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https://www.readbyqxmd.com/read/28437180/a-novel-drug-induced-hybrid-electrospun-pcl-cell-derived-ecm-scaffold-for-liver-tissue-engineering
#1
Rhiannon Grant, David Hay, Anthony Callanan
Liver transplant is the only treatment option for patients with end-stage liver failure, however there are too few donor livers available for transplant. Whole organ tissue engineering presents a potential solution to the problem of rapidly escalating donor liver shortages world-wide. A major challenge for liver tissue engineers is the creation of a hepatocyte micro-environment; a niche in which liver cells can survive and function optimally. While polymers and decellularized tissues pose an attractive option for scaffold manufacturing, neither alone has thus far proved sufficient...
February 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28436937/efficacy-of-anti-sclerostin-monoclonal-antibody-bps804-in-adult-patients-with-hypophosphatasia
#2
Lothar Seefried, Jasmin Baumann, Sarah Hemsley, Christine Hofmann, Erdmute Kunstmann, Beate Kiese, Yue Huang, Simon Chivers, Marie-Anne Valentin, Babul Borah, Ronenn Roubenoff, Uwe Junker, Franz Jakob
BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder resulting in variable alterations of bone formation and mineralization that are caused by mutations in the ALPL gene, encoding the tissue-nonspecific alkaline phosphatase (ALP) enzyme. METHODS: In this phase IIA open-label, single-center, intra-patient, dose-escalating study, adult patients with HPP received 3 ascending intravenous doses of 5, 10, and 20 mg/kg BPS804, a fully human anti-sclerostin monoclonal antibody, on days 1, 15, and 29, respectively...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28434798/prognostic-value-of-dynamic-hypoxia-pet-in-head-and-neck-cancer-results-from-a-planned-interim-analysis-of-a-randomized-phase-ii-hypoxia-image-guided-dose-escalation-trial
#3
Stefan Welz, David Mönnich, Christina Pfannenberg, Konstantin Nikolaou, Mathias Reimold, Christian La Fougère, Gerald Reischl, Paul-Stefan Mauz, Frank Paulsen, Markus Alber, Claus Belka, Daniel Zips, Daniela Thorwarth
BACKGROUND AND PURPOSE: To prospectively assess the prognostic value of tumour hypoxia determined by dynamic [(18)F]Fluoromisonidazole (dynFMISO) PET/CT, and to evaluate both feasibility and toxicity in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided dose escalation (DE) using dose-painting by contours. PATIENTS AND METHODS: We present a planned interim analysis of a randomized phase II trial...
April 20, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28434660/reduced-dose-radiotherapy-for-human-papillomavirus-associated-squamous-cell-carcinoma-of-the-oropharynx-a-single-arm-phase-2-study
#4
Allen M Chen, Carol Felix, Pin-Chieh Wang, Sophia Hsu, Vincent Basehart, Jordan Garst, Phillip Beron, Deborah Wong, Michael H Rosove, Shyam Rao, Heather Melanson, Edward Kim, Daphne Palmer, Lihong Qi, Karen Kelly, Michael L Steinberg, Patrick A Kupelian, Megan E Daly
BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1...
April 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#5
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28433432/ascende-rt-an-analysis-of-treatment-related-morbidity-for-a-randomized-trial-comparing-a-low-dose-rate-brachytherapy-boost-with-a-dose-escalated-external-beam-boost-for-high-and-intermediate-risk-prostate-cancer
#6
Sree Rodda, Scott Tyldesley, W James Morris, Mira Keyes, Ross Halperin, Howard Pai, Michael McKenzie, Graeme Duncan, Gerard Morton, Jeremy Hamm, Nevin Murray
PURPOSE: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. METHODS AND MATERIALS: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost...
January 6, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28433413/stereotactic-ablative-radiotherapy-in-the-treatment-of-low-and-intermediate-risk-prostate-cancer-is-there-an-optimal-dose
#7
Joelle Helou, Laura D'Alimonte, Harvey Quon, Andrea Deabreu, Kristina Commisso, Patrick Cheung, William Chu, Alexandre Mamedov, Melanie Davidson, Ananth Ravi, Andrew Loblaw
PURPOSE: To investigate if stereotactic ablative radiotherapy (SABR) dose is associated with PSA at 3years (PSA3y) in the treatment of localized prostate cancer and to explore predictors of late genitourinary (GU) toxicity. MATERIALS AND METHODS: Three prospective trials of SABR were undertaken at our institution: 1) 35Gy/5 fractions/29days; 2) 40Gy/5 fractions/29days; 3) 40Gy/5 fractions/11 or 29days. PSA3y was analyzed as a continuous variable. Toxicity was defined as the worst new toxicity and assessed using the radiation therapy oncology group (RTOG) late morbidity scheme...
April 19, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28432748/future-challenges-and-therapeutic-opportunities-in-type-2-diabetes-changing-the-paradigm-of-current-therapy
#8
REVIEW
D R Owens, L Monnier, A H Barnett
Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment escalation until glycated haemoglobin (HbA1c) fails to reach the recommended target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen ('treat to failure'). Clinical inertia and/or poor adherence to therapy contribute to patients not reaching glycaemic targets when managed according to this paradigm. Clinical inertia exists across the entire spectrum of anti-diabetes therapies, although it is most pronounced when initiating and optimizing insulin therapy...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432176/a-phase-i-study-of-the-cdk4-6-inhibitor-ribociclib-lee011-in-pediatric-patients-with-malignant-rhabdoid-tumors-neuroblastoma-and-other-solid-tumors
#9
Birgit Geoerger, Franck Bourdeaut, Steven G DuBois, Matthias Fischer, James I Geller, Nicholas G Gottardo, Aurélien Marabelle, Andrew D J Pearson, Shakeel Modak, Thomas Cash, Giles W Robinson, Marlyane Motta, Alessandro Matano, Suraj G Bhansali, Jason R Dobson, Sudha Parasuraman, Susan N Chi
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off)...
April 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28430806/incidence-and-risk-factors-for-post-penetrating-keratoplasty-glaucoma-a-systematic-review-and-meta-analysis
#10
Suqian Wu, Jianjiang Xu
OBJECTIVES: To establish the incidence and risk factors for post penetrating keratoplasty glaucoma (PKKG). METHODS: Studies published between 1947 and 2016 regarding penetrating keratoplasty (PK) were identified using an electronic search and reviewed. For search purpose, PKKG was defined as ocular hypertension (> 21mmHg) after PK. The incidence and risk factors of PKKG were extracted for all studies. Pooled incidence, odd ratios (ORs) and 95% confidence intervals (CIs) were calculated...
2017: PloS One
https://www.readbyqxmd.com/read/28428816/physical-health-policies-and-metabolic-screening-in-mental-health-care-systems-of-sub-saharan-african-countries-a-systematic-review
#11
REVIEW
James Mugisha, Marc De Hert, Brendon Stubbs, David Basangwa, Davy Vancampfort
BACKGROUND: There is a need for interventions to address the escalating mental health burden in sub-Saharan Africa (SSA). Addressing physical health needs should have a central role in reducing the burden and facilitating recovery in people with severe mental illness (SMI). We systematically investigated (1) physical health policies in the current mental health plans, and (2) the routine metabolic screening rates for people with SMI in SSA. METHODS: The Mental Health Atlas and MiNDbank of the World Health Organization were screened for physical health policies in mental health plans...
2017: International Journal of Mental Health Systems
https://www.readbyqxmd.com/read/28428119/timing-of-high-efficacy-therapy-in-relapsing-remitting-multiple-sclerosis-a-systematic-review
#12
REVIEW
Bernd Merkel, Helmut Butzkueven, Anthony L Traboulsee, Eva Havrdova, Tomas Kalincik
BACKGROUND: Immunotherapy initiated early after first presentation of relapsing-remitting multiple sclerosis is associated with improved long-term outcomes. One can therefore speculate that early initiation of highly effective immunotherapies, with an average efficacy that is superior to the typical first-line therapies, could further improve relapse and disability outcomes. However, the most common treatment strategy is to commence first-line therapies, followed by treatment escalation in patients who continue to experience on-treatment disease activity...
April 17, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28426675/indicators-of-suboptimal-biologic-therapy-over-time-in-patients-with-ulcerative-colitis-and-crohn-s-disease-in-the-united-states
#13
Haridarshan Patel, Trevor Lissoos, David T Rubin
This study assessed the occurrence of indicators for suboptimal biologic therapy among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the United States (US). Data from a large US claims database (2005-2013) were used to retrospectively identify patients with diagnosed with either UC or CD who were new biologic users. Indicators of suboptimal biologic therapy included: dose escalation during the maintenance phase, discontinuation of the initial biologic, switch to another biologic within 90 days following the last day of supply of the initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD-related surgery, UC- or CD-related urgent care, and development of fistula (for CD only)...
2017: PloS One
https://www.readbyqxmd.com/read/28426355/income-levels-and-response-to-contingency-management-for-smoking-cessation
#14
Carla López-Núñez, Roberto Secades-Villa, Elsa Peña-Suárez, Sergio Fernández-Artamendi, Sara Weidberg
BACKGROUND: Contingency management (CM) has demonstrated its efficacy in treating many drug addictions, including nicotine. However, one of the most commonly perceived limitations with regard to its dissemination into community settings is whether this protocol could be equally effective for treating patients across different income levels. OBJECTIVE: This study aimed to examine whether individuals' income levels affect treatment success in a cognitive behavioral treatment (CBT) that included a voucher-based CM protocol for smoking cessation...
June 7, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28426137/hydroxyurea-hydroxycarbamide-for-sickle-cell-disease
#15
REVIEW
Sarah J Nevitt, Ashley P Jones, Jo Howard
BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting...
April 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28425767/chronic-total-coronary-occlusion-treatment-results
#16
Martin Kirk Christensen, Phillip Fischer Freeman, Jeppe Groendal Rasmussen, Anton Boel Villadsen, Bent Raungaard, Svend Eggert Jensen, Leif Thuesen
OBJECTIVES: To describe the clinical and procedural coronary chronic total occlusion (CTO) treatment results in a Nordic PCI centre during the implementation of a CTO treatment program. DESIGN: In a retrospective registry study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart failure score, (3) lesion complexity and (4) adverse events during hospital stay and three months following the index procedure...
April 20, 2017: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/28424962/phase-i-dose-escalation-study-of-milciclib-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#17
Sandrine Aspeslagh, Kunwar Shailubhai, Rastilav Bahleda, Anas Gazzah, Andréa Varga, Antoine Hollebecque, Christophe Massard, Anna Spreafico, Michele Reni, Jean-Charles Soria
BACKGROUND: This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m(2)/day, n = 3; 60 mg/m(2)/day, n = 3; and 80 mg/m(2)/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m(2)/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424876/extent-of-surgical-resection-and-adjuvant-temozolomide-improves-survival-in-pediatric-gbm-a-single-center-experience
#18
Subhash Gupta, Supriya Mallick, Rony Benson, K P Haresh, Pramod Kumar Julka, Goura Kishor Rath
BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m(2). Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy...
April 19, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28424801/problem-based-review-immune-mediated-complications-of-checkpoint-inhibitors-for-the-acute-physician
#19
Philip Webb, Terry W Rice, Tim Cooksley
Immunotherapy with 'checkpoint-inhibitors' has significantly improved outcomes for patients with a range of malignancies. However, significant immune-mediated toxicities of these therapies are well-described. These immune-mediated toxicities can affect virtually all organ systems and are potentially fatal. The timing of onset of the adverse effects is dependent on the organ system affected and can occur after completion of the treatment. The increasing utilisation of 'checkpoint-inhibitors' means that Acute Physicians are likely to see a number of immune-mediated complications presenting to the AMU...
2017: Acute Medicine
https://www.readbyqxmd.com/read/28423367/imatinib-dose-escalation-versus-sunitinib-as-a-second-line-treatment-against-advanced-gastrointestinal-stromal-tumors-a-nationwide-population-based-cohort-study
#20
Jun-Te Hsu, Puo-Hsien Le, Chang-Fu Kuo, Meng-Jiun Chiou, Chia-Jung Kuo, Tsung-Hsing Chen, Chun-Jung Lin, Jen-Shi Chen, Huang-Pin Yu, Chun-Nan Yeh, Yi-Yin Jan, Ta-Sen Yeh
BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively...
April 3, 2017: Oncotarget
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