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Background: Endobronchial administration of local anesthetics such as lidocaine is often used for cough suppression during bronchoscopy. To achieve a better distribution of lidocaine in the tracheobronchial tree, spray catheters have been developed, allowing nebulization of the local anesthetic solution. However, there are little data on the efficacy and safety of this approach, or on the consumption of sedative drugs and lidocaine during nebulized administration. Objectives: To investigate the tolerability of nebulized lidocaine compared to conventional lidocaine administration via syringe through the working channel of the broncho-scope in patients undergoing bronchoscopy. Consumption of sedative drugs and lidocaine was also compared between the two lidocaine administration approaches. Methods: Patients requiring bronchoscopy with endobronchial or trans-bronchial biopsy were randomly assigned to receive topical lidocaine either via syringe or via nebulizer. Endpoints were consumption of lidocaine and sedative drugs, as well as patient tolerance and safety. Results: Thirty patients were included, 15 in each group. Patients in the nebulizer group required lower doses of endobronchial lidocaine (184.7 ± 67.98 vs. 250.7 ± 21.65 mg, p = 0.0045) and intravenous fentanyl (0.033 ± 0.041 vs. 0.067 ± 0.045 mg, p = 0.0236) than those in the syringe group; midazolam or propofol dosages did not differ between the two groups. In addition, there were no between-group differences in patient tolerance or safety (all p > 0.05). Conclusion: Endobronchial administration of lidocaine during bronchoscopy via nebulizer was found to be well tolerated and safe and was associated with reduced lidocaine and fentanyl dosages compared to ad ministration via syringe. [ABSTRACT FROM AUTHOR]

Background: Tracheal tissue engineering is a promising option for the treatment of tracheal defects. In a previous study we proved the suitability of fibrin gel as a scaffold for tracheal tissue engineering. This study investigates whether the differentiation of respiratory epithelium can be increased by culturing epithelial cells in a three dimensional system containing fibroblasts embedded into fibrin gel. Methods: Respiratory epithelial cells were isolated from porcine trachea, seeded onto a fibrin gel and kept in air-liquid-interface culture for 33 days. Morphology as well as pan-cytokeratin, MUC5AC and claudin-1 expression of cells cultured on pure fibrin gel were compared to culture on gels containing fibroblasts. Results: After two weeks, cells seeded on pure fibrin gel were multilayered, showed hyperproliferation and dedifferentiation. Co-cultured cells built up a pseudostratified epithelium. The differentiation and organization of epithelial structure improved with respect to time. After four weeks, morphology of the co-cultured respiratory epithelium resembled native tracheal epithelium. Immunohistochemistry showed that respiratory epithelium co-cultured with fibroblasts had an increasing similarity of pan-cytokeratin expression compared to native trachea. Cells cultured without fibroblasts differed in pan-cytokeratin expression from native trachea and did not show any improvement of differentiation. Immunohistochemical staining of MUC5AC and claudin-1 proved seeded cells being respiratory epithelial cells. Conclusions: This study indicates that adding fibroblasts to fibrin gel positively influences the differentiation of respiratory epithelium. [ABSTRACT FROM AUTHOR]

Abstract: Cytokines are key to control cellular communication. Interleukin-31 (IL-31) was recently discovered as a new member of the IL-6 family of cytokines. IL-31 signals through a heterodimeric receptor composed of OSMR and IL-31RA, a complex that stimulates the JAK-STAT, the RAS/ERK and the PI3K/AKT signal transduction pathways. The available data suggests that IL-31 is important for both innate and adaptive immunity in tissues that are in close contact with the environment, i.e. the skin, the airways and the lung, and the lining of the intestine. Enhanced expression of IL-31 is associated with a number of diseases, including pruritic diseases such as atopic dermatitis, but also in allergy and inflammatory bowel disease. In these tissues IL-31 coordinates the interaction of different immune cells, including T-cells, mast cells, and eosinophils, with epithelial cells. In this review we have summarized the available data on IL-31 and its receptor, their expression pattern and how they are regulated. We describe the current state of knowledge of the involvement of IL-31 in diseases, both in humans and in mouse models. From these studies it is becoming clear that IL-31 plays an important role in the proper functioning of the skin and of airway and intestinal epithelia. The findings available suggest that IL-31 might be an interesting target for directed drug therapy. [Copyright &y& Elsevier]

The original version of this article unfortunately contained a mistake. The captions of Fig. 2 and Fig. 3 are mismatched. [ABSTRACT FROM AUTHOR]

Introduction: Bronchoscopic spraying has potential for the application of therapeutic drugs in distal regions of the lung by bypassing the upper airways. However, there is a lack of understanding about the underlying fluid transport phenomena that are responsible for the intrapulmonary propagation of applied liquid. Methods: By using a transparent airway model, this study provides first experimental insights into relevant transport phenomena of bronchoscopic spraying. Furthermore, the penetration depth of the application is quantitatively evaluated. Laser-induced fluorescence is used to analyze fluid propagation in the transparent channels. Potential influencing factors such as the positioning in different airways, application number, breathing pattern, and lung obstructions are varied within this study to determine their influence on liquid deposition. Findings: This study shows that the method of bronchoscopic spraying allows the application of liquid in distal regions of the airway model. The position of the bronchoscope is a key influencing factor in increasing the penetration depth. We found that fluid transport along the distal airways essentially occurs by the film and plug flow phenomenon during application, which is similar to the transport mechanisms during instillation. Liquid plugs in lower airways are responsible for the reorganization of liquid during proximal movements and thereby influence the penetration depth in subsequent applications. [ABSTRACT FROM AUTHOR]

• The sensitivity and specificity of seven serological assays for SARS-CoV-2 were compared. • No single assay offered a combination of very high sensitivity and very high specificity. • To maximize sensitivity and specificity two assays should be combined. There is an ongoing need for highly reliable serological assays to detect individuals with past SARS-CoV-2 infection. Using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR, we investigated the sensitivity and specificity of the Liaison SARS-CoV-2 S1/S2 IgG assay (DiaSorin), the Elecsys Anti-SARS-CoV-2 assay (Roche), and the ID Screen SARS-CoV-2-N IgG indirect kit (IDVet). We determined a sensitivity of 95.5 %, 95.5 %, and 100 % and a specificity of 90.5 %, 96.2 %, and 92.5 % for the DiaSorin assay, the Roche assay, and the IDVet assay, respectively. We conclude that serologic assays combining very high sensitivity and specificity are still not commercially available for SARS-CoV-2. For maximizing sensitivity and specificity of SARS-CoV-2 serological diagnostics, the combination of two assays may be helpful. [ABSTRACT FROM AUTHOR]

• 4 new SARS-CoV-2 IgG assays can identify individuals with past SARS-CoV-2 infection. • Combination of two different assays may increase sensitivity and specificity. • Two assays were identified allowing quantification over a broad linear range. Facing the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for serological assays identifying individuals with past coronavirus disease 2019 (COVID-19). Our study is the first to compare four new commercially available assays using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR: the anti SARS-CoV-2 ELISA (IgG) (Euroimmun, Germany), the EDI New Coronavirus COVID-19 IgG ELISA, (Epitope diagnostics (EDI), USA), the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Germany), and the SARS-CoV-2 Virachip IgG (Viramed, Germany). We found a sensitivity of 86.4 %, 100 %, 86.4 %, and 77.3 % and a specificity of 96,2 %, 88,7 %, 100 %, and 100 % for the Euroimmun assay, the EDI assay, the Mikrogen assay, and the Viramed assay, respectively. Commercially available SARS-CoV-2 IgG assays have a sufficient specificity and sensitivity for identifying individuals with past SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

• PANGAEA continues to assess the real-world effectiveness and safety of fingolimod. • Data spanning 48 months from over 3000 patients were included in this analysis. • Relapse rates and disability activity were stable across natalizumab washout groups. • Findings were consistent with those in patients switching from other treatments. • Findings support natalizumab washout durations recommended in German guidelines. The risk of progressive multifocal leukoencephalopathy limits the duration over which patients can receive natalizumab before requiring a switch to other therapies such as fingolimod. To date, no studies have assessed the long-term real-world effectiveness and safety of fingolimod following a switch from natalizumab. We aimed to investigate the benefit–risk profile of fingolimod over 48 months in patients switching from natalizumab, and the impact of washout duration after natalizumab discontinuation on outcomes during fingolimod treatment. This analysis used data from PANGAEA, an ongoing German multicenter, prospective, non-interventional, observational study. In total, 3912 patients were included: 530 had switched from natalizumab (natalizumab subpopulation), and a reference population of 3382 had switched from other treatments or were treatment-naïve (non-natalizumab subpopulation). The natalizumab subpopulation was stratified by washout duration (30–89 days, 90–149 days, and ≥ 150 days) prior to fingolimod initiation. In the natalizumab subpopulation over 48 months of fingolimod treatment, 58.2% (n = 227/390) of patients remained on fingolimod. Over this period, mean annualized relapse rates (ARRs) and proportions of patients who relapsed were similar across washout durations, and ranged from 0.455 (95% confidence interval [CI]: 0.363–0.571) to 0.546 (95% CI: 0.446–0.669) and 54.1% (n = 92/170) to 60.2% (n = 127/211), respectively. Overall, 17.1% (n = 36/211) had 6-month confirmed disability worsening. In the non-natalizumab subpopulation, ARR was 0.300, 40.9% (n = 1325/3237) of patients relapsed, and a similar proportion to the natalizumab subpopulation had 6-month disability worsening (16.6% n = 232/1394]). In both subpopulations, the safety profile of fingolimod was consistent with that observed in randomized controlled trials. In patients discontinuing natalizumab, fingolimod has a favorable benefit–risk profile over 48 months. These findings also suggest using a short washout following natalizumab discontinuation, consistent with guidelines and current clinical practice in Germany. [ABSTRACT FROM AUTHOR]

Background: Survey-based studies are frequently used to describe the economic impact of multiple sclerosis (MS). However, there is no validated health resource survey available, preventing comparison of study results and meaningful conclusions regarding the efficiency of long-term treatments.Objective: The aim of this study was to develop and validate a tablet- and paper-based MS health resource utilization survey.Methods: We developed and validated the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS), consisting of 24 cost items for paper and tablet users. Data for validation came from two large German observational studies. Survey practicability was assessed according to the response rate. Reliability was described using test-retest reliability as well as Guttman lambda. Construct validity was assessed as convergent and discriminant validity via correlations with associated patient-reported outcomes and known-group analyses.Results: In total, 2207 out of 2388 (response rate: 92.4%) patients completed the survey and were included to determine psychometric properties. The test-retest reliability had an intraclass correlation coefficient of 0.828 over a course of 3 months. Convergent validity analyses showed that total costs correlated positively with increased disability (r=0.411, P<.001). For discriminant validity, correlations of total costs with the Treatment Satisfaction Questionnaire for Medication ranged from -0.006 (convenience) to -0.216 (effectiveness). The mean annual cost was €28,203 (SD €14,808) (US $39,203; SD US $20,583) with disease-modifying therapies.Conclusions: The MS-HRS is a multilingual, reliable, valid, electronically available, and easy-to-administer questionnaire providing a holistic cross-sectional and longitudinal assessment of resource utilization in patients with MS. [ABSTRACT FROM AUTHOR]