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Zhdanovich, Yauheniya ; Ackermann, Jörg ; Wild, Peter Johannes ; Köllermann, Jens ; Bankov, Katrin ; Döring, Claudia ; Flinner, Nadine ; Reis, Henning ; Wenzel, Mike ; Höh, Robert Benedikt ; Mandel, Philipp ; Vogl, Thomas J. ; Harter, Patrick Nikolaus ; Filipski, Katharina Johanna ; Koch, Ina ; Bernatz, Simon
Background: Prostate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efcient diagnostic algorithms.
Methods: Retrospectively, 106 prostate tissue samples from 48 patients (mean age,
66 ± 6.6 years) were included in the study. Patients sufered from prostate cancer (n = 38) or benign prostatic hyperplasia (n = 10) and were treated with radical prostatectomy or Holmium laser enucleation of the prostate, respectively. We constructed tissue microarrays (TMAs) comprising representative malignant (n = 38) and benign (n = 68) tissue cores. TMAs were processed to histological slides, stained, digitized and assessed for the applicability of machine learning strategies and open–source tools in diagnosis of prostate cancer. We applied the software QuPath to extract features for shape, stain intensity, and texture of TMA cores for three stainings, H&E, ERG, and PIN-4. Three machine learning algorithms, neural network (NN), support vector machines (SVM), and random forest (RF), were trained and cross-validated with 100 Monte Carlo random splits into 70% training set and 30% test set. We determined AUC values for single color channels, with and without optimization of hyperparameters by exhaustive grid search. We applied recursive feature elimination to feature sets of multiple color transforms.
Results: Mean AUC was above 0.80. PIN-4 stainings yielded higher AUC than H&E and
ERG. For PIN-4 with the color transform saturation, NN, RF, and SVM revealed AUC of 0.93 ± 0.04, 0.91 ± 0.06, and 0.92 ± 0.05, respectively. Optimization of hyperparameters improved the AUC only slightly by 0.01. For H&E, feature selection resulted in no increase of AUC but to an increase of 0.02–0.06 for ERG and PIN-4.
Conclusions: Automated pipelines may be able to discriminate with high accuracy between malignant and benign tissue. We found PIN-4 staining best suited for classifcation. Further bioinformatic analysis of larger data sets would be crucial to evaluate the reliability of automated classifcation methods for clinical practice and to evaluate potential discrimination of aggressiveness of cancer to pave the way to automatic precision medicine.
Koch, Vitali ; Conrades, Lena Marie ; Grünewald, Leon David ; Eichler, Katrin ; Martin, Simon ; Booz, Christian ; D'Angelo, Tommaso ; Yel, Ibrahim ; Bernatz, Simon ; Mahmoudi, Scherwin ; Albrecht, Moritz Hans Ernst ; Scholtz, Jan-Erik ; Scholtz, Jan-Erik ; Thalhammer, Axel ; Zangos, Stephan ; Vogl, Thomas J. ; Gruber-Rouh, Tatjana
This prospective study sought to evaluate potential savings of radiation dose to medical staff using real-time dosimetry coupled with visual radiation dose feedback during angiographic interventions. For this purpose, we analyzed a total of 214 angiographic examinations that consisted of chemoembolizations and several other types of therapeutic interventions. The Unfors RaySafe i2 dosimeter was worn by the interventionalist at chest height over the lead protection. A total of 110 interventions were performed with real-time radiation dosimetry allowing the interventionalist to react upon higher x-ray exposure and 104 examinations served as the comparative group without real-time radiation monitoring. By using the real-time display during interventions, the overall mean operator radiation dose decreased from 3.67 (IQR, 0.95–23.01) to 2.36 μSv (IQR, 0.52–12.66) (−36%; p = 0.032) at simultaneously reduced operator exposure time by 4.5 min (p = 0.071). Dividing interventions into chemoembolizations and other types of therapeutic interventions, radiation dose decreased from 1.31 (IQR, 0.46-3.62) to 0.95 μSv (IQR, 0.53-3.11) and from 24.39 (IQR, 12.14-63.0) to 10.37 μSv (IQR, 0.85-36.84), respectively, using live-screen dosimetry (p ≤ 0.005). Radiation dose reductions were also observed for the participating assistants, indicating that they could also benefit from real-time visual feedback dosimetry during interventions (−30%; p = 0.039). Integration of real-time dosimetry into clinical processes might be useful in reducing occupational radiation exposure time during angiographic interventions. The real-time visual feedback raised the awareness of interventionalists and their assistants to the potential danger of prolonged radiation exposure leading to the adoption of radiation-sparing practices. Therefore, it might create a safer environment for the medical staff by keeping the applied radiation exposure as low as possible.
Maawi, Sarah al- ; Valenzuela, Priscilia Yvonne ; Dohle, Eva ; Heselich, Anja ; Sader, Robert ; Ghanaati, Sharam Michael
The combination of histological and biomolecular analyses provides deep understanding of different biological processes and is of high interest for basic and applied research. However, the available analytical methods are still limited, especially when considering bone samples. This study compared different fixation media to identify a sufficient analytical method for the combination of histological, immuno-histological and biomolecular analyses of the same fixed, processed and paraffin embedded bone sample. Bone core biopsies of rats’ femurs were fixed in different media (RNAlater + formaldehyde (R + FFPE), methacarn (MFPE) or formaldehyde (FFPE)) for 1 week prior to decalcification by EDTA and further histological processing and paraffin embedding. Snap freezing (unfixed frozen tissue, UFT) and incubation in RNAlater were used as additional controls. After gaining the paraffin sections for histological and immunohistological analysis, the samples were deparaffined and RNA was isolated by a modified TRIZOL protocol. Subsequently, gene expression was evaluated using RT-qPCR. Comparable histo-morphological and immuno-histological results were evident in all paraffin embedded samples of MFPE, FFPE and R + FFPE. The isolated RNA in the group of MFPE showed a high concentration and high purity, which was comparable to the UFT and RNAlater groups. However, in the groups of FFPE and R + FFPE, the RNA quality and quantity were statistically significantly lower when compared to MFPE, UFT and RNAlater. RT-qPCR results showed a comparable outcome in the group of MFPE and UFT, whereas the groups of FFPE and R + FFPE did not result in a correctly amplified gene product. Sample fixation by means of methacarn is of high interest for clinical samples to allow a combination of histological, immunohistological and biomolecular analysis. The implementation of such evaluation method in clinical research may allow a deeper understanding of the processes of bone formation and regeneration.
Höh, Robert Benedikt ; Flammia, Rocco Simone ; Hohenhorst, Lukas ; Sorce, Gabriele ; Panunzio, Andrea ; Tappero, Stefano ; Tian, Zhe ; Saad, Fred ; Gallucci, Michele ; Briganti, Alberto ; Terrone, Carlo ; Shariat, Shahrokh F. ; Graefen, Markus ; Tilki, Derya ; Antonelli, Alessandro ; Kosiba, Marina ; Mandel, Philipp ; Kluth, Luis ; Becker, Andreas ; Chun, Felix ; Karakiewicz, Pierre I.
Background: Survival data regarding cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) patients according to the type and extent of tumor-associated vascular thrombus are scarce.
Objective: To test for survival differences in mRCC patients treated with CN according to the type and extent of tumor-associated vascular thrombus.
Design, setting, and participants: Within Surveillance, Epidemiology, and End Results Research Plus (2004–2017), we identified CN mRCC patients with renal vein (pT3a-TT) versus infradiaphragmatic inferior vena cava (IVC; pT3b) versus supradiaphragmatic IVC tumor thrombus/IVC invasion (pT3c).
Outcome measurements and statistical analysis: Overall survival (OS) was addressed in Kaplan-Meier and Cox regression analyses, in addition to 3-mo landmark analyses.
Results and limitations: Of 2170 mRCC patients, 1880 (87%), 204 (9%), and 86 (4%) harbored pT3a-TT, pT3b, and pT3c, respectively. The respective median OS periods were 21, 23, and 12 mo (p < 0.001). In multivariable Cox regression models, pT3c stage, but not pT3b stage, was an independent predictor of higher overall mortality (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.09–1.73; p = 0.007), as well as in 6-mo landmark analyses (HR: 1.36; 95% CI: 1.02–1.80; p = 0.04). In the sensitivity analysis, relying on all pT3a patients, the predictor status of pT3c stage remained unchanged (HR: 1.37; 95% CI: 1.09–1.71; p = 0.007). Limitations have to be addressed regarding the sample size and the retrospective design of the current study.
Conclusions: Although overall mortality is significantly higher in pT3c mRCC patients than in their pT3b and pT3a-TT counterparts, these individuals may still expect 12-mo or better OS after CN versus virtually 2-yr OS in their pT3a and pT3b counterparts.
Patient summary: In this study, we looked at the survival outcomes of metastatic renal cell carcinoma patients who presented with tumor thrombus at cytoreductive nephrectomy. Even though these patients with most advanced tumor thrombus stage demonstrated lower survival rates, the median overall survival was still 1 yr.
Ana I., González-González ; Dinh, Truc Sophia ; Brünn, Robin ; Brückle, Janina Maria-Sophie ; Schwarz, Christine ; Dieckelmann, Mirjam ; Müller, Beate ; Akker, Marjan van den
Middle-aged persons with multimorbidity have to take their illnesses into account in their daily work, family and leisure activities. The MuMiA project aims to identify early preventive measures that make it easier for those between 30 and 60 years of age with multiple chronic diseases to manage their illnesses in their everyday lives. An interdisciplinary workshop and interviews with multimorbid middle-aged adults and their principal healthcare providers will be used to collect information on the management of care in the contexts of patients’ daily work, family and leisure activities. Data obtained in the interviews will be coded inductively and analysed using content analysis. Workshop outputs will be transcribed and evaluated by the authors. This study has received ethical approval from the Faculty of Medicine Ethics Committee of Goethe University (2021-47). The project will generate prevention recommendations that reflect the experiences of middle-aged persons living with multimorbidity and the views of their principal healthcare providers. The findings will be disseminated via conferences and peer-reviewed publications.
Development of a multidimensional pain questionnaire in professional dance (MPQDA): a pilot study
(2022)
Background: Pain is part of the everyday life of professional dancers. It can indicate health risks and impair the ability to work. Suitable screening tools can be used to identify pain and its risk potential. A comprehensive, multidimensional, differentiated assessment tool for pain in professional dance does not currently exist.
Methods: An initial questionnaire was developed in German and English and was assessed in a qualitative pretest. In a field study with a cross-sectional design including n = 72 dancers from Germany (n = 36 responses each in the English and German language versions), the questionnaire was optimized by item analysis, its psychometric properties (dimensionality, construct validity, reliability) were examined and the ability of the pain dimensions to classify the subjective ability to work in training was analyzed (ROC analysis).
Results: The developed Multidimensional Pain Questionnaire in Professional Dance (MPQDA) was reduced and optimized in its psychometric properties. Following questions were reduced in their items or answer categories: pain localizations (from 20 to 15 regions), accompanying symptoms (from 6 to 3 items), sensory and affective pain quality (from 20 to 10 items), pain frequency (from 4 to 3 answer categories), and the motives of working with pain (from 14 to 12 items). Regarding the subjective ability to work in training, the variables of the ability to work in rehearsals and in performances, as well as the accompanying symptoms of tension and mobility restrictions, showed a relatively good classification ability (Area under the Curve (AUC) ≥ 0.7 in the 95% confidence interval) and significant, moderate to strong correlations (Somers' D > 0.25, p < 0.05). The classification ability of the other pain dimensions was largely absent or poor.
Conclusion: The MPQDA differentiates various pain dimensions in professional dancers and is available in a compatible manner in German and English. The clinical relevance needs to be explored further in the future.
Wanke, Eileen M. ; Zimmermann, Olga Louisa ; Schmidt, Mike ; Ohlendorf, Daniela Maren ; Wallner, Alexandra ; Fischer, Tanja C.
Up to the present, there has been a lack of studies on the skin health of professional and recreational dancers. Dancers are at risk of skin diseases due to contact with allergenic or irritating substances and working in humid environments. The aim of the present study was, therefore, to examine skin health in two different dance styles and training periods. Methods: Physical dermatological examination of professional dancers (PD; n = 35) and Latin American formation dancers (LD; n = 79) after a 4-week period of recovery (T0) and a period of high training or work load (T1). Results: PD are significantly more frequently affected by skin dermatoses than LD (T0, p = 0.004) (frontal traction alopecia, hair loss, facial seborrhoea, xerosis cutis of the trunk and extremities, and facial folliculitis). The following significant differences between the sexes were observed in the LD: more folliculitis of the trunk in male subjects (T0 and T1, p = 0.009), more frequent xerosis cutis of the extremities (p < 0.001) and perioral dermatitis in female subjects (T1, p = 0.043). Subjects with skin lesions trained more frequently, performed more times per year, and had longer dance experience. Discussion: Based on the findings, preventive measures for skin protection (especially informing dancers about skin health) are necessary. At the same time, further studies on this topic are important.
The deep fascia is intimately linked to skeletal muscle and may be involved in delayed onset muscle soreness (DOMS). The present study therefore explored the effect of eccentric exercise on fascia stiffness and its relation with DOMS. Healthy active male adults (n = 19, 27 ± 4 years) performed 6 x 10 maximal eccentric knee flexions using an isokinetic dynamometer. Before (baseline) as well as immediately (T0), 1 hour (T1), and each day up to 72 hours (T24 to T72) afterwards, shear wave elastography was used to measure the mechanical stiffness of the biceps femoris muscle and the overlying fascia. As a surrogate of DOMS, pain upon palpation was captured by means of a 100mm visual analogue scale. While muscle stiffness remained unchanged (p > 0.05), deep fascia stiffness increased from baseline to T24 (median: 18 kPa to 21.12 kPa, p = 0.017) and T72 (median: 18 kPa to 21.3 kPa, p = 0.001) post-exercise. Linear regression showed an association of stiffness changes at T24 and pressure pain at T72 (r2 = 0.22, p < 0.05). Maximal eccentric exercise leads to a stiffening of the fascia, which, in turn, is related to the magnitude of future DOMS. Upcoming research should therefore gauge the effectiveness of interventions modifying the mechanical properties of the connective tissue in order to accelerate recovery.
Noone, Stephanie ; Flinspach, Armin Niklas ; Fichtlscherer, Stephan ; Zacharowski, Kai ; Sonntagbauer, Michael ; Raimann, Florian
Background: Primary viral myocarditis associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection is a rare diagnosis.
Case presentation: We report the case of an unvaccinated, healthy patient with cardiogenic shock in the context of a COVID-19-associated myocarditis and therapy with simultaneous veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and percutaneous left ventricular decompression therapy with an Impella. The aim of this review is to provide an overview of therapeutic options for patients with COVID-19-associated myocarditis.
Conclusions: The majority of patients required a combination of two assist devices to achieve sufficient cardiac output until recovery of left ventricular ejection fraction. Due to the rapid onset of this fulminant cardiogenic shock immediate invasive bridging therapy in a specialized center was lifesaving.