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Störmann, Philipp ; Klug, Alexander ; Nau, Christoph ; Verboket, René ; Leiblein, Maximilian ; Müller, Daniel ; Schweigkofler, Uwe ; Hoffmann, Reinhard ; Marzi, Ingo ; Lustenberger, Thomas
Since the introduction of rental E-scooters in Germany in mid-June 2019, the safety of this new means of transport has been the subject of extensive public debate. However, valid data on injuries and usage habits are not yet available. This retrospective two-center study included a total of 76 patients who presented to the emergency department following E-scooter-related accidents. The mean age was 34.3 ± 12.4 years and 69.7% of the patients were male. About half of the patients were admitted by ambulance (42.1%). Fractures were found in 48.6% of patients, and 27.6% required surgical treatment due to a fracture. The upper extremities were the most commonly affected body region, followed by injuries to the lower extremity and to the head and face. Only one patient had worn a helmet. In-hospital treatment was necessary for 26.3% of the cases. Patients presented to the emergency department mainly during the weekend and on-call times. This is the first report on E-scooter-related injuries in Germany. Accidents with E-scooters can cause serious injuries and, therefore, represent a further burden to emergency departments. The use of E-scooters appears to be mostly recreational, and the rate of use of protective gear is low.
Würnschimmel, Christoph ; Kachanov, Mykyta ; Wenzel, Mike ; Mandel, Philipp ; Karakiewicz, Pierre I. ; Maurer, Tobias ; Steuber, Thomas ; Tilki, Derya ; Graefen, Markus ; Budäus, Lars
Background: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports.
Material and Methods: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy.
Results: Absolute rates of D'Amico low risk decreased (−30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (−50.0%), while GGG II–V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were −1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between −0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001).
Conclusion: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.
Wenzel, Mike ; Preißer, Felix Martin ; Höh, Robert Benedikt ; Schröder, Maria ; Würnschimmel, Christoph ; Steuber, Thomas ; Heinzer, Hans ; Banek, Séverine ; Ahrens, Marit ; Becker, Andreas ; Karakiewicz, Pierre I. ; Chun, Felix ; Kluth, Luis A. ; Mandel, Philipp
Background: To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC.
Material and Methods: Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR <12, 12-18, 18-24, and >24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS.
Results: Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR <12 months, 18.1% for 12-18 months, 15.2% for 18-24 months, and 25.5% for >24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR <12 months patients had the worst OS, followed by TTCR 12-18 months, 18-24 months, and >24 months, in that order (p<0.001). After multivariable adjustment, a 4.07-, 3.31-, and 6.40-fold higher mortality was observed for TTCR 18-24 months, 12-18 months, and <12 months patients, relative to TTCR >24 months (all p<0.05). Conversely, OS after development of mCRPC was not influenced by TTCR stratification (all p>0.05).
Conclusion: Patients with TTCR <12 months are at the highest OS disadvantage in mHSPC. This OS disadvantage persisted even after multivariable adjustment. Interestingly, TTCR stratified analyses did not influence OS in mCRPC patients.
Höh, Robert Benedikt ; Hohenhorst, Jan Lukas ; Wenzel, Mike ; Humke, Clara Julia ; Preißer, Felix Martin ; Wittler, Clarissa ; Brand, Marie ; Köllermann, Jens ; Steuber, Thomas ; Graefen, Markus ; Tilki, Derya ; Karakiewicz, Pierre I. ; Becker, Andreas ; Kluth, Luis ; Chun, Felix ; Mandel, Philipp
The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (≥ 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1–2, 4% 3–5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51–27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%.
Illhardt, Toni ; Ebinger, Martin ; Schwarze, Carl Philipp ; Feuchtinger, Tobias ; Furtwängler, Rhoikos ; Schlegel, Paul-Gerhardt ; Klingebiel, Thomas ; Greil, Johann ; Beck, James F. ; Handgretinger, Rupert ; Lang, Peter
Background: High-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) is a treatment option for pediatric patients with relapsed nephroblastoma. We present long term results of 9 patients treated between 1993 and 2013 at our center.
Procedure: Reinduction therapy was carried out according to GPOH and SIOP recommendations. The conditioning regimen consisted of carboplatin (1 200 mg/m²), etoposide (800 mg/m² or 40 mg/kg) and melphalan (180 mg/m²). Purging of the grafts with immunomagnetic CD34 positive selection was performed in 5 patients.
Results: 8 of 9 Patients (90%) are alive without evidence of disease after a median follow-up of 8.5 years. Leukocyte engraftment occurred after a median of 10 days (range 8-12). Median numbers of 667/µl CD3+, 329/µl CD4+, 369/µl CD8+T cells and 949/µl B cells were reached after 180 days. No negative impact of CD34 selection was observed. No transplantation-related death occurred. Acute toxicity comprised mucositis III°-IV° in all and veno-occlusive disease in one patient. Long term effects probably related to treatment occurred in 3/7 evaluable patients and comprised hearing impairment, reduced renal phosphate reabsorption, mild creatinine elevation and hypothyroidism (n=1, each).
Conclusion: Thus, in our experience HDC with ASCR is an effective treatment of recurrent or refractory nephroblastoma with acceptable side effects. However, a randomized trial proving its efficiency with a high level of evidence is needed.
In the mouse retina, three different types of photoreceptors provide input to 14 bipolar cell (BC) types. Classically, most BC types are thought to contact all cones within their dendritic field; ON-BCs would contact cones exclusively via so-called invaginating synapses, while OFF-BCs would form basal synapses. By mining publically available electron microscopy data, we discovered interesting violations of these rules of outer retinal connectivity: ON-BC type X contacted only ~20% of the cones in its dendritic field and made mostly atypical non-invaginating contacts. Types 5T, 5O and 8 also contacted fewer cones than expected. In addition, we found that rod BCs received input from cones, providing anatomical evidence that rod and cone pathways are interconnected in both directions. This suggests that the organization of the outer plexiform layer is more complex than classically thought.
Bauer, Michael ; Glenn, Tasha ; Achtyes, Eric D. ; Agaoglu, Esen ; Altınbaş, Kürşat ; Andreassen, Ole A. ; Angelopoulos, Elias ; Ardau, Raffaella ; Arrua Vares, Edgar ; Aydin, Memduha ; Ayhan, Yavuz ; Baethge, Christopher Jan ; Bauer, Rita ; Baune, Bernhard T. ; Balaban, Ceylan ; Becerra-Palars, Claudia ; Behere, Aniruddh P. ; Behere, Prakash B. ; Belete, Habte ; Belete, Tilahun ; Belizario, Gabriel Okawa ; Bellivier, Frank ; Belmaker, Robert H. ; Benedetti, Francesco ; Berk, Michael ; Bersudsky, Yuly ; Bicakci, Şule ; Birabwa-Oketcho, Harriet ; Bjella, Thomas D. ; Brady, Conan ; Cabrera, Jorge ; Cappucciati, Marco ; Castro, Angela Marianne Paredes ; Chen, Wei-Ling ; Cheung, Eric Y. Wo ; Chiesa, Silvia ; Crowe, Marie ; Cuomo, Alessandro ; Dallaspezia, Sara ; Del Zompo, Maria ; Desai, Pratikkumar ; Dodd, Seetal ; Donix, Markus ; Etain, Bruno ; Fagiolini, Andrea ; Fellendorf, Frederike Tabea ; Ferensztajn-Rochowiak, Ewa ; Fiedorowicz, Jess G. ; Fountoulakis, Kostas N. ; Frye, Mark A. ; Geoffroy, Pierre A. ; Gonzalez-Pinto, Ana ; Gottlieb, John F. ; Grof, Paul ; Haarman, Bartholomeus C. M. ; Harima, Hirohiko ; Hasse-Sousa, Mathias ; Henry, Chantal ; Høffding, Lone ; Houenou, Josselin ; Imbesi, Massimiliano ; Isometsä, Erkki T. ; Ivkovic, Maja ; Janno, Sven ; Johnsen, Simon ; Kapczinski, Flávio ; Karakatsoulis, Gregory N. ; Kardell, Mathias ; Kessing, Lars Vedel ; Kim, Seong Jae ; König, Barbara ; Kot, Timur L. ; Koval, Michael ; Kunz, Mauricio ; Lafer, Beny ; Landén, Mikael ; Larsen, Erik R. ; Lenger, Melanie ; Lewitzka, Ute ; Licht, Rasmus W. ; Lopez-Jaramillo, Carlos ; MacKenzie, Alan ; Madsen, Helle Østergaard ; Madsen, Simone Alberte Kongstad A. ; Mahadevan, Jayant ; Mahardika, Agustine ; Manchia, Mirko ; Marsh, Wendy ; Martinez-Cengotitabengoa, Monica ; Martiny, Klaus ; Mashima, Yuki ; McLoughlin, Declan M. ; Meesters, Ybe ; Melle, Ingrid ; Meza-Urzúa, Fátima ; Ming, Mok Yee ; Monteith, Scott ; Moorthy, Muthukumaran ; Morken, Gunnar ; Mosca, Enrica ; Mozzhegorov, Anton A. ; Munoz, Rodrigo ; Mythri, Starlin V. ; Nacef, Fethi ; Nadella, Ravi K. ; Nakanotani, Takako ; Nielsen, René Ernst ; O'Donovan, Claire ; Omrani, Adel ; Osher, Yamima ; Ouali, Uta ; Pantovic-Stefanovic, Maja ; Pariwatcharakul, Pornjira ; Petite, Joanne ; Pfennig, Andrea ; Pica Ruiz, Yolanda ; Pilhatsch, Maximilian ; Pinna, Marco ; Pompili, Maurizio ; Porter, Richard ; Quiroz, Danilo ; Rabelo-da-Ponte, Francisco Diego ; Ramesar, Raj ; Rasgon, Natalie ; Ratta-apha, Woraphat ; Ratzenhofer, Michaela ; Redahan, Maria ; Reddy, M. S. ; Reif, Andreas ; Reininghaus, Eva Z. ; Richards, Jenny Gringer ; Ritter, Philipp ; Rybakowski, Janusz K. ; Sathyaputri, Leela ; Scippa, Ângela M. ; Simhandl, Christian ; Severus, Emanuel ; Smith, Daniel ; Smith, José ; Stackhouse Jr., Paul W. ; Stein, Dan J. ; Stilwell, Kellen ; Strejilevich, Sergio ; Su, Kuan-Pin ; Subramaniam, Mythily ; Sulaiman, Ahmad Hatim ; Suominen, Kirsi ; Tanra, Andi J. ; Tatebayashi, Yoshitaka ; Teh, Wen Lin ; Tondo, Leonardo ; Torrent, Carla ; Tuinstra, Daniel ; Uchida, Takahito ; Vaaler, Arne E. ; Veeh, Julia ; Vieta, Eduard ; Viswanath, Biju ; Yoldi-Negrete, Maria ; Yalcinkaya, Oguz Kaan ; Young, Allan H. ; Zgueb, Yosra ; Whybrow, Peter C.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Liveblog München, 3. Februar
(2013)
Live von der Münchner Sicherheitskonferenz bloggen hier Christopher Daase, Tobias Bunde, Thomas Mohr und Ingo Henneberg und von der Friedenskonferenz Hans Georg Klee und das SiPoBlog–Team. Weitere Informationen gibt es hier. Die Kommentarfunktion ist natürlich zusätzlich geöffnet für alle.
Die Sicherheitskonferenz beginnt wieder um 9h mit einer Session zu aktuellen Krisen (Mali, Syrien). Bei der Friedenskonferenz ist um 11.30h das Friedensgebet angesetzt.
Liveblog München, 2. Februar
(2013)
Liveblog München, 1. Februar
(2013)
Mohr, Thomas ; Bunde, Tobias ; Klee, Hans Georg ; Offermann, Philipp ; Daase, Christopher ; Henneberg, Ingo
Live von der Münchner Sicherheitskonferenz bloggen hier Christopher Daase, Tobias Bunde, Thomas Mohr und Ingo Henneberg und von der Friedenskonferenz Hans Georg Klee und euer SiPo-Team. Weitere Informationen gibt es hier. Die Kommentarfunktion ist natürlich weiterhin offen.Die Sicherheitskonferenz wird um 15h eröffnet, erste Eindrücke unten.
Höh, Robert Benedikt ; Wenzel, Mike ; Müller, Matthias ; Wittler, Clarissa ; Schlenke, Eva ; Hohenhorst, Jan L. ; Köllermann, Jens ; Steuber, Thomas ; Graefen, Markus ; Tilki, Derya ; Bernatz, Simon ; Karakiewicz, Pierre I. ; Preißer, Felix ; Becker, Andreas ; Kluth, Luis ; Mandel, Philipp ; Chun, Felix
Background: To test the impact of urethral sphincter length (USL) and anatomic variants of prostatic apex (Lee-type classification) in preoperative multiparametric magnet resonance imaging (mpMRI) on mid-term continence in prostate cancer patients treated with radical prostatectomy (RP). Methods: We relied on an institutional tertiary-care database to identify patients who underwent RP between 03/2018 and 12/2019 with preoperative mpMRI and data available on mid-term (>6 months post-surgery) urinary continence, defined as usage 0/1 (-safety) pad/24 h. Univariable and multivariable logistic regression models were fitted to test for predictor status of USL and prostatic apex variants, defined in mpMRI measurements. Results: Of 68 eligible patients, rate of mid-term urinary continence was 81% (n = 55). Median coronal (15.1 vs. 12.5 mm) and sagittal (15.4 vs. 11.1 mm) USL were longer in patients reporting urinary continence in mid-term follow-up (both p < 0.01). No difference was recorded for prostatic apex variants distribution (Lee-type) between continent vs. incontinent patients (p = 0.4). In separate multivariable logistic regression models, coronal (odds ratio (OR): 1.35) and sagittal (OR: 1.67) USL, but not Lee-type, were independent predictors for mid-term continence. Conclusion: USL, but not apex anatomy, in preoperative mpMRI was associated with higher rates of urinary continence at mid-term follow-up.
Won, Sae-Yeon ; Freiman, Thomas Michael ; Reif, Philipp Sebastian ; Dubinski, Daniel ; Hattingen, Elke ; Herrmann, Eva ; Seifert, Volker ; Rosenow, Felix ; Strzelczyk, Adam ; Konczalla, Jürgen
Background: Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.
Methods: In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study's primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2-4 years of follow-up.
Discussion: The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.
Trial registration: ClinicalTrials.gov identifier no. NCT04211233.
Thomas, Anita ; Reetz, Sascha ; Stenzel, Philipp J. ; Tagscherer, Katrin ; Roth, Wilfried ; Schindeldecker, Mario ; Michaelis, Martin ; Rothweiler, Florian ; Cinatl, Jindrich ; Cinatl, Jaroslav ; Dotzauer, Robert Hans ; Vakhrusheva, Olesya ; Albersen, Maarten ; Macher-Göppinger, Stephan ; Haferkamp, Axel ; Jüngel, Eva ; Neisius, Andreas ; Tsaur, Igor
Simple Summary: Penile cancer is a rare but aggressive malignancy characterized by rapid tumor growth as well as prompt metastasis in groin lymphatics. While localized diseases can be successfully cured by surgery in most cases, no truly effective treatment options have been established for metastatic diseases as of yet. In the current investigation, we assessed the value of selected members of the PI3K/mTOR/AKT pathway to serve as tumor markers or therapeutic targets for this disease. Higher expression of AKT was significantly more prevalent in high-grade tumors and independently predictive of the worse survival parameters, while increased expression of pmTOR was associated with an inferior prognosis as well. Treatment with the pan-AKT inhibitor capivasertib in PeCa cell lines induced significant reduction of cell viability and movement capacity. These findings might aid in the understanding of the molecular tumor background as well as development of novel treatment options for advanced penile cancer.
Abstract: The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.
Preißer, Felix ; Chun, Felix ; Banek, Séverine ; Wenzel, Mike ; Graefen, Markus ; Steuber, Thomas ; Tilki, Derya ; Mandel, Philipp
Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we are challenged with different scenarios in clinical practice, where different treatment options may apply. In the last years, several prospective studies have focused on the treatment of patients with de novo oligometastatic hormone-sensitive prostate cancer. Not only the addition of systemic therapeutic treatments, such as chemotherapy with docetaxel, abiraterone, enzalutamide, and apalutamide, next to androgen deprivation therapy, demonstrated to improve outcomes in these patients but also local therapy of the primary has been demonstrated to improve outcomes of low-volume metastatic disease. Next to radiotherapy, also radical prostatectomy has been reported as a feasible and safe treatment option. Additional metastasis-directed therapy in de novo metastatic disease is currently examined by four trials. In the recurrent metastatic setting, less data are available, and it remains uncertain if patients can be treated in the same way as synchronous oligometastatic disease. Metastasis-directed therapy has demonstrated to prolong outcomes, while data on survival are still missing.
Ott, Sebastian Robert ; Meier, Niklaus ; Kolditz, Martin ; Bauer, Torsten Thomas ; Rohde, Gernot Gerhard Ulrich ; Presterl, Elisabeth ; Schürmann, Dirk ; Lepper, Philipp Moritz ; Ringshausen, Felix Christian ; Flick, Holger ; Leib, Stephen L. ; Pletz, Mathias Wilhelm Rudolf
Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge is derived from case reports or smaller case series. Recently, increasing PN incidence rates have been reported. We aim to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates.
Methods: Retrospective evaluation (1995 to 2011) of the clinical course of and risk factors for PN in patients from 11 hospitals in four European countries (Germany, Austria, Switzerland and The Netherlands). Calculation of population-based estimates of hospitalization rates of PN in Germany (2005 to 2011) using official German nationwide diagnosis-related groups (DRG) hospital statistics.
Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven with extrapulmonary dissemination. Within the 43 patients, major PN risk factors were immunocompromising (83.7%) and/or pulmonary (58.1%; in 27.9% as only comorbidity) comorbidities. Median duration of PN targeted therapy was 12 weeks. Distinguished patterns of resistance were observed (imipenem susceptibility: N. farcinica 33.3%; N. asteroides 66.7%). Overall mortality rate was 18.9%; in disseminated PN 50%. Over time, annual PN hospitalization rates remained unchanged at around 0.04/100′000 with the highest rate among men aged 75–84 years (0.24/100′000).
Conclusion: PN is rare, but potentially life-threatening, and mainly affects immunocompromised elder males. Overall annual hospitalization rates remained stable between 2005 and 2011.
Hackbarth, Christoph Bernhard ; Vogl, Thomas J. ; Naguib, Nagy Naguib Naeem ; Albrecht, Moritz Hans Ernst ; Knebel Doeberitz, Philipp L. von
Background: Various studies have been made about the most effective and safest type of treatment for vertebral compression fractures (VCFs). Long-term results are needed for qualitative evaluation.
Purpose: The purpose of the study is to evaluate the effectiveness of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) procedures for VCFs.
Materials and Methods: Forty-nine patients who received either PVP or PKP between 2002 and 2015 returned a specially developed questionnaire and were included in a cross-sectional outcome analysis. The questionnaire assessed pain development by use of a visual analog scale (VAS). Imaging data (CT scans) were retrospectively analyzed for identification of cement leakage.
Results: Patients’ VAS scores significantly decreased after treatment (7.0 ± 3.4 => 3.7 ± 3.4), (p < 0.001). The average pain reduction in patients treated with PVP was −3.3 ± 3.8 (p < 0.001) (median −3.5) and −4.0 ± 3.9 (p < 0.001) (median −4.5) in patients treated with PKP. Fifteen Patients (41.7%) receiving PVP and four patients (30.7%) receiving PKP experienced recurrence of pain. Cement leakage occurred in 10 patients (22.73%). Patients with cement leakage showed comparable VAS scores after treatment (6.8 ± 3.5 => 1.4 ± 1.6), (p = 0.008). Thirty-nine patients reported an increase in mobility (79.6%) and 41 patients an improvement in quality of life (83.7%).
Conclusion: Pain reduction by means of PVP or PKP in patients with VCFs was discernible over the period of observation. Percutaneous vertebroplasty and PKP contribute to the desired treatment results. However, the level of low pain may not remain constant.
Medema, Marnix H. ; Kottmann, Renzo ; Yilmaz, Pelin ; Cummings, Matthew ; Biggins, John B. ; Kai, Blin ; de Bruijn, Irene ; Chooi, Yit Heng ; Claesen, Jan ; Coates, R. Cameron ; Cruz-Morales, Pablo ; Duddela, Srikanth ; Düsterhus, Stephanie ; Edwards, Daniel J. ; Fewer, David P. ; Garg, Neha ; Geiger, Christoph ; Gomez-Escribano, Juan Pablo ; Greule, Anja ; Hadjithomas, Michalis ; Haines, Anthony S. ; Helfrich, Eric J. N. ; Hillwig, Matthew L. ; Ishida, Keishi ; Jones, Adam C. ; Jones, Carla S. ; Jungmann, Katrin ; Kegler, Carsten ; Kim, Hyun Uk ; Kötter, Peter ; Krug, Daniel ; Masschelein, Joleen ; Melnik, Alexey V. ; Mantovan, Simone M. ; Monroe, Emily A. ; Moore, Marcus ; Moss, Nathan ; Nützmann, Hans-Wilhelm ; Pan, Guohui ; Pati, Amrita ; Petras, Daniel ; Reen, F. Jerry ; Rosconi, Federico ; Rui, Zhe ; Tian, Zhenhua ; Tobias, Nicholas J. ; Tsunematsu, Yuta ; Wiemann, Philipp ; Wyckoff, Elizabeth ; Yan, Xiaohui ; Yim, Grace ; Yu, Fengan ; Xie, Yunchang ; Aigle, Bertrand ; Apel, Alexander K. ; Balibar, Carl J. ; Balskus, Emily P. ; Barona-Gómez, Francisco ; Bechthold, Andreas ; Bode, Helge Björn ; Borriss, Rainer ; Brady, Sean F. ; Brakhage, Axel A. ; Caffrey, Patrick ; Cheng, Yi-Qiang ; Clardy, Jon ; Cox, Russell J. ; De Mot, René ; Donadio, Stefano ; Donia, Mohamed S. ; van der Donk, Wilfred A. ; Dorrestein, Pieter C. ; Doyle, Sean ; Driessen, Arnold J. M. ; Ehling-Schulz, Monika ; Entian, Karl-Dieter ; Fischbach, Michael A. ; Gerwick, Lena ; Gerwick, William H. ; Gross, Harald ; Gust, Bertolt ; Hertweck, Christian ; Höfte, Monica ; Jensen, Susan E. ; Ju, Jianhua ; Katz, Leonard ; Kaysser, Leonard ; Klassen, Jonathan L. ; Keller, Nancy P. ; Kormanec, Jan ; Kuipers, Oscar P. ; Kuzuyama, Tomohisa ; Kyrpides, Nikos C. ; Kwon, Hyung-Jin ; Lautru, Sylvie ; Lavigne, Rob ; Lee, Chia Y. ; Linquan, Bai ; Liu, Xinyu ; Liu, Wen ; Luzhetskyy, Andriy ; Mahmud, Taifo ; Mast, Yvonne ; Méndez, Carmen ; Metsä-Ketelä, Mikko ; Micklefield, Jason ; Mitchell, Douglas A. ; Moore, Bradley S. ; Moreira, Leonilde M. ; Müller, Rolf ; Neilan, Brett A. ; Nett, Markus ; Nielsen, Jens ; O’Gara, Fergal ; Oikawa, Hideaki ; Osbourn, Anne ; Osburne, Marcia S. ; Ostash, Bohdan ; Payne, Shelley M. ; Pernodet, Jean-Luc ; Petricek, Miroslav ; Piel, Jörn ; Ploux, Olivier ; Raaijmakers, Jos M. ; Salas, José A. ; Schmitt, Esther K. ; Scott, Barry ; Seipke, Ryan F. ; Shen, Ben ; Sherman, David H. ; Sivonen, Kaarina ; Smanski, Michael J. ; Sosio, Margherita ; Stegmann, Evi ; Süssmuth, Roderich D. ; Tahlan, Kapil ; Thomas, Christopher M. ; Tang, Yi ; Truman, Andrew W. ; Viaud, Muriel ; Walton, Jonathan D. ; Walsh, Christopher T. ; Weber, Tilmann ; van Wezel, Gilles P. ; Wilkinson, Barrie ; Willey, Joanne M. ; Wohlleben, Wolfgang ; Wright, Gerard D. ; Ziemert, Nadine ; Zhang, Changsheng ; Zotchev, Sergey B. ; Breitling, Rainer ; Takano, Eriko ; Glöckner, Frank Oliver
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Prall, Matthias ; Durante, Marco ; Berger, Thomas ; Przybyla, Bartos ; Graef, Christian ; Lang, Philipp-M. ; LaTessa, Chiara ; Shestov, Lev ; Simoniello, Palma ; Danly, Chris R. ; Mariam, Fesseha G. ; Merrill, Frank Edward ; Nedrow, Paul ; Wilde, Carl ; Varentsov, Dmitry
The charged particle community is looking for techniques exploiting proton interactions instead of X-ray absorption for creating images of human tissue. Due to multiple Coulomb scattering inside the measured object it has shown to be highly non-trivial to achieve sufficient spatial resolution. We present imaging of biological tissue with a proton microscope. This device relies on magnetic optics, distinguishing it from most published proton imaging methods. For these methods reducing the data acquisition time to a clinically acceptable level has turned out to be challenging. In a proton microscope, data acquisition and processing are much simpler. This device even allows imaging in real time. The primary medical application will be image guidance in proton radiosurgery. Proton images demonstrating the potential for this application are presented. Tomographic reconstructions are included to raise awareness of the possibility of high-resolution proton tomography using magneto-optics.
Kurth, Florian Michael ; Develoux, Michel ; Mechain, Matthieu ; Malvy, Denis ; Clerinx, Jan ; Antinori, Spinello ; Gjørup, Ida E. ; Gascon, Joaquím ; Mørch, Kristine ; Nicastri, Emanuele ; Ramharter, Michael ; Bartoloni, Alessandro ; Visser, Leo ; Rolling, Thierry ; Zanger, Philipp ; Calleri, Guido ; Salas‑Coronas, Joaquín ; Nielsen, Henrik ; Just‑Nübling, Gudrun ; Neumayr, Andreas ; Hachfeld, Anna ; Schmid, Matthias L. ; Antonini, Pietro ; Lingscheid, Tilman ; Kern, Peter ; Kapaun, Annette ; Cunha, José Saraiva da ; Pongratz, Peter ; Soriano‑Arandes, Antoni ; Schunk, Mirjam ; Suttorp, Norbert ; Hatz, Christoph ; Zoller, Thomas
Background: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria.
Methods: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria.
Results: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate.
Conclusion: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.
Löser, Heike ; Krämer, Max ; Gebauer, Florian ; Bruns, Christiane ; Schröder, Wolfgang ; Zander, Thomas ; Persa, Oana-Diana ; Alakus, Hakan ; Hölscher, Arnulf H. ; Büttner, Reinhard ; Lohneis, Philipp ; Quaas, Alexander
Immune checkpoint modulation in cancer has been demonstrated as a high-value therapeutic strategy in many tumor entities. VISTA is an immune checkpoint receptor regulating T-cell function. To the best of our knowledge, nothing is known about the expression and prognostic impact of VISTA on tumor infiltrating lymphocytes (TILs) in the tumor microenvironment of esophageal adenocarcinoma (EAC). We analyzed in total 393 EACs within a test-cohort (n = 165) and a validation-cohort (n = 228) using a monoclonal antibody (clone D1L2G). These data were statistically correlated with clinical as well as molecular data. 22.2% of the tumor cohort presented with a VISTA expression on TILs. These patients demonstrated an improved median overall survival compared to patients without VISTA expression (202.2 months vs. 21.6 months; p < 0.0001). The favorable outcome of VISTA positive tumors is significant in the entire cohort but mainly driven by the general better prognosis of T1/T2 tumors. However, in the pT1/2 group, VISTA positive tumors show a tremendous survival benefit compared to VISTA negative tumors revealing real long-term survivors in this particular subgroup. The survival difference is independent of the T-stage. This unique characteristic could influence neoadjuvant therapy concepts for EAC, since a profit of therapy could be reduced in the already favorable subgroup of VISTA positive tumors. VISTA emerges as a prognostic biomarker for long-term survival especially in the group of early TNM-stages. Future studies have to show the relevance of VISTA positive TILs within a tumor concerning response to specific immune checkpoint inhibition.
Hofmann, Wolf-Peter ; Buggisch, Peter ; Schubert, Lisa ; Dikopoulos, Nektarios ; Schwenzer, Jeannette ; Muche, Marion ; Felten, Gisela ; Heyne, Renate ; Ingiliz, Patrick Philipp ; Schmidt, Anna ; Stein, Kerstin ; Wedemeyer, Heiner ; Berg, Thomas ; Wiegand, Johannes ; Lammert, Frank ; Zeuzem, Stefan ; Schattenberg, Jörn Markus
Background & Aims: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. Conclusions: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. Lay summary: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Malte ; Aliberti, Riccardo ; Amoroso, Antonio ; An, M.R. ; An, Qi ; Bai, Xuhong ; Bai, Yu ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Berger, Niklaus ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, Hao ; Cai, Xiao ; Calcaterra, Alessandro ; Cao, G.F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, Jinfan ; Chang, W.L. ; Chelkov, Gueorgui A. ; Chen, D.Y. ; Chen, G. ; Chen, Hesheng ; Chen, M.L. ; Chen, S.J. ; Chen, X.R. ; Chen, Yuanbo ; Chen, Z.J. ; Cheng, W.S. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X.F. ; Dai, Hongliang ; Dai, Xinchen ; Dbeyssi, Alaa ; Boer, Remco E. de ; Dedovich, Dmitri V. ; Deng, Ziyan ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Yanchun ; Dong, C. ; Dong, J. ; Dong, Liaoyuan ; Dong, Mingyi ; Dong, X. ; Du, Shuxian ; Fan, Y.L. ; Fang, J. ; Fang, Shuangshi ; Fang, Y. ; Farinelli, Riccardo ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C.Q. ; Feng, J.H. ; Fritsch, Miriam ; Fu, Chengdong ; Gao, Y. ; Gao, Y. ; Gao, Y. ; Gao, Y.G. ; Garzia, Isabella ; Ge, P.T. ; Geng, C. ; Gersabeck, Evelina ; Gilman, A. ; Götzen, Klaus ; Gong, L. ; Gong, Wenxuan ; Gradl, Wolfgang ; Greco, M. ; Gu, L.M. ; Gu, Minhao ; Gu, S. ; Gu, Y.T. ; Guan, C.Y. ; Guo, Aiqiang ; Guo, L.B. ; Guo, R.P. ; Guo, Yuping ; Guskov, Alexey ; Han, T.T. ; Han, W.Y. ; Hao, Xiqing ; Harris, Frederick Allan ; Hüsken, Nils ; He, K.L. ; Heinsius, Fritz-Herbert ; Heinz, C.H. ; Held, T. ; Heng, Yuekun ; Herold, Christoph ; Himmelreich, Mathilde ; Holtmann, Tobias ; Hou, G.Y. ; Hou, Y.R. ; Hou, Zhilong ; Hu, Haiming ; Hu, J.F. ; Hu, T. ; Hu, Y. ; Huang, G.S. ; Huang, L.Q. ; Huang, Xingtao ; Huang, Y.P. ; Huang, Z. ; Hussain, Tahir ; Ikegami Andersson, Walter ; Imoehl, William ; Irshad, M. ; Jaeger, S. ; Janchiv, S. ; Ji, Quan ; Ji, Qingping ; Ji, X.B. ; Ji, X.L. ; Ji, Y.Y. ; Jiang, H.B. ; Jiang, Xiaoshan ; Jiao, J.B. ; Jiao, Z. ; Jin, Shan ; Jin, Y. ; Jing, M.Q. ; Johansson, Tord ; Kalantar-Nayestanaki, Nasser ; Kang, X. S. ; Kappert, Rosa ; Kavatsyuk, Myroslav O. ; Ke, Bai-Cian ; Keshk, Iman ; Khoukaz, Alfons ; Kiese, P. ; Kiuchi, Ryuta ; Kliemt, Ralf ; Koch, Leonard ; Kolcu, Onur Bugra ; Kopf, Bertram ; Kuemmel, M. ; Küßner, Meike ; Kupsc, Andrzej ; Kurth, Matthew Glenn ; Kühn, Wolfgang ; Lane, John Jake ; Lange, Jens Sören ; Larin, Paul ; Lavania, Anita ; Lavezzi, Lia ; Lei, Z.H. ; Leithoff, Hans Heinrich ; Lellmann, Max ; Lenz, Thomas ; Li, C. ; Li, C.H. ; Li, Cheng ; Li, D.M. ; Li, F. ; Li, G. ; Li, H. ; Li, H. ; Li, Haibo ; Li, H.J. ; Li, J.L. ; Li, J.Q. ; Li, J.S. ; Li, Ke ; Li, L.K. ; Li, Lei ; Li, P.R. ; Li, S.Y. ; Li, Weidong ; Li, Weiguo ; Li, X.H. ; Li, Xing Long ; Li, Xiaoyu ; Li, Z.Y. ; Liang, H. ; Liang, H. ; Liang, H. ; Liang, Y.F. ; Liang, Y.T. ; Liao, G.R. ; Liao, L.Z. ; Libby, J. ; Lin, C.X. ; Lin, D.X. ; Liu, B.J. ; Liu, C.X. ; Liu, D. ; Liu, Fu-Hu ; Liu, Fang ; Liu, Feng ; Liu, H.B. ; Liu, H.M. ; Liu, Huanhuan ; Liu, Huihui ; Liu, J.B. ; Liu, J.L. ; Liu, J.Y. ; Liu, K. ; Liu, K.Y. ; Liu, L. ; Liu, M.H. ; Liu, P.L. ; Liu, Q. ; Liu, Q. ; Liu, S.B. ; Liu, Shuai ; Liu, T. ; Liu, W.M. ; Liu, X. ; Liu, Y. ; Liu, Y.B. ; Liu, Zhen-An ; Liu, Z.Q. ; Lou, Xinchou ; Lu, F.X. ; Lu, F.X. ; Lu, H.J. ; Lu, J.D. ; Lu, Junguang ; Lu, X.L. ; Lu, Y. ; Lu, Yunpeng ; Luo, Chenglin ; Luo, M.X. ; Luo, P.W. ; Luo, Tao ; Luo, X.L. ; Lusso, S. ; Lyu, Xiao-Rui ; Ma, Fengcai ; Ma, Hailong ; Ma, Lianliang ; Ma, M.M. ; Ma, Qiumei ; Ma, R.Q. ; Ma, R.T. ; Ma, X.X. ; Ma, Xiaoyan ; Maas, Frank E. ; Maggiora, Marco ; Maldaner, Stephan ; Malde, Sneha ; Malik, Qadeer Afzal ; Mangoni, Alessio ; Mao, Yajun ; Mao, Zepu ; Marcello, Simonetta ; Meng, Z.X. ; Messchendorp, Johannes Gerhardus ; Mezzadri, Giulio ; Min, T.J. ; Mitchell, Ryan Edward ; Mo, Xiaohu ; Mo, Y.J. ; Muchnoi, Nikolai Yu. ; Muramatsu, Hajime ; Nakhoul, Simon ; Nefedov, Yury ; Nerling, Frank ; Nikolaev, Ivan Borisovich ; Ning, Z. ; Nisar, Shabana ; Olsen, Stephen L. ; Ouyang, Qun ; Pacetti, Simone ; Pan, Xiang ; Pan, Y. ; Pathak, A. ; Patteri, Piero ; Pelizäus, Marc ; Peng, H. P. ; Peters, Klaus ; Pettersson, J. ; Ping, J.L. ; Ping, R.G. ; Poling, Ronald ; Prasad, Vindhyawasini ; Qi, H. ; Qi, H.R. ; Qi, K.H. ; Qi, Ming ; Qi, T.Y. ; Qi, T.Y. ; Qian, S. ; Qian, W.B. ; Qian, Z. ; Qiao, Congfeng ; Qin, L.Q. ; Qin, X.P. ; Qin, X.S. ; Qin, Zhonghua ; Qiu, Jinfa ; Qu, S.Q. ; Rashid, K.H. ; Ravindran, Krishnakumar ; Redmer, Christoph Florian ; Rivetti, Angelo ; Rodin, Viktor ; Da Rocha Rolo, Manuel Dionisio ; Rong, Gang ; Rosner, Christoph ; Rump, Marcel Andre ; Sang, H.S. ; Sarantsev, Andrei V. ; Schelhaas, Yasemin ; Schnier, Claudius ; Schönning, Karin ; Scodeggio, Marco ; Shan, D.C. ; Shan, Wei ; Shan, Xinyu ; Shangguan, J.F. ; Shao, M. ; Shen, C.P. ; Shen, H.F. ; Shen, P.X. ; Shen, X.Y. ; Shi, H.C. ; Shi, R.S. ; Shi, X. ; Shi, X.D. ; Song, J.J. ; Song, W.M. ; Song, Y.X. ; Sosio, Stefano ; Spataro, Stefano ; Su, K.X. ; Su, P.P. ; Sui, F.F. ; Sun, Gongxing ; Sun, H.K. ; Sun, J.F. ; Sun, L. ; Sun, S.S. ; Sun, T. ; Sun, W.Y. ; Sun, W.Y. ; Sun, X. ; Sun, Y.J. ; Sun, Y.K. ; Sun, Y.Z. ; Sun, Z.T. ; Tan, Y.H. ; Tan, Y.X. ; Tang, C.J. ; Tang, G.Y. ; Tang, J. ; Teng, J.X. ; Thoren, Viktor ; Tian, W.H. ; Uman, Ismail ; Wang, B. ; Wang, C.W. ; Wang, D.Y. ; Wang, H.J. ; Wang, H.P. ; Wang, K. ; Wang, L.L. ; Wang, M. ; Wang, M.Z. ; Wang, Meng ; Wang, W. ; Wang, W.H. ; Wang, W.P. ; Wang, X. ; Wang, X.F. ; Wang, X.L. ; Wang, Y. ; Wang, Y. ; Wang, Y.D. ; Wang, Y.F. ; Wang, Y.Q. ; Wang, Y.Y. ; Wang, Z. ; Wang, Zongyuan ; Wang, Ziyi ; Wang, Zongyuan ; Wei, D.H. ; Weidenkaff, Philipp ; Weidner, Frederik ; Wen, Shuopin ; White, D.J. ; Wiedner, Ulrich ; Wilkinson, Guy ; Wolke, Magnus ; Wollenberg, Leonard ; Wu, J.F. ; Wu, Linghui ; Wu, L.J. ; Wu, X. ; Wu, Z. ; Xia, Lei ; Xiao, H. ; Xiao, S.Y. ; Xiao, Zhenjun ; Xie, X.H. ; Xie, Y.G. ; Xie, Y.H. ; Xing, T.Y. ; Xu, Guofa ; Xu, Q.J. ; Xu, W. ; Xu, Xinping ; Xu, Y.C. ; Yan, F. ; Yan, L. ; Yan, W.B. ; Yan, W.C. ; Yan, Xu ; Yang, H.J. ; Yang, Hongxun ; Yang, L. ; Yang, S.L. ; Yang, Yongxu ; Yang, Yifan ; Yang, Zhi ; Ye, M. ; Ye, Minghan ; Yin, J.H. ; You, Z.Y. ; Yu, Boxiang ; Yu, C.X. ; Yu, G. ; Yu, J.S. ; Yu, T. ; Yuan, Chang-Zheng ; Yuan, L. ; Yuan, X.Q. ; Yuan, Y. ; Yuan, Z.Y. ; Yue, C.X. ; Yüncü, Alperen ; Zafar, A.A. ; Zeng, X. ; Zeng, Y. ; Zhang, A. Q. ; Zhang, B. X. ; Zhang, Guangyi ; Zhang, Haitao ; Zhang, H.H. ; Zhang, H.H. ; Zhang, Hongyu ; Zhang, J.J. ; Zhang, J.L. ; Zhang, J.Q. ; Zhang, J.W. ; Zhang, Jianyong ; Zhang, J.Z. ; Zhang, Jianyu ; Zhang, Jiawei ; Zhang, L.Q. ; Zhang, Lei ; Zhang, S. ; Zhang, S.F. ; Zhang, Shulei ; Zhang, X.D. ; Zhang, X.Y. ; Zhang, Y. ; Zhang, Y.H. ; Zhang, Y.T. ; Zhang, Yan ; Zhang, Yao ; Zhang, Yi ; Zhang, Z.H. ; Zhang, Z.Y. ; Zhao, G. ; Zhao, J. ; Zhao, J.Y. ; Zhao, J.Z. ; Zhao, Lei ; Zhao, Ling ; Zhao, Ming-Gang ; Zhao, Q. ; Zhao, Shujun ; Zhao, Yubin ; Zhao, Y.X. ; Zhao, Zhengguo ; Zhemchugov, Alexey ; Zheng, B. ; Zheng, Jianping ; Zheng, Y. ; Zheng, Y.H. ; Zhong, B. ; Zhong, C. ; Zhou, L. P. ; Zhou, Q. ; Zhou, X. ; Zhou, X.K. ; Zhou, X.R. ; Zhu, A.N. ; Zhu, Jianhui ; Zhu, K. ; Zhu, Kejun ; Zhu, S.H. ; Zhu, T.J. ; Zhu, W.J. ; Zhu, W.J. ; Zhu, Y.C. ; Zhu, Zian ; Zou, B.S. ; Zou, Jiaheng
The electromagnetic process is studied with the initial-state-radiation technique using 7.5 fb−1 of data collected by the BESIII experiment at seven energy points from 3.773 to 4.600 GeV. The Born cross section and the effective form factor of the proton are measured from the production threshold to 3.0 GeV/ using the invariant-mass spectrum. The ratio of electric and magnetic form factors of the proton is determined from the analysis of the proton-helicity angular distribution.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Malte ; Aliberti, Riccardo ; Amoroso, Antonio ; An, M. R. ; An, Qi ; Bai, Xuhong ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Berger, K. ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, Hao ; Cai, Xiao ; Calcaterra, Alessandro ; Cao, G. F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, Jinfan ; Chang, W. L. ; Chelkov, Gueorgui A. ; Chen, D. Y. ; Chen, G. ; Chen, Hesheng ; Chen, M. L. ; Chen, S. J. ; Chen, X. R. ; Chen, Y. B. ; Chen, Z. J. ; Cheng, W. S. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X. F. ; Dai, Hongliang ; Dai, Xinchen ; Dbeyssi, Alaa ; Boer, Remco E. de ; Dedovich, Dmitri V. ; Deng, Ziyan ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Yanchun ; Dong, C. ; Dong, J. ; Dong, Liaoyuan ; Dong, Mingyi ; Dong, X. ; Du, Shuxian ; Fan, Y. L. ; Fang, J. ; Fang, Shuangshi ; Fang, Y. ; Farinelli, Riccardo ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C. Q. ; Feng, J. H. ; Fritsch, Miriam ; Fu, Chengdong ; Gao, Y. ; Gao, Y. ; Gao, Y. ; Gao, Y. G. ; Garzia, Isabella ; Ge, P. T. ; Geng, C. ; Gersabeck, Evelina ; Gilman, A. ; Götzen, Klaus ; Gong, L. ; Gong, Wenxuan ; Gradl, Wolfgang ; Greco, M. ; Gu, L. M. ; Gu, Minhao ; Gu, S. ; Gu, Y. T. ; Guan, C. Y. ; Guo, Aiqiang ; Guo, L. B. ; Guo, R. P. ; Guo, Yuping ; Guskov, Alexey ; Han, T. T. ; Han, W. Y. ; Hao, Xiqing ; Harris, Frederick Allan ; Hüsken, Nils ; He, K. L. ; Heinsius, Fritz-Herbert ; Heinz, C. H. ; Held, T. ; Heng, Yuekun ; Herold, Christoph ; Himmelreich, Mathilde ; Holtmann, Tobias ; Hou, G. Y. ; Hou, Y. R. ; Hou, Zhilong ; Hu, Haiming ; Hu, J. F. ; Hu, T. ; Hu, Y. ; Huang, G. S. ; Huang, L. Q. ; Huang, X. T. ; Huang, Y. P. ; Huang, Z. ; Hussain, Tahir ; Ikegami Andersson, Walter ; Imoehl, William ; Irshad, M. ; Jaeger, S. ; Janchiv, S. ; Ji, Quan ; Ji, Qingping ; Ji, X. B. ; Ji, X. L. ; Ji, Y. Y. ; Jiang, H. B. ; Jiang, Xiaoshan ; Jiao, J. B. ; Jiao, Z. ; Jin, Shan ; Jin, Y. ; Jing, M. Q. ; Johansson, Tord ; Kalantar-Nayestanaki, Nasser ; Kang, X. S. ; Kappert, Rosa ; Kavatsyuk, Myroslav O. ; Ke, Bai-Cian ; Keshk, Iman ; Khoukaz, Alfons ; Kiese, P. ; Kiuchi, Ryuta ; Kliemt, Ralf ; Koch, Leonard ; Kolcu, Onur Bugra ; Kopf, Bertram ; Kümmel, Miriam ; Küßner, Meike ; Kupsc, Andrzej ; Kurth, M. G. ; Kühn, Wolfgang ; Lane, John Jake ; Lange, Jens Sören ; Larin, Paul ; Lavania, Anita ; Lavezzi, Lia ; Lei, Z. H. ; Leithoff, Hans Heinrich ; Lellmann, Max ; Lenz, Thomas ; Li, C. ; Li, C. H. ; Li, Cheng ; Li, D. M. ; Li, F. ; Li, G. ; Li, H. ; Li, H. ; Li, Haibo ; Li, H. J. ; Li, J. L. ; Li, J. Q. ; Li, J. S. ; Li, Ke ; Li, L. K. ; Li, Lei ; Li, P. R. ; Li, S. Y. ; Li, Weidong ; Li, Weiguo ; Li, X. H. ; Li, Xing Long ; Li, Xiaoyu ; Li, Z. Y. ; Liang, H. ; Liang, H. ; Liang, H. ; Liang, Y. F. ; Liang, Y. T. ; Liao, G. R. ; Liao, L. Z. ; Libby, J. ; Lin, C. X. ; Liu, B. J. ; Liu, C. X. ; Liu, D. ; Liu, Fu-Hu ; Liu, Fang ; Liu, Feng ; Liu, H. B. ; Liu, H. M. ; Liu, Huanhuan ; Liu, Huihui ; Liu, J. B. ; Liu, J. L. ; Liu, J. Y. ; Liu, K. ; Liu, K. Y. ; Liu, L. ; Liu, M. H. ; Liu, P. L. ; Liu, Q. ; Liu, Q. ; Liu, S. B. ; Liu, Shuai ; Liu, T. ; Liu, W. M. ; Liu, X. ; Liu, Y. ; Liu, Y. B. ; Liu, Zhen-An ; Liu, Z. Q. ; Lou, Xinchou ; Lu, F. X. ; Lu, F. X. ; Lu, H. J. ; Lu, J. D. ; Lu, Junguang ; Lu, X. L. ; Lu, Y. ; Lu, Yunpeng ; Luo, C. L ; Luo, M. X. ; Luo, P. W. ; Luo, Tao ; Luo, X. L. ; Lusso, S. ; Lyu, Xiao-Rui ; Ma, Fengcai ; Ma, Hailong ; Ma, Lianliang ; Ma, M. M. ; Ma, Qiumei ; Ma, R. Q. ; Ma, R. T. ; Ma, X. X. ; Ma, Xiaoyan ; Maas, Frank E. ; Maggiora, Marco ; Maldaner, Stephan ; Malde, Sneha ; Malik, Qadeer Afzal ; Mangoni, Alessio ; Mao, Yajun ; Mao, Zepu ; Marcello, Simonetta ; Meng, Z. X. ; Messchendorp, Johannes Gerhardus ; Mezzadri, Giulio ; Min, T. J. ; Mitchell, Ryan Edward ; Mo, Xiaohu ; Mo, Y. J. ; Muchnoi, Nikolai Yu. ; Muramatsu, Hajime ; Nakhoul, Simon ; Nefedov, Yury ; Nerling, Frank ; Nikolaev, Ivan Borisovich ; Ning, Z. ; Nisar, Shabana ; Olsen, Stephen L. ; Ouyang, Qun ; Pacetti, Simone ; Pan, Xiang ; Pan, Y. ; Pathak, A. ; Patteri, Piero ; Pelizäus, Marc ; Peng, H. P. ; Peters, Klaus ; Pettersson, J. ; Ping, J. L. ; Ping, R. G. ; Poling, Ronald ; Prasad, Vindhyawasini ; Qi, H. ; Qi, H. R. ; Qi, K. H. ; Qi, Ming ; Qi, T. Y. ; Qi, T. Y. ; Qian, S. ; Qian, W. B. ; Qian, Z. ; Qiao, Congfeng ; Qin, L. Q. ; Qin, X. P. ; Qin, X. S. ; Qin, Zhonghua ; Qiu, Jinfa ; Qu, S. Q. ; Rashid, K. H. ; Ravindran, Krishnakumar ; Redmer, Christoph Florian ; Rivetti, Angelo ; Rodin, Viktor ; Da Rocha Rolo, Manuel Dionisio ; Rong, Gang ; Rosner, Christoph ; Rump, Marcel Andre ; Sang, H. S. ; Sarantsev, Andrei V. ; Schelhaas, Yasemin ; Schnier, Claudius ; Schönning, Karin ; Scodeggio, Marco ; Shan, D. C. ; Shan, Wei ; Shan, Xinyu ; Shi, X. ; Shi, X. D. ; Song, J. J. ; Song, W. M. ; Song, Y. X. ; Sosio, Stefano ; Spataro, Stefano ; Su, K. X. ; Su, P. P. ; Sui, F. F. ; Sun, Gongxing ; Sun, H. K. ; Sun, J. F. ; Sun, L. ; Sun, S. S. ; Sun, T. ; Sun, W. Y. ; Sun, W. Y. ; Sun, X. ; Sun, Y. J. ; Sun, Y. K. ; Sun, Y. Z. ; Sun, Z. T. ; Tan, Y. H. ; Tan, Y. X. ; Tang, C. J. ; Tang, G. Y. ; Tang, J. ; Teng, J. X. ; Thoren, Viktor ; Tian, W. H. ; Uman, Ismail ; Wang, B. ; Wang, C. W. ; Wang, D. Y. ; Wang, H. J. ; Wang, H. P. ; Wang, K. ; Wang, L. L. ; Wang, M. ; Wang, M. Z. ; Wang, Meng ; Wang, W. ; Wang, W. H. ; Wang, W. P. ; Wang, X. ; Wang, X. F. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Y. D. ; Wang, Y. F. ; Wang, Y. Q. ; Wang, Y. Y. ; Wang, Z. ; Wang, Zongyuan ; Wang, Ziyi ; Wang, Zongyuan ; Wei, D. H. ; Weidenkaff, Philipp ; Weidner, Frederik ; Wen, Shuopin ; White, D. J. ; Wiedner, Ulrich ; Wilkinson, Guy ; Wolke, Magnus ; Wollenberg, Leonard ; Wu, J. F. ; Wu, Linghui ; Wu, L. J. ; Wu, X. ; Wu, Z. ; Xia, Lei ; Xiao, H. ; Xiao, S. Y. ; Xiao, Zhenjun ; Xie, X. H. ; Xie, Y. G. ; Xie, Y. H. ; Xing, T. Y. ; Xu, Guofa ; Xu, Q. J. ; Xu, W. ; Xu, Xinping ; Xu, Y. C. ; Yan, F. ; Yan, L. ; Yan, W. B. ; Yan, W. C. ; Yan, Xu ; Yang, H. J. ; Yang, Hongxun ; Yang, L. ; Yang, S. L. ; Yang, Yongxu ; Yang, Yifan ; Yang, Zhi ; Ye, M. ; Ye, Minghan ; Yin, J. H. ; You, Z. Y. ; Yu, Boxiang ; Yu, C. X. ; Yu, G. ; Yu, J. S. ; Yu, T. ; Yuan, Chang-Zheng ; Yuan, L. ; Yuan, X. Q. ; Yuan, Y. ; Yuan, Z. Y. ; Yue, C. X. ; Yüncü, Alperen ; Zafar, A. A. ; Zeng ; Zeng, Y. ; Zhang, A. Q. ; Zhang, Guangyi ; Zhang, Haitao ; Zhang, H. H. ; Zhang, H. H. ; Zhang, Hongyu ; Zhang, J. J. ; Zhang, J. L. ; Zhang, J. Q. ; Zhang, J. W. ; Zhang, Jianyong ; Zhang, J. Z. ; Zhang, Jianyu ; Zhang, Jiawei ; Zhang, L. Q. ; Zhang, Lei ; Zhang, S. ; Zhang, S. F. ; Zhang, Shulei ; Zhang, X. D.
Relative fractions and phases of the intermediate decays are determined. With the detection efficiency estimated by the results of the amplitude analysis, the branching fraction of Dþ s → K−Kþπþπ0 decay is measured to be ð5.42 0.10stat 0.17systÞ%.
Pati, Sarthak ; Baid, Ujjwal ; Edwards, Brandon ; Sheller, Micah ; Wang, Shih-Han ; Reina, G. Anthony ; Foley, Patrick ; Gruzdev, Alexey ; Karkada, Deepthi ; Davatzikos, Christos ; Sako, Chiharu ; Ghodasara, Satyam ; Bilello, Michel ; Mohan, Suyash ; Vollmuth, Philipp ; Brugnara, Gianluca ; Jayachandran Preetha, Chandrakanth ; Sahm, Felix ; Maier-Hein, Klaus ; Zenk, Maximilian ; Bendszus, Martin ; Wick, Wolfgang ; Calabrese, Evan ; Rudie, Jeffrey ; Villanueva-Meyer, Javier ; Cha, Soonmee ; Ingalhalikar, Madhura ; Jadhav, Manali ; Pandey, Umang ; Saini, Jitender ; Garrett, John ; Larson, Matthew ; Jeraj, Robert ; Currie, Stuart ; Frood, Russell ; Fatania, Kavi ; Huang, Raymond Y. ; Chang, Ken ; Balaña, Carmen ; Capellades, Jaume ; Puig, Josep ; Trenkler, Johannes ; Pichler, Josef ; Necker, Georg ; Haunschmidt, Andreas ; Meckel, Stephan ; Shukla, Gaurav ; Liem, Spencer ; Alexander, Gregory S. ; Lombardo, Joseph ; Palmer, Joshua D. ; Flanders, Adam E. ; Dicker, Adam P. ; Sair, Haris I. ; Jones, Craig K. ; Venkataraman, Archana ; Jiang, Meirui ; So, Tiffany Y. ; Chen, Cheng ; Heng, Pheng Ann ; Dou, Qi ; Kozubek, Michal ; Lux, Filip ; Michálek, Jan ; Matula, Petr ; Keřkovský, Miloš ; Kopřivová, Tereza ; Dostál, Marek ; Vybíhal, Václav ; Vogelbaum, Michael A. ; Mitchell, J. Ross ; Farinhas, Joaquim ; Maldjian, Joseph A. ; Bangalore Yogananda, Chandan Ganesh ; Pinho, Marco C. ; Reddy, Divya ; Holcomb, James ; Wagner, Benjamin C. ; Ellingson, Benjamin M. ; Cloughesy, Timothy F. ; Raymond, Catalina ; Oughourlian, Talia ; Hagiwara, Akifumi ; Wang, Chencai ; To, Minh-Son ; Bhardwaj, Sargam ; Chong, Chee ; Agzarian, Marc ; Falcão, Alexandre Xavier ; Martins, Samuel B. ; Teixeira, Bernardo Corrêa de Almeida ; Sprenger, Flávia ; Menotti, David ; Lucio, Diego R. ; LaMontagne, Pamela ; Marcus, Daniel ; Wiestler, Benedikt ; Kofler, Florian ; Ezhov, Ivan ; Metz, Marie ; Jain, Rajan ; Lee, Matthew ; Lui, Yvonne W. ; McKinley, Richard ; Slotboom, Johannes ; Radojewski, Piotr ; Meier, Raphael ; Wiest, Roland Gerhard Rudi ; Murcia, Derrick ; Fu, Eric ; Haas, Rourke ; Thompson, John ; Ormond, David Ryan ; Badve, Chaitra ; Sloan, Andrew E. ; Vadmal, Vachan ; Waite, Kristin ; Colen, Rivka R. ; Pei, Linmin ; Ak, Murat ; Srinivasan, Ashok ; Bapuraj, Jayapalli Rajiv ; Rao, Arvind ; Wang, Nicholas ; Yoshiaki, Ota ; Moritani, Toshio ; Turk, Sevcan ; Lee, Joonsang ; Prabhudesai, Snehal ; Morón, Fanny ; Mandel, Jacob ; Kamnitsas, Konstantinos ; Glocker, Ben ; Dixon, Luke V. M. ; Williams, Matthew ; Zampakis, Peter ; Panagiotopoulos, Vasileios ; Tsiganos, Panagiotis ; Alexiou, Sotiris ; Haliassos, Ilias ; Zacharaki, Evangelia I. ; Moustakas, Konstantinos ; Kalogeropoulou, Christina ; Kardamakis, Dimitrios M. ; Choi, Yoon Seong ; Lee, Seung-Koo ; Chang, Jong Hee ; Ahn, Sung Soo ; Luo, Bing ; Poisson, Laila ; Wen, Ning ; Tiwari, Pallavi ; Verma, Ruchika ; Bareja, Rohan ; Yadav, Ipsa ; Chen, Jonathan ; Kumar, Neeraj ; Smits, Marion ; Voort, Sebastian R. van der ; Alafandi, Ahmed ; Incekara, Fatih ; Wijnenga, Maarten M. J. ; Kapsas, Georgios ; Gahrmann, Renske ; Schouten, Joost W. ; Dubbink, Hendrikus J. ; Vincent, Arnaud J. P. E. ; Van den Bent, Martin J. ; French, Pim J. ; Klein, Stefan ; Yuan, Yading ; Sharma, Sonam ; Tseng, Tzu-Chi ; Adabi, Saba ; Niclou, Simone P. ; Keunen, Olivier ; Hau, Ann-Christin ; Vallières, Martin ; Fortin, David ; Lepage, Martin ; Landman, Bennett ; Ramadass, Karthik ; Xu, Kaiwen ; Chotai, Silky ; Chambless, Lola B. ; Mistry, Akshitkumar ; Thompson, Reid C. ; Gusev, Yuriy ; Bhuvaneshwar, Krithika ; Sayah, Anousheh ; Bencheqroun, Camelia ; Belouali, Anas ; Madhavan, Subha ; Booth, Thomas C. ; Chelliah, Alysha ; Modat, Marc ; Shuaib, Haris ; Dragos, Carmen ; Abayazeed, Aly ; Kolodziej, Kenneth ; Hill, Michael ; Abbassy, Ahmed ; Gamal, Shady ; Mekhaimar, Mahmoud ; Qayati, Mohamed ; Reyes, Mauricio ; Park, Ji Eun ; Yun, Jihye ; Kim, Ho Sung ; Mahajan, Abhishek ; Muzi, Mark ; Benson, Sean ; Beets-Tan, Regina G. H. ; Teuwen, Jonas ; Herrera-Trujillo, Alejandro ; Trujillo, Maria ; Escobar, William ; Abello, Ana Lorena ; Bernal, Jose ; Gómez, Jhon ; Choi, Joseph ; Baek, Stephen ; Kim, Yusung ; Ismael, Heba ; Allen, Bryan ; Buatti, John M. ; Kotrotsou, Aikaterini ; Li, Hongwei ; Weiss, Tobias ; Weller, Michael ; Bink, Andrea ; Pouymayou, Bertrand ; Shaykh, Hassan F. ; Saltz, Joel ; Prasanna, Prateek ; Shrestha, Sampurna ; Mani, Kartik M. ; Payne, David ; Kurc, Tahsin ; Pelaez, Enrique ; Franco-Maldonado, Heydy ; Loayza, Francis ; Quevedo Sacoto, Andrés Sebastián ; Guevara, Pamela ; Torche, Esteban ; Mendoza, Cristobal ; Vera, Franco ; Ríos, Elvis ; López, Eduardo ; Velastin, Sergio Alejandro ; Ogbole, Godwin ; Soneye, Mayowa ; Oyekunle, Dotun ; Odafe-Oyibotha, Olubunmi ; Osobu, Babatunde ; Shu’aibu, Mustapha ; Dorcas, Adeleye ; Dako, Farouk ; Simpson, Amber L. ; Hamghalam, Mohammad ; Peoples, Jacob J. ; Hu, Ricky ; Tran, Anh ; Cutler, Danielle ; Moraes, Fabio Y. ; Boss, Michael A. ; Gimpel, James ; Kattil Veettil, Deepak ; Schmidt, Kendall ; Bialecki, Brian ; Marella, Sailaja ; Price, Cynthia ; Cimino, Lisa ; Apgar, Charles ; Shah, Prashant ; Menze, Bjoern Holger ; Barnholtz-Sloan, Jill S. ; Martin, Jason ; Bakas, Spyridon
Pati, Sarthak ; Baid, Ujjwal ; Edwards, Brandon ; Sheller, Micah ; Wang, Shih-Han ; Reina, G. Anthony ; Foley, Patrick ; Gruzdev, Alexey ; Karkada, Deepthi ; Davatzikos, Christos ; Sako, Chiharu ; Ghodasara, Satyam ; Bilello, Michel ; Mohan, Suyash ; Vollmuth, Philipp ; Brugnara, Gianluca ; Jayachandran Preetha, Chandrakanth ; Sahm, Felix ; Maier-Hein, Klaus ; Zenk, Maximilian ; Bendszus, Martin ; Wick, Wolfgang ; Calabrese, Evan ; Rudie, Jeffrey ; Villanueva-Meyer, Javier ; Cha, Soonmee ; Ingalhalikar, Madhura ; Jadhav, Manali ; Pandey, Umang ; Saini, Jitender ; Garrett, John ; Larson, Matthew ; Jeraj, Robert ; Currie, Stuart ; Frood, Russell ; Fatania, Kavi ; Huang, Raymond Y. ; Chang, Ken ; Balaña, Carmen ; Capellades, Jaume ; Puig, Josep ; Trenkler, Johannes ; Pichler, Josef ; Necker, Georg ; Haunschmidt, Andreas ; Meckel, Stephan ; Shukla, Gaurav ; Liem, Spencer ; Alexander, Gregory S. ; Lombardo, Joseph ; Palmer, Joshua D. ; Flanders, Adam E. ; Dicker, Adam P. ; Sair, Haris I. ; Jones, Craig K. ; Venkataraman, Archana ; Jiang, Meirui ; So, Tiffany Y. ; Chen, Cheng ; Heng, Pheng Ann ; Dou, Qi ; Kozubek, Michal ; Lux, Filip ; Michálek, Jan ; Matula, Petr ; Keřkovský, Miloš ; Kopřivová, Tereza ; Dostál, Marek ; Vybíhal, Václav ; Vogelbaum, Michael A. ; Mitchell, J. Ross ; Farinhas, Joaquim ; Maldjian, Joseph A. ; Bangalore Yogananda, Chandan Ganesh ; Pinho, Marco C. ; Reddy, Divya ; Holcomb, James ; Wagner, Benjamin C. ; Ellingson, Benjamin M. ; Cloughesy, Timothy F. ; Raymond, Catalina ; Oughourlian, Talia ; Hagiwara, Akifumi ; Wang, Chencai ; To, Minh-Son ; Bhardwaj, Sargam ; Chong, Chee ; Agzarian, Marc ; Falcão, Alexandre Xavier ; Martins, Samuel B. ; Teixeira, Bernardo Corrêa de Almeida ; Sprenger, Flávia ; Menotti, David ; Lucio, Diego R. ; LaMontagne, Pamela ; Marcus, Daniel ; Wiestler, Benedikt ; Kofler, Florian ; Ezhov, Ivan ; Metz, Marie ; Jain, Rajan ; Lee, Matthew ; Lui, Yvonne W. ; McKinley, Richard ; Slotboom, Johannes ; Radojewski, Piotr ; Meier, Raphael ; Wiest, Roland Gerhard Rudi ; Murcia, Derrick ; Fu, Eric ; Haas, Rourke ; Thompson, John ; Ormond, David Ryan ; Badve, Chaitra ; Sloan, Andrew E. ; Vadmal, Vachan ; Waite, Kristin ; Colen, Rivka R. ; Pei, Linmin ; Ak, Murat ; Srinivasan, Ashok ; Bapuraj, Jayapalli Rajiv ; Rao, Arvind ; Wang, Nicholas ; Yoshiaki, Ota ; Moritani, Toshio ; Turk, Sevcan ; Lee, Joonsang ; Prabhudesai, Snehal ; Morón, Fanny ; Mandel, Jacob ; Kamnitsas, Konstantinos ; Glocker, Ben ; Dixon, Luke V. M. ; Williams, Matthew ; Zampakis, Peter ; Panagiotopoulos, Vasileios ; Tsiganos, Panagiotis ; Alexiou, Sotiris ; Haliassos, Ilias ; Zacharaki, Evangelia I. ; Moustakas, Konstantinos ; Kalogeropoulou, Christina ; Kardamakis, Dimitrios M. ; Choi, Yoon Seong ; Lee, Seung-Koo ; Chang, Jong Hee ; Ahn, Sung Soo ; Luo, Bing ; Poisson, Laila ; Wen, Ning ; Tiwari, Pallavi ; Verma, Ruchika ; Bareja, Rohan ; Yadav, Ipsa ; Chen, Jonathan ; Kumar, Neeraj ; Smits, Marion ; Voort, Sebastian R. van der ; Alafandi, Ahmed ; Incekara, Fatih ; Wijnenga, Maarten M. J. ; Kapsas, Georgios ; Gahrmann, Renske ; Schouten, Joost W. ; Dubbink, Hendrikus J. ; Vincent, Arnaud J. P. E. ; Van den Bent, Martin J. ; French, Pim J. ; Klein, Stefan ; Yuan, Yading ; Sharma, Sonam ; Tseng, Tzu-Chi ; Adabi, Saba ; Niclou, Simone P. ; Keunen, Olivier ; Hau, Ann-Christin ; Vallières, Martin ; Fortin, David ; Lepage, Martin ; Landman, Bennett ; Ramadass, Karthik ; Xu, Kaiwen ; Chotai, Silky ; Chambless, Lola B. ; Mistry, Akshitkumar ; Thompson, Reid C. ; Gusev, Yuriy ; Bhuvaneshwar, Krithika ; Sayah, Anousheh ; Bencheqroun, Camelia ; Belouali, Anas ; Madhavan, Subha ; Booth, Thomas C. ; Chelliah, Alysha ; Modat, Marc ; Shuaib, Haris ; Dragos, Carmen ; Abayazeed, Aly ; Kolodziej, Kenneth ; Hill, Michael ; Abbassy, Ahmed ; Gamal, Shady ; Mekhaimar, Mahmoud ; Qayati, Mohamed ; Reyes, Mauricio ; Park, Ji Eun ; Yun, Jihye ; Kim, Ho Sung ; Mahajan, Abhishek ; Muzi, Mark ; Benson, Sean ; Beets-Tan, Regina G. H. ; Teuwen, Jonas ; Herrera-Trujillo, Alejandro ; Trujillo, Maria ; Escobar, William ; Abello, Ana Lorena ; Bernal, Jose ; Gómez, Jhon ; Choi, Joseph ; Baek, Stephen ; Kim, Yusung ; Ismael, Heba ; Allen, Bryan ; Buatti, John M. ; Kotrotsou, Aikaterini ; Li, Hongwei ; Weiss, Tobias ; Weller, Michael ; Bink, Andrea ; Pouymayou, Bertrand ; Shaykh, Hassan F. ; Saltz, Joel ; Prasanna, Prateek ; Shrestha, Sampurna ; Mani, Kartik M. ; Payne, David ; Kurc, Tahsin ; Pelaez, Enrique ; Franco-Maldonado, Heydy ; Loayza, Francis ; Quevedo Sacoto, Andrés Sebastián ; Guevara, Pamela ; Torche, Esteban ; Mendoza, Cristobal ; Vera, Franco ; Ríos, Elvis ; López, Eduardo ; Velastin, Sergio Alejandro ; Ogbole, Godwin ; Soneye, Mayowa ; Oyekunle, Dotun ; Odafe-Oyibotha, Olubunmi ; Osobu, Babatunde ; Shu’aibu, Mustapha ; Dorcas, Adeleye ; Dako, Farouk ; Simpson, Amber L. ; Hamghalam, Mohammad ; Peoples, Jacob J. ; Hu, Ricky ; Tran, Anh ; Cutler, Danielle ; Moraes, Fabio Y. ; Boss, Michael A. ; Gimpel, James ; Kattil Veettil, Deepak ; Schmidt, Kendall ; Bialecki, Brian ; Marella, Sailaja ; Price, Cynthia ; Cimino, Lisa ; Apgar, Charles ; Shah, Prashant ; Menze, Bjoern Holger ; Barnholtz-Sloan, Jill S. ; Martin, Jason ; Bakas, Spyridon
Stenzinger, Albrecht ; Endris, Volker ; Pfarr, Nicole ; Andrulis, Mindaugas ; Jöhrens, Korinna ; Klauschen, Frederick ; Siebolts, Udo ; Wolf, Thomas ; Koch, Philipp-Sebastian ; Schulz, Miriam ; Hartschuh, Wolfgang ; Goerdt, Sergij ; Lennerz, Jochen K. ; Wickenhauser, Claudia ; Klapper, Wolfram ; Anagnostopoulos, Ioannis ; Weichert, Wilko
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.
Thomas, Anita ; Slade, Kimberly Sue ; Blaheta, Roman A. ; Markowitsch, Sascha Dennis ; Stenzel, Philipp J. ; Tagscherer, Katrin ; Roth, Wilfried ; Schindeldecker, Mario ; Michaelis, Martin ; Rothweiler, Florian ; Cinatl, Jaroslav ; Dotzauer, Robert Hans ; Vakhrusheva, Olesya ; Albersen, Maarten ; Haferkamp, Axel ; Jüngel, Eva ; Cinatl, Jindrich ; Tsaur, Igor
Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular elements may have prognostic and therapeutic utility in PeCa. Formalin-fixed, paraffin-embedded tumor tissue from therapy-naïve patients with invasive PeCa was used for tissue microarray (TMA) analysis. Immunohistochemical staining was performed to determine the expression of the proteins c-MET, PPARg, β-catenin, snail, survivin, and n-MYC. In total, 94 PeCa patients with available tumor tissue were included. The median age was 64.9 years. High-grade tumors were present in 23.4%, and high-risk HPV was detected in 25.5%. The median follow-up was 32.5 months. High expression of snail was associated with HPV-positive tumors. Expression of β-catenin was inversely associated with grading. In both univariate COX regression analysis and the log-rank test, an increased expression of PPARg and c-MET was predictive of inferior disease-specific survival (DSS). Moreover, in multivariate analysis, a higher expression of c-MET was independently associated with worse DSS. Blocking c-MET with cabozantinib and tivantinib induced a significant decrease in viability in the primary PeCa cell line UKF-PeC3 isolated from the tumor tissue as well as in cisplatin- and osimertinib-resistant sublines. Strikingly, a higher sensitivity to tivantinib could be detected in the latter, pointing to the promising option of utilizing this agent in the second-line treatment setting.
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.