Effects of shape and structure of a new 3D-printed personalized bioresorbable tracheal stent on fit and biocompatibility in a rabbit model.

To date, several types of airway stents are available to treat central airway obstructions. However, the ideal stent that can overcome anatomical, mechanical and microbiological issues is still awaited. In addition, therapeutic effect and self-elimination of these stents are desirable properties, which pose an additional challenge for development and manufacturing. We aimed to create a prototype bioresorbable tracheal stent with acceptable clinical tolerance, fit and biocompatibility, that could be tested in a rabbit model and in the future be further optimized to enable drug-elution and ensure local therapeutic effect. Twenty-one New Zealand White Rabbits received five different types of bioresorbable tracheal stents, 3D-printed from poly(D,L-lactide-co-ε-caprolactone) metacrylates. Various configurations were tested for their functionality and improved until the best performing prototype could undergo detailed in vivo assessment, regarding clinical tolerance, migration and biocompatibility. Previously tested types of 3D printed stents in our preliminary study required improvement due to several problems, mainly related to breakage, unreliable stability and/or migration within the trachea. Abandoned or refined pre-prototypes were not analyzed in a comparative way. The final best performing prototype stent (GSP2 (Group Stent Prototype 2), n = 8) allowed a transoral application mode and showed good clinical tolerance, minimal migration and acceptable biocompatibility. The good performance of stent type GSP2 was attributed to the helix-shaped surface structure, which was therefore regarded as a key-feature. This prototype stent offers the possibility for further research in a large animal model to confirm the promising data and assess other properties such as bioresorption.

Endoscopic treatment of benign tracheal stenosis: a single-centre study.

BACKGROUND: Benign tracheal stenosis is relatively rare but remains a significant chronic disease due to its drastic symptoms including dyspnoea and inspiratory stridor, and consequent negative effect on quality of life. Traditionally, the surgical approach by resection of the stenotic tracheal segment has been the therapy of choice. However, endoscopic techniques have arisen and may offer a safe and less invasive alternative. OBJECTIVES: The aim of the retrospective study was to evaluate procedure-related safety and outcome of endoscopic treatment of benign tracheal stenosis at a single centre. METHODS: The study included all patients at our institution who between 2013 and 2022 had received endoscopic treatment of benign tracheal stenosis by rigid tracheoscopy, radial incision by electric papillotomy needle and dilation (endoscopic tracheoplasty) followed by triamcinolone acetonide as a local submucosal injection and additionally, from 2020, budesonide inhalation. RESULTS: A total of 22 patients were treated in a total of 38 interventions, each resulting in immediate improvement of symptoms. There were no peri-interventional complications or mortality. Of the 38 interventions, 11 received no triamcinolone acetonide administration, resulting in a 54.5% recurrence rate after an average of 21.1 (±18.0) months, while 27 had local triamcinolone acetonide, with a 37% recurrence rate. Since 2020, we additionally initiated post-interventional budesonide inhalation as recurrence prophylaxis for newly admitted patients and patients with recurrences(n = 8), of whom only one (12.5%) has to date experienced a recurrence. CONCLUSION: Our results indicate that endoscopic tracheoplasty offers a safe and successful, minimally invasive alternative to open surgery for patients with benign tracheal stenosis. We recommend local administration of triamcinolone into the mucosa as an additional treatment to decrease the risk of recurrence. However, given the uncontrolled study design and low sample size, safety and effectiveness cannot be conclusively demonstrated. Nonetheless, our findings suggest promising avenues for further investigation. Further studies on the additional benefit of inhaled corticosteroids are warranted.

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18F-FDG uptake.

Objective: Immunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of the heart. Methods: We conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020. Results: We identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial 18F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed. Conclusion: TNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF.

One-Lung Ventilation during Rigid Bronchoscopy Using a Single-Lumen Endotracheal Tube: A Descriptive, Retrospective Single-Center Study.

Using one-lung ventilation (OLV) through a single-lumen endotracheal tube (SLT) in the untreated lung during rigid bronchoscopy (RB) and jet ventilation, high oxygenation can be guaranteed, whilst procedures requiring thermal energy in the other lung are still able to be used. This pilot study aimed to examine the bronchoscopy-associated risks and feasibility of OLV using an SLT during RB in patients with malignant airway stenosis. All consecutive adult patients with endobronchial malignant lesions receiving OLV during RB from 1 January 2017 to 12 May 2021 were included. We assessed perioperative complications in 25 RBs requiring OLV. Bleeding grades 1, 2, and 3 complicated the procedure in two (8%), five (20%), and five (20%) patients, respectively. The median saturation of peripheral oxygen remained at 94% (p = 0.09), whilst the median oxygen supply did not increase significantly from 0 L/min to 2 L/min (p = 0.10) within three days after the bronchoscopy. The 30-day survival rate of the patients was 79.1% (95% CI 58.4-91.1%), all of whom reported an improvement in subjective well-being after the bronchoscopy. OLV using an SLT during RB could be a new treatment approach for endobronchial ablative procedures without increasing bronchoscopy-associated risks, allowing concurrent high-energy treatments.

Lung Ultrasound for the Exclusion of Pneumothorax after Interventional Bronchoscopies-A Retrospective Study.

A chest X-ray (CXR) is recommended after bronchoscopies with an increased risk of pneumothorax (PTX). However, concerns regarding radiation exposure, expenses and staff requirements exist. A lung ultrasound (LUS) is a promising alternative for the detection of PTX, though data are scarce. This study aims to investigate the diagnostic yield of LUS compared to CXR, to exclude PTX after bronchoscopies with increased risk. This retrospective single-centre study included transbronchial forceps biopsies, transbronchial lung cryobiopsies and endobronchial valve treatments. Post-interventional PTX screening consisted of immediate LUS and CXR within two hours. In total, 271 patients were included. Early PTX incidence was 3.3%. Sensitivity, specificity, and the positive and negative predictive values of LUS were 67.7% (95% CI 29.93-92.51%), 99.2% (95% CI 97.27-99.91%), 75.0% (95% CI 41.16-92.79%) and 98.9% (95% CI 97.18-99.54%), respectively. PTX detection by LUS enabled the immediate placement of two pleural drains along with the bronchoscopy. With CXR, three false-positives and one false-negative were observed; the latter evolved into a tension-PTX. LUS correctly diagnosed these cases. Despite low sensitivity, LUS enables early diagnosis of PTX, thus preventing treatment delays. We recommend immediate LUS, in addition to LUS or CXR after two to four hours and monitoring for signs and symptoms. Prospective studies with higher sample sizes are needed.

[What Is an Acute COPD Exacerbation? Results of a Survey among Primary Care Physicians in the German-Speaking Part of Switzerland]. / Was ist eine akute COPD-Exazerbation? Resultate einer Umfrage bei grundversorgenden Ärztinnen und Ärzten in der Deutschschweiz.

What Is an Acute COPD Exacerbation? Results of a Survey among Primary Care Physicians in the German-Speaking Part of Switzerland Abstract. Acute exacerbations have a relevant impact on morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), which is why prophylactic and early treatment have become indispensable. However, COPD exacerbations are significantly under-diagnosed, possibly due to linguistic discrepancies between physician and patient. The aim of this study was to disclose how exacerbations are perceived by the GPs (general practitioners) and their patients and what linguistic conventions they use. This survey showed that GPs and their patients quite often have a divergent notion a common of COPD exacerbations.

Cost-effectiveness analysis of surgical lung volume reduction compared with endobronchial valve treatment in patients with severe emphysema.

BACKGROUND: Lung volume reduction, either by surgery or bronchoscopically by endobronchial valve treatment have been shown to be a cost-effective alternative compared with conservative therapy. However, there is no comparative analysis of lung volume reduction by surgery and bronchoscopic lung volume reduction using endobronchial valves. OBJECTIVES: The aim of this retrospective study was to provide a cost-effectiveness analysis of lung volume reduction by surgery compared with bronchoscopic lung volume reduction using endobronchial valves. METHODS: The effectiveness of lung volume reduction was assessed using forced expiratory volume in the first second (FEV1), residual volume (RV) and 6-minute walking distance (6MWD), measured at baseline and at 4 to 12 weeks. Cost unit accounting derived from SwissDRG was used as a surrogate of the costs from the payer's perspective. RESULTS: In total, 67 patients (37 men and 30 women) with a mean age of 68.3 ± 7.4 years were included. Both clinical effectiveness and costs were comparable between surgical and bronchoscopic lung reduction. The incremental cost-effectiveness ratios (ICERs) for bronchoscopic compared with lung volume reduction by surgery for FEV1, RV and 6MWD were -101, 4 and 58, respectively. For RV and 6MWD, it could be shown that endobronchial valve treatment is justified as a probably cost-effective alternative to lung volume reduction by surgery. Endobronchial valve treatment resulted in an improvement of 0.25 quality-adjusted life years (QALYs) and an ICER of € 7657 per QALY gained. CONCLUSION: A robust statement on the superiority of one of the two procedures in terms of cost-effectiveness cannot be made from the present study. Therefore, the study is not suitable for resource allocation. Two upcoming trials comparing lung volume reduction surgery and endobronchial valve treatment may be able to answer this question.

Endobronchial Ultrasound-Guided Transbronchial Forceps Biopsy: A Retrospective Bicentric Study Using the Olympus 1.5 mm Mini-Forceps.

When evaluating mediastinal/hilar lymphadenopathy (LAD) or masses, guidelines recommend endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) as an initial technique for tissue analysis and diagnosis. However, owing to the small sample size obtained by needle aspiration, its diagnostic yield (DY) is limited. EBUS transbronchial forceps biopsy (TBFB) used as a complimentary technique to EBUS-TBNA might allow for better histopathological evaluation, thus improving DY. In this retrospective bicentric study, we assessed the DY and safety of an EBUS-guided 1.5 mm mini-forceps biopsy combined with EBUS-TBNA for the diagnosis of mediastinal/hilar LAD or masses compared to EBUS-TBNA alone. In total, 105 patients were enrolled. The overall DY was 61.9% and 85.7% for TBNA alone and EBUS-TBNA combined with EBUS-TBFB, respectively (p < 0.001). While the combined approach was associated with a significantly higher DY for lung cancer diagnosis (97.1% vs. 76.5%, p = 0.016) and sarcoidosis (85.2% vs. 44.4%, p = 0.001), no significant differences in DY were calculated for subgroups with smaller sample sizes such as lymphoma. No major adverse events were observed. Using a 1.5 mm mini-forceps is a safe and feasible technique for biopsy of mediastinal or hilar LAD or masses with superior overall DY compared to EBUS-TBNA as a standalone technique.

The prevalence of obstructive sleep apnea in sarcoidosis and its impact on sleepiness, fatigue, and sleep-associated quality of life: a cross-sectional study with matched controls (the OSASA study).

STUDY OBJECTIVES: Patients with sarcoidosis experience fatigue and excessive daytime sleepiness (EDS). However, the underlying pathomechanism is unclear. Studies suggested undiagnosed obstructive sleep apnea (OSA) to be an important contributor, but reliable data on prevalence and impact of OSA in sarcoidosis are scarce. METHODS: 71 adult patients with sarcoidosis, 1-to-1 matched to 71 adult controls according to sex, age, and body mass index were included. Participants underwent structured interviews (including Epworth Sleepiness Scale [ESS], Fatigue Assessment Scale [FAS], and Functional Outcome of Sleep Questionnaire [FOSQ-30]) and level-3 respiratory polygraphy. OSA was defined as apnea-hypopnea index ≥ 5 events/h. Prevalence of OSA was assessed and possible risk factors for OSA in sarcoidosis were investigated. RESULTS: Mild OSA (AHI ≥ 5 events/h) was prevalent in 32 (45%) sarcoidosis patients vs 22 (31%) controls (P = .040). Sarcoidosis patients presented higher ESS compared with matched controls (P = .037). FAS scores (median [quartile] of 21.5 [16, 27.5]) indicated fatigue in sarcoidosis patients. Patients with EDS (ESS ≥ 11) presented reduced FOSQ-30 results (median [quartile] of 16.7 [15.2, 17.8]). ESS, FAS, and FOSQ were not associated with AHI in sarcoidosis patients. Body mass index, sex, neck circumference, and NoSAS score were predictors for OSA in sarcoidosis. CONCLUSIONS: The risk for mild OSA is 2.5-fold higher in sarcoidosis patients compared with matched controls. OSA seems not to be the reason for increased sleepiness or fatigue in sarcoidosis. Risk factors such as body mass index, sex, neck circumference, and NoSAS score can be used to screen for OSA in sarcoidosis patients. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Obstructive Sleep Apnoea in Sarcoidosis (OSASA); URL: https://clinicaltrials.gov/ct2/history/NCT04156789?V_2=View; Identifier: NCT04156789. CITATION: Roeder M, Sievi NA, Schneider A, et al. The prevalence of obstructive sleep apnea in sarcoidosis and its impact on sleepiness, fatigue, and sleep-associated quality of life: a cross-sectional study with matched controls (the OSASA study). J Clin Sleep Med. 2022;18(10):2415-2422.

Pyrolysis of engineered beach-cast seaweed: Performances and life cycle assessment.

The blooming of beach-cast seaweed has caused environmental degradation in some coastal regions. Therefore, a proper treating and utilizing method of beach-cast seaweed is demanded. This study investigated the potential of producing power or biofuel from pyrolysis of beach-cast seaweed and the effect of the ash-washing process. First, the raw and washed beach-cast seaweeds (RS and WS) were prepared. Thereafter, thermogravimetric analysis (TG), bench-scale pyrolysis experiment, process simulation, and life cycle assessment (LCA) were conducted. The TG results showed that the activation energies of thermal decomposition of the main organic contents of RS and WS were 44.23 and 58.45 kJ/mol, respectively. Three peak temperatures of 400, 500, and 600 °C were used in the bench-scale pyrolysis experiments of WS. The 600 °C case yielded the most desirable gas and liquid products. The bench-scale pyrolysis experiment of RS was conducted at 600 °C as well. Also, an LCA was conducted based on the simulation result of 600 °C pyrolysis of WS. The further process simulation and LCA results show that compare to producing liquid biofuel and syngas, a process designed for electricity production is most favored. It was estimated that treating 1 ton of dry WS can result in a negative cumulative energy demand of -2.98 GJ and carbon emissions of -790.89 kg CO2 equivalence.

Digital Light 3D Printed Bioresorbable and NIR-Responsive Devices with Photothermal and Shape-Memory Functions.

Digital light processing (DLP) 3D printing is a promising technique for the rapid manufacturing of customized medical devices with high precision. To be successfully translated to a clinical setting, challenges in the development of suitable photopolymerizable materials have yet to be overcome. Besides biocompatibility, it is often desirable for the printed devices to be biodegradable, elastic, and with a therapeutic function. Here, a multifunctional DLP printed material system based on the composite of gold nanorods and polyester copolymer is reported. The material demonstrates robust near-infrared (NIR) responsiveness, allowing rapid and stable photothermal effect leading to the time-dependent cell death. NIR light-triggerable shape transformation is demonstrated, resulting in a facilitated insertion and expansion of DLP printed stent ex vivo. The proposed strategy opens a promising avenue for the design of multifunctional therapeutic devices based on nanoparticle-polymer composites.

Transbronchial Cryobiopsy Compared to Forceps Biopsy for Diagnosis of Acute Cellular Rejection in Lung Transplants: Analysis of 63 Consecutive Procedures.

BACKGROUND: Acute cellular rejection (ACR) is a complication after lung transplantation (LTx). The diagnosis of ACR is based on histologic findings using transbronchial forceps biopsy (FB). However, its diagnostic accuracy is limited because of the small biopsy size and crush artifacts. Transbronchial cryobiopsy (CB) provides a larger tissue size compared with FB. METHODS: FB and CB were obtained consecutively during the same bronchoscopy (February 2020-April 2021). All biopsies were scored according to the ISHLT criteria by three pathologists. Interobserver agreement was scored by the kappa index. We assessed the severity of bleeding and the presence of pneumothorax. RESULTS: In total, 35 lung transplant recipients were included, and 126 CBs and 315 FBs were performed in 63 consecutive bronchoscopies. ACR (A1-A3, minimal-moderate) was detected in 18 cases (28.6%) by CB, whereas ACR was detected in 3 cases (4.8%) by FB. Moderate and severe bleeding complicated FB and CB procedures in 23 cases (36.5%) and 1 case (1.6%), respectively. Pneumothorax occurred in 6.3% of patients. The interobserver agreement was comparable for both CB and FB. CONCLUSIONS: CB provided an improved diagnostic yield for ACR diagnosis, leading to reclassification and changes in treatment strategies in 28.6% of cases. Prospective studies should better define the role of CB after LTx.

The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK: An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH: General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION: Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make.

Impact of Bayesian penalized likelihood reconstruction on quantitative and qualitative aspects for pulmonary nodule detection in digital 2-[18F]FDG-PET/CT.

To evaluate the impact of block sequential regularized expectation maximization (BSREM) reconstruction on quantitative and qualitative aspects of 2-[18F]FDG-avid pulmonary nodules compared to conventional ordered subset expectation maximization (OSEM) reconstruction method. Ninety-one patients with 144 2-[18F]FDG-avid pulmonary nodules (all ≤ 20 mm) undergoing PET/CT for oncological (re-)staging were retrospectively included. Quantitative parameters in BSREM and OSEM (including point spread function modelling) were measured, including maximum standardized uptake value (SUVmax). Nodule conspicuity in BSREM and OSEM images was evaluated by two readers. Wilcoxon matched pairs signed-rank test was used to compare quantitative and qualitative parameters in BSREM and OSEM. Pulmonary nodule SUVmax was significantly higher in BSREM images compared to OSEM images [BSREM 5.4 (1.2-20.7), OSEM 3.6 (0.7-17.4); p = 0.0001]. In a size-based analysis, the relative increase in SUVmax was more pronounced in smaller nodules (≤ 7 mm) as compared to larger nodules (8-10 mm, or > 10 mm). Lesion conspicuity was higher in BSREM than in OSEM (p < 0.0001). BSREM reconstruction results in a significant increase in SUVmax and a significantly improved conspicuity of small 2-[18F]FDG-avid pulmonary nodules compared to OSEM reconstruction. Digital 2-[18F]FDG-PET/CT reading may be enhanced with BSREM as small lesion conspicuity is improved.

Early Spirometry Following Bronchoscopic Lung Volume Reduction with Endobronchial Valves.

Bronchoscopic lung volume reduction (BLVR) by endobronchial valve (EBV) implantation has been shown to improve dyspnea, pulmonary function, exercise capacity, and quality of life in highly selected patients with severe emphysema and hyperinflation. The most frequent adverse event is a pneumothorax (PTX), occurring in approximately one-fifth of the cases due to intrathoracic volume shifts. The majority of these incidents are observed within 48 h post-procedure. However, the delayed occurrence of PTX after hospital discharge is a matter of concern. There is currently no approved concept for its prevention. Particularly, it is unknown whether and when respiratory manoeuvers such as spirometry post EBV treatment are feasible and safe. As per standard operating procedure at the University Hospital Zurich, early spirometry is scheduled after BLVR and prior to the discharge of the patient in order to monitor treatment success. The aim of our retrospective study was to investigate the feasibility and safety of early spirometry. In addition, we hypothesized that early spirometry could be useful to identify patients at risk for late PTX, which may occur after hospital discharge. All patients who underwent BLVR using EBVs between January 2018 and January 2020 at our hospital were enrolled in this study. After excluding 16 patients diagnosed post-procedure with PTX and four patients for other reasons, early spirometry was performed in 61 cases. There was neither a clinically relevant PTX during or after early spirometry nor a late PTX following hospital discharge. In conclusion, we found early spirometry, conducted not sooner than three days following EBV treatment, to be feasible and safe. Furthermore, early spirometry seems to be a useful predictor for successful BLVR, and it may help to decide whether a patient can be discharged. Given the small sample size and the retrospective design of our study, a prospective study that includes routine chest imaging after early spirometry to definitively exclude PTX is needed to recommend early spirometry as part of the standard protocol following EBV treatment.

Sarcoidosis - a multisystem disease.

Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways.

Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case-control study.

PURPOSE: Immune-checkpoint inhibitors (ICI) present a new treatment for malignancies by boosting the immune system. This has led to a variety of immune-related adverse events, including ICI-associated pneumonitis (ICIaP). Diagnosis thereof is often challenging, and its pathogenesis has not yet been fully understood. The aim of this cross-sectional case-control study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICIaP compared to controls consisting of healthy individuals, patients with lung cancer and patients with interstitial lung diseases (ILD) other than ICIaP. METHODS: From January 2018 until June 2019, 401 adult patients with various lung diseases were prospectively enrolled in a BALF- and serum biobank, called BALOTHEK. Of these, 12 patients were diagnosed with ICIaP (Pembrolizumab, Ipilimumab, or both, and Durvalumab) serving as case group. Subjects with one of three diagnosis groups from BALOTHEK, including lung cancer, ILD other than ICIaP, and healthy individuals, served as matched controls. The following 11 cytokines were simultaneously analyzed in BALF and serum of each study participant: interferon gamma, tumor necrosis factor alpha, interleukin (IL) 1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13 and IL-17A. This study was approved by the local ethic review committee (BASEC-ID 2017-02,307 and 2018-01,724). RESULTS: Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control groups. For the investigated cytokines in BALF, a significant increase of IL-6 level was shown for patients with ICIaP compared to control groups (p = 0.031, adjusted for multiple comparisons). CONCLUSION: Cytokine profile assessed in BALF shows promising potential for facilitating diagnosis and understanding of pathophysiology of ICIaP. IL-6 may not only contribute to better understanding of pathophysiology but also herald therapeutic implications for Tocilizumab.

Cost-benefit analysis of beach-cast harvest: Closing land-marine nutrient loops in the Baltic Sea region.

Harvesting beach-cast can help mitigate marine eutrophication by closing land-marine nutrient loops and provide a blue biomass raw material for the bioeconomy. Cost-benefit analysis was applied to harvest activities during 2009-2018 on the island of Gotland in the Baltic Sea, highlighting benefits such as nutrient removal from the marine system and improved recreational opportunities as well as costs of using inputs necessary for harvest. The results indicate that the activities entailed a net gain to society, lending substance to continued funding for harvests on Gotland and assessments of upscaling of harvest activities to other areas in Sweden and elsewhere. The lessons learnt from the considerable harvest experience on Gotland should be utilized for developing concrete guidelines for carrying out sustainable harvest practice, paying due attention to local conditions but also to what can be generalized to a wider national and international context.