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Item Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment(NATURE RESEARCH, 2020-01-01) Chng, Kern Rei; Li, Chenhao; Bertrand, Denis; Ng, Amanda Hui Qi; Kwah, Junmei Samantha; Low, Hwee Meng; Tong, Chengxuan; Natrajan, Maanasa; Zhang, Michael Hongjie; Xu, Licheng; Ko, Karrie Kwan Ki; Ho, Eliza Xin Pei; Av-Shalom V, Tamar; Teo, Jeanette Woon Pei; Khor, Chiea Chuen; Chen, Swaine L.; Mason, Christopher E.; Ng, Oon Tek; Marimuthu, Kalisvar; Ang, Brenda; Nagarajan, Niranjan; Danko, David; Bezdan, Daniela; Afshinnekoo, Ebrahim; Ahsanuddin, Sofia; Bhattacharya, Chandrima; Butler, Daniel J.; De Filippis, Francesca; Hecht, Jochen; Kahles, Andre; Karasikov, Mikhail; Kyrpides, Nikos C.; Leung, Marcus H. Y.; Meleshko, Dmitry; Mustafa, Harun; Mutai, Beth; Neches, Russell Y.; Ng, Amanda; Nieto-Caballero, Marina; Nikolayeva, Olga; Nikolayeva, Tatyana; Png, Eileen; Sanchez, Jorge L.; Shaaban, Heba; Sierra, Maria A.; Tong, Xinzhao; Young, Ben; Alicea, Josue; Bhattacharyya, Malay; Blekhman, Ran; Castro-Nallar, Eduardo; Canas, Ana M.; Chatziefthimiou, Aspassia D.; Crawford, Robert W.; Deng, Youping; Desnues, Christelle; Dias-Neto, Emmanuel; Donnellan, Daisy; Dybwad, Marius; Elhaik, Eran; Ercolini, Danilo; Frolova, Alina; Graf, Alexandra B.; Green, David C.; Hajirasouliha, Iman; Hernandez, Mark; Iraola, Gregorio; Jang, Soojin; Jones, Angela; Kelly, Frank J.; Knights, Kaymisha; Labaj, Pawel P.; Lee, Patrick K. H.; Shawn, Levy; Ljungdahl, Per; Lyons, Abigail; Mason-Buck, Gabriella; McGrath, Ken; Mongodin, Emmanuel F.; Moraes, Milton Ozorio; Noushmehr, Houtan; Oliveira, Manuela; Ossowski, Stephan; Osuolale, Olayinka O.; Ozcan, Orhan; Paez-Espino, David; Rascovan, Nicolas; Richard, Hugues; Raetsch, Gunnar; Schriml, Lynn M.; Semmler, Torsten; Sezerman, Osman U.; Shi, Leming; Song, Le Huu; Suzuki, Haruo; Court, Denise Syndercombe; Thomas, Dominique; Tighe, Scott W.; Udekwu I, Klas; Ugalde, Juan A.; Valentine, Brandon; Vassilev I, Dimitar; Vayndorf, Elena; Velavan, Thirumalaisamy P.; Zambrano, Maria M.; Zhu, Jifeng; Zhu, Sibo; Consortium, MetaSU. B.Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60\% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.Item Multi-center real-world comparison of the fully automated Idylla (TM) microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer(SPRINGER, 2021-01-01) Velasco, Ana; Tokat, Fatma; Bonde, Jesper; Trim, Nicola; Bauer, Elisabeth; Meeney, Adam; de Leng, Wendy; Chong, George; Dalstein, Veronique; Kis, Lorand L.; Lorentzen, Jon A.; Tomic, Snjezana; Thwaites, Keeley; Putzova, Martina; Birnbaum, Astrid; Qazi, Romena; Primmer, Vanessa; Dockhorn-Dworniczak, Barbara; Hernandez-Losa, Javier; Soares, Fernando A.; Gertler, Asaf A.; Kalman, Michal; Wong, Chris; Carraro, Dirce M.; Sousa, Ana C.; Reis, Rui M.; Fox, Stephen B.; Fassan, Matteo; Brevet, Marie; Merkelbach-Bruse, Sabine; Colling, Richard; Soilleux, Elizabeth; Teo, Ryan Yee Wei; D'Haene, Nicky; Nolet, Serge; Ristimaki, Ari; Vaisanen, Timo; Chapusot, Caroline; Soruri, Afsaneh; Unger, Tina; Wecgowiec, Johanna; Biscuola, Michele; Frattini, Milo; Long, Anna; Campregher V, Paulo; Matias-Guiu, XavierMicrosatellite instability (MSI) is present in 15-20\% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla (TM) MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla (TM) testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla (TM) results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla (TM) MSI Assay were equally distributed over the seven biomarkers, and 84.48\% of the MSI-high samples had >= 5 mutated biomarkers, while 98.25\% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla (TM) MSI Assay and immunohistochemistry was 96.39\% (988/1025)Item Current state of the art and recommendations in robotic mitral valve surgery(OXFORD UNIV PRESS, 2022-01-01) Palmen, Meindert; Navarra, Emiliano; Bonatti, Johannes; Franke, Ulrich; Cerny, Stepan; Musumeci, Francesco; Modi, Paul; Singh, Sandeep; Sandoval, Elena; Pettinari, Matteo; Segers, Patrique; Gianoli, Monica; van Praet, Frank; de Praetere, Herbert; Vojacek, Jan; Cebotaru, Theodor; Onan, Burak; Bolcal, Cengiz; Alhan, Cem; Ouda, Ahmed; Melly, Ludovic; Malapert, Ghislain; Labrousse, Louis; Agnino, Alfonso; Phillipsen, Tine; Jansens, Jean-Luc; Folliguet, Thierry; Suwalski, Piotr; Cathenis, Koen; Doguet, Fabien; Tomsic, Anton; Oosterlinck, Wouter; Pereda, DanielItem Robotic coronary revascularization in Europe, state of art and future of EACTS-endorsed Robotic Cardiothoracic Surgery Taskforce(OXFORD UNIV PRESS, 2022-01-01) Pettinari, Matto; Gianoli, Monica; Palmen, Meindert; Cerny, Stepan; Onan, Burak; Singh, Sandeep; Segers, Patrique; Bolcal, Cengiz; Alhan, Cem; Navarra, Emiliano; De Praetere, Herbert; Vojacek, Jan; Cebotaru, Theodor; Modi, Paul; Doguet, Fabien; Franke, Ulrich; Ouda, Ahmed; Melly, Ludovic; Malapert, Ghislain; Labrousse, Louis; Agnino, Alfonso; Philipsen, Tine; Jansens, Jean-Luc; Folliguet, Thierry; Pereda, Daniel; Musumeci, Francesco; Suwalski, Piotr; Cathenis, Koen; Van Praet, Frank; Bonatti, Johannes; Oosterlinck, Wouter; ERCTSItem Headache as the sole presenting symptom of cerebral venous sinuses thrombosis: Subgroup analysis of data from the VENOST study(KARE PUBL, 2021-01-01) Duman, Taskin; Cinar, Nilgun; Uluduz, Derya; Domac, Fusun Mayda; Ozturk, Serefnur; Yayla, Vildan; Karahan, Ali Yavuz; Afsar, Nazire; Sungur, Mehmet Ali; Goksu, Eylem Ozaydin; Yurekli, Vedat Ali; Genc, Hamit; Utku, Uygar; Sahin, Sevki; Tekeli, Hakan; Tokuc, Firdevs Ezgi; Uzuner, Nevzat; Senol, Mehmet Guney; Yilmaz, Arda; Gokce, Mustafa; Demirci, Seden; Kusbeci, Ozge Yilmaz; Uzuner, Gulnur Tekgol; Caglayan, Hale Zeynep Batur; Acikgoz, Mustafa; Kurucu, Hatice; Ozdag, Mehmet Fatih; Baybas, Sevim; Ekmekci, Hakan; Cabalar, Murat; Yaman, Mehmet; Bektas, Hesna; Kaplan, Yuksel; Goksel, Basak Karakurum; Milanlioglu, Aysel; Orken, Dilek Necioglu; Aluclu, Mehmet Ufuk; Colakoglu, Sena; Tufekci, Ahmet; Bakar, Mustafa; Nazliel, Bijen; Tascilar, Nida; Goksan, Baki; Kozak, Hasan Huseyin; Misirli, Cemile Handan; Kucukoglu, Hayriye; Midi, Ipek; Mengulluoglu, Necdet; Aytac, Emrah; Yesilot, Nilufer; Ince, Birsen; Yalin, Osman Ozgur; Gunes, Taskin; Oruc, Serdar; Demir, SerkanObjectives: Headache is the most common complaint in cerebral venous sinus thrombosis (CVST) and it may sometimes be the only symptom in these patients. This retrospective and prospective study was an investigation of any differences in terms of clinical risk factors, radiological findings, or prognosis in patients with CVST who presented with isolated headache (IH) and cases with other concomitant findings (non-isolated headache {[}NIH]). Methods: A total of 1144 patients from a multicenter study of cerebral venous sinus thrombosis ( VENOST study) were enrolled in this research. The demographic, biochemical, clinical, and radiological aspects of 287 IH cases and 857 NIH cases were compared. Results: There were twice as many women as men in the study group. In the IH group, when gender distribution was evaluated by age group, no statistically significant difference was found. The onset of headache was frequently subacute and chronic in the IH group, but an acute onset was more common in the NIH group. Other neurological findings were observed in 29\% of the IH group during follow-up. A previous history of deep, cerebral, or other venous thromboembolism was less common in the IH group than in the NIH group. Transverse sinus involvement was greater in the IH group, whereas sagittal sinus involvement was greater in the NIH group. The presence of a plasminogen activator inhibitor (PAI) mutation was significantly greater in the IH group. Conclusion: IH and CVST should be kept in mind if a patient has subacute or chronic headache. PAI, which has an important role in thrombolytic events, may be a risk factor in CVST. Detailed hematological investigations should be considered. Additional studies are needed.Item Image-guided breast biopsy and localisation: recommendations for information to women and referring physicians by the European Society of Breast Imaging(SPRINGEROPEN, 2020-01-01) Bick, Ulrich; Trimboli, Rubina M.; Athanasiou, Alexandra; Balleyguier, Corinne; Baltzer, Pascal A. T.; Bernathova, Maria; Borbely, Krisztina; Brkljacic, Boris; Carbonaro, Luca A.; Clauser, Paola; Cassano, Enrico; Colin, Catherine; Esen, Gul; Evans, Andrew; Fallenberg, Eva M.; Fuchsjaeger, Michael H.; Gilbert, Fiona J.; Helbich, Thomas H.; Heywang-Koebrunner, Sylvia H.; Herranz, Michel; Kinkel, Karen; Kilburn-Toppin, Fleur; Kuhl, Christiane K.; Lesaru, Mihai; Lobbes, Marc B. I.; Mann, Ritse M.; Martincich, Laura; Panizza, Pietro; Pediconi, Federica; Pijnappel, Ruud M.; Pinker, Katja; Schiaffino, Simone; Sella, Tamar; Thomassin-Naggara, Isabelle; Tardivon, Anne; Van Ongeval, Chantal; Wallis, Matthew G.; Zackrisson, Sophia; Forrai, Gabor; Herrero, Julia Camps; Sardanelli, Francesco; EUSOBI, European Soc Breast ImagingWe summarise here the information to be provided to women and referring physicians about percutaneous breast biopsy and lesion localisation under imaging guidance. After explaining why a preoperative diagnosis with a percutaneous biopsy is preferred to surgical biopsy, we illustrate the criteria used by radiologists for choosing the most appropriate combination of device type for sampling and imaging technique for guidance. Then, we describe the commonly used devices, from fine-needle sampling to tissue biopsy with larger needles, namely core needle biopsy and vacuum-assisted biopsy, and how mammography, digital breast tomosynthesis, ultrasound, or magnetic resonance imaging work for targeting the lesion for sampling or localisation. The differences among the techniques available for localisation (carbon marking, metallic wire, radiotracer injection, radioactive seed, and magnetic seed localisation) are illustrated. Type and rate of possible complications are described and the issue of concomitant antiplatelet or anticoagulant therapy is also addressed. The importance of pathological-radiological correlation is highlighted: when evaluating the results of any needle sampling, the radiologist must check the concordance between the cytology/pathology report of the sample and the radiological appearance of the biopsied lesion. We recommend that special attention is paid to a proper and tactful approach when communicating to the woman the need for tissue sampling as well as the possibility of cancer diagnosis, repeat tissue sampling, and or even surgery when tissue sampling shows a lesion with uncertain malignant potential (also referred to as ``high-risk{''} or B3 lesions). Finally, seven frequently asked questions are answered.Item Cerebral Venous Sinus Thrombosis in Women: Subgroup Analysis of the VENOST Study(HINDAWI LTD, 2020-01-01) Uluduz, Derya; Sahin, Sevki; Duman, Taskin; Ozturk, Serefnur; Yayla, Vildan; Afsar, Nazire; Uzuner, Nevzat; Midi, Ipek; Cinar, Nilgun; Sungur, Mehmet Ali; Domac, Fusun Mayda; Ince, Birsen; Goksan, Baki; Misirli, Cemile Handan; Bakar, Mustafa; Kozak, Hasan Huseyin; Colakoglu, Sena; Karahan, Ali Yavuz; Goksu, Eylem Ozaydin; Ozdag, Fatih; Senol, Mehmet Guney; Yurekli, Vedat Ali; Aluclu, Ufuk; Demir, Serkan; Kucukoglu, Hayriye; Oruc, Serdar; Yesilot, Nilufer; Kusbeci, Ozge Yimaz; Nazliel, Bijen; Tokuc, Firdevs Ezgi Ucan; Bektas, Hesna; Tascilar, Fatma Nida; Aytac, Emrah; Gokce, Mustafa; Caglayan, Hale Zeynep Batur; Tufekci, Ahmet; Uzuner, Gulnur; Orken, Dilek Necioglu; Yalin, Osman Ozgur; Utku, Uygar; Yilmaz, Arda; Genc, Hamit; Cabalar, Murat; Milanlioglu, Aysel; Ekmekci, Hakan; Zeydan, Burcu; Baybas, Sevim; Kablan, Yuksel; Goksel, Basak Karakurum; Acikgoz, Mustafa; Kurucu, Hatice; Demirci, Seden; Gunes, TaskinBackground. Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelaeItem Cytologic grading of primary malignant salivary gland tumors: A blinded review by an international panel(WILEY, 2020-01-01) Johnson, Daniel N.; Onenerk, Mine; Krane, Jeffrey F.; Rossi, Esther Diana; Baloch, Zubair; Barkan, Guliz; Bongiovanni, Massimo; Callegari, Fabiano; Canberk, Sule; Dixon, Glen; Field, Andrew; Griffith, Christopher C.; Jhala, Nirag; Jiang, Sara; Kurtycz, Daniel; Layfield, Lester; Lin, Oscar; Maleki, Zahra; Perez-Machado, Miguel; Pusztaszeri, Marc; Vielh, Philippe; Wang, He; Zarka, Matthew A.; Faquin, William C.Background Fine needle aspiration (FNA) is commonly used for the preoperative evaluation of salivary gland tumors. Tumor grade is a key factor influencing clinical management of salivary gland carcinomas (SGCs). To assess the ability to grade nonbasaloid SGCs in FNA specimens, an international panel of cytopathologists convened to review and score SGC cases. Methods The study cohort included 61 cases of primary SGC from the pathology archives of 3 tertiary medical centers. Cases from 2005 to 2016 were selected, scanned, and digitized. Nineteen cytopathologists blinded to the histologic diagnosis reviewed the digitized cytology slides and graded them as low, high, or indeterminate. The panelists' results were then compared to the tumor grades based on histopathologic examination of the corresponding resection specimens. Results All but 2 of the 19 (89.5\%) expert panelists review more than 20 salivary gland FNAs per yearItem Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study(TAYLOR \& FRANCIS LTD, 2022-01-01) Basoglu, Tugba; Sakin, Abdullah; Erol, Cihan; Ozden, Ercan; cabuk, Devrim; Cilbir, Ebru; Tataroglu ozyukseler, Deniz; Ayhan, Murat; Sendur, Mehmet Ali; Dogan, Mutlu; Oksuzoglu, Berna; Eryilmaz, Melek Karakurt; Er, Ozlem; Tasci, Elif Senocak; Ozyurt, Neslihan; Dulgar, Ozgecan; Ozen, Mirac; Hacibekiroglu, Ilhan; Oner, Irem; Bekmez, Esma Turkmen; Cagri Yildirim, Hasan; Yalcin, Suayib; Paydas, Semra; Yekeduz, Emre; Aksoy, Asude; Ozcelik, Melike; Oyman, Abdilkerim; Almuradova, Elvina; Karabulut, Bulent; Demir, Nazan; Dincer, Murat; Ozdemir, Nuriye; Erdem, Dilek; Ak, Naziye; Inal, Ali; Salim, Derya Kivrak; Deniz, Gulhan Ipek; Sakalar, Teoman; Gulmez, Ahmet; Kacan, Turgut; Ozdemir, Ozlem; Alan, Ozkan; Unal, Caglar; Karakas, Yusuf; Turhal, Serdar; Yumuk, Perran FuldenNeoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4\%), DCF (17.4\%) and ECF (8.1\%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2\%, R0 resection rate 86.4\%, and D2 dissection rate was 66.8\%. Rate of pCR and near-CR (24\%), and R0 resection (84\%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95\% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95\% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68\%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.Item A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer(NATURE PORTFOLIO, 2020-01-01) Wagner, Alex H.; Walsh, Brian; Mayfield, Georgia; Tamborero, David; Sonkin, Dmitriy; Krysiak, Kilannin; Deu-Pons, Jordi; Duren, Ryan P.; Gao, Jianjiong; McMurry, Julie; Patterson, Sara; Fitz, Catherine; Pitel, Beth A.; Sezerman, Ozman U.; Ellrott, Kyle; Warner, Jeremy L.; Rieke, Damian T.; Aittokallio, Tero; Cerami, Ethan; Ritter, Deborah I.; Schriml, Lynn M.; Freimuth, Robert R.; Haendel, Melissa; Raca, Gordana; Madhavan, Subha; Baudis, Michael; Beckmann, Jacques S.; Dienstmann, Rodrigo; Chakravarty, Debyani; Li, Xuan Shirley; Mockus, Susan; Elemento, Olivier; Schultz, Nikolaus; Lopez-Bigas, Nuria; Lawler, Mark; Goecks, Jeremy; Griffith, Malachi; Griffith, Obi L.; Margolin, Adam A.; Co, Variant Interpretation For CancPrecision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33\% per individual knowledgebase to 57\% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface () for exploring the harmonized interpretations from these six knowledgebases.