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Maximilian Boesch,1 Florent Baty,1 Stefan Bilz,2 Martin H Brutsche,1 Frank Rassouli1 1Lung Center, Cantonal Hospital St.Gallen, St.Gallen, Switzerland; 2Division of Endocrinology & Diabetes, Cantonal Hospital St.Gallen, St.Gallen, SwitzerlandCorrespondence: Maximilian Boesch, Ph.D., Lung Center, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, St. Gallen, CH-9007, Switzerland, Tel +41-71-494-7143, Email maximilian.boesch@kssg.chIntroduction: Lung function constraints and comorbidities such as coronary heart disease, sarcopenia, and mood disorders make chronic obstructive pulmonary disease (COPD) patients avoid physical activity (PA). However, PA represents an important pillar of COPD management and is explicitly recommended by professional associations to enhance physical functioning and positively modulate disease progression.Methods: In this monocentric, prospective, observational feasibility study, it was our primary objective to investigate the association between PA and the evolution of the COPD assessment test (CAT) and the occurrence of acute exacerbations of COPD (AECOPD), respectively. To this end, we equipped 42 COPD patients with an activity tracking wearable and telemonitored their daily PA levels over one year using a dedicated web-based interface. Patients additionally provided weekly CAT scores using the same telehealth platform and came in for 3 study visits to assess functional parameters and biochemical markers related to nutrition and inflammation.Results: A principal study finding was that PA was inversely associated with CAT score (drop of 0.21 points associated with an increase of 1000 daily steps, p = 0.004), and that the 50% of patients with higher PA levels showed less CAT score progression over time (0.42 points per year) than the 50% of patients with lower PA levels (3.26 points per year) (p < 0.001). In addition, higher PA levels were significantly associated with a lower likelihood of experiencing a moderate-to-severe AECOPD (31% risk reduction associated with an increase of 1000 daily steps, p = 0.0097).Discussion: Our study demonstrates the relevance of PA for key COPD outcome metrics in a real-world setting and underpins the importance of PA for COPD self-management in everyday life. Our study paves the way for future intervention trials to prospectively identify medically relevant PA thresholds and establish training recommendations for different patient subgroups.Keywords: CAT score, COPD, physical activity, telemonitoring, wearable device

Frank Rassouli,1,* Peter Tinschert,2,* Filipe Barata,3 Claudia Steurer-Stey,4,5 Elgar Fleisch,2,3 Milo Alan Puhan,4 Florent Baty,1 Tobias Kowatsch,2,3 Martin Hugo Brutsche1 1Lung Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; 2Center for Digital Health Interventions, Institute of Technology Management, University of St. Gallen, St. Gallen, Switzerland; 3Center for Digital Health Interventions, Department of Management, Technology, and Economics, ETH Zurich, Zurich, Switzerland; 4Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 5mediX Group Practice Zurich, Zurich, Switzerland*These authors contributed equally to this workCorrespondence: Frank RassouliLung Center, Cantonal Hospital St. Gallen, Rorschacher Strasse 95, St. Gallen CH-9007, SwitzerlandTel +41 71 494 60 20Email Frank.Rassouli@kssg.chIntroduction: The nature of nocturnal cough is largely unknown. It might be a valid marker for asthma control but very few studies characterized it as a basis for better defining its role and its use as clinical marker. This study investigated prevalence and characteristics of nocturnal cough in asthmatics over the course of four weeks.Methods: In two centers, 94 adult patients with physician-diagnosed asthma were recruited. Patient-reported outcomes and nocturnal sensor data were collected by a smartphone with a chat-based study app.Results: Patients coughed in 53% of 2212 nights (range: 0– 345 coughs/night). Median coughs per hour were 0 (IQR 0– 1). Nocturnal cough rates showed considerable inter-individual variance. The highest counts were measured in the first 30 min in bed (4.5-fold higher than rest of night). Eighty-six percent of coughs were part of a cough cluster. Clusters consisted of a median of two coughs (IQR 2– 4). Nocturnal cough was persistent within patient.Conclusion: To the best of the authors’ knowledge, this study is the first to describe prevalence and characteristics of nocturnal cough in asthma over a period of one month, demonstrating that it was a prevalent symptom with large variance between patients and high persistence within patients. Cough events in asthmatics were 4.5 times more frequent within the first 30 min in bed indicating a potential role of positional change, and not more frequent during the early morning hours. An important next step will investigate the association between nocturnal cough and asthma control.Keywords: asthma, nocturnal cough, passive monitoring

Peter Tinschert,1,* Frank Rassouli,2,* Filipe Barata,3 Claudia Steurer-Stey,4,5 Elgar Fleisch,1,3 Milo Alan Puhan,4 Tobias Kowatsch,1,3 Martin Hugo Brutsche2 1Center for Digital Health Interventions, Institute of Technology Management, University of St. Gallen, St. Gallen, Switzerland; 2Lung Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; 3Center for Digital Health Interventions, Department of Management, Technology, and Economics, ETH Zurich, Zurich, Switzerland; 4Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 5mediX Group Practice Zurich, Zurich, Switzerland*These authors contributed equally to this workCorrespondence: Peter TinschertCenter for Digital Health Interventions, Institute of Technology Management, University of St. Gallen, Dufourstrasse 40a, CH-9000, St. Gallen, SwitzerlandTel +41 76 403 34 66Email peter.tinschert@unisg.chIntroduction: Objective markers for asthma, that can be measured without extra patient effort, could mitigate current shortcomings in asthma monitoring. We investigated whether smartphone-recorded nocturnal cough and sleep quality can be utilized for the detection of periods with uncontrolled asthma or meaningful changes in asthma control and for the prediction of asthma attacks.Methods: We analyzed questionnaire and sensor data of 79 adults with asthma. Data were collected in situ for 29 days by means of a smartphone. Sleep quality and nocturnal cough frequencies were measured every night with the Pittsburgh Sleep Quality Index and by manually annotating coughs from smartphone audio recordings. Primary endpoint was asthma control assessed with a weekly version of the Asthma Control Test. Secondary endpoint was self-reported asthma attacks.Results: Mixed-effects regression analyses showed that nocturnal cough and sleep quality were statistically significantly associated with asthma control on a between- and within-patient level (p < 0.05). Decision trees indicated that sleep quality was more useful for detecting weeks with uncontrolled asthma (balanced accuracy (BAC) 68% vs 61%; Δ sensitivity − 12%; Δ specificity − 2%), while nocturnal cough better detected weeks with asthma control deteriorations (BAC 71% vs 56%; Δ sensitivity 3%; Δ specificity − 34%). Cut-offs using both markers predicted asthma attacks up to five days ahead with BACs between 70% and 75% (sensitivities 75 - 88% and specificities 57 - 72%).Conclusion: Nocturnal cough and sleep quality have useful properties as markers for asthma control and seem to have prognostic value for the early detection of asthma attacks. Due to the limited study duration per patient and the pragmatic nature of the study, future research is needed to comprehensively evaluate and externally validate the performance of both biomarkers and their utility for asthma self-management.Keywords: asthma, digital biomarker, nocturnal cough, sleep quality, asthma control assessment, asthma attack prediction

Frank Rassouli,1 David Boutellier,2 Jonas Duss,2 Stephan Huber,2 Martin H Brutsche1 1Lung Center, Department of Internal Medicine, Cantonal Hospital St Gallen, St Gallen, Switzerland; 2Kaia Health GmbH, Munich, Germany Background: Concerning COPD, pulmonary rehabilitation (PR) has a positive effect on disease progression and mortality, is cost-effective, and is a part of recommendations of international guidelines. Only a minority of patients profit from conventional PR due to a lack of resources, physicians’ guideline adherence, or patients’ motivation. Novel digital therapies like Kaia COPD, a smartphone application that digitizes PR in COPD, are promising solutions to fill this void.Methods: Kaia COPD provides a digital version of PR and is certified as a class-I medical device in the European Union. We investigated anonymized data from users of the Kaia COPD app on in-app retention and the change in health-related quality of life (COPD assessment test and Chronic Respiratory Disease Questionnaire [CRQ]) during a period of 20 exercise days with the app.Results: Of 349 app downloads, 56 users fulfilled inclusion criteria and 34 (61%) had finished day 20 at the time of analysis and were included. Users took 33±11 days to complete the 20-day core program. Users finishing the program reduced their COPD assessment test scores (mean 2.5 units from 21.6±7.7 to 19.1±8.4 units, P=0.008). In finishers, there was a statistically significant effect above the minimum clinically important threshold of the CRQ score on the domains of fatigue, mastery, and emotional function. There was a statistically significant but not clinically relevant effect on the domain of dyspnea of CRQ.Conclusion: Digitalizing PR with a smartphone app is feasible and accepted by selected patients. The app leads to short-term improvement of health-related quality of life in patients completing a 20-day core program. Due to its observational character, this study has several methodological limitations and was intended to show the feasibility and to extrapolate effect sizes for planned prospective randomized-controlled trials to confirm these findings. Keywords: COPD, pulmonary rehabilitation, telehealth care, telerehabilitation

Frank Rassouli,1 Florent Baty,1 Daiana Stolz,2 Werner Christian Albrich,3 Michael Tamm,2 Sandra Widmer,1 Martin Hugo Brutsche1 1Department of Pulmonary and Sleep Medicine, Cantonal Hospital St Gallen, St Gallen, Switzerland; 2Department of Pulmonary and Sleep Medicine, University Hospital Basel, Basel, Switzerland; 3Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St Gallen, Switzerland Background: There are only scarce data regarding the evolution of the chronic obstructive pulmonary disease (COPD) assessment test (CAT) over time. Our aim was to investigate the evolution of the CAT in a telehealthcare (THC) cohort and to evaluate its potential to predict exacerbations.Patients and methods: The CAT was measured weekly over up to 1 year in 40 COPD patients undergoing a THC intervention. The evolution of the CAT was analyzed using linear regression. The association between this evolution and the occurrence of exacerbations was evaluated using the Andersen–Gill formulation of the Cox proportional hazards model for the analysis of recurrent time-to-event data with time-varying predictors.Results: The median CAT at inclusion was 17 (interquartile range 13–22) points. During the study, 25% of patients had a significant negative slope (median –7 points per year [ppy]), 38% were stable (median +0 ppy) and 38% had a significant positive slope (median +6 ppy). The median slope of the CAT in the overall cohort was +1 (interquartile range –3 to +6) ppy. A significant positive association was found between the change in CAT scores and the risk of exacerbations (hazard ratio =1.08, 95% CI: 1.03–1.13; p

Background: Protective measures applied during the Covid-19 pandemic had a marked impact on the incidence of pneumonia. However, systematic data are lacking for hospitalizations for pneumonia and acute exacerbations of chronic obstructive lung diseases (AECOPD) not caused by SARS-CoV-2 in Switzerland. We aimed to compare the incidences of hospitalization for these entities between 2020/2021 and prepandemic years., Methods: This retrospective study examined all nationwide hospitalizations for non-Covid-19-pneumonia and AECOPD listed as primary diagnoses based on ICD-10 codes between 2015 and 2021 in a publicly available hospitalization database of the Swiss Federal Statistical Office. Hospitalizations for acute coronary syndrome (ACS) and stroke were used as controls. Changes of monthly incidences of hospitalizations, length of stay (LOS) and mortality were compared between 2020/2021 and the average of 2015-2019., Results: The incidences of hospitalizations for AECOPD and for pneumonia showed seasonal variations from 2015 to 2019 followed by significant and almost identical decreases in 2020/2021 (incidence rate ratio [IRR] 0.59, 95% CI: 0.45-0.77, p < 0.001, and IRR: 0.62, 95% CI: 0.52-0.74, p < 0.001, respectively). Hospital-mortality was slightly higher in 2020/2021 for AECOPD (2015-2019: 3.8%; 2020/2021: 4.2%, odds ratio [OR] 1.24, 95% CI: 1.07-1.44, p = 0.004) and for pneumonia (2015-2019: 4.5%, 2020/2021: 4.6%, odds ratio [OR] 1.17, 95% CI: 1.07-1.28, p < 0.001). Median LOS slightly decreased for AECOPD (2015-2019: 8 [IQR: 5-14] days; 2020/2021: 7 [IQR: 4-13] days, Wilcoxon test: p < 0.001) but slightly increased for pneumonia (2015-2019: 7 [IQR: 4-11] days; 2020/2021: 7 [IQR: 4-13] days, Wilcoxon test: p < 0.001). Throughout 2020/2021, there were no significant fluctuations observed in the incidences of ACS and stroke. (IRR: 0.98, 95% CI: 0.83-1.16, p = 0.810, IRR: 0.96, 95% CI: 0.81-1.14, p = 0.636, respectively)., Conclusion: The first two years of the Covid-19 pandemic showed a marked decrease in incidences in AECOPD and non-Covid-19 pneumonia hospitalizations in Switzerland. It is likely that this effect is associated with the society-based, at first vigorous, social distancing measures., (© 2024. The Author(s).)

Objective: Smoking, with a prevalence of about 25%-30% in Switzerland, is proven to cause major systemic, avoidable diseases including lung cancer, increasing societies morbidity and mortality. Diverse strong quitting smoking recommendations have been made available providing advice facilitating smoking cessation globally. In other European countries like Germany, clinical practice guidelines for smoking cessation services have been implemented. However, in Switzerland, there is still no national consensus on a comprehensive smoking cessation program for lung cancer patients nor on the adequate provider. Our primary aim was to assess the current status of smoking cessation practice among specialists, mainly involved in lung cancer care, in Switzerland in order to uncover potential shortcomings., Material and Methods: A self-designed 14-items questionnaire, which was reviewed and approved by our working group consisting of pneumologists and thoracic surgeons, on demographics of the participants, the status of smoking cessation in Switzerland and specialists' opinion on smoking cessation was sent to thoracic surgeons and pneumologists between January 2024 and March 2024 via the commercially available platform www.surveymonkey.com. Data was collected and analysed with descriptive statistics., Results: Survey response rate was 22.25%. Smoking cessation was felt to positively affect long term survival and perioperative outcome in lung cancer surgery. While 33 (37.08%) physicians were offering smoking cessation themselves usually and always (35.96%), only 12 (13.48%) were always referring their patients for smoking cessation. Patient willingness was clearly identified as main factor for failure of cessation programs by 63 respondents (70.79%). Pneumologists were deemed to be the most adequate specialist to offer smoking cessation (49.44%) in a combination of specialist counselling combined with pharmaceutic support (80.90%)., Conclusion: The development of Swiss national guidelines for smoking cessation and the implementation of cessation counselling in standardized lung cancer care pathways is warranted in Switzerland to improve long-term survival and perioperative outcome of lung cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Minervini, Kestenholz, Rassouli, Pohle and Mayer.)

The traditional picture of cancer patients as weak individuals requiring maximum rest and protection is beginning to dissolve. Too much focus on the medical side and one's own vulnerability and mortality might be counterproductive and not doing justice to the complexity of human nature. Unlike cytotoxic and lympho-depleting treatments, immune-engaging therapies strengthen the immune system and are typically less harmful for patients. Thus, cancer patients receiving checkpoint inhibitors are not viewed as being vulnerable per se , at least not in immunological and physical terms. This perspective article advocates a holistic approach to cancer immunotherapy, with an empowered patient in the center, focusing on personal resources and receiving domain-specific support from healthcare professionals. It summarizes recent evidence on non-pharmaceutical interventions to enhance the efficacy of immune checkpoint blockade and improve quality of life. These interventions target behavioral factors such as diet, physical activity, stress management, circadian timing of checkpoint inhibitor infusion, and waiving unnecessary co-medication curtailing immunotherapy efficacy. Non-pharmaceutical interventions are universally accessible, broadly applicable, instantly actionable, scalable, and economically sustainable, creating value for all stakeholders involved. Most importantly, this holistic framework re-emphasizes the patient as a whole and harnesses the full potential of anticancer immunity and checkpoint blockade, potentially leading to survival benefits. Digital therapeutics are proposed to accompany the patients on their mission toward change in lifestyle-related behaviors for creating optimal conditions for treatment efficacy and personal growth., Competing Interests: TK is affiliated with the Centre for Digital Health Interventions (CDHI), a joint initiative of the Institute for Implementation Science in Health Care, University of Zurich, the Department of Management, Technology, and Economics at ETH Zurich, and the Institute of Technology Management and School of Medicine at the University of St.Gallen. CDHI is funded in part by CSS, a Swiss health insurer. TK is also cofounder of Pathmate Technologies, a university spin-off company that creates and delivers digital clinical pathways. However, neither CSS nor Pathmate Technologies were involved in this article. All other authors declare no conflicts of interest with relevance to this article. No medical writer or generative AI tool was involved in the preparation of the manuscript., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Nation-wide hospitalization databases include diagnostic information at the level of an entire population over an extended period of time. Comorbidity network and early disease development can be unveiled. Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition for which it is crucial to identify early disease indicators. The identification of gender-specific conditions preceding the onset of COPD may reveal disease progression patterns allowing for early diagnosis and intervention. The objective of the study was to investigate the antecedent hospitalization history of patients newly diagnosed with COPD and to retrace a gender-specific trajectory of coded entities prior to the onset of COPD., Material and Methods: A population-wide hospitalization database including information about all hospitalizations in Switzerland between 2002 and 2018 was used. COPD cases were extracted from the database and comorbidities occurring prior to the onset of COPD identified. Comorbidities significantly over-represented in COPD compared with a 1:1, age- and sex-matched control population were identified and their longitudinal evolution was analyzed., Results: Between 2002 and 2018, 697,714 hospitalizations with coded COPD were recorded in Switzerland. Sixty-two diagnoses were significantly over-represented before onset of COPD. These preceding comorbidities included both well-established conditions and novel links to COPD. Early pre-conditions included nicotine and alcohol abuse, obesity and cardiovascular diseases. Later comorbidities included atrial fibrillation, diseases of the genitourinary system and pneumonia. Atherosclerotic heart diseases were more prevalent in males, whereas hypothyroidism, varicose and intestinal disorders were more frequent in females. Disease trajectories were validated using an independent data set., Conclusions: Gender-specific disease trajectories highlight early indicators and pathogenetic links between COPD and antecedent diseases and could allow for early detection and intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hagmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Cough represents a cardinal symptom of acute respiratory tract infections. Generally associated with disease activity, cough holds biomarker potential and might be harnessed for prognosis and personalised treatment decisions. Here, we tested the suitability of cough as a digital biomarker for disease activity in coronavirus disease 2019 (COVID-19) and other lower respiratory tract infections., Methods: We conducted a single-centre, exploratory, observational cohort study on automated cough detection in patients hospitalised for COVID-19 (n=32) and non-COVID-19 pneumonia (n=14) between April and November 2020 at the Cantonal Hospital St Gallen, Switzerland. Cough detection was achieved using smartphone-based audio recordings coupled to an ensemble of convolutional neural networks. Cough levels were correlated to established markers of inflammation and oxygenation., Measurements and Main Results: Cough frequency was highest upon hospital admission and declined steadily with recovery. There was a characteristic pattern of daily cough fluctuations, with little activity during the night and two coughing peaks during the day. Hourly cough counts were strongly correlated with clinical markers of disease activity and laboratory markers of inflammation, suggesting cough as a surrogate of disease in acute respiratory tract infections. No apparent differences in cough evolution were observed between COVID-19 and non-COVID-19 pneumonia., Conclusions: Automated, quantitative, smartphone-based detection of cough is feasible in hospitalised patients and correlates with disease activity in lower respiratory tract infections. Our approach allows for near real-time telemonitoring of individuals in aerosol isolation. Larger trials are warranted to decipher the use of cough as a digital biomarker for prognosis and tailored treatment in lower respiratory tract infections., Competing Interests: Conflict of interest: Three of the authors (P. Tinschert, I. Shih and D. Cleres) have co-founded or hold shares in Resmonics AG, Zurich, Switzerland. Conflict of interest: The other authors have no conflicts of interest to declare. No medical writer was involved in the preparation of the manuscript., (Copyright ©The authors 2023.)

Background: Clinical deterioration can go unnoticed in hospital wards for hours. Mobile technologies such as wearables and smartphones enable automated, continuous, noninvasive ward monitoring and allow the detection of subtle changes in vital signs. Cough can be effectively monitored through mobile technologies in the ward, as it is not only a symptom of prevalent respiratory diseases such as asthma, lung cancer, and COVID-19 but also a predictor of acute health deterioration. In past decades, many efforts have been made to develop an automatic cough counting tool. To date, however, there is neither a standardized, sufficiently validated method nor a scalable cough monitor that can be deployed on a consumer-centric device that reports cough counts continuously. These shortcomings limit the tracking of coughing and, consequently, hinder the monitoring of disease progression in prevalent respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19 in the ward., Objective: This exploratory study involved the validation of an automated smartphone-based monitoring system for continuous cough counting in 2 different modes in the ward. Unlike previous studies that focused on evaluating cough detection models on unseen data, the focus of this work is to validate a holistic smartphone-based cough detection system operating in near real time., Methods: Automated cough counts were measured consistently on devices and on computers and compared with cough and noncough sounds counted manually over 8-hour long nocturnal recordings in 9 patients with pneumonia in the ward. The proposed cough detection system consists primarily of an Android app running on a smartphone that detects coughs and records sounds and secondarily of a backend that continuously receives the cough detection information and displays the hourly cough counts. Cough detection is based on an ensemble convolutional neural network developed and trained on asthmatic cough data., Results: In this validation study, a total of 72 hours of recordings from 9 participants with pneumonia, 4 of whom were infected with SARS-CoV-2, were analyzed. All the recordings were subjected to manual analysis by 2 blinded raters. The proposed system yielded a sensitivity and specificity of 72% and 99% on the device and 82% and 99% on the computer, respectively, for detecting coughs. The mean differences between the automated and human rater cough counts were -1.0 (95% CI -12.3 to 10.2) and -0.9 (95% CI -6.5 to 4.8) coughs per hour within subject for the on-device and on-computer modes, respectively., Conclusions: The proposed system thus represents a smartphone cough counter that can be used for continuous hourly assessment of cough frequency in the ward., (©Filipe Barata, David Cleres, Peter Tinschert, Chen-Hsuan Iris Shih, Frank Rassouli, Maximilian Boesch, Martin Brutsche, Elgar Fleisch. Originally published in JMIR Formative Research (https://formative.jmir.org), 20.02.2023.)

Background: Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS., Methods: This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization., Discussion: Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19., Trial Registration: ClinicalTrials.gov, NCT04536350 . Registered 02 September 2020., (© 2022. The Author(s).)

Cough, a symptom associated with many prevalent respiratory diseases, can serve as a potential biomarker for diagnosis and disease progression. Consequently, the development of cough monitoring systems and, in particular, automatic cough detection algorithms have been studied since the early 2000s. Recently, there has been an increased focus on the efficiency of such algorithms, as implementation on consumer-centric devices such as smartphones would provide a scalable and affordable solution for monitoring cough with contact-free sensors. Current algorithms, however, are incapable of discerning between coughs of different individuals and, thus, cannot function reliably in situations where potentially multiple individuals have to be monitored in shared environments. Therefore, we propose a weakly supervised metric learning approach for cougher recognition based on smartphone audio recordings of coughs. Our approach involves a triplet network architecture, which employs convolutional neural networks (CNNs). The CNNs of the triplet network learn an embedding function, which maps Mel spectrograms of cough recordings to an embedding space where they are more easily distinguishable. Using audio recordings of nocturnal coughs from asthmatic patients captured with a smartphone, our approach achieved a mean accuracyof 88 % ( ± 10 % SD) on two-way identification tests with 12 enrollment samples and accuracy of 80 % and an equal error rate (EER) of 20 % on verification tests. Furthermore, our approach outperformed human raters with regard to verification tests on average by 8% in accuracy, 4% in false acceptance rate (FAR), and 12% in false rejection rate (FRR). Our code and models are publicly available.

Purpose: COPD has large impact on patient morbidity and mortality worldwide. Acute exacerbations (AECOPD) are mostly triggered by respiratory infections including influenza. While corticosteroids are strongly recommended in AECOPD, they are potentially harmful during influenza. We aimed to evaluate if steroid treatment for AECOPD due to influenza may worsen outcomes., Methods: A retrospective analysis of a Swiss nation-wide hospitalization database was conducted identifying all AECOPD hospitalisations between 2012 and 2017. In separate analyses, outcomes concerning length-of-stay (LOS), in-hospital mortality, rehospitalisation rate, empyema and aspergillosis were compared between AECOPD during and outside influenza season; AECOPD with and without laboratory-confirmed influenza; and AECOPD plus pneumonia with and without laboratory-confirmed influenza., Results: Patients hospitalized for AECOPD during influenza season showed shorter LOS (11.3 vs. 11.6 day, p < 0.001) but higher rehospitalisation rates (33 vs 31%, p < 0.001) compared to those hospitalized outside influenza season. Patients with confirmed influenza infection had lower in-hospital mortality (3.3 vs. 5.5%, p = 0.010) and rehospitalisation rates (29 vs. 37%, p < 0.001) than those without confirmed influenza., Conclusion: Using different indicators for influenza as the likely cause of AECOPD, we found no consistent evidence of worse outcomes of AECOPD due to influenza for hospitalized patients. Assuming that most of these patients received corticosteroids, as it is accepted standard of care in Switzerland, this study gives no evidence to change the current practice of using corticosteroids for hospitalized AECOPD independent of the influenza status., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Text mining can be applied to automate knowledge extraction from unstructured data included in medical reports and generate quality indicators applicable for medical documentation. The primary objective of this study was to apply text mining methodology for the analysis of polysomnographic medical reports in order to quantify sources of variation - here the diagnostic precision vs. the inter-rater variability - in the work-up of sleep-disordered breathing. The secondary objective was to assess the impact of a text block standardization on the diagnostic precision of polysomnography reports in an independent test set., Results: Polysomnography reports of 243 laboratory-based overnight sleep investigations scored by 9 trained sleep specialists of the Sleep Center St. Gallen were analyzed using a text-mining methodology. Patterns in the usage of discriminating terms allowed for the characterization of type and severity of disease and inter-rater homogeneity. The variation introduced by the inter-rater (technician/physician) heterogeneity was found to be twice as high compared to the variation introduced by effective diagnostic information. A simple text block standardization could significantly reduce the inter-rater variability by 44%, enhance the predictive value and ultimately improve the diagnostic accuracy of polysomnography reports., Conclusions: Text mining was successfully used to assess and optimize the quality, as well as the precision and homogeneity of medical reporting of diagnostic procedures - here exemplified with sleep studies. Text mining methodology could lay the ground for objective and systematic qualitative assessment of medical reports., (© 2022. The Author(s).)

Objectives: Despite advances in the treatment of adult T-cell leukemia/lymphoma (ATLL), the survival rate of this malignancy remains significantly low. Auraptene (AUR) is a natural coumarin with broad-spectrum anticancer activities. To introduce a more effective therapeutic strategy for ATLL, we investigated the combinatorial effects of AUR and arsenic trioxide (ATO) on MT-2 cells., Materials and Methods: The cells were treated with different concentrations of AUR for 24, 48, and 72 hr, and viability was measured by alamarBlue assay. Then, the combination of AUR (20 μg/ml) and ATO (3 μg/ml) was administrated and the cell cycle was analyzed by PI staining followed by flow cytometry analysis. In addition, the expression of NF-κB (REL-A), CD44, c-MYC , and BMI-1 was evaluated via qPCR., Results: Assessment of cell viability revealed increased toxicity of AUR and ATO when used in combination. Our findings were confirmed by accumulation of cells in the sub G1 phase of the cell cycle and significant down-regulation of NF-κB (REL-A), CD44, c-MYC, and BMI-1 ., Conclusion: Obtained findings suggest that combinatorial use of AUR and ATO could be considered for designing novel chemotherapy regimens for ATLL.

Background: Diagnostic precision and the identification of rare diseases is a daily challenge, which needs specialized expertise. We hypothesized, that there is a correlation between the distance of residence to the next tertiary medical facility with highly specialized care and the diagnostic precision, especially for rare diseases., Results: Using a nation-wide hospitalization database, we found a negative association between diagnostic diversity and travel time to the next tertiary referral hospital when including all cases throughout the overall International Classification of Diseases version 10 German Modification (ICD-10-GM) diagnosis codes. This was paralleled with a negative association of standardized incidence rates in all groups of rare diseases defined by the Orphanet rare disease nomenclature, except for rare teratologic and rare allergic diseases., Conclusion: Our findings indicate a higher risk of being mis-, under- or late diagnosed especially in rare diseases when living more distant to a tertiary medical facility. Greater distance to the next tertiary medical facility basically increases the chance for hospitalization in a non-comprehensive regional hospital with less diagnostic capacity, and, thus, impacts on adapted health care access. Therefore, solutions for overcoming the distance to specialized care as an indicator of health care access are a major goal in the future.

Background: Radiotherapy has become a part of therapeutic process of more than 50 percent of patients suffering from cancer. However, recent studies have shown that radiation therapy might affect the expression of adhesive molecule related genes such as E-cadherin and cause cancer cells to move and migrate. Besides, various studies have reported that the expression of E-cadherin changes differently after radiation treatment. There are several studies which showed the loss of E-cadherin function after radiation; however, this reduction has not been observed in others., Objective: This study aims to investigate the effect of different radiation doses of X-ray on changes that might occur in the expression of E-cadherin gene in colorectal cancer cell line HT-29., Material and Methods: In this experimental study, the cells cultured in flasks were irradiated with X- rays in different doses, including 0.1, 2.5, 5, and 10 Gy; then, the expression of E-cadherin gene was measured using real-time PCR., Results: The expression of E-cadherin did not change significantly in post-irradiated HT-29 cell line after different radiation doses of X-ray., Conclusion: The results showed that low, medium and high doses of X- radiation did not change the expression of E-cadherin gene in HT-29 cancer cells. However, it has been reported that radiation mostly downregulated the expression of E-cadherin and mediated metastasis formation and invasiveness in different cancer cell lines. Therefore, further studies need to be conducted to investigate the effects of radiation dose on the molecular pathways contributing to regulation of E-cadherin in HT-29 cell line., (Copyright: © Journal of Biomedical Physics and Engineering.)

Background: Asthma is one of the most prevalent chronic respiratory diseases. Despite increased investment in treatment, little progress has been made in the early recognition and treatment of asthma exacerbations over the last decade. Nocturnal cough monitoring may provide an opportunity to identify patients at risk for imminent exacerbations. Recently developed approaches enable smartphone-based cough monitoring. These approaches, however, have not undergone longitudinal overnight testing nor have they been specifically evaluated in the context of asthma. Also, the problem of distinguishing partner coughs from patient coughs when two or more people are sleeping in the same room using contact-free audio recordings remains unsolved., Objective: The objective of this study was to evaluate the automatic recognition and segmentation of nocturnal asthmatic coughs and cough epochs in smartphone-based audio recordings that were collected in the field. We also aimed to distinguish partner coughs from patient coughs in contact-free audio recordings by classifying coughs based on sex., Methods: We used a convolutional neural network model that we had developed in previous work for automated cough recognition. We further used techniques (such as ensemble learning, minibatch balancing, and thresholding) to address the imbalance in the data set. We evaluated the classifier in a classification task and a segmentation task. The cough-recognition classifier served as the basis for the cough-segmentation classifier from continuous audio recordings. We compared automated cough and cough-epoch counts to human-annotated cough and cough-epoch counts. We employed Gaussian mixture models to build a classifier for cough and cough-epoch signals based on sex., Results: We recorded audio data from 94 adults with asthma (overall: mean 43 years; SD 16 years; female: 54/94, 57%; male 40/94, 43%). Audio data were recorded by each participant in their everyday environment using a smartphone placed next to their bed; recordings were made over a period of 28 nights. Out of 704,697 sounds, we identified 30,304 sounds as coughs. A total of 26,166 coughs occurred without a 2-second pause between coughs, yielding 8238 cough epochs. The ensemble classifier performed well with a Matthews correlation coefficient of 92% in a pure classification task and achieved comparable cough counts to that of human annotators in the segmentation of coughing. The count difference between automated and human-annotated coughs was a mean -0.1 (95% CI -12.11, 11.91) coughs. The count difference between automated and human-annotated cough epochs was a mean 0.24 (95% CI -3.67, 4.15) cough epochs. The Gaussian mixture model cough epoch-based sex classification performed best yielding an accuracy of 83%., Conclusions: Our study showed longitudinal nocturnal cough and cough-epoch recognition from nightly recorded smartphone-based audio from adults with asthma. The model distinguishes partner cough from patient cough in contact-free recordings by identifying cough and cough-epoch signals that correspond to the sex of the patient. This research represents a step towards enabling passive and scalable cough monitoring for adults with asthma., (©Filipe Barata, Peter Tinschert, Frank Rassouli, Claudia Steurer-Stey, Elgar Fleisch, Milo Alan Puhan, Martin Brutsche, David Kotz, Tobias Kowatsch. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.07.2020.)

Background: Pneumococcal pneumonia is a disease of the extremes of age. However, as other traditional risk factors for pneumococcal pneumonia also increase with older age, it is unclear if older age itself should be an indication for pneumococcal vaccination. Therefore, we assessed the effect of age on risk for hospitalization for pneumonia and for pneumococcal pneumonia. Methods: Using a national hospitalization dataset, all patients ≥16 years hospitalized in a Swiss hospital with a diagnosis of pneumonia or pneumococcal pneumonia between 2002 and 2015 were included. Multivariable logistic regression analysis was used to test the association between age (≥50 or ≥65 years) and hospitalization for pneumonia or pneumococcal pneumonia after adjusting for pneumococcal vaccine indications. Similar analyses were performed for effect of age on length of stay (LOS) and mortality. Results: Among a total of 17,619,016 hospitalizations a diagnosis of pneumonia was present in 421,760 (2.4%) and a diagnosis of pneumococcal pneumonia in 21,610 (0.12%). Age ≥50 years (OR: 3.52 and 2.12, respectively; p for both <0.001) and age ≥65 years (OR: 2.98 and 1.80, respectively; p for both <0.001) as well as most Swiss pneumococcal vaccine indications were independent predictors of hospitalization with a pneumonia and pneumococcal pneumonia diagnosis, respectively. Older age with both age cut-offs were associated with increased LOS (≥50 years: aRR: 1.19 and 1.24, respectively; age ≥65 years: aRR: 1.60 and 1.20, respectively; p < 0.001 for all) and mortality (≥50 years: aOR: 4.73 and 2.84, respectively; age ≥65 years: aOR: 2.38 and 2.69, respectively, p < 0.001 for all) in patients with a pneumonia and pneumococcal pneumonia diagnosis, respectively. The effects of pneumococcal vaccine indications decreased with older age. The incidences of hospitalizations with a pneumonia diagnosis and a pneumococcal pneumonia diagnosis increased significantly from the pre-vaccine era to the PCV7 era and the PCV13 era ( p for trend for both analyses <0.001). Conclusion: This study confirms the Swiss indications for pneumococcal vaccination as independent risk factors for pneumonia hospitalizations. Older age itself should be considered as an additional vaccine indication. Pneumonia and pneumococcal pneumonia in adults have increased despite pneumococcal vaccination in children., (Copyright © 2019 Albrich, Rassouli, Waldeck, Berger and Baty.)

Lead (Pb) is one of the most abundant toxic metals in the environment that can cause a variety of harmful effects. During embryonic development of vertebrates, somites are temporary organs that give rise to skeletal muscle, cartilage, tendon, endothelial cells, and dermis. In this study, we investigated the effects of lead on the development of somites and their derivatives in chick embryos under in vitro conditions. For this propose, fertilized eggs of Gallus gallus domesticus were incubated until they reached the stage of 15-20 somites. The somites and notochord were isolated and treated with different concentrations of lead acetate (500, 1000, 2000, and 4000 ng ml -1 ) for 72 h. Our results indicated that high concentrations of lead reduced the nucleus diameter, reduced the synthesis of collagen, inhibited the formation of the cartilage matrix in somite cells, and disturbed the formation and order of myotubes. In conclusion, the results of the current study for the first time indicated the disturbing effects of lead on the development of somites in the chick embryo. Our results revealed that lead disturbed the development of somites in the chick embryo, which suggested that at high concentrations it can cause a serious mortal danger to life.

Introduction: Nocturnal cough is a burdensome asthma symptom. However, knowledge about the prevalence of nocturnal cough in asthma is limited. Furthermore, prior research has shown that nocturnal cough and impaired sleep quality are associated with asthma control, but the association between these two symptoms remains unclear. This study further investigates the potential of these symptoms as markers for asthma control and the accuracy of automated, smartphone-based passive monitoring for nocturnal cough detection and sleep quality assessment., Methods and Analysis: The study is a multicentre, longitudinal observational study with two stages. Sensor and questionnaire data of 94 individuals with asthma will be recorded for 28 nights by means of a smartphone. On the first and the last study day, a participant's asthma will be clinically assessed, including spirometry and fractionated exhaled nitric oxide levels. Asthma control will be assessed by the Asthma Control Test and sleep quality by means of the Pittsburgh Sleep Quality Index. In addition, nocturnal coughs from smartphone microphone recordings will be labelled and counted by human annotators. Relatively unrestrictive eligibility criteria for study participation are set to support external validity of study results. Analysis of the first stage is concerned with the prevalence and trends of nocturnal cough and the accuracies of smartphone-based automated detection of nocturnal cough and sleep quality. In the second stage, patient-reported asthma control will be predicted in a mixed effects regression model with nocturnal cough frequencies and sleep quality of past nights as the main predictors., Ethics and Dissemination: The study was reviewed and approved by the ethics commission responsible for research involving humans in eastern Switzerland (BASEC ID: 2017-01872). All study data will be anonymised on study termination. Results will be published in medical and technical peer-reviewed journals., Trial Registration Number: NCT03635710; Pre-results., Competing Interests: Competing interests: PT, FB, EF and TK are affiliated with the Center for Digital Health Interventions (www.c4dhi.org), a joint initiative of the Department of Management, Technology and Economics at ETH Zurich and the Institute of Technology Management at the University of St. Gallen, which is funded in part by the Swiss health insurer CSS. EF and TK are also cofounders of Pathmate Technologies, a university spin-off company that creates and delivers digital clinical pathways and has used the open source MobileCoach platform for that purpose, too. However, Pathmate Technologies is not involved in the study app described in this paper., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Our aim was to estimate the diagnostic performance of institutions and healthcare regions from a nationwide hospitalisation database., Methods: The Shannon diversity index was used as an indicator of diagnostic performance based on the International Classification of Disease, 10th revision, German Modification (ICD-10-GM codes). The dataset included a total of 9,325,326 hospitalisation cases from 2009 to 2015 and was provided by the Swiss Federal Office for Statistics. A total of 16,435 diagnostic items from the ICD-10-GM codes were taken as the basis for the calculation of the diagnostic diversity index (DDI). Numerical simulations were performed to evaluate the effect of misdiagnoses in the DDI. We arbitrarily defined the minimum clinically important difference (MCID) as 10% misdiagnoses. The R statistical software was used for all analyses., Results: Diagnostic performance of institutions and healthcare regions as measured by the DDI were strongly associated with caseload and number of inhabitants, respectively. A caseload of &gt;7217 hospitalisations per year for institutions and a population size &gt;363,522 for healthcare regions were indicators of an acceptable diagnostic performance. Among hospitals, there was notable heterogeneity of diagnostic diversity, which was strongly associated with caseload. Application of misdiagnosis-thresholds within each ICD-10-GM category allowed classification of hospitals in four distinct groups: high-volume hospitals with an all-over comprehensive diagnostic performance; high- to mid-volume hospitals with extensive to relevant basic diagnostic performance in most categories; low-volume specialised hospitals with a high diagnostic performance in a single category; and low-volume hospitals with inadequate diagnostic performance in all categories. The diagnostic diversity observed in the 26 Swiss healthcare regions showed relevant heterogeneity, an association with ICD-10-GM code utilisation, and was strongly associated with the size of the healthcare region. The limited diagnostic performance in small healthcare regions was partially, but not fully, compensated for by consumption of health services outside of their own healthcare region., Conclusion: Calculation of the DDI from ICD-10 codes is easy and complements the information derived from other quality indicators as it sheds a light on the fitness of the institutionalised interplay between primary and specialised medical inpatient care. &nbsp.

The early postnatal period is a critical period of hippocampus development, which is highly dependent on insulin receptor (IR) signaling and very important in cognitive function. The present study was conducted in order to present a model of neonatal transient brain insulin system dysfunction through finding an appropriate dose of injection of streptozotocin (STZ) during the neonatal period. Sixty male Wistar rat pups were divided into 4 groups of 15 and received intracerebroventricular saline or STZ (icv-STZ) (15, 20 and 25μg/kg) on postnatal day 7. Gene expression of IR and target genes for IR signaling (choline acetyltransferase (ChAT) and Tau) were measured at the ages of 2 and 7 weeks. Behavioral tests were performed at the ages of 3 and 6 weeks to assess short- and long-term cognitive function. 20μg/kg dose of icv-STZ was estimated as the optimal dose causing transient alteration in gene expression of IR, ChAT and Tau. Additionally, cognitive function of the animals restored to normal level at the age of 6 weeks. Therefore, 20μg/kg dose of icv-STZ is proposed as a new approach to generating transient brain insulin system dysfunction associated with transient cognitive impairments at a critical postnatal period of brain development., (Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

Background: The accurate early diagnosis of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Cystatin C might improve the early detection of AKI., Methods: 207 patients presenting to the emergency department with AHF were enrolled. Cystatin C was measured in plasma in a blinded fashion at presentation and serially thereafter. The potential of Cystatin C levels to predict AKI was assessed as the primary endpoint. Long-term mortality was assessed as a secondary endpoint., Results: At presentation, creatinine (140μmol/L [91-203] vs. 97μmol/L [76-132], p<0.01) and Cystatin C (2.00mg/L [1.30-3.08] vs. 1.45mg/L [1.00-1.90], p<0.01) levels were significantly higher in AKI compared to Non-AKI patients. The diagnostic accuracy for AKI quantified by the area under the receiver operating characteristic curve was mediocre and comparable for both markers (creatinine 0.68; 95%CI 0.58-78 vs. Cystatin C 0.67; 95%CI 0.58-0.76). Serial measurements of Cystatin C did not further increase the prognostic accuracy for AKI. Cystatin C levels were significantly higher in decedents than in survivors (1.90mg/L [1.30-2.70] vs. 1.30mg/L [1.0-1.6], p<0.001). The combination of Cystatin C and BNP levels significantly improved the prediction of mortality provided by either parameter alone. In multivariable regression analysis Cystatin C remained independently associated with mortality (HR 1.41; 95%CI 1.02-1.95)., Conclusion: Plasma Cystatin C levels do not adequately predict AKI in patients with AHF. However, in multivariable regression analysis Cystatin C predicted mortality after the adjustment for baseline renal function, AKI, BNP levels and heart failure risk factors., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Significance and clinical utility of multiple virus detection by multiplex real-time polymerase chain reaction (rtPCR) in respiratory tract infection remain unclear., Methods: This retrospective cohort study analyzed how virus detection affected clinical management. During a 27-month period, clinical and laboratory information was collected from all children and adults in two Swiss tertiary centres whose respiratory samples were tested for respiratory viruses with a 16-plex rtPCR test., Results: Pathogens were identified in 140 of 254 patients (55%); of those patients, there was ≥1 virus in 91 (65%), ≥ 1 bacterium in 53 (38%), and ≥1 virus and bacterium in 11 (8%). Of 80 patients with viral infection, 59 (74%) received antibiotics. Virus detection was associated with discontinuation of antibiotics in 2 of 20 adults (10%) and 6 of 14 children (43%). Overall 12 adults (34%) and 18 children (67%) were managed correctly without antibiotics after virus detection ( p  = 0.01). When taking biomarkers, radiologic presentations, and antibiotic pre-treatment into account, the impact of rtPCR and appropriateness of therapy for clinically viral infections increased to 100% in children and 62% in adults., Conclusions: A substantial reduction of unnecessary antibiotic prescriptions seems possible. Appropriate application of rtPCR results in respiratory tract infections should be encouraged.

Background: Cystic fibrosis (CF) is a life-threatening genetic disorder, characterized by chronic microbial lung infections due to abnormally viscous mucus secretions within airways. The clinical management of CF typically involves regular respiratory-tract cultures in order to identify pathogens and to guide treatment. However, culture-based methods can miss atypical or slow-growing microbes. Furthermore, the isolated microbes are often not classified at the strain level due to limited taxonomic resolution., Results: Here, we show that untargeted metagenomic sequencing of sputum DNA can provide valuable information beyond the possibilities of culture-based diagnosis. We sequenced the sputum of six CF patients and eleven control samples (including healthy subjects and chronic obstructive pulmonary disease patients) without prior depletion of human DNA or cell size selection, thus obtaining the most unbiased and comprehensive characterization of CF respiratory tract microbes to date. We present detailed descriptions of the CF and healthy lung microbiome, reconstruct near complete pathogen genomes, and confirm that the CF lungs consistently exhibit reduced microbial diversity. Crucially, the obtained genomic sequences enabled a detailed identification of the exact pathogen strain types, when analyzed in conjunction with existing multi-locus sequence typing databases. We also detected putative pathogenicity islands and indicators of antibiotic resistance, in good agreement with independent clinical tests., Conclusions: Unbiased sputum metagenomics provides an in-depth profile of the lung pathogen microbiome, which is complementary to and more detailed than standard culture-based reporting. Furthermore, functional and taxonomic features of the dominant pathogens, including antibiotics resistances, can be deduced-supporting accurate and non-invasive clinical diagnosis.

In this study, we examined cytotoxic effect of GL-9 peptide on A459 cell line through studying the changes in TNF-α and CD44 gene expression and ROS production. Real-time PCR analysis showed that the treated A549 cells highly over expressed TNF-α, which was associated with a significant reduction of CD44 gene expression levels (p  <  0.05). ROS production rate was measured through the usage of DCFH-DA primer. Results demonstrated that GL-9 peptide could also induce cell death via ROS production. The effect of GL-9 peptide on human erythrocytes and leukocytes was analyzed. GL-9 peptide showed no significant toxic effect on human blood cells. Our results suggested that the GL-9 peptide as a potent natural agent could modulate gene expression of cancer cell markers.

Background: Earlier detection of acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) could reduce emergency admissions and hospitalisations. Studies investigating COPD management programs supported by telehealthcare (THC) have shown conflicting results., Objectives: To test the feasibility, safety and acceptance of THC for COPD., Methods: Patients daily filled out an online questionnaire focused on the detection of AECOPD. The THC platform is integrated in a comprehensive electronic patient data repository, which has to be available for all patients in Switzerland by law by 2017. The study team called the patient by phone in case of suspected AECOPD., Results: Of 339 screened patients, 14% were included. Main reasons for exclusion were missing technical equipment and unwillingness to participate in a study (50%). Data completeness was 88%; 94% completed the study. The current THC approach triggered 230 telephone calls, which led to the verification of 60 AECOPD in 22 patients. Three AECOPD were not detected. Sensitivity, specificity, positive and negative predictive value of the questionnaire-based THC approach in detecting AECOPD was 95, 98, 26 and 99.9%, respectively. Overall patient satisfaction in respect to their health condition improved significantly (VAS 8-8.7; p = 0.002)., Conclusions: Adding THC to state-of-the-art COPD management is feasible in a selected subgroup of patients. We estimate that up to 50% of COPD patients could be eligible for a THC strategy. Patient compliance, acceptance and satisfaction were very high. With the proposed approach, we missed only very few AECOPD events. However, a telephone-based verification of THC alerts was required. Overall, in this proof-of-concept study, we experienced a positive effort-to-benefit ratio., (© 2016 S. Karger AG, Basel.)

Dyspnoea is a common symptom of exercice intolerance. Tests performed at rest often leave the reason open. Cardiopulmonary exercise testing (CPET) is a tool for the qualitative and quantitative assessment of the cardio-circulatory, pulmonary and metabolic response to exercise. It is the gold-standard in the evaluation of dyspnoea and identifying its etiology (obstructive/restrictive lung disease, heart failure, physical fitness …). CPET is particularly useful, if previous evaluations including history, physical examination, ECG, pulmonary function testing (PFT), X-ray, blood tests, and blood gases do not lead to a decisive diagnosis. The measurement of peak oxygen consumption, carbon dioxide production, minute ventilation and heart rate provides substantial diagnostic and prognostic information in a wide variety of clinical settings. Interpreting CPET requires pathophysiological knowledge and can sometimes be challenging. An easy-to-use algorithm may provide a useful assistance for interpretation the results. In addition to its use as a diagnostic tool, CPET can be used to support sportsmen reaching their training goals and evaluate subject's ability to work.

A traditional belief in Iranian culture indicates that parental consumption of chicory leaves (Chicorium intybus L.) affects the gender of newborns. The aim of this study was to investigate the effect of aqueous extract of chicory on offspring sex ratio in rat. All rats in experimental groups 1 and 2 were i.p. injected with either 1.0 or 0.7 g/kg body weight (LD50 = 2.244 g/kg) of an aqueous extract of chicory leaves for 30 days at 72 h intervals. The control rats were injected with distilled water in the same manner. After the 8th injection, blood pH, and Na(+), K(+), Ca(2+) and Mg(2+) serum levels, were measured in all groups. On day 30, all the rats were mated within and between groups. The results revealed that in comparison with the control group, there were significant increases (p < 0.01) in Na(+) and K(+) levels, as well as the sex ratio of male to female offspring (10.23%) in experimental group 1. Therefore, it can be concluded that the administration of chicory leaf extract has a significant effect on the sex ratio of the rat offspring., (Copyright 2010 John Wiley & Sons, Ltd.)