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Bridging therapy

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https://www.readbyqxmd.com/read/27903882/cap-analogs-modified-with-1-2-dithiodiphosphate-moiety-protect-mrna-from-decapping-and-enhance-its-translational-potential
#1
Malwina Strenkowska, Renata Grzela, Maciej Majewski, Katarzyna Wnek, Joanna Kowalska, Maciej Lukaszewicz, Joanna Zuberek, Edward Darzynkiewicz, Andreas N Kuhn, Ugur Sahin, Jacek Jemielity
Along with a growing interest in mRNA-based gene therapies, efforts are increasingly focused on reaching the full translational potential of mRNA, as a major obstacle for in vivo applications is sufficient expression of exogenously delivered mRNA. One method to overcome this limitation is chemically modifying the 7-methylguanosine cap at the 5' end of mRNA (m(7)Gppp-RNA). We report a novel class of cap analogs designed as reagents for mRNA modification. The analogs carry a 1,2-dithiodiphosphate moiety at various positions along a tri- or tetraphosphate bridge, and thus are termed 2S analogs...
November 16, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903010/heartmate-ii-left-ventricular-assist-device-pump-exchange-a-single-institution-experience
#2
Asad F Shaikh, Susan M Joseph, Brian Lima, Shelley A Hall, Rajasekhar Malyala, Aldo E Rafael, Gonzalo V Gonzalez-Stawinski, Themistokles Chamogeorgakis
Background Left ventricular assist devices (LVADs) have revolutionized the treatment of patients with end-stage heart failure. These devices are replaced when pump complications arise if heart transplant is not possible. We present our experience with HeartMate II (HMII (Thoratec, Plesanton, California, United States)) LVAD pump exchange. Materials and Methods We retrospectively reviewed all cases that required pump exchange due to LVAD complication from November 2011 until June 2016 at a single high-volume institution...
November 30, 2016: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/27900445/bridging-locoregional-therapy-prolongs-survival-in-patients-listed-for-liver-transplant-with-hepatocellular-carcinoma
#3
Minzhi Xing, Sonali Sakaria, Renumathy Dhanasekaran, Samir Parekh, James Spivey, Stuart J Knechtle, Di Zhang, Hyun S Kim
BACKGROUND AND AIMS: To evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria. METHODS: Our transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times...
November 29, 2016: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/27898593/coinfection-with-hiv-and-hepatitis-c-virus-in-229-children-and-young-adults-living-in-europe
#4
(no author information available yet)
OBJECTIVE: To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment. DESIGN: Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts. METHODS: Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27898438/rescue-therapies-for-acute-respiratory-distress-syndrome-what-to-try-first
#5
Onnen Moerer, Tommaso Tonetti, Michael Quintel
PURPOSE OF REVIEW: Severe respiratory failure due to the acute respiratory distress syndrome (ARDS) might require rescue therapy measures beyond even extended standard care to ensure adequate oxygenation and survival. This review provides a summary and assessment of treatment options that can be beneficial when the standard approach fails. RECENT FINDINGS: 'Life-threatening' conditions or refractory hypoxemia during mechanical ventilation are more a matter of personal rating than an objective diagnosis based on defined and/or unanimously agreed thresholds that would mandate the use of rescue therapies...
November 24, 2016: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/27891522/biomolecular-network-based-synergistic-drug-combination-discovery
#6
REVIEW
Xiangyi Li, Guangrong Qin, Qingmin Yang, Lanming Chen, Lu Xie
Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27890252/aml-in-2016-where-we-are-now
#7
REVIEW
Jacob M Rowe
A high relapse rate for patients with acute myeloid leukemia (AML) is still a major barrier to the long-term survival of these patients. Nevertheless, considerable progress has been made both in the biology and therapy of the disease. Specifically, progress has been made in the areas of integrated genomic analysis for prognosis, the widening application of minimal residual disease (MRD) monitoring in clinical practice, the development of new agents, and the increasing use of drugs, such as IDH and FLT3 inhibitors, as a bridge to transplant...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27887724/facial-deformations-during-nasal-continuous-positive-airway-pressure-therapy
#8
Andrew Sims, Anne Simmons, Mark Hoffman, Klaus Schindhelm
Obstructive Sleep Apnoea (OSA), characterised by repeated collapse of the pharyngeal airway during sleep, causes cessation of breathing followed by arousal, restoring normality. Continuous Positive Airway Pressure (CPAP) is a non-invasive, effective treatment for OSA where positive pressure is applied to the airway through a mask, maintaining patency. Nasal masks are commonly used, contacting the face across the upper lip, sides of the nose and the nasal bridge. Despite health benefits, therapy compliance is sub-optimal, often due to poor mask fit and discomfort...
October 22, 2016: Journal of Biomechanics
https://www.readbyqxmd.com/read/27884494/consensus-conference-on-tips-management-techniques-indications-contraindications
#9
Stefano Fagiuoli, Raffaele Bruno, Wilma Debernardi Venon, Filippo Schepis, Francesco Vizzutti, Pierluigi Toniutto, Marco Senzolo, Paolo Caraceni, Francesco Salerno, Paolo Angeli, Roberto Cioni, Alessandro Vitale, Maurizio Grosso, Andrea De Gasperi, Gennaro D'Amico, Alfredo Marzano
The trans jugular intrahepatic Porto systemic shunt (TIPS) is no longer viewed as a salvage therapy or a bridge to liver transplantation and is currently indicated for a number of conditions related to portal hypertension with positive results in survival. Moreover, the availability of self-expandable polytetrafluoroethylene (PTFE)-covered endoprostheses has dramatically improved the long-term patency of TIPS. However, since the last updated International guidelines have been published (year 2009) new evidence have come, which have open the field to new indications and solved areas of uncertainty...
October 29, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27875721/percutaneous-mitral-valve-repair-the-last-chance-for-symptoms-improvement-in-advanced-refractory-chronic-heart-failure
#10
Alessandra Berardini, Elena Biagini, Francesco Saia, Davide Stolfo, Mario Previtali, Francesco Grigioni, Bruno Pinamonti, Gabriele Crimi, Alessandro Salvi, Maurizio Ferrario, Antonio De Luca, Fabrizio Gazzoli, Maria Letizia Bacchi Reggiani, Claudia Raineri, Gianfranco Sinagra, Claudio Rapezzi
BACKGROUND: The role of percutaneous mitral valve repair (PMVR) in patients with end-stage heart failure (HF) and functional mitral regurgitation (FMR) is unclear. METHODS: Seventy-five consecutive patients with FMR grade≥3+ and severe HF symptoms despite optimal medical therapy and resynchronization therapy underwent PMVR with the MitraClip system (Abbott, Abbott Park, IL, USA) at 3 centers. Clinical evaluation, echocardiography and pro-BNP measurement were performed at baseline and at 6-month...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27873215/current-and-future-treatment-approaches-in-transthyretin-familial-amyloid-polyneuropathy
#11
REVIEW
Philippe Kerschen, Violaine Planté-Bordeneuve
Treatment of transthyretin familial amyloid polyneuropathy (TTR FAP) must be tailored to disease stage. Patients with early stage disease (i.e., without major impairment in walking ability), especially younger patients, should be referred as soon as possible for liver transplantation (LT) in the absence of major comorbid conditions. LT remains the most effective treatment option to date and should be offered to these patients as early as possible. Bridging therapy with an oral TTR stabilizer (tafamidis or diflunisal, according to local access to these treatments) should be started as soon as the diagnosis of TTR FAP is established...
December 2016: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/27872622/an-evaluation-of-20-years-of-eu-framework-programme-funded-immune-mediated-inflammatory-translational-research-in-non-human-primates
#12
Krista G Haanstra, Margreet Jonker, Bert A 't Hart
Aging western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health-care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primates can help to bridge the gap between drug discovery and drug prescription. Translational research covers various stages of drug development of which preclinical efficacy tests in valid animal models is usually the last stage...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27872099/conflicting-signals-for-cancer-treatment
#13
Pierre Sujobert, Alain Trautmann
Next-generation sequencing technologies have provided us with a precise description of the mutational burden of cancers, making it possible to identify targetable oncogene addictions. However, the emergence of resistant clones is an inevitable limitation of therapies targeting these addictions. Alternative approaches to cancer treatment are therefore required. We propose here a novel approach, based on the notion of conflicting signals and on a phenotypic description of cancer cells. "Phenotype" is an inherently complex notion that we describe in the conceptual framework of the epigenetic landscape, with a view to bridging the gap between theory and practice at the patient's bedside...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27870978/towards-the-standardization-of-stem-cell-therapy-studies-for-ischemic-heart-diseases-bridging-the-gap-between-animal-models-and-the-clinical-setting
#14
REVIEW
Fábio Trindade, Adelino Leite-Moreira, João Ferreira-Martins, Rita Ferreira, Inês Falcão-Pires, Rui Vitorino
Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements...
November 14, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27869082/reoptimization-of-intensity-modulated-proton-therapy-plans-based-on-linear-energy-transfer
#15
Jan Unkelbach, Pablo Botas, Drosoula Giantsoudi, Bram L Gorissen, Harald Paganetti
PURPOSE: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. METHODS AND MATERIALS: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams...
December 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27867824/safety-of-heparin-bridging-therapy-for-transrectal-ultrasound-guided-prostate-biopsy-in-patients-requiring-temporary-discontinuation-of-antithrombotic-agents
#16
Itsuto Hamano, Shingo Hatakeyama, Tohru Yoneyama, Yuki Tobisawa, Osamu Soma, Teppei Matsumoto, Hayato Yamamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
BACKGROUND: Safety of heparin bridging therapy for transrectal ultrasound-guided prostate (TRUS) biopsy in patients requiring temporary discontinuation of antithrombotic therapy is unknown. This study aimed to assess the relationship between heparin bridging therapy and the incidence of complications after TRUS biopsy. METHODS: From January 2005 to November 2015, we performed 1307 consecutive TRUS biopsies on 1134 patients in our hospital. The patients were assigned to two groups: those without heparin bridging (the control group) and those with temporary discontinuation of antithrombotic agents with heparin bridging therapy (the bridging group)...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27867681/local-ablative-treatments-for-hepatocellular-carcinoma-an-updated-review
#17
REVIEW
Antonio Facciorusso, Gaetano Serviddio, Nicola Muscatiello
Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety...
November 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27867020/a-randomized-dose-escalation-study-of-intravenous-baclofen-in-healthy-volunteers-clinical-tolerance-and-pharmacokinetics
#18
Natalie S Schmitz, Linda E Krach, Lisa D Coles, Usha Mishra, Suresh K Agarwal, James C Cloyd, Robert L Kriel
BACKGROUND: Abrupt discontinuation of baclofen can result in a potentially severe withdrawal syndrome. The current treatment for baclofen withdrawal is inadequate, resulting in a critical need to develop an alternative method to prevent or treat this withdrawal syndrome. OBJECTIVE: To evaluate the safety profile and pharmacokinetics of oral (PO) and investigational intravenous (IV) baclofen formulations at clinically relevant doses. DESIGN: Randomized, open-label, dose escalation, crossover study SETTING: Contract Research Organization (CRO) METHODS: Three cohorts of 12 healthy adults received single doses of PO baclofen (10mg, 15 mg or 20 mg) and 10-minute infusions of IV baclofen (7...
November 17, 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/27865732/prevention-of-heartmate-ii-pump-thrombosis-through-clinical-management-the-prevent-multi-center-study
#19
Simon Maltais, Ahmet Kilic, Sriram Nathan, Mary Keebler, Sitaramesh Emani, John Ransom, Jason N Katz, Brett Sheridan, Andreas Brieke, Gregory Egnaczyk, John W Entwistle, Robert Adamson, John Stulak, Nir Uriel, John B O'Connell, David J Farrar, Kartik S Sundareswaran, Igor Gregoric
BACKGROUND: Recommended structured clinical practices including implant technique, anti-coagulation strategy, and pump speed management (PREVENT [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management] recommendations) were developed to address risk of early (<3 months) pump thrombosis (PT) risk with HeartMate II (HMII; St. Jude Medical, Inc. [Thoratec Corporation], Pleasanton, CA). We prospectively assessed the HMII PT rate in the current era when participating centers adhered to the PREVENT recommendations...
November 16, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/27865034/prevention-of-hepatitis-c-recurrence-by-bridging-sofosbuvir-ribavirin-from-pre-to-post-liver-transplant-a-real-life-strategy
#20
Maria Francesca Donato, Cristina Morelli, Renato Romagnoli, Federica Invernizzi, Chiara Mazzarelli, Rosa Maria Iemmolo, Marzia Montalbano, Ilaria Lenci, Sherrie Bhoori, Giulia Pieri, Sonia Berardi, Paolo Caraceni, Silvia Martini
BACKGROUND AND AIMS: Hepatitis C virus (HCV) reinfection following liver transplant (LT) is associated with reduced graft and patients survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 week HCV-RNA undetectability at the time of transplant...
November 19, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
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