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Böhmert, Stephanie ; Kübel, Sarah ; Müller, Markus Matthias ; Weber, Christian Friedrich ; Adam, Elisabeth ; Dröse, Stefan ; Zacharowski, Kai ; Fischer, Dania
Background: Conditions during blood product storage and transportation should maintain quality. The aim of this in vitro study was to investigate the effect of interruption of agitation, temporary cooling (TC), and pneumatic tube system transportation (PTST) on the aggregation ability (AA) and mitochondrial function (MF) of platelet concentrates (PC).
Study Design and Methods: A PC was divided equally into four subunits and then allocated to four test groups. The control group (I) was stored as recommended (continuous agitation, 22 ± 2°C) for 4 days. The test groups were stored without agitation (II), stored as recommended, albeit 4°C for 60 minutes on day (d)2 (III) and PTST (IV). Aggregometry was measured using Multiplate (RocheAG; ADPtest, ASPItest, TRAPtest, COLtest) and MF using Oxygraph‐2k (Oroboros Instruments). The basal and maximum mitochondrial respiratory rate (MMRR) were determined. AA and MF were measured daily in I and II and AA in III and IV on d2 after TC/PTST. Statistical analysis was performed using tests for matched observations.
Results: Eleven PCs were used. TRAP‐6 induced AA was significantly lower in II when compared to I on d4 (P = 0.015*). In III the ASPItest was significantly lower (P = 0.032*). IV showed no significant differences. The basal and MMRR were significantly reduced over 4 days in I and II (for both rates in both groups: P = <0.0001*). No significant differences occurred on d4 (P = 0.495).
Conclusion: Our results indicate that ex vivo AA and MF of PCs are unaffected, even in no‐ideal storage and transport circumstances with respect to agitation, temperature, and force.
Baltes, Peter ; Bota, Marc ; Albert, Jörg Gerhard ; Philipper, Michael ; Hörster, Hans-Georg ; Hagenmüller, Friedrich ; Steinbrück, Ingo ; Jakobs, Ralf ; Bechtler, Matthias ; Hartmann, Dirk ; Neuhaus, Horst ; Charton, Jean-Pierre ; Mayershofer, Rupert ; Hohn, Horst ; Rösch, Thomas ; Groth, Stefan ; Nowak, Tanja ; Wohlmuth, Peter ; Keuchel, Martin
Aim: To evaluate the ability of PillCamColon2 to visualize colonic segments missed by incomplete optical colonoscopy (OC) and to assess the diagnostic yield.
Methods: This prospective multicentre study included 81 patients from nine centres who underwent second-generation colon capsule endoscopy (CCE) following incomplete OC performed by an experienced gastroenterologist (> 1000 colonoscopies). Patients with stenosis were excluded. According to patient preferences, CCE was performed the following day (protocol A) after staying on clear liquids and 0.75 L Moviprep in the morning or within 30 d after new split-dose Moviprep (protocol B). Boosts consisted of 0.75 L and 0.25 L Moviprep, and phospho-soda was given as a rescue if the capsule was not excreted after seven hours.
Results: Seventy-four patients were analysed (51% of them in group A; 49% in group B). Bowel cleansing was adequate in 67% of cases, and CCE could visualize colonic segments missed by incomplete colonoscopy in 90% of patients under protocol A and 97% of patients under protocol B (P = 0.35, n.s.). Significant polyps including adenocarcinoma were detected in 24% of cases. Detection rates for all polyps and significant polyps per patient were similar in both protocols. Polyps were found predominantly in the right colon (86%) in segments that were not reached by OC. Extracolonic findings - such as reflux esophagitis, suspected Barrett esophagus, upper GI-bleeding, gastric polyps, gastric erosions and angiectasia - were detected in eight patients. PillCamColon2 capsule was retained in the ileum of one patient (1.4%) without symptoms and removed during an uneventful resection for unknown Crohn’s disease that was diagnosed as the cause of anemia, which was the indication for colonoscopy. CCE was well tolerated. One patient suffered from self-limiting vomiting after consuming the phospho-soda.
Conclusion: Second-generation CCE using a low-volume preparation is useful after incomplete OC, and it allows for the detection of additional relevant findings, but cleansing efficiency could be improved.
Suinesiaputra, Avan ; Bluemke, David A. ; Cowan, Brett R. ; Friedrich, Matthias G. ; Kramer, Christopher M. ; Kwong, Raymond Y. ; Plein, Sven ; Schulz-Menger, Jeanette ; Westenberg, Jos J. M. ; Young, Alistair A. ; Nagel, Eike
Background: High reproducibility of LV mass and volume measurement from cine cardiovascular magnetic resonance (CMR) has been shown within single centers. However, the extent to which contours may vary from center to center, due to different training protocols, is unknown. We aimed to quantify sources of variation between many centers, and provide a multi-center consensus ground truth dataset for benchmarking automated processing tools and facilitating training for new readers in CMR analysis.
Methods: Seven independent expert readers, representing seven experienced CMR core laboratories, analyzed fifteen cine CMR data sets in accordance with their standard operating protocols and SCMR guidelines. Consensus contours were generated for each image according to a statistical optimization scheme that maximized contour placement agreement between readers.
Results: Reader-consensus agreement was better than inter-reader agreement (end-diastolic volume 14.7 ml vs 15.2–28.4 ml; end-systolic volume 13.2 ml vs 14.0–21.5 ml; LV mass 17.5 g vs 20.2–34.5 g; ejection fraction 4.2 % vs 4.6–7.5 %). Compared with consensus contours, readers were very consistent (small variability across cases within each reader), but bias varied between readers due to differences in contouring protocols at each center. Although larger contour differences were found at the apex and base, the main effect on volume was due to small but consistent differences in the position of the contours in all regions of the LV.
Conclusions: A multi-center consensus dataset was established for the purposes of benchmarking and training. Achieving consensus on contour drawing protocol between centers before analysis, or bias correction after analysis, is required when collating multi-center results.
Kim, Raymond J. ; Simonetti, Orlando P. ; Westwood, Mark ; Kramer, Christopher M. ; Narang, Akhil ; Friedrich, Matthias ; Powell, Andrew J. ; Carr, James C. ; Schulz-Menger, Jeanette ; Nagel, Eike ; Chan, Wing Suen ; Bremerich, Jens ; Ordovas, Karen G. ; Rollings, Robert C. ; Patel, Amit R. ; Ferrari, Victor A.
Hundley, William Gregory ; Bluemke, David A. ; Bogaert, Jan ; Flamm, Scott D. ; Fontana, Marianna ; Friedrich, Matthias ; Große-Wortmann, Lars ; Karamitsos, Theodoros D. ; Kramer, Christopher M. ; Kwong, Raymond Y. ; McConnell, Michael ; Nagel, Eike ; Neubauer, Stefan ; Nijveldt, Robin ; Pennell, Dudley J. ; Petersen, Steffen Erhard ; Raman, Subha V. ; Rossum, Albert C. van
Seidler, Andreas ; Bergmann, Annekatrin ; Jäger, Matthias ; Ellegast, Rolf Peter ; Ditchen, Dirk Marcel ; Elsner, Gine ; Grifka, Joachim ; Haerting, Johannes ; Hofmann, Friedrich ; Linhardt, Oliver ; Luttmann, Alwin ; Michaelis, Martina ; Petereit-Haack, Gabriela ; Schumann, Barbara ; Bolm-Audorff, Ulrich
Background The to date evidence for a dose-response relationship between physical workload and the development of lumbar disc diseases is limited. We therefore investigated the possible etiologic relevance of cumulative occupational lumbar load to lumbar disc diseases in a multi-center case-control study. Methods In four study regions in Germany (Frankfurt/Main, Freiburg, Halle/Saale, Regensburg), patients seeking medical care for pain associated with clinically and radiologically verified lumbar disc herniation (286 males, 278 females) or symptomatic lumbar disc narrowing (145 males, 206 females) were prospectively recruited. Population control subjects (453 males and 448 females) were drawn from the regional population registers. Cases and control subjects were between 25 and 70 years of age. In a structured personal interview, a complete occupational history was elicited to identify subjects with certain minimum workloads. On the basis of job task-specific supplementary surveys performed by technical experts, the situational lumbar load represented by the compressive force at the lumbosacral disc was determined via biomechanical model calculations for any working situation with object handling and load-intensive postures during the total working life. For this analysis, all manual handling of objects of about 5 kilograms or more and postures with trunk inclination of 20 degrees or more are included in the calculation of cumulative lumbar load. Confounder selection was based on biologic plausibility and on the change-in-estimate criterion. Odds ratios (OR) and 95% confidence intervals (CI) were calculated separately for men and women using unconditional logistic regression analysis, adjusted for age, region, and unemployment as major life event (in males) or psychosocial strain at work (in females), respectively. To further elucidate the contribution of past physical workload to the development of lumbar disc diseases, we performed lag-time analyses. Results We found a positive dose-response relationship between cumulative occupational lumbar load and lumbar disc herniation as well as lumbar disc narrowing among men and women. Even past lumbar load seems to contribute to the risk of lumbar disc disease. Conclusions According to our study, cumulative physical workload is related to lumbar disc diseases among men and women.
Gröschel, Stefan ; Hübschmann, Daniel ; Raimondi, Francesco ; Horak, Peter ; Warsow, Gregor ; Fröhlich, Martina ; Klink, Barbara ; Gieldon, Laura ; Hutter, Barbara ; Kleinheinz, Kortine ; Bonekamp, David ; Marschal, Oliver ; Chudasama, Priya ; Mika, Jagoda ; Groth, Marie ; Uhrig, Sebastian ; Krämer, Stephen ; Heining, Christoph ; Heilig, Christoph E. ; Richter, Daniela ; Reisinger, Eva ; Pfütze, Katrin ; Eils, Roland ; Wolf, Stephan ; Kalle, Christof von ; Brandts, Christian Hubertus ; Scholl, Claudia ; Weichert, Wilko ; Richter, Stephan ; Bauer, Sebastian ; Penzel, Roland ; Schröck, Evelin ; Stenzinger, Albrecht ; Schlenk, Richard Friedrich ; Brors, Benedikt ; Russell, Robert B. ; Glimm, Hanno ; Schlesner, Matthias ; Fröhling, Stefan
Chordomas are rare bone tumors with few therapeutic options. Here we show, using whole-exome and genome sequencing within a precision oncology program, that advanced chordomas (n = 11) may be characterized by genomic patterns indicative of defective homologous recombination (HR) DNA repair and alterations affecting HR-related genes, including, for example, deletions and pathogenic germline variants of BRCA2, NBN, and CHEK2. A mutational signature associated with HR deficiency was significantly enriched in 72.7% of samples and co-occurred with genomic instability. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, which is preferentially toxic to HR-incompetent cells, led to prolonged clinical benefit in a patient with refractory chordoma, and whole-genome analysis at progression revealed a PARP1 p.T910A mutation predicted to disrupt the autoinhibitory PARP1 helical domain. These findings uncover a therapeutic opportunity in chordoma that warrants further exploration, and provide insight into the mechanisms underlying PARP inhibitor resistance.