@article{MaasMischingerComperatetal.2021,
  author    = {Maas, Moritz and Mischinger, Johannes and Comp{\´e}rat, Eva and Scharpf, Marcus and Fend, Falko and Todenh{\"o}fer, Timlan and Stenzl, Arnulf and Gakis, Georgios and Rausch, Steffen},
  title     = {Utility of pT3 substaging in lymph node-negative urothelial carcinoma of the bladder: do pathologic parameters add to prognostic sub-stratification?},
  series = {World Journal of Urology},
  volume    = {39},
  journal   = {World Journal of Urology},
  number    = {11},
  issn      = {1433-8726},
  doi       = {10.1007/s00345-021-03697-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266535},
  pages     = {4021-4027},
  year      = {2021},
  abstract  = {Purpose The value of bladder cancer (BC) substaging into macroscopic (pT3b) and microscopic (pT3a) perivesical fat extension in lymph node (Ln)-negative patients is controversially discussed and limited evidence for prognostic relevance of additional histopathological factors in pT3 BC exists. We evaluated the prognostic value of pT3 substaging and established pathological and clinical parameters with focus on tumor invasive front (TIF) and tumor size. Methods Specimens of 52 patients treated with radical cystectomy (RC) for pT3 a/b muscle-invasive BC were reviewed and re-evaluated by a pathologist specialized in uropathology. Clinical variables and standard histopathologic characteristics were assessed including TIF and tumor size. Their value as prognosticators for overall survival (OS) and recurrence-free survival (RFS) was evaluated. Results Mean age of patients was 67.55 years. Tumors were staged pT3a in 28 patients (53.8\%) and pT3b in 24 (46.8\%). Median OS was 34.51 months. Median tumor size was 3.2 cm, median TIF was 11.0 mm. Differences in OS between pT3a and pT3b were not significant (p = 0.45). Carcinoma in situ (CIS) and lymphovascular invasion (LVI) were significantly associated with pT3b tumors. Univariate analysis could not identify pathological prognosticators like TIF or tumor size for OS and RFS (p for all > 0.05). Conclusion No significant differences in OS or RFS were observed comparing Ln-negative pT3 BC following radical cystectomy. Additional pathologic variables like TIF could not be identified as prognosticator. Relevance of pT3 BC substaging needs reevaluation in larger prospective cohorts.},
  language  = {en}
}
@article{HaenscheidHartrampfSchirbeletal.2021,
  author    = {H{\"a}nscheid, Heribert and Hartrampf, Philipp E. and Schirbel, Andreas and Buck, Andreas K. and Lapa, Constantin},
  title     = {Intraindividual comparison of [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {8},
  issn      = {1619-7089},
  doi       = {10.1007/s00259-020-05177-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265470},
  pages     = {2566-2572},
  year      = {2021},
  abstract  = {Purpose The radiolabelled somatostatin analogue [\(^{177}\)Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [\(^{177}\)Lu]Lu-DOTA-TOC. Methods Activity kinetics in organs and tumours after [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy. Resuluts In comparison to [\(^{177}\)Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [\(^{177}\)Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [\(^{177}\)Lu]Lu-DOTA-TOC in 4 of 5 patients. Conclusions Prior to a treatment with [\(^{177}\)Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances.},
  language  = {en}
}
@article{SchumannEberleinLapaetal.2021,
  author    = {Schumann, S. and Eberlein, U. and Lapa, C. and M{\"u}ller, J. and Serfling, S. and Lassmann, M. and Scherthan, H.},
  title     = {α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [\(^{223}\)Ra]RaCl\(_{2}\)-treated prostate cancer patients},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {9},
  issn      = {1619-7089},
  doi       = {10.1007/s00259-020-05170-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265462},
  pages     = {2761-2770},
  year      = {2021},
  abstract  = {Purpose One therapy option for prostate cancer patients with bone metastases is the use of [\(^{223}\)Ra]RaCl\(_{2}\). The α-emitter \(^{223}\)Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [\(^{223}\)Ra]RaCl\(_{2}\). Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [\(^{223}\)Ra]RaCl\(_{2}\), up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h - 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.},
  language  = {en}
}
@article{SeifertGruberGburecketal.2021,
  author    = {Seifert, Annika and Gruber, Julia and Gbureck, Uwe and Groll, J{\"u}rgen},
  title     = {Morphological control of freeze-structured scaffolds by selective temperature and material control in the ice-templating process},
  series = {Advanced Engineering Materials},
  volume    = {24},
  journal   = {Advanced Engineering Materials},
  number    = {3},
  doi       = {10.1002/adem.202100860},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256330},
  year      = {2021},
  abstract  = {Herein, it is aimed to highlight the importance of the process parameter choice during directional solidification of polymer solutions, as they have a significant influence on the pore structure and orientation. Biopolymer solutions (alginate and chitosan) are directionally frozen, while systematically varying parameters such as the external temperature gradient, the temperature of the overall system, and the temperatures of the cooling surfaces. In addition, the effect of material properties such as molecular weight, solution concentration, or viscosity on the sample morphology is investigated. By selecting appropriate temperature gradients and cooling surface temperatures, aligned pores ranging in size between (50 ± 22) μm and (144 ± 56) μm are observed in the alginate samples, whereas the pore orientation is influenced by altering the external temperature gradient. As this gradient increases, the pores are increasingly oriented perpendicular to the sample surface. This is also observed in the chitosan samples. However, if the overall system is too cold, that is, using temperatures of the lower cooling surface down to -60 °C combined with low temperatures of the upper cooling surface, control over pore orientation is lost. This is also found when viscosity of chitosan solutions is above ≈5 Pas near the freezing point.},
  language  = {en}
}
@article{ReisPoppSchmidetal.2021,
  author    = {Reis, Stefanie and Popp, Maria and Schmid, Benedikt and Stegemann, Miriam and Metzendorf, Maria-Inti and Kranke, Peter and Meybohm, Patrick and Weibel, Stephanie},
  title     = {Safety and efficacy of intermediate- and therapeutic-dose anticoagulation for hospitalised patients with COVID-19: a systematic review and meta-analysis},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {1},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11010057},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252285},
  year      = {2021},
  abstract  = {Background: COVID-19 patients are at high thrombotic risk. The safety and efficacy of different anticoagulation regimens in COVID-19 patients remain unclear. Methods: We searched for randomised controlled trials (RCTs) comparing intermediate- or therapeutic-dose anticoagulation to standard thromboprophylaxis in hospitalised patients with COVID-19 irrespective of disease severity. To assess efficacy and safety, we meta-analysed data for all-cause mortality, clinical status, thrombotic event or death, and major bleedings. Results: Eight RCTs, including 5580 patients, were identified, with two comparing intermediate- and six therapeutic-dose anticoagulation to standard thromboprophylaxis. Intermediate-dose anticoagulation may have little or no effect on any thrombotic event or death (RR 1.03, 95\% CI 0.86-1.24), but may increase major bleedings (RR 1.48, 95\% CI 0.53-4.15) in moderate to severe COVID-19 patients. Therapeutic-dose anticoagulation may decrease any thrombotic event or death in patients with moderate COVID-19 (RR 0.64, 95\% CI 0.38-1.07), but may have little or no effect in patients with severe disease (RR 0.98, 95\% CI 0.86-1.12). The risk of major bleedings may increase independent of disease severity (RR 1.78, 95\% CI 1.15-2.74). Conclusions: Certainty of evidence is still low. Moderately affected COVID-19 patients may benefit from therapeutic-dose anticoagulation, but the risk for bleeding is increased.},
  language  = {en}
}
@article{StreckGaalForsteretal.2021,
  author    = {Streck, Laura Elisa and Gaal, Chiara and Forster, Johannes and Konrads, Christian and Hertzberg-Boelch, Sebastian Philipp von and Rueckl, Kilian},
  title     = {Defining a synovial fluid white blood cell count threshold to predict periprosthetic infection after shoulder arthroplasty},
  series = {Journal of Clinical Medicine},
  volume    = {11},
  journal   = {Journal of Clinical Medicine},
  number    = {1},
  issn      = {2077-0383},
  doi       = {10.3390/jcm11010050},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252275},
  year      = {2021},
  abstract  = {Background: The diagnosis of periprosthetic shoulder infection (PSI) requires a thorough diagnostic workup. Synovial fluid aspiration has been proven to be a reliable tool in the diagnosis of joint infections of the lower extremity, but shoulder specific data is limited. This study defines a threshold for synovial fluid white blood cell count (WBC) and assesses the reliability of microbiological cultures. Methods: Retrospective study of preoperative and intraoperative fluid aspiration of 31 patients who underwent a revision of a shoulder arthroplasty (15 with PSI defined by IDSA criteria, 16 without infection). The threshold for WBC was calculated by ROC/AUC analysis. Results: WBC was significantly higher in patients with PSI than in other patients. A threshold of 2800 leucocytes/mm\(^3\) showed a sensitivity of 87\% and a specificity of 88\% (AUROC 0.92). Microbiological cultures showed a sensitivity of 76\% and a specificity of 100\%. Conclusions: A threshold of 2800 leucocytes/mm\(^3\) in synovial fluid can be recommended to predict PSI. Microbiological culture has an excellent specificity and allows for targeted antibiotic therapy. Joint aspiration presents an important pillar to diagnose PSI.},
  language  = {en}
}
@article{SchleeSimoesPryss2021,
  author    = {Schlee, Winfried and Simoes, Jorge and Pryss, R{\"u}diger},
  title     = {Auricular acupressure combined with self-help intervention for treating chronic tinnitus: a longitudinal observational study},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {18},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10184201},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246209},
  year      = {2021},
  abstract  = {Tinnitus is a phantom sound perception in the ears or head and can arise from many different medical disorders. Currently, there is no standard treatment for tinnitus that reliably reduces tinnitus. Individual patients reported that acupressure at various points around the ear can help to reduce tinnitus, which was investigated here. With this longitudinal observational study, we report a systematic evaluation of auricular acupressure on 39 tinnitus sufferers, combined with a self-help smartphone app. The participants were asked to report on tinnitus, stress, mood, neck, and jaw muscle tensions twice a day using an ecological momentary assessment study design for six weeks. On average, 123.6 questionnaires per person were provided and used for statistical analysis. The treatment responses of the participants were heterogeneous. On average, we observed significant negative trends for tinnitus loudness (Cohen's d effect size: -0.861), tinnitus distress (d = -0.478), stress (d = -0.675), and tensions in the neck muscles (d = -0.356). Comparison with a matched control group revealed significant improvements for tinnitus loudness (p = 0.027) and self-reported stress level (p = 0.003). The positive results of the observational study motivate further research including a randomized clinical trial and long-term assessment of the clinical improvement.},
  language  = {en}
}
@article{MeintrupBorgmannSeidletal.2021,
  author    = {Meintrup, David and Borgmann, Stefan and Seidl, Karlheinz and Stecher, Melanie and Jakob, Carolin E. M. and Pilgram, Lisa and Spinner, Christoph D. and Rieg, Siegbert and Isberner, Nora and Hower, Martin and Vehreschild, Maria and G{\"o}pel, Siri and Hanses, Frank and Nowak-Machen, Martina},
  title     = {Specific risk factors for fatal outcome in critically ill COVID-19 patients: results from a European multicenter study},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {17},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10173855},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245191},
  year      = {2021},
  abstract  = {(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06-1.10), cardiovascular disease (OR 1.64, CI 1.06-2.55), pulmonary disease (OR 1.87, CI 1.16-3.03), baseline Statin treatment (0.54, CI 0.33-0.87), oxygen saturation (unit = 1\%, OR 0.94, CI 0.92-0.96), leukocytes (unit 1000/μL, OR 1.04, CI 1.01-1.07), lymphocytes (unit 100/μL, OR 0.96, CI 0.94-0.99), platelets (unit 100,000/μL, OR 0.70, CI 0.62-0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05-1.18), kidney failure (OR 1.68, CI 1.05-2.70), congestive heart failure (OR 2.62, CI 1.11-6.21), severe liver failure (OR 4.93, CI 1.94-12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14-2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.},
  language  = {en}
}
@article{SchwaabBjarnasonWehrensMengetal.2021,
  author    = {Schwaab, Bernhard and Bjarnason-Wehrens, Birna and Meng, Karin and Albus, Christian and Salzwedel, Annett and Schmid, Jean-Paul and Benzer, Werner and Metz, Matthes and Jensen, Katrin and Rauch, Bernhard and B{\"o}nner, Gerd and Brzoska, Patrick and Buhr-Schinner, Heike and Charrier, Albrecht and Cordes, Carsten and D{\"o}rr, Gesine and Eichler, Sarah and Exner, Anne-Kathrin and Fromm, Bernd and Gielen, Stephan and Glatz, Johannes and Gohlke, Helmut and Grilli, Maurizio and Gysan, Detlef and H{\"a}rtel, Ursula and Hahmann, Harry and Herrmann-Lingen, Christoph and Karger, Gabriele and Karoff, Marthin and Kiwus, Ulrich and Knoglinger, Ernst and Krusch, Christian-Wolfgang and Langheim, Eike and Mann, Johannes and Max, Regina and Metzendorf, Maria-Inti and Nebel, Roland and Niebauer, Josef and Predel, Hans-Georg and Preßler, Axel and Razum, Oliver and Reiss, Nils and Saure, Daniel and von Schacky, Clemens and Sch{\"u}tt, Morten and Schultz, Konrad and Skoda, Eva-Maria and Steube, Diethard and Streibelt, Marco and St{\"u}ttgen, Martin and St{\"u}ttgen, Michaela and Teufel, Martin and Tschanz, Hansueli and V{\"o}ller, Heinz and Vogel, Heiner and Westphal, Ronja},
  title     = {Cardiac rehabilitation in German speaking countries of Europe — evidence-based guidelines from Germany, Austria and Switzerland LLKardReha-DACH — part 2},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {14},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10143071},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242645},
  year      = {2021},
  abstract  = {Background: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. Methods: Generation of evidence and search of literature have been described in part 1. Results: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. Conclusions: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.},
  language  = {en}
}
@article{MamontovaTrifaultBotenetal.2021,
  author    = {Mamontova, Victoria and Trifault, Barbara and Boten, Lea and Burger, Kaspar},
  title     = {Commuting to work: Nucleolar long non-coding RNA control ribosome biogenesis from near and far},
  series = {Non-Coding RNA},
  volume    = {7},
  journal   = {Non-Coding RNA},
  number    = {3},
  issn      = {2311-553X},
  doi       = {10.3390/ncrna7030042},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242756},
  year      = {2021},
  abstract  = {Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.},
  language  = {en}
}