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https://www.readbyqxmd.com/read/29351303/automated-inverse-optimization-facilitates-lower-doses-to-normal-tissue-in-pancreatic-stereotactic-body-radiotherapy
#1
Ivaylo B Mihaylov, Eric A Mellon, Raphael Yechieli, Lorraine Portelance
PURPOSE: Inverse planning is trial-and-error iterative process. This work introduces a fully automated inverse optimization approach, where the treatment plan is closely tailored to the unique patient anatomy. The auto-optimization is applied to pancreatic stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: The automation is based on stepwise reduction of dose-volume histograms (DVHs). Five uniformly spaced points, from 1% to 70% of the organ at risk (OAR) volumes, are used...
2018: PloS One
https://www.readbyqxmd.com/read/29350463/brim-p-a-phase-i-open-label-multicenter-dose-escalation-study-of-vemurafenib-in-pediatric-patients-with-surgically-incurable-braf-mutation-positive-melanoma
#2
Julia C Chisholm, Jozef Suvada, Ira J Dunkel, Michela Casanova, Weijiang Zhang, Natasha Ritchie, YounJeong Choi, Jane Park, Meghna Das Thakur, Stephen Simko, Nga Wan Rachel Tam, Andrea Ferrari
BACKGROUND: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We conducted a phase I, open-label, dose-escalation study in pediatric patients aged 12-17 years with this tumor type (NCT01519323). PROCEDURE: Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3 + 3 design. Patients were monitored for dose-limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29349757/management-of-the-axilla-in-early-breast-cancer
#3
Monica G Valero, Mehra Golshan
Management of the axilla in early breast cancer patients has significantly evolved in the last several decades. With the arrival of the sentinel lymph node biopsy, surgical practice for axillary staging in patients with early breast cancer has become gradually less invasive and formal axillary lymph node dissection has been confined to selected patients. Over the last two decades, evidence from randomized clinical trials have allowed for the de-escalation of axillary surgery in the management of early stage breast cancer...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29348828/dose-escalation-by-image-guided-intensity-modulated-radiotherapy-leads-to-an-increase-in-pain-relief-for-spinal-metastases-a-comparison-study-with-a-regimen-of-30-gy-in-10-fractions
#4
Jinlan He, Jianghong Xiao, Xingchen Peng, Baofeng Duan, Yan Li, Ping Ai, Min Yao, Nianyong Chen
Purpose: Under the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60-66 Gy in 20-30 fractions for spinal metastases. Results: In the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348589/novel-miniature-membrane-active-lipopeptidomimetics-against-planktonic-and-biofilm-embedded-methicillin-resistant-staphylococcus-aureus
#5
Seema Joshi, Sana Mumtaz, Jyotsna Singh, Santosh Pasha, Kasturi Mukhopadhyay
Escalating multidrug resistance and highly evolved virulence mechanisms have aggravated the clinical menace of methicillin-resistant Staphylococcus aureus (MRSA) infections. Towards development of economically viable staphylocidal agents here we report eight structurally novel tryptophan-arginine template based peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S-7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and good to potent activity against clinically relevant pathogens MRSA, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (MIC: 1...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348486/phase-i-dose-escalation-study-of-copanlisib-in-combination-with-gemcitabine-or-cisplatin-plus-gemcitabine-in-patients-with-advanced-cancer
#6
R D Kim, S R Alberts, C Peña, I Genvresse, A Ajavon-Hartmann, C Xia, A Kelly, J E Grilley-Olson
BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant PI3K-α/δ activity that has demonstrated clinical activity and manageable safety when administered as monotherapy in a phase II study. Combination therapy may overcome compensatory signalling that could occur with PI3K pathway inhibition, resulting in enhanced inhibitory activity, and preclinical studies of copanlisib with gemcitabine have demonstrated potent anti-tumour activity in vivo...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29348280/marked-cachexia-in-probable-invasive-pulmonary-aspergillosis-with-bronchopleural-fistula
#7
Christiana Page, Laura Blazy, Melanie Jenkins, Rosalba Spiritoso
A 49-year-old man with a medical history of diabetes and heavy smoking was admitted to intensive care with severe bilateral pneumonia associated with marked cachexia. He developed a complex right-sided bronchopleural fistula and was transferred to our tertiary centre for consideration of surgical intervention.Despite escalation of antibiotic therapy, he did not improve and further investigations led to a diagnosis of invasive pulmonary aspergillosis. Definitive treatment plans required a right pneumonectomy; however, given the severity of cachexia, he remained unable to undergo such a large operation...
January 17, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29346478/differentiation-syndrome-associated-with-enasidenib-a-selective-inhibitor-of-mutant-isocitrate-dehydrogenase-2-analysis-of-a-phase-1-2-study
#8
Amir T Fathi, Courtney D DiNardo, Irina Kline, Laurie Kenvin, Ira Gupta, Eyal C Attar, Eytan M Stein, Stephane de Botton
Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2) protein inhibitor that promotes differentiation of leukemic myeloblasts, was recently approved by the US Food and Drug Administration for use in relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the first study of enasidenib in humans, a minority of patients with advanced myeloid neoplasms experienced unexpected signs/symptoms of a differentiation syndrome (DS), a potentially lethal entity...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346247/concurrent-versus-sequential-intrapleural-instillation-of-tissue-plasminogen-activator-and-deoxyribonuclease-for-pleural-infection
#9
Fayez Kheir, George Cheng, Estefania Rivera, Alejandro Folch, Erik Folch, Fernandez-Bussy Sebastian, Colleen Keyes, Mihir Parikh, Colleen Channick, Alex Chee, Adnan Majid
BACKGROUND: Treatment of pleural infection with instillation of sequential intrapleural tissue plasminogen activator (tPA) and human recombinant deoxyribonuclease (DNase) twice daily for a total of 6 doses has been shown to decrease surgical referral and improve radiographic imaging. This labor-intensive regimen was empirically chosen. Thus, it remains unclear whether the 2 drugs can be administered immediately one after the other (concurrent administration) instead of instilling them separately with a 1-hour to 2-hour interval in between (sequential administration)...
January 16, 2018: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/29345855/increased-estradiol-in-hepatitis-e-virus-infected-pregnant-women-promote-viral-replication
#10
Chenchen Yang, Wenhai Yu, Yanhong Bi, Feiyan Long, Yunlong Li, Daqiao Wei, Xianhui Hao, Jianwen Situ, Yongqin Zhao, Fen Huang
Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high mortality (> 25%) in pregnant women. HEV replication is aggressively escalated in pregnant women, especially in the third trimester of pregnancy. Estrogen plays an important role in pregnancy. However, the pathogenesis of HEV in pregnant women or immunosuppressive pregnant women (such as HIV-infected, or organ-transplanted pregnant women) remains unclear. We investigated the role of estradiol in HEV infection in a cell culture system...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345517/pet-adapted-therapy-for-advanced-hodgkin-lymphoma-systematic-review
#11
Irina Amitai, Ronit Gurion, Liat Vidal, Eldad J Dann, Pia Raanani, Anat Gafter-Gvili
INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) performed after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome in advanced stage HL. METHODS: In August 2017, we searched electronic databases, conference proceedings and ongoing trials. We included all studies in which treatment modification for advanced HL was performed based on the results of the interim PET scan...
January 18, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29344926/the-mexican-drug-war-and-early-life-health-the-impact-of-violent-crime-on-birth-outcomes
#12
Ryan Brown
This study examines the relationship between exposure to violent crime in utero and birth weight using longitudinal data from a household survey conducted in Mexico. Controlling for selective migration and fertility, the results suggest that early gestational exposure to the recent escalation of the Mexican Drug War is associated with a substantial decrease in birth weight. This association is especially pronounced among children born to mothers of low socioeconomic status and among children born to mothers who score poorly on a mental health index...
January 17, 2018: Demography
https://www.readbyqxmd.com/read/29344836/boost-irradiation-integrated-to-whole-brain-radiotherapy-in-the-management-of-brain-metastases
#13
Ágnes Dobi, Emese Fodor, Anikó Maráz, Zsófia Együd, Adrienne Cserháti, László Tiszlavicz, Zita Reisz, Pál Barzó, Zoltán Varga, Katalin Hideghéty
Our retrospective analysis aimed to evaluate the clinical value of dose intensification schemes: WBRT and consecutive, delayed, or simultaneous integrated boost (SIB) in brain metastasis (BM) management. Clinical data and overall survival (OS) of 468 patients with BM from various primaries treated with 10 × 3 Gy WBRT (n = 195), WBRT+ 10 × 2 Gy boost (n = 125), or simultaneously 15 × 2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically analysed. Significant difference in OS could be detected with additional boost to WBRT (3...
January 17, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29343563/robotic-crabs-reveal-that-female-fiddler-crabs-are-sensitive-to-changes-in-male-display-rate
#14
Sophie L Mowles, Michael D Jennions, Patricia R Y Backwell
Males often produce dynamic, repetitive courtship displays that can be demanding to perform and might advertise male quality to females. A key feature of demanding displays is that they can change in intensity: escalating as a male increases his signalling effort, but de-escalating as a signaller becomes fatigued. Here, we investigated whether female fiddler crabs, Uca mjoebergi, are sensitive to changes in male courtship wave rate. We performed playback experiments using robotic male crabs that had the same mean wave rate, but either escalated, de-escalated or remained constant...
January 2018: Biology Letters
https://www.readbyqxmd.com/read/29343509/efficacy-and-safety-of-tregalizumab-in-patients-with-rheumatoid-arthritis-and-an-inadequate-response-to-methotrexate-results-of-a-phase-iib-randomised-placebo-controlled-trial
#15
Ronald F van Vollenhoven, Edward Clark Keystone, Vibeke Strand, Cesar Pacheco-Tena, Jiří Vencovský, Frank Behrens, Arthur Racewicz, Daniela Zipp, Faiza Rharbaoui, Ralf Wolter, Luise Knierim, Rainer Schmeidl, Xuefei Zhou, Silke Aigner, Benjamin Dälken, Andrea Wartenberg-Demand
OBJECTIVE: To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). METHODS: 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment...
January 17, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29343176/on-understanding-the-nature-of-interpersonal-conflict-between-coaches-and-athletes
#16
Svenja Wachsmuth, Sophia Jowett, Chris G Harwood
Conflict is a part of coach-athlete relationships and should be carefully considered as it can have effects on the quality of coaching and the level of performance. Despite its practical relevance, there is a dearth of research around coach-athlete conflict. Therefore, the current study aimed to explore the characteristics and topics of conflict, as well as coaches and athletes' emotional, cognitive and behavioural experiences during conflict. A total of 22 independent coaches and athletes participated in semi-structured interviews evolving around the nature of interpersonal conflict...
January 18, 2018: Journal of Sports Sciences
https://www.readbyqxmd.com/read/29341985/dexmedetomidine-as-single-continuous-sedative-during-noninvasive-ventilation-typical-usage-hemodynamic-effects-and-withdrawal
#17
Brittany L Shutes, Samantha W Gee, Cheryl L Sargel, Kelsey A Fink, Joseph D Tobias
OBJECTIVES: Dexmedetomidine use in pediatric critical care is increasing. Its prolonged effects as a single continuous agent for sedation are not well described. The aim of the current study was to describe prolonged dexmedetomidine therapy without other continuous sedation, specifically the hemodynamic effects, discontinuation strategies, and risk factors for withdrawal. DESIGN: Retrospective chart review. SETTING: Large, single-center, quaternary care pediatric academic institution...
January 16, 2018: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/29341844/empiric-antibiotics-for-sepsis
#18
Sara A Buckman, Isaiah R Turnbull, John E Mazuski
BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Early recognition and treatment are the cornerstones of management. METHODS: Review of the English-language literature. RESULTS: For both sepsis and septic shock "antimicrobials [should be] be initiated as soon as possible and within one hour" (Surviving Sepsis Campaign). The risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started...
January 17, 2018: Surgical Infections
https://www.readbyqxmd.com/read/29341836/a-cohort-study-of-patient-reported-outcomes-and-healthcare-utilization-in-acute-myeloid-leukemia-patients-receiving-active-cancer-therapy-in-the-last-six-months-of-life
#19
Jared R Lowe, Yinxi Yu, Steven Wolf, Greg Samsa, Thomas W LeBlanc
BACKGROUND: Evidence about the unique palliative care needs of patients with acute myeloid leukemia (AML) is limited. Improving the care of these patients will require a better understanding of their unmet needs, including symptom burden at the end of life, and patterns of healthcare utilization. OBJECTIVE: To describe AML patients' experiences in the last six months of life regarding symptom burden, blood product utilization, and use of palliative care services...
January 17, 2018: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/29341491/clinical-outcomes-of-carbon-ion-radiotherapy-with-concurrent-chemotherapy-for-locally-advanced-uterine-cervical-adenocarcinoma-in-a-phase-1-2-clinical-trial-protocol-1001
#20
Noriyuki Okonogi, Masaru Wakatsuki, Shingo Kato, Kumiko Karasawa, Hiroki Kiyohara, Shintaro Shiba, Daijiro Kobayashi, Takashi Nakano, Tadashi Kamada, Makio Shozu
We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty-three patients were enrolled between April 2010 and March 2014. Treatment consisted of C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2 . In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C-ion RT...
January 17, 2018: Cancer Medicine
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