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Daniela Gompelmann,1,2,* Hyun-ju Lim,3,4,* Ralf Eberhardt,1,2 Vasiliki Gerovasili,5 Felix JF Herth,1,2 Claus Peter Heussel,2–4 Monika Eichinger3,4 1Pneumology and Critical Care Medicine, Thoraxklinik at University of Heidelberg, 2Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, 3Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, 4Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany; 5First Critical Care Department, National and Kapodistrian University of Athens, Athens, Greece *These authors contributed equally to this work Background: Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. Methods: Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). Finding: Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). Interpretation: Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy. Keywords: endoscopic lung volume reduction, COPD, emphysema, pneumothorax, valve therapy

Background Age is a critical factor for the assessment of patients attended by emergency medical services (EMSs). However, how age modifies early warning scores' (EWSs) predictive ability should be unveiled. Aim To determine how age influences the performance of EWS [National Early Warning Score 2 (NEWS2), VitalPAC-Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and modified Rapid Emergency Medicine Score (mREMS)] to predict 2-day mortality. The secondary objective was to determine the performance of EWSs at different age ranges. Design A prospective, observational study performed between November 2019 and July 2023. Methods A multicenter, ambulance-based study, considering 38 basic life support units and six advanced life support units referring to four tertiary care hospitals. Eligible patients were adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments. The primary outcome was 2-day in-hospital mortality (includes all-cause mortality). The main measures were demographical and vital signs needed for EWS calculation. Results and discussion A total of 8028 participants fulfilled the inclusion criteria, with 7654 survivors and 374 non-survivors. Among age ranges, the 2-day mortality was 2.8% for the ≤44 years, 3.3% for the 45–64 years, 4.1% for the 65–74 years and 6.7% for the ≥75-year age group. The inclusion of age significantly improved the Area Under the Curve (AUC) in all the scores (P  = 0.006 for non-age-adjusted mREMS, P  = 0.001 for NEWS2, P  = 0.002 for ViEWS, P  = 0.028 for RAPS, all compared with their counterparts with age). Conclusion Our results demonstrated that the incorporation of age into the EWS improved the performance of the scores. These results will allow the EMS to improve patient management and resource optimization by including an easy-to-obtain variable. [ABSTRACT FROM AUTHOR]

This article discusses a study that aimed to analyze the interactions between respiration and cardiac function under normal conditions. The researchers used real-time MRI and MR-compatible spirometry to measure changes in the heart and lungs during deep breathing. They found that certain parameters, such as the left ventricular end-diastolic eccentricity index and the mid-ventricular areas of the right and left cavity, varied with respiratory volume and timing. The study concludes that this combination of imaging techniques is valuable for understanding the respiratory dependence of ventricular parameters and may be useful for studying pathological conditions in the future. [Extracted from the article]

This article discusses a study that used real-time magnetic resonance imaging (MRI) to investigate the influence of breathing on cardiac function in pediatric patients with chronic right ventricular (RV) volume overload due to congenital heart disease (CHD). The study included six CHD patients and six healthy controls, and the results showed that RV end-diastolic volume and RV stroke volume increased during inspiration in both groups, but the increase in RV ejection fraction was significantly lower in the CHD patients. Additionally, the study found that the Frank-Starling relationship of the RV was impaired in the CHD patients. The authors conclude that real-time MRI combined with respiratory-based binning can provide a noninvasive and dynamic parameter of right ventricular function in pediatric CHD patients with chronic RV volume overload. [Extracted from the article]

Presents a hybrid method for molecular dynamics simulations of solutes in complex solvents. Combination of a quantum mechanical (QM) description of the solute with a molecular mechanics (MM) approach for the solvent; Use of density functional theory to treat the QM fragment of a simulation system.

This paper assesses how considering variation in DOC availability and cell maintenance in bacterial models affects Bacterial Growth Efficiency (BGE) estimations. For this purpose, we conducted two biodegradation experiments simultaneously. In experiment one, a given amount of substrate was added to the culture at the start of the experiment whilst in experiment two, the same amount of substrate was added, but using periodic pulses over the time course of the experiment. Three bacterial models, with different levels of complexity, (the Monod, Marr-Pirt and the dynamic energy budget - DEB - models), were used and calibrated using the above experiments. BGE has been estimated using the experimental values obtained from discrete samples and from model generated data. Cell maintenance was derived experimentally, from respiration rate measurements. The results showed that the Monod model did not reproduce the experimental data accurately, whereas the Marr-Pirt and DEB models demonstrated a good level of reproducibility, probably because cell maintenance was built into their formula. Whatever estimation method was used, the BGE value was always higher in experiment two (the periodically pulsed substrate) as compared to the initially one-pulsed-substrate experiment. Moreover, BGE values estimated without considering cell maintenance (Monod model and empirical formula) were always smaller than BGE values obtained from models taking cell maintenance into account. Since BGE is commonly estimated using constant experimental systems and ignore maintenance, we conclude that these typical methods underestimate BGE values. On a larger scale, and for biogeochemical cycles, this would lead to the conclusion that, for a given DOC supply rate and a given DOC consumption rate, these BGE estimation methods overestimate the role of bacterioplankton as CO2 producers. [ABSTRACT FROM AUTHOR]

Abstract Background Radiotherapy, preferably combined with chemotherapy, is the treatment standard for locally advanced, unresectable non-small cell lung cancer (NSCLC). The tumor response to different therapy protocols is variable, with hypoxia known to be a major factor that negatively influences treatment effectiveness. Visualisation of tumor hypoxia prior to the use of modern radiation therapy strategies, such as intensity modulated radiation therapy (IMRT), might allow optimized dose applications to the target volume, leading to improvement of therapy outcome. 18 F-fluoromisonidazole dynamic positron emission tomography and computed tomography (18 F-FMISO dPET-CT) and functional magnetic resonance imaging (functional MRI) are attractive options for imaging tumor hypoxia. Methods/design The HIL trial is a single centre study combining multimodal hypoxia imaging with 18 F-FMISO dPET-CT and functional MRI, with intensity modulated radiation therapy (IMRT) in patients with inoperable stage III NSCLC. 15 patients will be recruited in the study. All patients undergo initial FDG PET-CT and serial 18 F-FMISO dPET-CT and functional MRI before treatment, at week 5 of radiotherapy and 6 weeks post treatment. Radiation therapy is performed as inversely planned IMRT based on 4D-CT. Discussion Primary objectives of the trial are to characterize the correlation of 18 F-FMISO dPET-CT and functional MRI for tumor hypoxia imaging in NSCLC and evaluate possible effects of radiation therapy on tumor re-oxygenation. Further objectives include the generation of data regarding the prognostic value of 18 F-FMISO dPET-CT and functional MRI for locoregional control, progression free survival and overall survival of NSCLC treated with IMRT, which will form the basis for larger clinical trials focusing on possible interactions between tumor oxygenation and radiotherapy outcome. Trial registration The ClinicalTrials.gov protocol ID is NCT01617980

Abstract: Objectives: Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. Methods: CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. Results: Manual measurements of the tumor longest diameter were significantly (p <0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p <0.001) and area (0.995 vs. 0.988; p =0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2–3 times that of semi-automated measurement. Conclusions: By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients. [Copyright &y& Elsevier]

Rationale: The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data., Objectives: To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI)., Methods: 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr. MRI was assessed using a validated MRI scoring system., Measurements and Main Results: The MRI global score continuously increased from 5.5±4.6 at infancy (0yr) to 17.9±8.4 at adolescence (range 12-18yr), and the MRI morphology score from 5.0±3.9 to 12.4±6.0 (P<0.001). Bronchiectasis/wall thickening prevalence increased from 89.1% at infancy to approx. 100% from preschool age (1-5yr), and the subscore increased from 3.1±1.9 at infancy to 6.6±2.1 at adolescence (P<0.001). Mucus plugging prevalence increased from 55.4% at infancy to 83.5% at adolescence, and the subscore increased from 1.2±1.6 to 3.7±2.5 in the same period (P<0.001). Perfusion abnormalities were found in 44.4% at infancy, and increased to approx. 90% from preschool age (P<0.001). The MRI perfusion score increased from 1.1±1.6 at infancy to 5.6±3.0 at adolescence (P<0.001). Chronic Pseudomonas aeruginosa infection was associated with higher MRI scores from school age (6-11yr, P<0.05-0.001)., Conclusions: This is the first study assessing longitudinal changes in lung morphology and perfusion in CF throughout the pediatric age range, providing percentiles as age-specific reference for lung disease severity. Our data may facilitate the use of MRI as an endpoint in clinical trials in children with CF.

Background: Invasive blood pressure measurement is the in-hospital gold standard to guide hemodynamic management and consecutively cerebral perfusion pressure in patients with traumatic brain injury (TBI). Its prehospital use is controversial since it may delay further care. The primary aim of this study was to test the hypothesis that patients with severe traumatic brain injury who receive prehospital arterial cannulation, compared to those with in-hospital cannulation, do not have a prolonged time between on-scene arrival and first computed tomography (CT) of the head by more than ten minutes., Methods: This retrospective study included patients 18 years and older with isolated severe TBI and prehospital induction of emergency anaesthesia who received treatment in the resuscitation room of the University Hospital of Graz between January 1st, 2015, and December 31st, 2022. A Wilcoxon rank-sum test was used to test for non-inferiority (margin = ten minutes) of the time interval between on-scene arrival and first head CT., Results: We included data of 181 patients in the final analysis. Prehospital arterial line insertion was performed in 87 patients (48%). Median (25-75th percentile) durations between on-scene arrival and first head CT were 73 (61-92) min for prehospital arterial cannulation and 75 (60-93) min for arterial cannulation in the resuscitation room. Prehospital arterial line insertion was significantly non-inferior within a margin of ten minutes with a median difference of 1 min (95% CI - 6 to 7, p = 0.003)., Conclusion: Time-interval between on-scene arrival and first head CT in patients with isolated severe traumatic brain injury who received prehospital arterial cannulation was not prolonged compared to those with in-hospital cannulation. This supports early out-of-hospital arterial cannulation performed by experienced providers., (© 2024. The Author(s).)

Background: Prehospital blood gas analysis (BGA) is an evolving field that offers the potential for early identification and management of critically ill patients. However, the utility and accuracy of prehospital BGA are subjects of ongoing debate., Objectives: We aimed to provide a comprehensive summary of the current literature on prehospital BGA, including its indications, methods, and feasibility., Methods: We performed a scoping review of prehospital BGA. A thorough search of the PubMed, Embase, and Web of Science databases was conducted to identify relevant studies focusing on prehospital BGA in adult patients., Results: Fifteen studies met the inclusion criteria. Prehospital BGA was most frequently performed in patients in out-of-hospital cardiac arrest, followed by traumatic and nontraumatic cases. The parameters most commonly analyzed were pH, pCO 2 , pO 2 , and lactate. Various sampling methods, including arterial, venous, and intraosseous, were reported for prehospital BGA. While prehospital BGA shows promise in facilitating early identification of critical patients and guiding resuscitation efforts, logistical challenges are to be considered. The handling of preclinical BGA is described as feasible and useful in most of the included studies., Conclusion: Prehospital BGA holds significant potential for enhancing patient care in the prehospital setting, though technical challenges need to be considered. However, further research is required to establish optimal indications and demonstrate the benefits for prehospital BGA in specific clinical contexts., Competing Interests: Declaration of competing interest GP is author of an included study and was not involved in study selection. For the remaining authors, none were declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age., Objective: To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2 through 5 years., Methods: This phase 2 trial had two parts: Part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2 through 5 years (previously reported) was followed by a 48-week open-label treatment period where all children received LUM/IVA (Part 2; reported here). Endpoints assessed in Part 2 included absolute changes from baseline in chest magnetic resonance imaging (MRI) global score at week 96; weight-for-age, stature-for-age, and body mass index (BMI)-for-age z-scores at week 96; lung clearance index (LCI 2.5 ) through week 96; chest MRI morphological score, chest MRI perfusion score, weight, stature, BMI, and microbiology cultures (oropharyngeal swabs) at week 96; sweat chloride, serum levels of immunoreactive trypsinogen, fecal elastase-1 levels, and fecal calprotectin through week 96; and number of pulmonary exacerbations (PEx), time-to-first PEx, and number of CF-related hospitalizations., Results: Forty-nine children received ≥1 dose of LUM/IVA in the open-label period (33 in the LUM/IVA to LUM/IVA group and 16 in the placebo to LUM/IVA group); mean exposure 47.1 (SD, 5.2) weeks. The mean absolute change in MRI global score (negative value = improvement) from baseline at Week 96 was -2.7 (SD 7.0; 95% CI, -5.2 to -0.1) in the LUM/IVA to LUM/IVA group and -5.6 (SD 6.9; 95% CI, -9.2 to -1.9) in the placebo to LUM/IVA group. Improvements in LCI 2.5 , sweat chloride concentration, and markers of pancreatic function and intestinal inflammation were also observed in both groups. Growth parameters remained stable in both groups. The majority of children had adverse events (AEs) considered mild (38.8%) or moderate (40.8%). Two (4.1%) children discontinued LUM/IVA treatment due to AEs (distal intestinal obstruction syndrome [n=1] and alanine aminotransferase increase [n=1])., Conclusion: These findings confirm the potential for early LUM/IVA treatment to alter the trajectory of CF disease progression, including CF lung disease, in children as young as 2 years of age. Clinical trial registration available at www., Clinicaltrials: gov, ID: NCT03625466.

Introduction: Histological confirmation of a lung tumor is the prerequisite for treatment planning. It has been suspected that CT-guided needle biopsy (CTGNB) exposes the patient to a higher risk of pleural recurrence. However, the distance between tumor and pleura has largely been neglected as a possible confounder when comparing CTGNB to bronchoscopy., Methods: All patients with lung cancer histologically confirmed by bronchoscopy or CTGNB between 2010 and 2020 were enrolled and studied. Patients' medical histories, radiologic and pathologic findings and surgical records were reviewed. Pleural recurrence was diagnosed by pleural biopsy, fluid cytology, or by CT chest imaging showing progressive pleural nodules., Results: In this retrospective unicenter analysis, 844 patients underwent curative resection for early-stage lung cancer between 2010 and 2020. Median follow-up was 47.5 months (3-137). 27 patients (3.2 %) with ipsilateral pleural recurrence (IPR) were identified. The distance of the tumor to the pleura was significantly smaller in patients who underwent CTGNB. A tendency of increased risk of IPR was observed in tumors located in the lower lobe (HR: 2.18 [±0.43], p = 0.068), but only microscopic pleural invasion was a significant independent predictive factor for increased risk of IPR (HR: 5.33 [± 0.51], p = 0.001) by multivariate cox analysis. Biopsy by CTGNB did not affect IPR (HR: 1.298 [± 0.39], p = 0.504)., Conclusion: CTGNB is safe and not associated with an increased incidence of IPR in our cohort of patients. This observation remains to be validated in a larger multicenter patient cohort., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic transformed healthcare delivery with the rapid adoption of telehealth and digital technologies to access healthcare. Interventions are needed to ensure that older people in underserved communities do not face new technology-driven healthcare disparities. This article describes pioneering electronic medical record (EMR) embedded tools to assess and support each diverse patient's digital health literacy., Methods: We designed and validated a rapid EMR-embedded Digital Health Engagement Tool (DHET) to assess each patient's digital literacy in English and Spanish. We built a separate, EMR-generated auto-scoring function to assess patient use of telehealth and healthcare navigation as recorded within the EMR. Combined, the tools created a complete digital literacy assessment for each patient. We then deployed the tools to conduct a pilot study to elucidate disparities., Results: A total of 112 ethnic/racial diverse older patients were enrolled (mean age was 78, ranging from 57 to 96) years (SD = 8.04). The female participants were 72.3%. Among the participants, non-Hispanic Whites were 47.3%; Hispanic 25.0%; non-Hispanic Asian 19.6%; non-Hispanic others (including multi-race and non-Hispanic Black/African Americans) 8.0%. Digital literacy disparities were revealed for older adults, particularly those over 70 years old, female gender, and those reporting relying on a helper., Conclusion: New EMR-embedded tools enable healthcare systems to assess the ability of patients to navigate and utilize EMR capabilities, such as video telehealth appointments, messaging providers, reviewing labs/radiology reports, and requesting prescriptions. The study identified significant challenges for older patients in navigating EMRs and calls for healthcare systems to better support patient learning., (© 2024 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Objective: To assess the extent of perceived shared decision making (SDM) with parents of pediatric patients and to examine its association with characteristics of patients, professionals, and healthcare facilities., Methods: Parents of pediatric patients (n = 4383) were recruited in 15 social pediatric centers in Germany and provided information on perceived SDM (binary CollaboRATE pediatric score: optimal versus suboptimal extent of SDM), child age and sex, type of impairment, appointment, and healthcare professional present at the appointment. Organizational characteristics were assessed in a cross-sectional survey of staff at the study sites., Results: Overall, 58.4% of parents reported an optimal extent of SDM. The optimal extent of SDM was more likely reported by parents of girls (OR=1.27, p < 0.001) and children with physical (as opposed to cognitive and combined) impairments (OR=1.30, p = 0.006), and after appointments attended by allied health professionals (OR=1.28, p = 0.004). In addition, parents in facilities receiving financing in addition to compensation by statutory health insurance funds were less likely to report an optimal extent of perceived SDM., Conclusion: While SDM with parents was mostly related to individual characteristics of children and professionals at appointments, organizational characteristics seemed less relevant in our study., Practice Implications: Staff should be made aware of lower SDM with parents of boys, older children, and those with cognitive impairments, and trained to improve the SDM in these groups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Age is a critical factor for the assessment of patients attended by emergency medical services (EMSs). However, how age modifies early warning scores' (EWSs) predictive ability should be unveiled., Aim: To determine how age influences the performance of EWS [National Early Warning Score 2 (NEWS2), VitalPAC-Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and modified Rapid Emergency Medicine Score (mREMS)] to predict 2-day mortality. The secondary objective was to determine the performance of EWSs at different age ranges., Design: A prospective, observational study performed between November 2019 and July 2023., Methods: A multicenter, ambulance-based study, considering 38 basic life support units and six advanced life support units referring to four tertiary care hospitals. Eligible patients were adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments. The primary outcome was 2-day in-hospital mortality (includes all-cause mortality). The main measures were demographical and vital signs needed for EWS calculation., Results and Discussion: A total of 8028 participants fulfilled the inclusion criteria, with 7654 survivors and 374 non-survivors. Among age ranges, the 2-day mortality was 2.8% for the ≤44 years, 3.3% for the 45-64 years, 4.1% for the 65-74 years and 6.7% for the ≥75-year age group. The inclusion of age significantly improved the Area Under the Curve (AUC) in all the scores (P = 0.006 for non-age-adjusted mREMS, P = 0.001 for NEWS2, P = 0.002 for ViEWS, P = 0.028 for RAPS, all compared with their counterparts with age)., Conclusion: Our results demonstrated that the incorporation of age into the EWS improved the performance of the scores. These results will allow the EMS to improve patient management and resource optimization by including an easy-to-obtain variable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)