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Article ; Online: Exposure-response relationship of olaratumab for survival outcomes and safety when combined with doxorubicin in patients with soft tissue sarcoma.

Jones, Robin L / Mo, Gary / Baldwin, John R / Peterson, Patrick M / Ilaria, Robert L / Conti, Ilaria / Cronier, Damien M / Tap, William D

Cancer chemotherapy and pharmacology

2018 Volume 83, Issue 1, Page(s) 191–199

Abstract: Purpose: Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab ... ...

Abstract	Purpose: Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab exposure-response relationship for progression-free survival (PFS), overall survival (OS), and safety. Methods: PFS and OS data from the 133 patients enrolled in the phase 2 study were analysed using time-to-event modelling. The effect of olaratumab on PFS/OS was explored using the trough serum concentration after cycle 1 (C Results: PFS and OS were described by models with an exponential hazard function and inhibitory E Conclusions: PFS/OS benefits occurred without a rate change in TEAEs across quartiles. Maximum benefit in OS was achieved in the upper three quartiles and a potential of early disease progression in the lower quartile of olaratumab serum exposure. These results prompted a loading dose strategy in the ongoing phase 3 STS trial.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Doxorubicin/administration & dosage ; Follow-Up Studies ; Humans ; Prognosis ; Sarcoma/drug therapy ; Sarcoma/mortality ; Sarcoma/pathology ; Survival Rate
Chemical Substances	Antibodies, Monoclonal ; Doxorubicin (80168379AG) ; olaratumab (TT6HN20MVF)
Language	English
Publishing date	2018-11-08
Publishing country	Germany
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-018-3723-4
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Zs.A 1420: Show issues

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Article ; Online: Population Pharmacokinetic Modeling of Olaratumab, an Anti-PDGFRα Human Monoclonal Antibody, in Patients with Advanced and/or Metastatic Cancer.

Mo, Gary / Baldwin, John R / Luffer-Atlas, Debra / Ilaria, Robert L / Conti, Ilaria / Heathman, Michael / Cronier, Damien M

Clinical pharmacokinetics

2017 Volume 57, Issue 3, Page(s) 355–365

Abstract: Background and objectives: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for ... ...

Abstract	Background and objectives: Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population. Methods: Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and gastrointestinal stromal tumors) as a single agent or in combination with chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM Results: The PKs of olaratumab were best described by a two-compartment PK model with linear clearance (CL). Patient body weight was found to have a significant effect on both CL and central volume of distribution (V Conclusion: The PKs of olaratumab were best described by a model with linear disposition. Patient body weight and tumor size were found to be significant covariates. The PKs of olaratumab were not affected by immunogenicity or chemotherapeutic agents.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacokinetics ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics ; Body Weight ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Doxorubicin/administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/pathology ; Nonlinear Dynamics ; Receptor, Platelet-Derived Growth Factor alpha/antagonists & inhibitors ; Survival Rate ; Time Factors ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; Doxorubicin (80168379AG) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1) ; olaratumab (TT6HN20MVF)
Language	English
Publishing date	2017-08-07
Publishing country	Switzerland
Document type	Clinical Trial, Phase II ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-017-0562-0
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Zs.A 1246: Show issues

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Article ; Online: Tasisulam sodium (LY573636 sodium) as third-line treatment in patients with unresectable, metastatic non-small-cell lung cancer: a phase-II study.

Scagliotti, Giorgio V / Ilaria, Robert / Novello, Silvia / von Pawel, J / Fischer, Juergen R / Ermisch, Sabine / de Alwis, Dinesh P / Andrews, Joan / Reck, Martin / Crino, Lucio / Eschbach, Corinna / Manegold, Christian

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2012 Volume 7, Issue 6, Page(s) 1053–1057

Abstract: Introduction: Tasisulam sodium (hereafter referred to as tasisulam) is a novel anticancer compound that induces apoptosis and exhibits antiangiogenesis activity in a broad range of cancer models, including non-small-cell lung cancer (NSCLC).: Methods!# ...

Abstract	Introduction: Tasisulam sodium (hereafter referred to as tasisulam) is a novel anticancer compound that induces apoptosis and exhibits antiangiogenesis activity in a broad range of cancer models, including non-small-cell lung cancer (NSCLC). Methods: Tasisulam was administered as a 2-hour infusion every 21 days as third-line treatment in patients with advanced (stage IIIB/IV) NSCLC. Results: Thirty-two patients received a Cmax target dose of 420 µg/ml. Median time to progression was 3.12 months, median progression-free survival was 2.69 months, and median overall survival was 8.48 months. There were no objective responses; 43.8% of patients achieved stable disease. A high rate of grade-4 hematologic toxicity in the first 30 patients led to exploration of a lower Cmax target dose of 380 µg/ml. The rate of grade-4 hematologic toxicity (thrombocytopenia and/or neutropenia) at the 380-µg/ml dose (n = 20) was 20% versus 34% at the 420-µg/ml dose. Conclusions: Tasisulam has only modest activity as a third-line treatment of patients with unresectable/metastatic NSCLC. The high rate of grade-4 hematologic toxicity observed with this highly albumin- bound compound in this patient population provided challenges for fixed Cmax-based dosing. Alternative dosing methods, including varying the Cmax target dose by predose albumin, are under investigation in other studies.
MeSH term(s)	Adult ; Aged ; Benzamides/administration & dosage ; Benzamides/therapeutic use ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/secondary ; Contraindications ; Disease-Free Survival ; Female ; Follow-Up Studies ; Germany/epidemiology ; Humans ; Italy/epidemiology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; Retrospective Studies ; Sulfonamides/administration & dosage ; Sulfonamides/therapeutic use ; Treatment Outcome
Chemical Substances	Benzamides ; N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide ; Sulfonamides
Language	English
Publishing date	2012-06
Publishing country	United States
Document type	Clinical Trial, Phase II ; Comparative Study ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1097/JTO.0b013e3182519d79
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Zs.A 6664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 652: Show issues

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Article ; Online: Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120.

Chen, Shih-Hsun / Zhang, Youyan / Van Horn, Robert D / Yin, Tinggui / Buchanan, Sean / Yadav, Vipin / Mochalkin, Igor / Wong, Swee Seong / Yue, Yong Gang / Huber, Lysiane / Conti, Ilaria / Henry, James R / Starling, James J / Plowman, Gregory D / Peng, Sheng-Bin

Cancer discovery

2016 Volume 6, Issue 3, Page(s) 300–315

Abstract: Unlabelled: We have identified previously undiscovered BRAF in-frame deletions near the αC-helix region of the kinase domain in pancreatic, lung, ovarian, and thyroid cancers. These deletions are mutually exclusive with KRAS mutations and occur in 4.21% ...

Abstract	Unlabelled: We have identified previously undiscovered BRAF in-frame deletions near the αC-helix region of the kinase domain in pancreatic, lung, ovarian, and thyroid cancers. These deletions are mutually exclusive with KRAS mutations and occur in 4.21% of KRAS wild-type pancreatic cancer. siRNA knockdown in cells harboring BRAF deletions showed that the MAPK activity and cell growth are BRAF dependent. Structurally, the BRAF deletions are predicted to shorten the β3/αC-helix loop and hinder its flexibility by locking the helix in the active αC-helix-in conformation that favors dimer formation. Expression of L485-P490-deleted BRAF is able to transform NIH/3T3 cells in a BRAF dimer-dependent manner. BRAF homodimer is confirmed to be the dominant RAF dimer by proximity ligation assays in BRAF deletion cells, which are resistant to the BRAF inhibitor vemurafenib and sensitive to LY3009120, a RAF dimer inhibitor. In tumor models with BRAF deletions, LY3009120 has shown tumor growth regression, whereas vemurafenib is inactive. Significance: This study discovered oncogenic BRAF deletions with a distinct activation mechanism dependent on the BRAF dimer formation in tumor cells. LY3009120 is active against these cells and represents a potential treatment option for patients with cancer with these BRAF deletions, or other atypical BRAF mutations where BRAF functions as a dimer.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Ectopic Gene Expression ; Gene Deletion ; Gene Expression ; Humans ; MAP Kinase Signaling System ; Mice ; Models, Molecular ; Phenylurea Compounds/pharmacology ; Protein Conformation ; Protein Interaction Domains and Motifs/genetics ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Protein Multimerization ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/chemistry ; Proto-Oncogene Proteins B-raf/genetics ; Pyrimidines/pharmacology ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; LY3009120 ; Phenylurea Compounds ; Protein Kinase Inhibitors ; Pyrimidines ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-15-0896
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Zs.A 6916: Show issues

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Article ; Online: The genomic landscape of pediatric acute lymphoblastic leukemia.

Brady, Samuel W / Roberts, Kathryn G / Gu, Zhaohui / Shi, Lei / Pounds, Stanley / Pei, Deqing / Cheng, Cheng / Dai, Yunfeng / Devidas, Meenakshi / Qu, Chunxu / Hill, Ashley N / Payne-Turner, Debbie / Ma, Xiaotu / Iacobucci, Ilaria / Baviskar, Pradyuamna / Wei, Lei / Arunachalam, Sasi / Hagiwara, Kohei / Liu, Yanling /

Flasch, Diane A / Liu, Yu / Parker, Matthew / Chen, Xiaolong / Elsayed, Abdelrahman H / Pathak, Omkar / Li, Yongjin / Fan, Yiping / Michael, J Robert / Rusch, Michael / Wilkinson, Mark R / Foy, Scott / Hedges, Dale J / Newman, Scott / Zhou, Xin / Wang, Jian / Reilly, Colleen / Sioson, Edgar / Rice, Stephen V / Pastor Loyola, Victor / Wu, Gang / Rampersaud, Evadnie / Reshmi, Shalini C / Gastier-Foster, Julie / Guidry Auvil, Jaime M / Gesuwan, Patee / Smith, Malcolm A / Winick, Naomi / Carroll, Andrew J / Heerema, Nyla A / Harvey, Richard C / Willman, Cheryl L / Larsen, Eric / Raetz, Elizabeth A / Borowitz, Michael J / Wood, Brent L / Carroll, William L / Zweidler-McKay, Patrick A / Rabin, Karen R / Mattano, Leonard A / Maloney, Kelly W / Winter, Stuart S / Burke, Michael J / Salzer, Wanda / Dunsmore, Kimberly P / Angiolillo, Anne L / Crews, Kristine R / Downing, James R / Jeha, Sima / Pui, Ching-Hon / Evans, William E / Yang, Jun J / Relling, Mary V / Gerhard, Daniela S / Loh, Mignon L / Hunger, Stephen P / Zhang, Jinghui / Mullighan, Charles G

Nature genetics

2022 Volume 54, Issue 9, Page(s) 1376–1389

Abstract: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of ...

Abstract	Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4- and KMT2A-rearranged subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes.
MeSH term(s)	Child ; Chromosome Aberrations ; Exome/genetics ; Genomics ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
Language	English
Publishing date	2022-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-022-01159-z
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers.

Peng, Sheng-Bin / Henry, James R / Kaufman, Michael D / Lu, Wei-Ping / Smith, Bryan D / Vogeti, Subha / Rutkoski, Thomas J / Wise, Scott / Chun, Lawrence / Zhang, Youyan / Van Horn, Robert D / Yin, Tinggui / Zhang, Xiaoyi / Yadav, Vipin / Chen, Shih-Hsun / Gong, Xueqian / Ma, Xiwen / Webster, Yue / Buchanan, Sean /

Mochalkin, Igor / Huber, Lysiane / Kays, Lisa / Donoho, Gregory P / Walgren, Jennie / McCann, Denis / Patel, Phenil / Conti, Ilaria / Plowman, Gregory D / Starling, James J / Flynn, Daniel L

Cancer cell

2015 Volume 28, Issue 3, Page(s) 384–398

Abstract: LY3009120 is a pan-RAF and RAF dimer inhibitor that inhibits all RAF isoforms and occupies both protomers in RAF dimers. Biochemical and cellular analyses revealed that LY3009120 inhibits ARAF, BRAF, and CRAF isoforms with similar affinity, while ... ...

Abstract	LY3009120 is a pan-RAF and RAF dimer inhibitor that inhibits all RAF isoforms and occupies both protomers in RAF dimers. Biochemical and cellular analyses revealed that LY3009120 inhibits ARAF, BRAF, and CRAF isoforms with similar affinity, while vemurafenib or dabrafenib have little or modest CRAF activity compared to their BRAF activities. LY3009120 induces BRAF-CRAF dimerization but inhibits the phosphorylation of downstream MEK and ERK, suggesting that it effectively inhibits the kinase activity of BRAF-CRAF heterodimers. Further analyses demonstrated that LY3009120 also inhibits various forms of RAF dimers including BRAF or CRAF homodimers. Due to these unique properties, LY3009120 demonstrates minimal paradoxical activation, inhibits MEK1/2 phosphorylation, and exhibits anti-tumor activities across multiple models carrying KRAS, NRAS, or BRAF mutation.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Dimerization ; Humans ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/genetics ; Mitogen-Activated Protein Kinases/genetics ; Mutation/drug effects ; Mutation/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics ; Phenylurea Compounds/pharmacology ; Phosphorylation/drug effects ; Phosphorylation/genetics ; Protein Isoforms/antagonists & inhibitors ; Protein Isoforms/genetics ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins c-raf/genetics ; Pyrimidines/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; ras Proteins/genetics
Chemical Substances	Antineoplastic Agents ; LY3009120 ; Phenylurea Compounds ; Protein Isoforms ; Protein Kinase Inhibitors ; Pyrimidines ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Proto-Oncogene Proteins c-raf (EC 2.7.11.1) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2015-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2015.08.002
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

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Article ; Online: Gut microbiota density influences host physiology and is shaped by host and microbial factors.

Contijoch, Eduardo J / Britton, Graham J / Yang, Chao / Mogno, Ilaria / Li, Zhihua / Ng, Ruby / Llewellyn, Sean R / Hira, Sheela / Johnson, Crystal / Rabinowitz, Keren M / Barkan, Revital / Dotan, Iris / Hirten, Robert P / Fu, Shih-Chen / Luo, Yuying / Yang, Nancy / Luong, Tramy / Labrias, Philippe R / Lira, Sergio /

Peter, Inga / Grinspan, Ari / Clemente, Jose C / Kosoy, Roman / Kim-Schulze, Seunghee / Qin, Xiaochen / Castillo, Anabella / Hurley, Amanda / Atreja, Ashish / Rogers, Jason / Fasihuddin, Farah / Saliaj, Merjona / Nolan, Amy / Reyes-Mercedes, Pamela / Rodriguez, Carina / Aly, Sarah / Santa-Cruz, Kenneth / Peters, Lauren / Suárez-Fariñas, Mayte / Huang, Ruiqi / Hao, Ke / Zhu, Jun / Zhang, Bin / Losic, Bojan / Irizar, Haritz / Song, Won-Min / Di Narzo, Antonio / Wang, Wenhui / Cohen, Benjamin L / DiMaio, Christopher / Greenwald, David / Itzkowitz, Steven / Lucas, Aimee / Marion, James / Maser, Elana / Ungaro, Ryan / Naymagon, Steven / Novak, Joshua / Shah, Brijen / Ullman, Thomas / Rubin, Peter / George, James / Legnani, Peter / Telesco, Shannon E / Friedman, Joshua R / Brodmerkel, Carrie / Plevy, Scott / Cho, Judy H / Colombel, Jean-Frederic / Schadt, Eric E / Argmann, Carmen / Dubinsky, Marla / Kasarskis, Andrew / Sands, Bruce / Faith, Jeremiah J

eLife

2019 Volume 8

Abstract: To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic ... ...

Abstract	To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
MeSH term(s)	Adiposity ; Adult ; Aged ; Aged, 80 and over ; Animals ; Clostridioides difficile ; Clostridium Infections/microbiology ; Crohn Disease/microbiology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Homeostasis ; Humans ; Ileum/microbiology ; Immune System ; Inflammatory Bowel Diseases ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Middle Aged ; Mucous Membrane/microbiology ; Phenotype ; RNA, Ribosomal, 16S/metabolism ; Species Specificity ; Young Adult
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2019-01-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.40553
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Article ; Online: CO-FREE Alternative Test Products for Copper Reduction in Agriculture

Schmitt, Annegret / Scherf, Andrea / Mazzotta, S / Kühne, Stefan / Pertot, Ilaria / Köhl, Jürgen / Markellou, Emilia / Andrivon, Didier / Pellé, R / Bousseau, M / Chauvin, J-E / Thiéry, D / Delière, Laurent / Kowalska, Jolanta / Parveaud, Claude-Eric / Petit, Audrey / Giovinazzo, Robert / Brenner, Johanna / Kelderer, Markus /

Lammerts van Bueren, E.T. / Bruns, Christian / Finckh, Maria R. / Kleinhenz, Benno / Smith, Jo / Simon-Levert, A / Pujos, P. / Trapman, Marc / Stark, J / van Cutsem, P / Neerakkal, S / Kleeberg, Hubertus / Peters, Arne / Tamm, Lucius

2017

Abstract: The project CO-FREE (2012-2016) aimed to develop strategies to replace/reduce copper use in organic, integrated and conventional farming. CO-FREE alternative test products (CTPs) were tested and integrated together with decision support systems, disease- ... ...

Abstract	The project CO-FREE (2012-2016) aimed to develop strategies to replace/reduce copper use in organic, integrated and conventional farming. CO-FREE alternative test products (CTPs) were tested and integrated together with decision support systems, disease-tolerant varieties, and innovative breeding goals (ideotypes) into improved management strategies. CO-FREE focused on apple/apple scab (Venturia inaequalis), grape/downy mildew (Plasmopara viticola), and tomato and potato/late blight (Phytophthora infestans). Starting point of the project were ten CTPs with direct or indirect modes of action including Trichoderma atroviride SC1 and protein extract SCNB, Lysobacter spp., yeast-based derivatives, Cladosporium cladosporioides H39, the oligosaccharidic complex COS-OGA, Aneurinibacillus migulanus and Xenorhabdus bovienii, sage (Salvia officinalis) extract, liquorice (Glycyrrhiza glabra) extract, PLEX- and seaweed plant extracts. As the project progressed, further promising CTPs were included by the partners. Field trials were performed in different European countries in 2012-2015 following EPPO standards. In the first years, stand-alone applications of CTPs were tested. In the following years these were integrated into complete strategies. Effects on main and further diseases, on yield and on non-target organisms were assessed. Here, field trial results with CTPs are summarized.
Keywords	Crop health ; quality ; protection
Language	English
Publisher	Deutsche Phytomedi-zinische Gesellschaft
Publishing country	dk
Document type	Article ; Online
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Article ; Online: Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.

Johnson, Janel O / Chia, Ruth / Miller, Danny E / Li, Rachel / Kumaran, Ravindran / Abramzon, Yevgeniya / Alahmady, Nada / Renton, Alan E / Topp, Simon D / Gibbs, J Raphael / Cookson, Mark R / Sabir, Marya S / Dalgard, Clifton L / Troakes, Claire / Jones, Ashley R / Shatunov, Aleksey / Iacoangeli, Alfredo / Al Khleifat, Ahmad / Ticozzi, Nicola /

Silani, Vincenzo / Gellera, Cinzia / Blair, Ian P / Dobson-Stone, Carol / Kwok, John B / Bonkowski, Emily S / Palvadeau, Robin / Tienari, Pentti J / Morrison, Karen E / Shaw, Pamela J / Al-Chalabi, Ammar / Brown, Robert H / Calvo, Andrea / Mora, Gabriele / Al-Saif, Hind / Gotkine, Marc / Leigh, Fawn / Chang, Irene J / Perlman, Seth J / Glass, Ian / Scott, Anna I / Shaw, Christopher E / Basak, A Nazli / Landers, John E / Chiò, Adriano / Crawford, Thomas O / Smith, Bradley N / Traynor, Bryan J / Fallini, Claudia / Gkazi, Athina Soragia / Scotter, Emma L / Kenna, Kevin P / Keagle, Pamela / Tiloca, Cinzia / Vance, Caroline / Colombrita, Claudia / King, Andrew / Pensato, Viviana / Castellotti, Barbara / Baas, Frank / Ten Asbroek, Anneloor L M A / McKenna-Yasek, Diane / McLaughlin, Russell L / Polak, Meraida / Asress, Seneshaw / Esteban-Pérez, Jesús / Stevic, Zorica / D'Alfonso, Sandra / Mazzini, Letizia / Comi, Giacomo P / Del Bo, Roberto / Ceroni, Mauro / Gagliardi, Stella / Querin, Giorgia / Bertolin, Cinzia / van Rheenen, Wouter / Rademakers, Rosa / van Blitterswijk, Marka / Lauria, Giuseppe / Duga, Stefano / Corti, Stefania / Cereda, Cristina / Corrado, Lucia / Sorarù, Gianni / Williams, Kelly L / Nicholson, Garth A / Leblond-Manry, Claire / Rouleau, Guy A / Hardiman, Orla / Veldink, Jan H / van den Berg, Leonard H / Pall, Hardev / Turner, Martin R / Talbot, Kevin / Taroni, Franco / García-Redondo, Alberto / Wu, Zheyang / Glass, Jonathan D / Ratti, Antonia / Dalgard, Clifton L / Adeleye, Adelani / Soltis, Anthony R / Alba, Camille / Viollet, Coralie / Bacikova, Dagmar / Hupalo, Daniel N / Sukumar, Gauthaman / Pollard, Harvey B / Wilkerson, Matthew D / Martinez, Elisa McGrath / Ahmed, Sarah / Arepalli, Sampath / Baloh, Robert H / Bowser, Robert / Brady, Christopher B / Brice, Alexis / Broach, James / Campbell, Roy H / Camu, William / Cooper-Knock, John / Ding, Jinhui / Drepper, Carsten / Drory, Vivian E / Dunckley, Travis L / Eicher, John D / England, Bryce K / Faghri, Faraz / Feldman, Eva / Floeter, Mary Kay / Fratta, Pietro / Geiger, Joshua T / Gerhard, Glenn / Gibson, Summer B / Hardy, John / Harms, Matthew B / Heiman-Patterson, Terry D / Hernandez, Dena G / Jansson, Lilja / Kirby, Janine / Kowall, Neil W / Laaksovirta, Hannu / Landeck, Natalie / Landi, Francesco / Le Ber, Isabelle / Lumbroso, Serge / MacGowan, Daniel J L / Maragakis, Nicholas J / Mouzat, Kevin / Murphy, Natalie A / Myllykangas, Liisa / Nalls, Mike A / Orrell, Richard W / Ostrow, Lyle W / Pamphlett, Roger / Pickering-Brown, Stuart / Pioro, Erik P / Pletnikova, Olga / Pliner, Hannah A / Pulst, Stefan M / Ravits, John M / Rivera, Alberto / Robberecht, Wim / Rogaeva, Ekaterina / Rollinson, Sara / Rothstein, Jeffrey D / Scholz, Sonja W / Sendtner, Michael / Sidle, Katie C / Simmons, Zachary / Singleton, Andrew B / Smith, Nathan / Stone, David J / Troncoso, Juan C / Valori, Miko / Van Damme, Philip / Van Deerlin, Vivianna M / Van Den Bosch, Ludo / Zinman, Lorne / Angelocola, Stefania M / Ausiello, Francesco P / Barberis, Marco / Bartolomei, Ilaria / Battistini, Stefania / Bersano, Enrica / Bisogni, Giulia / Borghero, Giuseppe / Brunetti, Maura / Cabona, Corrado / Canale, Fabrizio / Canosa, Antonio / Cantisani, Teresa A / Capasso, Margherita / Caponnetto, Claudia / Cardinali, Patrizio / Carrera, Paola / Casale, Federico / Colletti, Tiziana / Conforti, Francesca L / Conte, Amelia / Conti, Elisa / Corbo, Massimo / Cuccu, Stefania / Dalla Bella, Eleonora / D'Errico, Eustachio / DeMarco, Giovanni / Dubbioso, Raffaele / Ferrarese, Carlo / Ferraro, Pilar M / Filippi, Massimo / Fini, Nicola / Floris, Gianluca / Fuda, Giuseppe / Gallone, Salvatore / Gianferrari, Giulia / Giannini, Fabio / Grassano, Maurizio / Greco, Lucia / Iazzolino, Barbara / Introna, Alessandro / La Bella, Vincenzo / Lattante, Serena / Liguori, Rocco / Logroscino, Giancarlo / Logullo, Francesco O / Lunetta, Christian / Mandich, Paola / Mandrioli, Jessica / Manera, Umberto / Manganelli, Fiore / Marangi, Giuseppe / Marinou, Kalliopi / Marrosu, Maria Giovanna / Martinelli, Ilaria / Messina, Sonia / Moglia, Cristina / Mosca, Lorena / Murru, Maria R / Origone, Paola / Passaniti, Carla / Petrelli, Cristina / Petrucci, Antonio / Pozzi, Susanna / Pugliatti, Maura / Quattrini, Angelo / Ricci, Claudia / Riolo, Giulia / Riva, Nilo / Russo, Massimo / Sabatelli, Mario / Salamone, Paolina / Salivetto, Marco / Salvi, Fabrizio / Santarelli, Marialuisa / Sbaiz, Luca / Sideri, Riccardo / Simone, Isabella / Simonini, Cecilia / Spataro, Rossella / Tanel, Raffaella / Tedeschi, Gioacchino / Ticca, Anna / Torriello, Antonella / Tranquilli, Stefania / Tremolizzo, Lucio / Trojsi, Francesca / Vasta, Rosario / Vacchiano, Veria / Vita, Giuseppe / Volanti, Paolo / Zollino, Marcella / Zucchi, Elisabetta

JAMA neurology

2021 Volume 78, Issue 10, Page(s) 1236–1248

Abstract: Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.: Objective: To identify the genetic variants associated with juvenile ALS.: Design, ...

Abstract	Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, setting, and participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main outcomes and measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
MeSH term(s)	Adolescent ; Adult ; Amyotrophic Lateral Sclerosis/genetics ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease/genetics ; Humans ; Mutation ; Serine C-Palmitoyltransferase/genetics ; Exome Sequencing ; Young Adult
Chemical Substances	SPTLC1 protein, human (EC 2.3.1.50) ; Serine C-Palmitoyltransferase (EC 2.3.1.50)
Language	English
Publishing date	2021-09-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2021.2598
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago.

Perrone, Gennaro / Giuffrida, Mario / Abu-Zidan, Fikri / Kruger, Vitor F / Livrini, Marco / Petracca, Gabriele Luciano / Rossi, Giorgio / Tarasconi, Antonio / Tian, Brian W C A / Bonati, Elena / Mentz, Ricardo / Mazzini, Federico N / Campana, Juan P / Gasser, Elisabeth / Kafka-Ritsch, Reinhold / Felsenreich, Daniel M / Dawoud, Christopher / Riss, Stefan / Gomes, Carlos Augusto /

Gomes, Felipe Couto / Gonzaga, Ricardo Alessandro Teixeira / Canton, Cassio Alfred Brattig / Pereira, Bruno Monteiro / Fraga, Gustavo P / Zem, Leticia Gonçalves / Cordeiro-Fonseca, Vinicius / de Mesquita Tauil, Renato / Atanasov, Boyko / Belev, Nikolay / Kovachev, Nikola / Meléndez, L Juan José / Dimova, Ana / Dimov, Stefan / Zelić, Zdravko / Augustin, Goran / Bogdanić, Branko / Morić, Trpimir / Chouillard, Elie / Bajul, Melinda / De Simone, Belinda / Panis, Yves / Esposito, Francesco / Notarnicola, Margherita / Lauka, Lelde / Fabbri, Anna / Hentati, Hassen / Fnaiech, Iskander / Aurélien, Venara / Bougard, Marie / Roulet, Maxime / Demetrashvili, Zaza / Pipia, Irakli / Merabishvili, Giorgi / Bouliaris, Konstantinos / Koukoulis, Georgios / Doudakmanis, Christos / Xenaki, Sofia / Chrysos, Emmanuel / Kokkinakis, Stamatios / Vassiliu, Panteleimon / Michalopoulos, Nikolaos / Margaris, Ioannis / Kechagias, Aristotelis / Avgerinos, Konstantinos / Katunin, Jevgeni / Lostoridis, Eftychios / Nagorni, Eleni-Aikaterini / Pujante, Antonio / Mulita, Francesk / Maroulis, Ioannis / Vailas, Michail / Marinis, Athanasios / Siannis, Ioannis / Bourbouteli, Eirini / Manatakis, Dimitrios K / Tasis, Nikolaos / Acheimastos, Vasileios / Maria, Sotiropoulou / Stylianos, Kapiris / Kuzeridis, Harilaos / Korkolis, Dimitrios / Fradelos, Evangelos / Kavalieratos, George / Petropoulou, Thalia / Polydorou, Andreas / Papacostantinou, Ioannis / Triantafyllou, Tania / Kimpizi, Despina / Theodorou, Dimitrios / Toutouzas, Konstantinos / Chamzin, Alexandros / Frountzas, Maximos / Schizas, Dimitrios / Karavokyros, Ioannis / Syllaios, Athanasios / Charalabopoulos, Alexandros / Boura, Maria / Baili, Efstratia / Ioannidis, Orestis / Loutzidou, Lydia / Anestiadou, Elissavet / Tsouknidas, Ioannis / Petrakis, Georgios / Polenta, Eleni / Bains, Lovenish / Gupta, Rahul / Singh, Sudhir K / Khanduri, Archana / Bala, Miklosh / Kedar, Asaf / Pisano, Marcello / Podda, Mauro / Pisanu, Adolfo / Martines, Gennaro / Trigiante, Giuseppe / Lantone, Giuliano / Agrusa, Antonino / Di Buono, Giuseppe / Buscemi, Salvatore / Veroux, Massimiliano / Gioco, Rossella / Veroux, Gastone / Oragano, Luigi / Zonta, Sandro / Lovisetto, Federico / Feo, Carlo V / Pesce, Antonio / Fabbri, Nicolò / Lantone, Giulio / Marino, Fabio / Perrone, Fabrizio / Vincenti, Leonardo / Papagni, Vincenzo / Picciariello, Arcangelo / Rossi, Stefano / Picardi, Biagio / Del Monte, Simone Rossi / Visconti, Diego / Osella, Giulia / Petruzzelli, Luca / Pignata, Giusto / Andreuccetti, Jacopo / D'Alessio, Rossella / Buonfantino, Massimo / Guaitoli, Eleonora / Spinelli, Stefano / Sampietro, Gianluca Matteo / Corbellini, Carlo / Lorusso, Leonardo / Frontali, Alice / Pezzoli, Isabella / Bonomi, Alessandro / Chierici, Andrea / Cotsoglou, Christian / Manca, Giuseppe / Delvecchio, Antonella / Musa, Nicola / Casati, Massimiliano / Letizia, Laface / Abate, Emmanuele / Ercolani, Giorgio / D'Acapito, Fabrizio / Solaini, Leonardo / Guercioni, Gianluca / Cicconi, Simone / Sasia, Diego / Borghi, Felice / Giraudo, Giorgio / Sena, Giuseppe / Castaldo, Pasquale / Cardamone, Eugenia / Portale, Giuseppe / Zuin, Matteo / Spolverato, Ylenia / Esposito, Marialusia / Isernia, Roberta Maria / Di Salvo, Maria / Manunza, Romina / Esposito, Giuseppe / Agus, Marcello / Asti, Emanuele Luigi Giuseppe / Bernardi, Daniele Tiziano / Tonucci, Tommaso Panici / Luppi, Davide / Casadei, Massimiliano / Bonilauri, Stefano / Pezzolla, Angela / Panebianco, Annunziata / Laforgia, Rita / De Luca, Maurizio / Zese, Monica / Parini, Dario / Jovine, Elio / De Sario, Giuseppina / Lombardi, Raffaele / Aprea, Giovanni / Palomba, Giuseppe / Capuano, Marianna / Argenio, Giulio / Orio, Gianluca / Armellino, Mariano Fortunato / Troian, Marina / Guerra, Martina / Nagliati, Carlo / Biloslavo, Alan / Germani, Paola / Aizza, Giada / Monsellato, Igor / Chahrour, Ali Chaouki / Anania, Gabriele / Bombardini, Cristina / Bagolini, Francesco / Sganga, Gabriele / Fransvea, Pietro / Bianchi, Valentina / Boati, Paolo / Ferrara, Francesco / Palmieri, Francesco / Cianci, Pasquale / Gattulli, Domenico / Restini, Enrico / Cillara, Nicola / Cannavera, Alessandro / Nita, Gabriela Elisa / Sarnari, Jlenia / Roscio, Francesco / Clerici, Federico / Scandroglio, Ildo / Berti, Stefano / Cadeo, Alessandro / Filippelli, Alice / Conti, Luigi / Grassi, Carmine / Cattaneo, Gaetano Maria / Pighin, Marina / Papis, Davide / Gambino, Giovanni / Bertino, Vanessa / Schifano, Domenico / Prando, Daniela / Fogato, Luisella / Cavallo, Fabio / Ansaloni, Luca / Picheo, Roberto / Pontarolo, Nicholas / Depalma, Norma / Spampinato, Marcello / D'Ugo, Stefano / Lepre, Luca / Capponi, Michela Giulii / Campa, Rossella Domenica / Sarro, Giuliano / Dinuzzi, Vincenza Paola / Olmi, Stefano / Uccelli, Matteo / Ferrari, Davide / Inama, Marco / Moretto, Gianluigi / Fontana, Michele / Favi, Francesco / Picariello, Erika / Rampini, Alessia / Barberis, Andrea / Azzinnaro, Antonio / Oliva, Alba / Totaro, Luigi / Benzoni, Ilaria / Ranieri, Valerio / Capolupo, Gabriella Teresa / Carannante, Filippo / Caricato, Marco / Ronconi, Maurizio / Casiraghi, Silvia / Casole, Giovanni / Pantalone, Desire / Alemanno, Giovanni / Scheiterle, Maximilian / Ceresoli, Marco / Cereda, Marco / Fumagalli, Chiara / Zanzi, Federico / Bolzon, Stefano / Guerra, Enrico / Lecchi, Francesca / Cellerino, Paola / Ardito, Antonella / Scaramuzzo, Rosa / Balla, Andrea / Lepiane, Pasquale / Tartaglia, Nicola / Ambrosi, Antonio / Pavone, Giovanna / Palini, Gian Marco / Veneroni, Simone / Garulli, Gianluca / Ricci, Claudio / Torre, Beatrice / Russo, Iris Shari / Rottoli, Matteo / Tanzanu, Marta / Belvedere, Angela / Milone, Marco / Manigrasso, Michele / De Palma, Giovanni Domenico / Piccoli, Micaela / Pattacini, Gianmaria Casoni / Magnone, Stefano / Bertoli, Paolo / Pisano, Michele / Massucco, Paolo / Palisi, Marco / Luzzi, Andrea-Pierre / Fleres, Francesco / Clarizia, Guglielmo / Spolini, Alessandro / Kobe, Yoshiro / Toma, Takayuki / Shimamura, Fumihiko / Parker, Robert / Ranketi, Sinkeet / Mitei, Mercy / Svagzdys, Saulius / Pauzas, Henrikas / Zilinskas, Justas / Poskus, Tomas / Kryzauskas, Marius / Jakubauskas, Matas / Zakaria, Andee Dzulkarnaen / Zakaria, Zaidi / Wong, Michael Pak-Kai / Jusoh, Asri Che / Zakaria, Muhammad Nazreen / Cruz, Daniel Rios / Elizalde, Aurea Barbara Rodriguez / Reynaud, Alejandro Bañon / Hernandez, Edgard Efren Lozada / Monroy, Jose Maria Victor Palomo / Hinojosa-Ugarte, Diego / Quiodettis, Martha / Du Bois, María Esther / Latorraca, José / Major, Piotr / Pędziwiatr, Michał / Pisarska-Adamczyk, Magdalena / Walędziak, Maciej / Kwiatkowski, Andrzej / Czyżykowski, Łukasz / da Costa, Silvia Dantas / Pereira, Bela / Ferreira, Ana Rita Oliveira / Almeida, Filipe / Rocha, Ricardo / Carneiro, Carla / Perez, Diego Pita / Carvas, João / Rocha, Catarina / Ferreira, Cátia / Marques, Rita / Fernandes, Urânia / Leao, Pedro / Goulart, André / Pereira, Rita Gonçalves / Patrocínio, Sara Daniela Direito / de Mendonça, Nuno Gonçalo Gonçalves / Manso, Maria Isabel Cerqueira / Morais, Henrique Manuel Cardoso / Cardoso, Paulo Sebastião / Calu, Valentin / Miron, Adrian / Toma, Elena Adelina / Gachabayov, Mahir / Abdullaev, Abakar / Litvin, Andrey / Nechay, Taras / Tyagunov, Alexander / Yuldashev, Anvar / Bradley, Alison / Wilson, Michael / Panyko, Arpád / Látečková, Zuzana / Lacko, Vladimír / Lesko, Dusan / Soltes, Marek / Radonak, Jozef / Turrado-Rodriguez, Victor / Termes-Serra, Roser / Morales-Sevillano, Xavier / Lapolla, Pierfrancesco / Mingoli, Andrea / Brachini, Gioia / Degiuli, Maurizio / Sofia, Silvia / Reddavid, Rossella / de Manzoni Garberini, Andrea / Buffone, Angelica / Del Pozo, Eduardo Perea / Aparicio-Sánchez, Daniel / Dos Barbeito, Sandra / Estaire-Gómez, Mercedes / Vitón-Herrero, Rebeca / de Los Ángeles Gil Olarte-Marquez, Mª / Gil-Martínez, José / Alconchel, Felipe / Nicolás-López, Tatiana / Rahy-Martin, Aida Cristina / Pelloni, María / Bañolas-Suarez, Raquel / Mendoza-Moreno, Fernando / Nisa, Francisca García-Moreno / Díez-Alonso, Manuel / Rodas, María Elisa Valle / Agundez, María Carmona / Andrés, María Inmaculada Pérez / Moreira, Claudia Cristina Lopes / Perez, Aintzane Lizarazu / Ponce, Iñigo Augusto / González-Castillo, Ana María / Membrilla-Fernández, Estela / Salvans, Silvia / Serradilla-Martín, Mario / Pardo, Pablo Sancho / Rivera-Alonso, Daniel / Dziakova, Jana / Huguet, Jose Mugüerza / Valle, Naila Pagès / Ruiz, Enrique Colás / Valcárcel, Cristina Rey / Moreno, Cristina Ruiz / Salazar, Yeniffer Tatiana Moreno / García, Juan Jesús Rubio / Micó, Silvia Sevila / López, Joaquín Ruiz / Farré, Silvia Pérez / Gomez, Maite Santamaria / Petit, Nuria Mestres / Titos-García, Alberto / Aranda-Narváez, Jose Manuel / Romacho-López, Laura / Sánchez-Guillén, Luis / Aranaz-Ostariz, Veronica / Bosch-Ramírez, Marina / Martínez-Pérez, Aleix / Martínez-López, Elías / Sebastián-Tomás, Juan Carlos / Jimenez-Riera, Granada / Jimenez-Vega, Javier / Cuellar, Jose Aurelio Navas / Campos-Serra, Andrea / Muñoz-Campaña, Anna / Gràcia-Roman, Raquel / Alegre, Javier Martínez / Pinto, Francisca Lima / O'Sullivan, Sara Nuñez / Antona, Francisco Blanco / Jiménez, Beatriz Muñoz / López-Sánchez, Jaime / Carmona, Zahira Gómez / Fernández, Rocio Torres / Sierra, Isabel Blesa / de León, Laura Román García / Moreno, Verónica Polaino / Iglesias, Eva / Cumplido, Paola Lora / Bravo, Altea Arango / Simó, Ignacio Rey / Domínguez, Carlota López / Caamaño, Aloia Guerreiro / Lozano, Rafael Calleja / Martínez, Manuel Durán / Torres, Álvaro Naranjo / de Quiros, Javier Tomas Morales Bernaldo / Pellino, Gianluca / Cloquell, Miriam Moratal / Moller, Elsa García / Jalal-Eldin, Sami / Abdoun, Ahmed K / Hamid, Hytham K S / Lohsiriwat, Varut / Mongkhonsupphawan, Aitsariya / Baraket, Oussama / Ayed, Karim / Abbassi, Imed / Ali, Ali Ben / Ammar, Houssem / Kchaou, Ali / Tlili, Ahmed / Zribi, Imen / Colak, Elif / Polat, Suleyman / Koylu, Zehra Alan / Guner, Ali / Usta, Mehmet Arif / Reis, Murat Emre / Mantoglu, Baris / Gonullu, Emre / Akin, Emrah / Altintoprak, Fatih / Bayhan, Zulfu / Firat, Necattin / Isik, Arda / Memis, Ufuk / Bayrak, Mehmet / Altıntaş, Yasemin / Kara, Yasin / Bozkurt, Mehmet Abdussamet / Kocataş, Ali / Das, Koray / Seker, Ahmet / Ozer, Nazmi / Atici, Semra Demirli / Tuncer, Korhan / Kaya, Tayfun / Ozkan, Zeynep / Ilhan, Onur / Agackiran, Ibrahim / Uzunoglu, Mustafa Yener / Demirbas, Eren / Altinel, Yuksel / Meric, Serhat / Hacım, Nadir Adnan / Uymaz, Derya Salim / Omarov, Nail / Balık, Emre / Tebala, Giovanni D / Khalil, Hany / Rana, Mridul / Khan, Mansoor / Florence, Charlotte / Swaminathan, Christie / Leo, Cosimo Alex / Liasis, Lampros / Watfah, Josef / Trostchansky, Ivan / Delgado, Edward / Pontillo, Marcelo / Latifi, Rifat / Coimbra, Raul / Edwards, Sara / Lopez, Ana / Velmahos, George / Dorken, Ander / Gebran, Anthony / Palmer, Amanda / Oury, Jeffrey / Bardes, James M / Seng, Sirivan Suon / Coffua, Lauren S / Ratnasekera, Asanthi / Egodage, Tanya / Echeverria-Rosario, Karla / Armento, Isabella / Napolitano, Lena M / Sangji, Naveen F / Hemmila, Mark / Quick, Jacob A / Austin, Tyler R / Hyman, Theodore S / Curtiss, William / McClure, Amanda / Cairl, Nicholas / Biffl, Walter L / Truong, Hung P / Schaffer, Kathryn / Reames, Summer / Banchini, Filippo / Capelli, Patrizio / Coccolini, Federico / Sartelli, Massimo / Bravi, Francesca / Vallicelli, Carlo / Agnoletti, Vanni / Baiocchi, Gian Luca / Catena, Fausto

World journal of emergency surgery : WJES

2024 Volume 19, Issue 1, Page(s) 14

Abstract: Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute ... ...

Abstract	Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception.
MeSH term(s)	Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Emergencies ; Prospective Studies ; Postoperative Complications/etiology ; Anastomosis, Surgical/methods ; Colorectal Neoplasms/surgery
Language	English
Publishing date	2024-04-16
Publishing country	England
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	2233734-9
ISSN	1749-7922 ; 1749-7922
ISSN (online)	1749-7922
ISSN	1749-7922
DOI	10.1186/s13017-024-00543-w
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