Health Consequences of Heat Stress as a Cross-sectional Task in the Health Care System]. / Vorschläge zur Vermeidung gesundheitlicher Folgen von Hitzebelastung als Querschnittsaufgabe im Gesundheitswesen.

INTRODUCTION: Climate change is the greatest threat to human health in the 21st century. Climate change poses a significant threat to human health in Germany, with increasing heatwaves causing high mortality rates. In recent years, the German medical profession has become increasingly concerned with the consequences of climate change, particularly extreme temperatures and heat, for human health. SUGGESTIONS: Although the Deutscher Wetterdienst (DWD) issues heat warnings, there is a lack of comprehensive heat action plans (HAPs). Initiatives such as the "Berlin Heat Protection Action Alliance" offer sector-specific plans for healthcare facilities. There is an urgent need for action in the healthcare sector, as doctors play a key role in implementing heat protection measures and advocating for action against climate change. In addition to initiatives such as signing the "Climate Pact for Health" and raising awareness among stakeholders in the healthcare sector, increased education about heat-related health risks is essential. CONCLUSION: The results emphasise the urgency of measures in the healthcare sector in the face of advancing climate change. The medical profession plays a key role in the implementation of heat protection measures and should be actively involved in the planning and implementation of HAPs. Education and training on heat and health is essential in the health sector. Registration for heat warnings from the DWD (www.hitzewarnungen.de) is recommended, followed by sensitisation of decision-makers and employees in healthcare facilities. The medical profession has a crucial responsibility in the implementation of heat protection measures and should actively position itself and contribute to the political discussion on heat and climate change.

Mortality in cancer patients with SARS-CoV-2 or seasonal influenza: an observational cohort study from a German-wide hospital network.

PURPOSE: At the beginning of the COVID-19 pandemic, SARS-CoV-2 was often compared to seasonal influenza. We aimed to compare the outcome of hospitalized patients with cancer infected by SARS-CoV-2 or seasonal influenza including intensive care unit admission, mechanical ventilation and in-hospital mortality. METHODS: We analyzed claims data of patients with a lab-confirmed SARS-CoV-2 or seasonal influenza infection admitted to one of 85 hospitals of a German-wide hospital network between January 2016 and August 2021. RESULTS: 29,284 patients with COVID-19 and 7442 patients with seasonal influenza were included. Of these, 360 patients with seasonal influenza and 1625 patients with COVID-19 had any kind of cancer. Cancer patients with COVID-19 were more likely to be admitted to the intensive care unit than cancer patients with seasonal influenza (29.4% vs 24.7%; OR 1.31, 95% CI 1.00-1.73 p < .05). No statistical significance was observed in the mechanical ventilation rate for cancer patients with COVID-19 compared to those with seasonal influenza (17.2% vs 13.6% OR 1.34, 95% CI 0.96-1.86 p = .09). 34.9% of cancer patients with COVID-19 and 17.9% with seasonal influenza died (OR 2.45, 95% CI 1.81-3.32 p < .01). Risk factors among cancer patients with COVID-19 or seasonal influenza for in-hospital mortality included the male gender, age, a higher Elixhauser comorbidity index and metastatic cancer. CONCLUSION: Among cancer patients, SARS-CoV-2 was associated with a higher risk for in-hospital mortality than seasonal influenza. These findings underline the need of protective measurements to prevent an infection with either COVID-19 or seasonal influenza, especially in this high-risk population.

[The Usefulness of ERAS Concepts for Colorectal Resections - an Economic Analysis under DRG Conditions]. / Sinnhaftigkeit von ERAS-Konzepten bei kolorektalen Resektionen ­ eine ökonomische Analyse unter DRG-Bedingungen.

BACKGROUND: ERAS (Enhanced Recovery After Surgery) describes a multimodal, interdisciplinary and interprofessional treatment concept that optimizes the postoperative convalescence of the patient through the use of evidence-based measures. GOAL OF THE WORK: The aim of this article is to examine the economic feasibility of the concept in the German DRG system. MATERIAL AND METHODS: Since August 2019, patients have been treated in our clinic according to the later certified ERAS concept. The last 20 patients before ERAS implementation are compared below with 20 patients after ERAS implementation, who were identified using a matched pair analysis. In addition to the comparison of costs and revenues, the clinical outcome of the patients is also presented. RESULTS: The cases of the patients in the pre-ERAS cohort caused median costs of € 7432.83. BWR of 3.38 were billable. The resulting DRG revenue for the patients in this group amounted to € 11325.78. The proceeds generated in the end amounted to € 4575.14. The cases of patients in the ERAS cohort resulted in costs of € 5582.96. BWR of 2.84 could be billed. The DRG proceeds for the patients in this group therefore amounted to € 10014.18. The profit generated was thus € 4993.84. DISCUSSION: The cost reduction generated by ERAS was comparable to the "loss" caused by the BWR decrease. ERAS is therefore also possible to cover costs in the German DRG system.

[The virtual ILD board: a pilot project]. / Das virtuelle ILD-Board ­ Erfahrungen aus einem Pilotprojekt.

Interstitial lung diseases are associated with high morbitity and mortality. Rapid diagnosis in a qualified center is necessary in order to provide the best possible treatment. However, geographic distance and organizational issues lead to unacceptable delays. To support pulmonologists in private practice, we have trialed a digital system that minimizes such delays. The "virtual ILD board" leads to a considerably faster diagnosis and is a helpful tool for pulmonologists in practice. Standardization increases patient safety by ensuring interdisciplinary assessment and thus makes a relevant contribution to the management and guideline-based care of interstitial lung diseases.

[Smoking Cessation in Patients with COPD]. / Tabakentwöhnung bei COPD.

Tobacco dependence is a common comorbidity in patients with COPD (Chronic Obstructive Pulmonary Disease) that negatively affects the course of the disease. However, clinically relevant improvement in COPD can only be achieved by complete and permanent abstinence. Therefore, abstinence from tobacco use is a central therapeutic concept in smoking patients with COPD and requires specific and targeted treatment.After detailed documentation of smoking behaviour and motivational counseling outlining the risks of smoking, all such patients shall be offered a structured therapy for tobacco cessation. There is high-quality evidence for the effectiveness of a combination therapy of behavioral therapy and medication (to treat the withdrawal syndrome). Due to insufficient data, there is currently no recommendation for the use of e-cigarettes as a primary option for a cessation attempt.Smoking is the most important cause of COPD. Smoking cessation is the most effective and cost-efficient single intervention to reduce the risk of developing and progressing COPD.

Machine learning-derived prediction of in-hospital mortality in patients with severe acute respiratory infection: analysis of claims data from the German-wide Helios hospital network.

BACKGROUND: Severe acute respiratory infections (SARI) are the most common infectious causes of death. Previous work regarding mortality prediction models for SARI using machine learning (ML) algorithms that can be useful for both individual risk stratification and quality of care assessment is scarce. We aimed to develop reliable models for mortality prediction in SARI patients utilizing ML algorithms and compare its performances with a classic regression analysis approach. METHODS: Administrative data (dataset randomly split 75%/25% for model training/testing) from years 2016-2019 of 86 German Helios hospitals was retrospectively analyzed. Inpatient SARI cases were defined by ICD-codes J09-J22. Three ML algorithms were evaluated and its performance compared to generalized linear models (GLM) by computing receiver operating characteristic area under the curve (AUC) and area under the precision-recall curve (AUPRC). RESULTS: The dataset contained 241,988 inpatient SARI cases (75 years or older: 49%; male 56.2%). In-hospital mortality was 11.6%. AUC and AUPRC in the testing dataset were 0.83 and 0.372 for GLM, 0.831 and 0.384 for random forest (RF), 0.834 and 0.382 for single layer neural network (NNET) and 0.834 and 0.389 for extreme gradient boosting (XGBoost). Statistical comparison of ROC AUCs revealed a better performance of NNET and XGBoost as compared to GLM. CONCLUSION: ML algorithms for predicting in-hospital mortality were trained and tested on a large real-world administrative dataset of SARI patients and showed good discriminatory performances. Broad application of our models in clinical routine practice can contribute to patients' risk assessment and quality management.

Effect of gender, age and vaccine on reactogenicity and incapacity to work after COVID-19 vaccination: a survey among health care workers.

BACKGROUND: The aim of our study was to assess the impact the impact of gender and age on reactogenicity to three COVID-19 vaccine products: Biontech/Pfizer (BNT162b2), Moderna (mRNA-1273) and AstraZeneca (ChAdOx). Additional analyses focused on the reduction in working capacity after vaccination and the influence of the time of day when vaccines were administered. METHODS: We conducted a survey on COVID-19 vaccinations and eventual reactions among 73,000 employees of 89 hospitals of the Helios Group. On May 19th, 2021 all employees received an email, inviting all employees who received at least 1 dose of a COVID-19 to participate using an attached link. Additionally, the invitation was posted in the group's intranet page. Participation was voluntary and non-traceable. The survey was closed on June 21st, 2021. RESULTS: 8375 participants reported on 16,727 vaccinations. Reactogenicity was reported after 74.6% of COVID-19 vaccinations. After 23.0% vaccinations the capacity to work was affected. ChAdOx induced impairing reactogenicity mainly after the prime vaccination (70.5%), while mRNA-1273 led to more pronounced reactions after the second dose (71.6%). Heterologous prime-booster vaccinations with ChAdOx followed by either mRNA-1273 or BNT162b2 were associated with the highest risk for impairment (81.4%). Multivariable analyses identified the factors older age, male gender and vaccine BNT162b as independently associated with lower odds ratio for both, impairing reactogenicity and incapacity to work. In the comparison of vaccine schedules, the heterologous combination ChAdOx + BNT162b or mRNA-1273 was associated with the highest and the homologue prime-booster vaccination with BNT162b with the lowest odds ratios. The time of vaccination had no significant influence. CONCLUSIONS: Around 75% of the COVID-19 vaccinations led to reactogenicity and nearly 25% of them led to one or more days of work loss. Major risk factors were female gender, younger age and the administration of a vaccine other than BNT162b2. When vaccinating a large part of a workforce against COVID-19, especially in professions with a higher proportion of young and women such as health care, employers and employees must be prepared for a noticeable amount of absenteeism. Assuming vaccine effectiveness to be equivalent across the vaccine combinations, to minimize reactogenicity, employees at risk should receive a homologous prime-booster immunisation with BNT162b2. TRIAL REGISTRATION: The study was approved by the Ethic Committee of the Aerztekammer Berlin on May 27th, 2021 (Eth-37/21) and registered in the German Clinical Trials Register (DRKS 00025745). The study was supported by the Helios research grant HCRI-ID 2021-0272.

The usefulness of Enhanced Recovery After Surgery concepts for colorectal resections: an economic analysis under DRG conditions.

PURPOSE: ERAS® (Enhanced Recovery After Surgery) describes a multimodal, interdisciplinary, and interprofessional treatment concept that optimizes the postoperative convalescence of the patient through the use of evidence-based measures. Goal of the work. The aim of this article is to examine the economic feasibility of the ERAS® concept in the German DRG (diagnosis-related groups) system. MATERIAL AND METHODS: Since August 2019, patients have been treated in our clinic according to the later certified ERAS® concept. The last 50 patients before ERAS® implementation are compared below with 50 patients after ERAS® implementation, who were identified using a matched pair analysis. In addition to the comparison of costs and revenues, the clinical outcome of the patients is also presented. RESULTS: The cases of the patients in the pre-ERAS® cohort caused median costs of € 7432.83. BWR (valuation ratio) of 3.38 were billable. The resulting DRG revenue for the patients in this group amounted to € 11,325.78. The proceeds generated in the end amounted to € 4575.14. The cases of patients in the ERAS® cohort resulted in costs of € 5582.96. BWR of 2.84 could be billed. The DRG proceeds for the patients in this group therefore amounted to € 10,014.18. The profit generated was thus € 4993.84. CONCLUSION: The cost reduction generated by ERAS® was more pronounced than the "loss" due to the decrease in BWR. ERAS® is therefore also possible in the German DRG system at absolutely cost-covering levels.

Mechanical stretch activates piezo1 in caveolae of alveolar type I cells to trigger ATP release and paracrine stimulation of surfactant secretion from alveolar type II cells.

Secretion of pulmonary surfactant in the alveoli of the lungs is essential to maintain lung function. Stretching of alveoli during lung inflation is the main trigger for surfactant secretion. Yet, the molecular mechanisms how mechanical distension of alveoli results in surfactant secretion are still elusive. The alveolar epithelium consists of alveolar epithelial type I (ATI) and surfactant secreting type II (ATII) cells. ATI, but not ATII cells, express caveolae, small plasma membrane invaginations that can respond to plasma membrane stresses and serve mechanotransductive roles. Within this study, we investigated the role of caveolae as mechanosensors in the alveolus. We generated a human caveolin-1 knockout ATI cell (hAELVicav-/- ) using CRISPR/Cas9. Wildtype (hAELViwt ) and hAELVicav-/- cells grown on flexible membranes responded to increasing stretch amplitudes with rises in intracellular Ca2+ . The response was less frequent and started at higher stretch amplitudes in hAELVicav-/- cells. Stretch-induced Ca2+ -signals depended on Ca2+ -entry via piezo1 channels, localized within caveolae in hAELViwt and primary ATI cells. Ca2+ -entry via piezo1 activated pannexin-1 hemichannels resulting in ATP release from ATI cells. ATP release was reduced in hAELVicav-/- cells. In co-cultures resembling the alveolar epithelium, released ATP stimulated Ca2+ signals and surfactant secretion from neighboring ATII cells when co-cultured with hAELViwt but not hAELVicav-/- cells. In summary, we propose that caveolae in ATI cells are mechanosensors within alveoli regulating stretch-induced surfactant secretion from ATII cells.

Emergency hospital admissions for psychiatric disorders in a German-wide hospital network during the COVID-19 outbreak.

PURPOSE: Psychiatric emergency hospital admissions for distinct psychiatric disorders and length of inpatient stay in the hospital during the Coronavirus disease 2019 (COVID-19) outbreak have not been thoroughly assessed. METHODS: A retrospective study was performed analyzing claims data from a large German Hospital network during the COVID-19 outbreak (study period: March 13-May 21, 2020) as compared to periods directly before the outbreak (same year control: January 1-March 12, 2020) and one year earlier (previous year control: March 13-May 21, 2019). RESULTS: A total of 13,151 emergency hospital admissions for psychiatric diagnoses were included in the analysis. For all psychiatric diagnoses combined, emergency admissions significantly decreased during the study period with mean (interquartile range) incidence rate ratios (IRRs) of 0.68 (0.65, 0.71) and 0.70 (0.67, 0.73) as compared to the same and previous year controls, respectively (both p < 0.00001). IRR ranged from 0.56 for mood affective disorders (F30-F39) to 0.75 for mental disorders due to psychoactive substance use (F10-F19; all p < 0.00001). Mean (standard deviation) length of hospital stay for all psychiatric diagnoses was significantly shorter during the study period [9.8 (11.6) days] as compared to same [14.7 (18.7) days] and previous [16.4 (23.9) days] year controls (both p < 0.00001). CONCLUSION: Both emergency hospital admissions and length of hospital stay significantly decreased for psychiatric disorders during the COVID-19 outbreak. It needs to be assessed in further studies whether healthcare systems will face increased demand for the provision of mental health care in the nearer future.

Hospitalisations for emergency-sensitive conditions in Germany during the COVID-19 pandemic: insights from the German-wide Helios hospital network.

BACKGROUND: While there are numerous reports that describe emergency care during the early COVID-19 pandemic, there is scarcity of data for later stages. This study analyses hospitalisation rates for 37 emergency-sensitive conditions in the largest German-wide hospital network during different pandemic phases. METHODS: Using claims data of 80 hospitals, consecutive cases between 1 January and 17 November 2020 were analysed and compared with a corresponding period in 2019. Incidence rate ratios (IRRs) comparing the two periods were calculated using Poisson regression to model the number of hospitalisations per day. RESULTS: There was a reduction in hospitalisations between 12 March and 13 June 2020 (coinciding with the first pandemic wave) with 32 807 hospitalisations (349.0/day) as opposed to 39 379 (419.0/day) in 2019 (IRR 0.83, 95% CI 0.82 to 0.85, p<0.01). During the following period (14 June-17 November 2020, including the start of second wave), hospitalisations were reduced from 63 799 (406.4/day) in 2019 to 59 910 (381.6/day) in 2020, but this reduction was not as pronounced (IRR 0.94, 95% CI 0.93 to 0.95, p<0.01). During the first wave hospitalisations for acute myocardial infarction, aortic aneurysm/dissection, pneumonitis, paralytic ileus/intestinal obstruction and pulmonary embolism declined but subsequently increased compared with the corresponding periods in 2019. In contrast, hospitalisations for sepsis, pneumonia, obstructive pulmonary disease and intracranial injuries were reduced during the entire observation period. CONCLUSIONS: There was an overall reduction of absolute hospitalisations for emergency-sensitive conditions in Germany during the first 10 months of the COVID-19 pandemic with heterogeneous effects on different disease categories. The increase in hospitalisations for acute myocardial infarction, aortic aneurysm/dissection and pulmonary embolism requires attention and further studies.

[Has the COVID19 Pandemic Changed the Emergency Situation in German Clinics? A Nationwide Analysis of Routine Data from 73 Acute Hospitals]. / Hat die COVID-19-Pandemie das Notfallgeschehen in deutschen Kliniken verändert? Eine bundesweite Analyse von Routinedaten aus 73 Akutkrankenhäusern.

COVID-19 has led to profound changes in the world as we have known it. Due to the sharp increase in intensive care, COVID patients, elective admissions and interventions have been postponed. But emergencies such as myocardial infarction have also decreased. The present study deals with the effects of the COVID pandemic on visceral surgical emergencies on the basis of 5 indicator operations. Routine data from 73 acute hospitals of the Helios Group were evaluated for this purpose. The interventions that were carried out between March 13, 2020 and March 12, 2021 were included. The data was compared with the period from March 13, 2019 to March 12, 2020. The number of interventions in serious emergencies (ileus, mesenteric ischemia and ulcer perforation) has remained constant. However, the length of stay in hospital in the pandemic year 2020 was significantly shorter than in the reference year 2019. The number of cholecystectomies and appendectomies in the pandemic year was significantly lower than in the reference year 2019. The outcome parameters intensive care, invasive ventilation and hospital mortality were comparable for the two periods for these interventions.

Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial.

BACKGROUND: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. METHODS: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 µg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. FINDINGS: All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P = .67). Overall survival (Kaplan-Meier survival estimates, P = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 µg group (93.1%) (P = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. INTERPRETATION: The IC43 100 µg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. TRIAL REGISTRATION: https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.

A Long-Term Follow-Up Investigation of Endobronchial Valves in Emphysema (the LIVE Study): Study Protocol and Six-Month Interim Analysis Results of a Prospective Five-Year Observational Study.

BACKGROUND: Randomized controlled trials indicate that significant lung volume reduction (ELVR) can be obtained with Zephyr® valves by occluding the target lobe in the absence of collateral ventilation, leading to relevant functional benefits in advanced emphysema patients. OBJECTIVES: To observe the long-term effects of endobronchial valve (EBV) implantation in emphysema patients screened by Chartis assessment in the context of daily pulmonology practice. METHODS: The LIVE Study is a prospective, observational, open-label, single-arm, multicenter trial conducted in Germany. 498 patients included in this interim analysis were enrolled between July 2, 2012, and September 16, 2014. The 6-month follow-up visit data were recorded for 343 patients (safety population), and complete data sets were available for 321 treated patients (efficacy population) - 56.4% male, age: 64.5 years, forced expiratory volume in 1 s (FEV1) % predicted: 31.3%, residual volume (RV) % predicted: 252%. RESULTS: Efficacy results at 6 months: FEV1 (l) increased by +100 ml (+11.9%), RV (l) decreased by -0.42 liter, and the COPD Assessment Test score decreased by -3.14 points (each p < 0.0001). Safety outcomes: A total of 66 adverse events (AEs; with 50 serious AEs - SAEs) were reported in 55 patients (16%) during the hospital stay for EBV placement - pneumothorax (35 cases), chronic obstructive pulmonary disease (COPD) exacerbation (5 cases), and pneumonia (4 cases). During the subsequent 6-month follow-up window, 170 SAEs were recorded in 125 patients (36.4%), predominantly COPD exacerbation (53% of the SAEs). CONCLUSION: The current results of this large-scale German observational study performed in the context of daily practice further demonstrates that ELVR with Zephyr® valves is an effective and well-tolerated treatment option in advanced emphysema.