Immunology of fibrotic lung disease: managing infections whilst preventing autoimmunity?

Interstitial lung disease (ILD) and lung fibrosis are characterized by different grades of fibrosis and inflammation. Persistent low-grade inflammation is believed to play a major pathogenic role, leading to an imbalance of cytokines, growth factors, and tissue proteinases. Recruited monocytes and macrophages play a pivotal role through their cytokine expression and possibly differentiation into fibrocytes, pericytes, or myofibroblasts. Atypical bacterial infections can cause ILD, although not usually in the form of usual interstitial pneumonia. On the other hand, bacterial colonization is frequently encountered in patients with chronic fibrotic lung disorders, and patients regularly undergo antibacterial treatment. As demonstrated in patients with diffuse panbronchiolitis and other chronic respiratory disorders, treatment with macrolides can be beneficial. This is partly explained by their antimicrobial effects but, for macrolides, immunomodulatory properties have been identified which might also be beneficial in patients with ILD or lung fibrosis. This article reviews the immunology of lung fibrogenesis and putative implications of macrolides for reinstallation of tolerance

Reduction in ulnar pressure distribution when walking with forearm crutches with a novel cuff design: Cross-sectional intervention study on the biomechanical efficacy of an ulnar recess

Walking with crutches is an effective way of reducing the load on the lower extremity and is often indicated after injury or surgery. However, walking with forearm crutches with conventional cuffs can trigger symptoms including tenosynovitis in the biceps tendon, ulnar neuropraxia at the wrist, pain, or skin hematoma. The purpose of this study was to test the hypothesis that a crutch cuff design with an ulnar recess reduces ulnar pressure during walking with forearm crutches. The pressure distribution between the forearm and crutch cuff was measured in 15 healthy participants for crutch walking with conventional and novel cuffs, respectively. Relative peak pressure in the proximal medial region compared to the overall peak pressure was reduced by 8.6% when walking with crutches with the novel cuff design compared to conventional cuffs (p < 0.001). Relative peak pressure in the distal intermediate and lateral regions were increased by 3.3% and 3.7% for the novel compared with conventional cuffs, respectively (p < 0.001 for both). Hence, the novel crutch cuffs shifted regions of high pressure away from the proximal ulnar region towards more distal regions that are covered by more soft tissue

Digital transformation of an academic hospital department: A case study on strategic planning using the balanced scorecard.

Digital transformation has a significant impact on efficiency and quality in hospitals. New solutions can support the management of data overload and the shortage of qualified staff. However, the timely and effective integration of these new digital tools in the healthcare setting poses challenges and requires guidance. The balanced scorecard (BSC) is a managerial method used to translate new strategies into action and measure their impact in an institution, going beyond financial values. This framework enables quicker operational adjustments and enhances awareness of real-time performance from multiple perspectives, including customers, internal procedures, and the learning organization. The aim of this study was to adapt the BSC to the evolving digital healthcare environment, encompassing factors like the recent pandemic, new technologies such as artificial intelligence, legislation, and user preferences. A strategic mapping with identification of corresponding key performance indicators was performed. To achieve this, we employed a qualitative research approach involving retreats, interdisciplinary working groups, and semi-structured interviews with different stakeholders (administrative, clinical, computer scientists) in a rheumatology department. These inputs served as the basis for customizing the BSC according to upcoming or already implemented solutions and to define actionable, cross-level performance indicators for all perspectives. Our defined values include quality of care, patient empowerment, employee satisfaction, sustainability and innovation. We also identified substantial changes in our internal processes, with the electronic medical record (EMR) emerging as a central element for vertical and horizontal digitalization. This includes integrating patient-reported outcomes, disease-specific digital biomarker, prediction algorithms to increase the quality of care as well as advanced language models in order save resources. Gaps in communication and collaboration between medical departments have been identified as a main target for new digital solutions, especially in patients with more than one disorder. From a learning institution's perspective, digital literacy among patients and healthcare professionals emerges as a crucial lever for successful implementation of internal processes. In conclusion, the BSC is a helpful tool for guiding digitalization in hospitals as a horizontally and vertically connected process that affects all stakeholders. Future studies should include empirical analyses and explore correlations between variables and above all input and user experience from patients

Hydrazine borane as a hydrogen storage material

In der vorliegenden Arbeit wurde das Wasserstoffabgabeverhalten von Hydrazinboran in einem Temperaturbereich von 70°C bis 150°C untersucht. Hierbei wurde das Ziel des DOE für 2015 (5,5 Gew.-% H2) erreicht. Die Pyrolyseprodukte wurden mit einer großen Bandbreite moderner Analysemethoden untersucht, um Hinweise auf Struktur und Zersetzungsmechanismus zu gewonnen. Sämtliche Ergebnisse sprechen dafür, dass eine von Goubeau und Ricker 1963 formulierte Reaktionsgleichung zutrifft und sich bei der Reaktion zunächst ein regelmäßiges Polymer der Form (BH2NHNHBH2)n bildet, in dem die Monomere über jeweils zwei Bor-Stickstoffbindungen miteinander verknüpft sind. Bei erhöhten Temperaturen scheint sowohl intra- als auch intermolekular zusätzlicher Wasserstoff aus dieser Verbindung abgespalten zu werden. Fallhammertests zeigten jedoch, dass die Zersetzungsprodukte mechanisch nur mäßig belastbar sind und teils explosiv reagieren. Um die Wasserstoffabgabe aus Hydrazinboran zu verbessern, wurden stöchiometrische Mengen an Leichtmetallhydriden zugegeben, was im Fall von Lithiumhydrid eine signifikante Steigerung der freigesetzten Mengen an Wasserstoff zur Folge hatte, wodurch schon bei 90°C das vom DOE für 2015 gesetzte Ziel erreicht wird. Da jedoch einerseits die hierbei benötigte Temperatur höher liegt als gefordert (85°C), und sich andererseits abzeichnete, dass die Reaktionsprodukte teilweise hochexplosiv auf mechanische Belastung reagieren, wurde versucht, die Reaktion mit Hilfe von Übergangsmetallchloriden in katalytischen Mengen zu beeinflussen. Insbesondere durch die Zugabe von Zinkchlorid und Kupfer(I)chlorid wurden bereits bei 70°C den Zielsetzungen des DOE entsprechende Ergebnisse erzielt. Dabei ist die Reaktion des Zinkchlorids von besonderem Interesse, da das entstehende Gas nur Spuren an Verunreinigungen aufweist. Trotz sehr guter Ergebnisse, die mit einem vergleichsweise geringen technischen und finanziellen Aufwand erreicht werden können, steht einer weitverbreiteten Anwendung von Hydrazinboran als Wasserstoffspeicher noch die Explosivität des hydrazinbasierten Systems im Weg. Möglichkeiten, dieses Risiko zu minimieren, könnten beispielsweise die Adsorption des Hydrazinborans in mesoporösen Materialien oder die katalytische Zersetzung in ionischen Flüssigkeiten sein.This work investigated the hydrogen release properties of hydrazine borane in a temperature range from 70°C to 150°C, and the DOE targets for 2015 (5,5 wt% H2) were reached. The reaction products of the pyrolysis were investigated with a wide range of modern analysis techniques in order to gain insight into both structure and decomposition mechanism. All results suggest that a reaction equation described by Goubeau and Ricker in 1963 is correct, and that the initial reaction product is a polymer consisting of (BH2NHNHBH2) monomers linked by two boron-nitrogen bonds at a time. At elevated temperatures, hydrogen release seems to occur due to both inter- and intramolecular reaction. Falling hammer tests however have shown that the decomposition products are only moderately stable under mechanical stress and sometimes react explosively. Stoichiometric amounts of light metal hydrides were added in order to improve the hydrogen release properties of hydrazine borane. In the case of lithium hydride, this induced a significant increase in the amount of hydrogen released, and the DOE targets for 2015 were already reached at a temperature of 90°C. Since this temperature is still higher than the specifications (85°C) and it also became apparent that the products of these reactions sometimes exhibit a high tendency to explode under even light mechanical stress, the influence of catalytic amounts of transition metal chlorides on the reactions was tested. The best results were achieved by addition of zinc chloride and copper(I) chloride, in which cases the DOE requirements were met at a temperature as low as 70°C. The reaction of the zinc chloride is of special interest since the resulting gas does contain only trace amounts of gaseous contaminants. However, even though outstanding results were achieved with a comparably low technical and monetary effort, the explosiveness of this hydrazine based system will most likely stand in the way of widespread practical applications. Potential solutions to minimize this risk could include the adsorption of hydrazine borane in mesoporous substances or the catalysed decomposition in ionic liquids

Stem cell transplantation for rheumatic autoimmune diseases

Immunoablative therapy and hematopoietic stem cell transplantation (HSCT) is an intensive treatment modality aimed at 'resetting' the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused hematopoietic stem cells, either from the patient (autologous HSCT) or a healthy donor (allogeneic HSCT). HSCT has been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells. Most of the available data have been collected through retrospective cohort analyses of autologous HSCT, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity and mortality have improved due to better patient selection and modifications of transplant regimens. Treatment-related mortality has decreased to approximately 7%. Prospective, randomised, controlled clinical trials are ongoing or planned in systemic sclerosis, systemic lupus erythematosus, and several nonrheumatological conditions

Allogeneic stem cell transplantation for rheumatic autoimmune diseases

Haematopoietic stem cell transplantation (HSCT) has evolved from an experimental concept to an effective treatment option for severe autoimmune diseases and has a unique ability to restore immune regulation. It is a complex multistep procedure involving the administration of high doses of immunosuppressive medication and transplantation of stem cells. Most HSCT procedures in autoimmune disease have involved autologous stem cells. In the case of allogeneic transplantation, stem cells are derived from peripheral blood or bone marrow of a healthy HLA-matched donor. Allogeneic HSCT has curative potential based on studies in experimental models of autoimmune disease, case reports, and a registry analysis but carries significant risks of rejection and graft-versus-host disease. Unless these risks become manageable, allogeneic HSCT should be offered only if all alternative treatment options have failed, if a patient has a suitable donor, and if a patient still has a chance to benefit significantly from the procedure

Marathon performance but not BMI affects post-marathon pro-inflammatory and cartilage biomarkers

We tested the hypothesis that changes in serum cartilage oligomeric matrix protein (COMP), tumour necrosis factor α (TNF-α), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) concentration after regular endurance training and running a marathon race depend on body mass index (BMI) and/or on marathon performance. Blood samples were collected from 45 runners of varying BMI and running experience before and after a 10-week marathon training programme and before, immediately and 24 h after a marathon race. Serum biomarker concentrations, BMI and marathon finishing time were measured. The mean (95% confidence interval (CI)) changes from before to immediately after the marathon were COMP: 4.09 U/L (3.39-4.79 U/L); TNF-α: -1.17 mg/L (-2.58 to 0.25 mg/L); IL-6: 12.0 pg/mL (11.4-12.5 pg/mL); and hsCRP: -0.08 pg/mL (-0.14 to -0.3 pg/mL). The mean (95% CI) changes from immediately after to 24 h after the marathon were COMP: 0.35 U/L (-0.88 to 1.57 U/L); TNF-α: -0.43 mg/L (-0.99 to 0.13 mg/L); IL-6: -9.9 pg/mL (-10.5 to -9.4 pg/mL); and hsCRP: 1.52 pg/mL (1.25-1.79 pg/mL). BMI did not affect changes in biomarker concentrations. Differences in marathon finishing time explained 32% of variability in changes in serum hsCRP and 28% of variability in changes in serum COMP during the 24 h recovery after the marathon race (P < 0.001). Slower marathon finishing time but not a higher BMI modulates increases in pro-inflammatory markers or cartilage markers following a marathon race

Differentiation Potential of CD14+ Monocytes into Myofibroblasts in Patients with Systemic Sclerosis

BACKGROUND: Circulating monocytes are a highly plastic and functionally heterogeneic cell type with an activated phenotype in patients with systemic sclerosis (SSc). CD14(+) monocytes have the potential to differentiate into extra-cellular matrix (ECM) producing cells, possibly participating in fibrogenesis. AIM: To study the effect of GM-CSF, IL-4 and endothelin -1 (ET-1) alone or in combination on monocyte differentiation into myofibroblasts. METHODS: CD14(+) cells were isolated from peripheral blood from 14 SSc patients and healthy controls by positive selection and incubated with different combinations of GM-CSF, IL-4 and ET-1 for 14 days. Type-1 collagen and α-SMA were detected by Western blot, qPCR and confocal microscopy. HLA-DR, CD11c and CD14 expression was analysed by flow cytometry. A collagen gel contraction assay was performed for functional myofibroblast assessment. RESULTS: GM-CSF both induced collagen and α-SMA expression after 14 days. ET-1 further increased GM-CSF-induced collagen expression in a dose dependent manner up to 30-fold. IL-4/GM-CSF combination leads to a more DC-like phenotype of monocytes associated with reduced collagen and α-SMA expression compared to GM-CSF alone. Collagen and α-SMA expression was higher in monocytes from SSc patients and monocytes were more prone to obtain a spindle form. In contrast to controls, ET-1 and IL-4 alone were sufficient to induce α-SMA expression in monocytes from SSc patients. Despite the induction of α-SMA expression, monocyte-derived myofibroblasts only had a moderate capability of contraction in functional analyses. CONCLUSION: SSc monocytes display increased maturation towards myofibroblasts demonstrated by their phenotype and α-SMA expression when compared to monocytes from healthy controls, however only with minor functional contraction properties