Data-driven prediction of COVID-19 cases in Germany for decision making

The COVID-19 pandemic has led to a high interest in mathematical models describing and predicting the diverse aspects and implications of the virus outbreak. Model results represent an important part of the information base for the decision process on different administrative levels. The Robert-Koch-Institute (RKI) initiated a project whose main goal is to predict COVID-19-specific occupation of beds in intensive care units: Steuerungs-Prognose von Intensivmedizinischen COVID-19 Kapazitäten (SPoCK). The incidence of COVID-19 cases is a crucial predictor for this occupation

Validation of a proxy‐reported SARC‐F questionnaire for current and retrospective screening of sarcopenia‐related functional impairments

BACKGROUND: The strength, assistance walking, rise from a chair, climb stairs, and falls (SARC‐F) questionnaire is a well‐established instrument for screening of sarcopenia and sarcopenia‐related functional impairments. As it is based on self‐reporting, its use precludes patients who are unable to answer the questionnaire as a consequence of severe acute diseases or cognitive impairment. Therefore, we aimed to validate a proxy‐reported version of the SARC‐F for both ad‐hoc as well as retrospective screening for severe sarcopenia‐related functional impairments. METHODS: Patients aged ≥60 years completed the SARC‐F and performed the short physical performance battery (SPPB) at baseline (T1). Proxies in Cohort A gave a simultaneous assessment of the patients' functional status with the proxy‐reported SARC‐F at T1 and again, retrospectively, after 3 months (T2). Proxies in Cohort B only completed the SARC‐F retrospectively at T2. The questionnaires' performances were assessed through sensitivity/specificity analyses and receiver operating characteristic (ROC) curves. For non‐inferiority analyses, results of both the patient‐reported and proxy‐reported SARC‐F were correlated with the SPPB total score as well as the results of the chair‐rise test subcategory; the respective correlation coefficients were tested against each other. RESULTS: One hundred and four patients and 135 proxies participated. Using a SPPB score < 9 points as the reference standard, the proxy‐reported SARC‐F identified patients at high risk for sarcopenia‐related functional impairment with a sensitivity of 0.81 (ad‐hoc), 0.88 (retrospective Cohort A), and 0.87 (retrospective Cohort B) as well as a specificity of 0.89 (ad‐hoc), 0.78 (retrospective Cohort A), and 0.64 (retrospective Cohort B). Areas under the ROC curves were ≥ 0.9 for the ad‐hoc proxy‐reported SARC‐F and the retrospective proxy‐reported SARC‐F in both cohorts. The proxy‐reported SARC‐F showed a non‐inferior correlation with the SPPB compared with the patient‐reported SARC‐F for ad‐hoc (P = <0.001) as well as retrospective screening for severe sarcopenia‐related functional impairment in both Cohorts A (P = 0.007) and B (P = 0.026). CONCLUSIONS: Proxy‐reported SARC‐F is a valid instrument for both ad‐hoc as well as retrospective screening for sarcopenia‐related functional impairment and could become the standard tool for evaluating this risk in older adults with severe acute disease, for example, in patients with quickly evolving haematological conditions

The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus

Objectives To investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE). Methods Twelve patients received a median of two (range 1–4) 21-day cycles of intravenous bortezomib (1.3 mg/m2) with the coadministration of dexamethasone (20 mg) for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti–double-stranded DNA (anti-dsDNA) and vaccine-induced protective antibodies were monitored. Flow cytometry was performed to analyse peripheral blood B-cells, PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN) activity. Results Upon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies. Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients. Serum antibody levels significantly declined, with greater reductions in anti-dsDNA (∼60%) than vaccine-induced protective antibody titres (∼30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼50%), but their numbers increased between cycles. Siglec-1 expression on monocytes significantly declined. Conclusions These findings identify proteasome inhibitors as a putative therapeutic option for patients with refractory SLE by targeting PCs and type-I IFN activity, but our results must be confirmed in controlled trials

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Mikroplastik in der Umwelt

The investigation of microplastics is an important task, which still has to be performed due to lack of long term data on composition and variability of pollution present. Currently, there is no standard operational protocol while several methods for sampling and microplastic extraction are available. The analysis of the effluent of two wastewater treatment plants on two different days showed exemplary, that the microplastic emissions at the effluent might be highly variable. The determined particle composition differs remarkably between the two days. Additionally our results showed that the post filtration unit in Oldenburg reduces the microplastic concentration by more than 70 % and removes particles > 300 µm with high efficiency. The overall determined particle sizes show a high emission of particles smaller 50 µm in size through the waste water treatment plant effluent, whereas particles > 100 µm were removed with good efficiency

Three-dimensional breast cancer model to investigate CCL5/CCR1 expression mediated by direct contact between breast cancer cells and adipose-derived stromal cells or adipocytes

The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell–cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor–stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell–cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer

Austria’s Competitiveness and its Determinants. Concepts, Developments, Relative Performance and Policy Options

Austria’s rather poor development in international competitiveness rankings gave rise to questions about the economic concept of competitiveness and about the determinants and policies that can make an economy thrive again. The three modules of this research project aim at finding answers to these questions. They analyze labor costs, labor productivity, total factor productivity (TFP) and economic potential using a wide range of methods including shift-share analysis, panel econometrics, Stochastic Frontier Analysis (SFA) and Data Envelopment Analysis (DEA). The authors gratefully acknowledge the financial support by the Anniversary Fund (“Jubiläumsfonds”) of the Oesterreichische Nationalbank (OeNB)

The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus

Objectives To investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE). Methods Twelve patients received a median of two (range 1–4) 21-day cycles of intravenous bortezomib (1.3 mg/m2) with the coadministration of dexamethasone (20 mg) for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti–double-stranded DNA (anti-dsDNA) and vaccine-induced protective antibodies were monitored. Flow cytometry was performed to analyse peripheral blood B-cells, PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN) activity. Results Upon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies. Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients. Serum antibody levels significantly declined, with greater reductions in anti-dsDNA (∼60%) than vaccine-induced protective antibody titres (∼30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼50%), but their numbers increased between cycles. Siglec-1 expression on monocytes significantly declined. Conclusions These findings identify proteasome inhibitors as a putative therapeutic option for patients with refractory SLE by targeting PCs and type-I IFN activity, but our results must be confirmed in controlled trials

Physical function of RA patients tapering treatment — a post hoc analysis of the randomized controlled RETRO trial

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a post hoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, and taper/stop) as the predictor. Two-hundred and eighty-two patients were analyzed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that the decline in functionality according to HAQ after tapering or discontinuation of DMARDs in RA patients with stable remission is associated with recurrence, but not with an overall functional decline