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https://www.readbyqxmd.com/read/28542523/impact-of-maintenance-immunosuppressive-therapy-on-the-fecal-microbiome-of-renal-transplant-recipients-comparison-between-an-everolimus-and-a-standard-tacrolimus-based-regimen
#1
Gianluigi Zaza, Alessandra Dalla Gassa, Giovanna Felis, Simona Granata, Sandra Torriani, Antonio Lupo
BACKGROUND: The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. METHODS: We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols...
2017: PloS One
https://www.readbyqxmd.com/read/28541542/reducing-stock-outs-of-essential-tuberculosis-medicines-a-system-dynamics-modelling-approach-to-supply-chain-management
#2
L Bam, Z M McLaren, E Coetzee, K H von Leipzig
The under-performance of supply chains presents a significant hindrance to disease control in developing countries. Stock-outs of essential medicines lead to treatment interruption which can force changes in patient drug regimens, drive drug resistance and increase mortality. This study is one of few to quantitatively evaluate the effectiveness of supply chain policies in reducing shortages and costs. This study develops a systems dynamics simulation model of the downstream supply chain for amikacin, a second-line tuberculosis drug using 10 years of South African data...
May 24, 2017: Health Policy and Planning
https://www.readbyqxmd.com/read/28527735/advances-in-combination-therapy-of-lung-cancer-rationales-delivery-technologies-and-dosage-regimens
#3
REVIEW
Lan Wu, Donglei Leng, Dongmei Cun, Camilla Foged, Mingshi Yang
Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#4
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28505268/pharmacodynamics-of-dose-escalated-front-loading-polymyxin-b-regimens-against-polymyxin-resistant-mcr-1-harbouring-escherichia-coli
#5
Nicholas M Smith, Zackery P Bulman, Arthur O Sieron, Jürgen B Bulitta, Patricia N Holden, Roger L Nation, Jian Li, Gerard D Wright, Brian T Tsuji
Objectives: Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to the 'last-line' polymyxins and have been reported worldwide. Our objective was to define the impact of increasing the initial polymyxin B dose intensity against an mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin resistance on the dynamics of bacterial killing and resistance. Methods: A hollow fibre infection model (HFIM) was used to simulate polymyxin B regimens against an mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days...
May 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28489271/successful-treatment-of-kshv-inflammatory-cytokine-syndrome-kics-after-kidney-liver-transplant-correlations-with-hhv8-mirnome-and-specific-t-cell-response
#6
Alessandra Mularoni, Alessia Gallo, Giovanni Riva, Patrizia Barozzi, Monica Miele, Giovanni Cardinale, Giovanni Vizzini, Riccardo Volpes, Paolo Grossi, Daniele Di Carlo, Angelo Luca, Tommaso Trenti, Mario Luppi, Pier Giulio Conaldi
In post-transplant patients, HHV-8/KSHV infection is known to cause aggressive tumors, as well as severe non-neoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyper-inflammatory host responses, typically characterized by high viral loads, elevated levels of cytokines and other inflammation biomarkers, cytopenia, organ failure, high fever, and worsening conditions (with no evidence of B-cell neoplasias). These disorders are associated with a high mortality rate, often due to lack of prompt diagnosis, effective therapeutic approaches, and adequate follow up...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28488013/monitoring-with-sensitive-tumor-markers-contributes-to-decision-making-and-better-prognosis-in-gastric-cancer-patients-with-peritoneal-recurrence
#7
Takuma Ohashi, Shuhei Komatsu, Daisuke Ichikawa, Toshiyuki Kosuga, Kazuma Okamoto, Tomohiro Arita, Hirotaka Konishi, Ryo Morimura, Yasutoshi Murayama, Atsushi Shiozaki, Yoshiaki Kuriu, Hisashi Ikoma, Masayoshi Nakanishi, Hitoshi Fujiwara, Eigo Otsuji
BACKGROUND: There is no evidence that monitoring tumor dynamics using sensitive tumor markers contributes to treatment decision-making and prognosis in gastric cancer patients with tumor recurrence. This study was designed to investigate the significance of tumor markers in monitoring peritoneal recurrence of gastric cancer. METHODS: We retrospectively analysed 102 consecutive patients who developed recurrence after curative gastrectomy for gastric cancer at our institute between 2002 and 2011...
May 9, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28484994/associations-of-blood-glucose-dynamics-with-antihyperglycemic-treatment-and-glycemic-variability-in-type-1-and-type-2-diabetes
#8
K-D Kohnert, P Heinke, L Vogt, P Augstein, A Thomas, E Salzsieder
AIMS: The dynamical structure of glucose fluctuation has largely been disregarded in the contemporary management of diabetes. METHODS: In a retrospective study of patients with diabetes, we evaluated the relationship between glucose dynamics, antihyperglycemic therapy, glucose variability, and glucose exposure, while taking into account potential determinants of the complexity index. We used multiscale entropy (MSE) analysis of continuous glucose monitoring data from 131 subjects with type 1 (n = 18), type 2 diabetes (n = 102), and 11 nondiabetic control subjects...
May 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28468516/clinical-efficacy-of-eribulin-mesylate-for-the-treatment-of-metastatic-soft-tissue-sarcoma
#9
Sheik Emambux, Antoine Italiano
Metastatic soft tissue sarcoma, a devastating disease, has a median overall survival of only 12-18 months. Treatment options remain scarce. However, eribulin mesylate, a first-in-class halichondrin B-based microtubule dynamics inhibitor, has recently been approved for the management of patients with advanced liposarcoma. Areas covered: Based on a review of the literature between 2005 and 2017, we present a summary of eribulin mesylate's mechanism of action and the studies showing its clinical efficacy in locally advanced or metastatic sarcomas...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28460624/dabigatran-metabolism-pharmacologic-properties-and-drug-interactions
#10
Nebojsa Antonijevic, Ivana Zivkovic, Ljubica Jovanovic, Dragan Matic, Mladen Kocica, Igor Mrdovic, Vladimir Kanjuh, Milica Culafic
The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration...
April 26, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28450729/collateral-sensitivity-networks-reveal-evolutionary-instability-and-novel-treatment-strategies-in-alk-mutated-non-small-cell-lung-cancer
#11
Andrew Dhawan, Daniel Nichol, Fumi Kinose, Mohamed E Abazeed, Andriy Marusyk, Eric B Haura, Jacob G Scott
Drug resistance remains an elusive problem in cancer therapy, particularly for novel targeted therapies. Much work is focused upon the development of an arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops over time. Currently, after failure of first line ALK TKI therapy, another ALK TKI is administered, though collateral sensitivity is not considered. To address this, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK TKIs, and performed a collateral sensitivity analysis...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28445881/absence-of-decline-of-kidney-function-in-human-immunodeficiency-virus-infected-patients-under-routine-clinical-management
#12
Julie Boucquemont, Sylvie Lawson-Ayayi, Claire Rigothier, Fabrice Bonnet, Cécile Proust-Lima, Didier Neau, Carine Greib, Ghada Miremont-Salamé, François Dabis, Michel Dupon, Frédéric-Antoine Dauchy
BACKGROUND: Since the introduction of antiretroviral therapy (ART), human immunodeficiency virus (HIV)-infected patients have a drastically improved prognosis but at the same time they are also more affected by non-HIV related complications, such as chronic kidney disease. The objective of our study was to investigate the effect of proteinuria and tenofovir (TDF)-containing ART regimens on the temporal evolution of estimated glomerular filtration rate (eGFR). METHODS: Between April 2008 and October 2012, we enrolled 395 patients with a complete renal evaluation among patients from the ANRS C03 Aquitaine cohort, a prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in southwestern France...
April 26, 2017: Nephron
https://www.readbyqxmd.com/read/28445109/distinct-prevalence-of-drug-resistant-tuberculosis-in-gansu-china-a-retrospective-study-on-drug-susceptibility-profiles-between-2010-and-2014
#13
XingFang Li, Lei Wang, Yanling Tan, Jun Hou, Jianjun Ma
Limited knowledge is available on regional distribution of antituberculosis (TB) drug resistance and on province-specific time-trends in TB drug susceptibility in China. To obtain the latest information about the dynamics of drug-resistant TB in Gansu province, we conducted a retrospective study and analyzed data on drug resistance among new TB cases diagnosed between June 2010 and May 2014 in Gansu, China. The data were collected from the only TB surveillance and treatment hospital in Gansu and, therefore, represented the epidemiology of TB in the province...
April 26, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28431319/response-of-plasma-glucagon-like-peptide-2-to-feeding-pattern-and-intraruminal-administration-of-volatile-fatty-acids-in-sheep
#14
M Elsabagh, Y Inabu, T Obitsu, T Sugino
Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L cells, has recently been identified as a key regulator of intestinal growth and absorptive function in ruminants. However, reports on GLP-2 secretion are few, and more information regarding its secretion dynamics is needed. In this study, two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion in response to feeding regimen and to investigate the effect of volatile fatty acids (VFA) on GLP-2 release in sheep...
March 11, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28428446/the-finite-state-projection-approach-to-analyze-dynamics-of-heterogeneous-populations
#15
Rob Johnson, Brian Munsky
Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity...
May 11, 2017: Physical Biology
https://www.readbyqxmd.com/read/28424085/the-within-host-population-dynamics-of-mycobacterium-tuberculosis-vary-with-treatment-efficacy
#16
Andrej Trauner, Qingyun Liu, Laura E Via, Xin Liu, Xianglin Ruan, Lili Liang, Huimin Shi, Ying Chen, Ziling Wang, Ruixia Liang, Wei Zhang, Wang Wei, Jingcai Gao, Gang Sun, Daniela Brites, Kathleen England, Guolong Zhang, Sebastien Gagneux, Clifton E Barry, Qian Gao
BACKGROUND: Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics...
April 19, 2017: Genome Biology
https://www.readbyqxmd.com/read/28410351/viral-dynamics-among-hepatitis-c-virus-chronic-infected-patients-during-direct-acting-antiviral-agents-therapy-impact-for-monitoring-and-optimizing-treatment-duration
#17
Andres Tabernilla, Marta Grandal, Berta Pernas, Angeles Castro-Iglesias, Iria Rodríguez-Osorio, Alvaro Mena, Manuel Delgado, Purificacion Cid, Jose D Pedreira, Eva Poveda
OBJECTIVES: Direct-acting antiviral agents (DAAs) have provided an ultimate treatment duration of 12 weeks for most hepatitis C virus (HCV)-infected patients. The opportunity to reduce treatment duration to 6 or 8 weeks is being evaluated. Here, the HCV viral dynamics at short times during HCV therapies and its implications for monitoring and optimizing treatment duration have been assessed. PATIENTS AND METHODS: HCV chronic infected patients who began HCV therapy (March 2014 to June 2015) at a reference hospital of the Northwest of Spain were selected...
April 13, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#18
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28369408/wgs-based-surveillance-of-third-generation-cephalosporin-resistant-escherichia-coli-from-bloodstream-infections-in-denmark
#19
Louise Roer, Frank Hansen, Martin Christen Frølund Thomsen, Jenny Dahl Knudsen, Dennis Schrøder Hansen, Mikala Wang, Jurgita Samulioniené, Ulrik Stenz Justesen, Bent L Røder, Helga Schumacher, Claus Østergaard, Leif Percival Andersen, Esad Dzajic, Turid Snekloth Søndergaard, Marc Stegger, Anette M Hammerum, Henrik Hasman
Objectives: To evaluate a genome-based surveillance of all Danish third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec ) from bloodstream infections between 2014 and 2015, focusing on horizontally transferable resistance mechanisms. Methods: A collection of 552 3GC-R Ec isolates were whole-genome sequenced and characterized by using the batch uploader from the Center for Genomic Epidemiology (CGE) and automatically analysed using the CGE tools according to resistance profile, MLST, serotype and fimH subtype...
March 22, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28356552/pharmacokinetic-pharmacodynamic-modelling-of-intracellular-mycobacterium-tuberculosis-growth-and-kill-rates-is-predictive-of-clinical-treatment-duration
#20
Ghaith Aljayyoussi, Victoria A Jenkins, Raman Sharma, Alison Ardrey, Samantha Donnellan, Stephen A Ward, Giancarlo A Biagini
Tuberculosis (TB) treatment is long and complex, typically involving a combination of drugs taken for 6 months. Improved drug regimens to shorten and simplify treatment are urgently required, however a major challenge to TB drug development is the lack of predictive pre-clinical tools. To address this deficiency, we have adopted a new high-content imaging-based approach capable of defining the killing kinetics of first line anti-TB drugs against intracellular Mycobacterium tuberculosis (Mtb) residing inside macrophages...
March 29, 2017: Scientific Reports
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