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    Lung Involvement in Primary Sjögren's Syndrome-An Under-Diagnosed Entity.

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    Interstitial lung disease (ILD) represents a frequent extra-glandular manifestation of primary Sjögren's Syndrome (pSS). Limited published data regarding phenotyping and treatment exists. Advances in managing specific ILD phenotypes have not been comprehensively explored in patients with coexisting pSS. This retrospective study aimed to phenotype lung diseases occurring in a well-described pSS-ILD cohort and describe treatment course and outcomes. Between April 2018 and February 2020, all pSS patients attending our Outpatient clinic were screened for possible lung involvement. Clinical, laboratory and high-resolution computed tomography (HRCT) findings were analyzed. Patients were classified according to HRCT findings into five groups: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), combined pulmonary fibrosis and emphysema (CPFE), and non-specific-ILD. Lung involvement was confirmed in 31/268 pSS patients (13%). One-third (10/31) of pSS-ILD patients were Ro/SSA antibody negative. ILD at pSS diagnosis was present in 19/31 (61%) patients. The commonest phenotype was UIP n = 13 (43%), followed by NSIP n = 9 (29%), DIP n = 2 (6 %), CPFE n = 2 (6 %), and non-specific-ILD n = 5 (16%). Forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) appeared lower in UIP and DIP, without reaching a significant difference. Treatment focused universally on intensified immunosuppression, with 13/31 patients (42%) receiving cyclophosphamide. No anti-fibrotic treatments were used. Median follow-up was 38.2 [12.4-119.6] months. Lung involvement in pSS is heterogeneous. Better phenotyping and tailored treatment may improve outcomes and requires further evaluation in larger prospective studies

    Role of MSC in the Tumor Microenvironment.

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    The tumor microenvironment represents a dynamically composed matrix in which tissue-associated cancer cells are embedded together with a variety of further cell types to form a more or less separate organ-like structure. Constantly mutual interactions between cells of the tumor microenvironment promote continuous restructuring and growth in the tumor. A distinct organization of the tumor stroma also facilitates the formation of transient cancer stem cell niches, thereby contributing to progressive and dynamic tumor development. An important but heterogeneous mixture of cells that communicates among the cancer cells and the different tumor-associated cell types is represented by mesenchymal stroma-/stem-like cells (MSC). Following recruitment to tumor sites, MSC can change their functionalities, adapt to the tumor's metabolism, undergo differentiation and synergize with cancer cells. Vice versa, cancer cells can alter therapeutic sensitivities and change metastatic behavior depending on the type and intensity of this MSC crosstalk. Thus, close cellular interactions between MSC and cancer cells can eventually promote cell fusion by forming new cancer hybrid cells. Consequently, newly acquired cancer cell functions or new hybrid cancer populations enlarge the plasticity of the tumor and counteract successful interventional strategies. The present review article highlights some important features of MSC within the tumor stroma

    Diverging Trends in Age at First Myocardial Infarction: Evidence from Two German Population-Based Studies.

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    Little is known about trends in the age of onset of first myocardial infarction. Thus, we examined trends in the age of onset distribution of first myocardial infarction using two population-based datasets from Germany. First, we used German claims data based on an annual case number of approximately 2 million women and men covering the period from 2006 to 2016. Second, we used data from the KORA (Cooperative Health Research in the Region of Augsburg) Myocardial Infarction Registry covering the period from 2000-2016. Analyses were performed by means of quantile regression to estimate trends across the whole distribution of age of onset. Overall, NSample 1 = 69627 and NSample 2 = 9954 first myocardial infarctions were observed. In both samples, we found highly heterogeneous trends in age of onset. In men, we consistently found that age of onset increased before 50 and after 70 but decreased within this age bracket. For women, on the other hand, we consistently found that age of onset decreased for first myocardial infarctions before 70 but increased slightly or remained relatively stable thereafter. Therefore, late myocardial infarctions tended to occur later in life, while regular myocardial infarctions tended to occur earlier. These results suggest that in myocardial infarction, both morbidity compression and morbidity expansion might have occurred at the same time but for different parts of the age at onset distribution

    Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD.

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    IL-17A and IL-17F cytokines are important regulators of acute graft-versus-host-disease (GVHD). However, contrary effects of these cytokines in inflammatory diseases have been reported. To investigate the effects of donor-derived IL-17A and IL-17F on GVHD, we made use of single (Il17a-/- or Il17f-/-) and double deficient (Il17af-/-) allogeneic donor CD4+ T cells. We could demonstrate that transplantation of Il17af-/- CD4+ donor T cells led to aggravated GVHD. However, this phenotype was not observed after transplantation of single, Il17a-/- or Il17f-/-, deficient CD4+ T cells, suggesting redundant effects of IL-17A and IL-17F. Moreover, Il17af-/- cell recipients showed an increase of systemic IFNγ, indicating a heightened pro-inflammatory state, as well as infiltration of IFNγ-secreting CD4+ T cells in the recipients' intestinal tract. These recipients exhibited significant gut leakage, and markedly macrophage infiltration in the gastrointestinal epithelial layer. Moreover, we saw evidence of impaired recovery of gut epithelial cells in recipients of Il17af-/- CD4+ T cells. In this study, we show that IL-17A/F double deficiency of donor CD4+ T cells leads to accelerated GVHD and therefore highlight the importance of these cytokines. Together, IL-17 cytokines might serve as a brake to an intensified Th1 response, leading to the exacerbated gut damage in acute GVHD

    Trends in self-rated health among the elderly population in Germany from 1995 to 2015 - the influence of temporal change in leisure time physical activity.

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    BACKGROUND:Against the backdrop of rising statutory retirement age in Germany, we analyzed time trends in self-rated health (SRH) among the elderly population between 50 and 70 years of age and explored the mediating role of leisure time physical activity (LTPA) on the relationship between time period and self-rated health (SRH). METHODS:We used longitudinal survey data (n = 23,161) from a national panel study (GSOEP) to analyze time trends in SRH and regular LTPA (at least once a week) by means of Generalized Estimation Equation (GEE) analysis for logistic regression. The Karlson-Holm-Breen (KHB) method was applied for decomposing trend effects into direct and indirect parts via LTPA. In addition to odds ratios (OR), we illustrated the results by means of predicted probabilities and average partial effects (APE). RESULTS:Over time, the predicted probabilities of good SRH and regular LTPA increased while those of poor SRH decreased. After adjusting for socioeconomic status (SES) 53.4% of the trend in good SRH in women (OR = 1.34 / APE = 6.8%-points) could be attributed to the rise in regular LTPA. In men, the remaining smaller effect (OR = 1.13 / APE = 2.7%) could be fully assigned to temporal changes in regular LTPA. With respect to poor health we found a suppression effect of LTPA in the adjusted model, indicating that without improvements in regular LTPA over time an increase in poor SRH would have occurred. CONCLUSIONS:The increase of regular LTPA accounted for improved SRH from 1995 to 2015 among the elderly, indicating that promoting LTPA might be a key factor to raise healthy working life expectancy

    Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair.

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    Rotator cuff tear is the most frequent tendon injury in the adult population. Despite current improvements in surgical techniques and the development of grafts, failure rates following tendon reconstruction remain high. New therapies, which aim to restore the topology and functionality of the interface between muscle, tendon and bone, are essentially required. One of the key factors for a successful incorporation of tissue engineered constructs is a rapid ingrowth of cells and tissues, which is dependent on a fast vascularization. The dorsal skinfold chamber model in female BALB/cJZtm mice allows the observation of microhemodynamic parameters in repeated measurements in vivo and therefore the description of the vascularization of different implant materials. In order to promote vascularization of implant material, we compared a porous polymer patch (a commercially available porous polyurethane based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fiber mats and chitosan-graft-PCL coated electrospun PCL (CS-g-PCL) fiber mats in vivo. Using intravital fluorescence microscopy microcirculatory parameters were analyzed repetitively over 14 days. Vascularization was significantly increased in CS-g-PCL fiber mats at day 14 compared to the porous polymer patch and uncoated PCL fiber mats. Furthermore CS-g-PCL fiber mats showed also a reduced activation of immune cells. Clinically, these are important findings as they indicate that the CS-g-PCL improves the formation of vascularized tissue and the ingrowth of cells into electrospun PCL scaffolds. Especially the combination of enhanced vascularization and the reduction in immune cell activation at the later time points of our study points to an improved clinical outcome after rotator cuff tear repair

    Association of Motor and Cognitive Symptoms with Health-Related Quality of Life and Caregiver Burden in a German Cohort of Advanced Parkinson's Disease Patients.

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    Parkinson's disease (PD) is a chronic progressive movement disorder with severe reduction in patients' health-related quality of life (HR-QoL). Motor and cognitive symptoms are especially linked with decreased PD patients' HR-QoL. However, the relationship of these symptoms to caregiver burden is relatively unclear. Influence of the Montreal Cognitive Assessment scale (MoCA) as a cognitive screening tool and Movement Disorders Society Unified Parkinson's disease Rating Scale MDS-UPDRS symptoms in relation to patients' HR-QoL and caregivers` burden was analyzed. PD patients (n = 124) completed MDS-UPDRS, MoCA, and the PD questionnaire 8 (PDQ-8) as a measure of quality of life. Caregivers (n = 78) were assessed by the PD caregiver burden inventory (PDCB). PDQ-8 and PDCB scores were regressed on MDS-UPDRS subscales and MoCA subscores. PDQ-8 correlated with attention (R 2 0.1282; p < 0.001) and executive (R 2 0.0882; p 0.001) MoCA subscores and all parts of the MDS-UPDRS. PDCB correlated most strongly with MDS-UPDRS part III motor symptoms (R 2 0.2070; p < 0.001) and the MoCA attention subscore (R 2 0.1815; p < 0.001). While all facets of PD symptoms assessed by the MDS-UPDRS relate to PD patients' quality of life, motor symptoms are the most relevant factor for the prediction of caregiver burden. In addition, patients' attentional symptoms seem to affect not only them, but also their caregivers. These findings show the potential of a detailed analysis of MDS-UPDRS and MoCA performance in PD patients

    Fixation Stability and Stiffness of Two Implant Systems for Proximal Femoral Varization Osteotomy

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    Proximal femoral varization osteotomy is a well-established surgical procedure in children with severe hip problems. This study aimed to evaluate the fixation stability and stiness of two new implant systems. A biomechanical testing model was created with a total of 12 synthetic femora. Proximal femoral varization osteotomy was performed in every femur, and the synthetic femora were fixed with two dierent implant systems (PediLoc Locking Proximal Femur Plate System versus PediLoc Locking Cannulated Blade Plate System; OrthoPediatrics,Warsaw, IN, USA). The average torsional stiness of the locking plate group was higher than for the cannulated blade plate group. Dierences in internal and external rotations were seen between the two groups, but they were not significant. Using the tested implants in severe osteoporotic bones might show other results. Therefore, it might be helpful to use the locking plate system in osteoporotic bones and in cases of revision operations where stability is of critical focus

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