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Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer
TAS-102, a combination of trifluridine and tipiracil in which tipiracil interferes with the deactivation of trifluridine, improved overall and progression-free survival in patients whose disease had progressed after treatment with fluorouracil-containing drug combinations.
Fluoropyrimidines have long represented the cornerstone of treatment for colorectal cancer.
1
Such compounds act primarily as inhibitors of thymidylate synthase, the rate-limiting enzyme in the synthesis of pyrimidine nucleotides.
2
Fluorouracil has been combined with folinic acid (also known as leucovorin) to enhance the capacity of fluorouracil to bind to thymidylate synthase.
2
The addition of irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) to fluorouracil and folinic acid, in combination with either a vascular endothelial growth factor inhibitor (bevacizumab) or an epidermal growth factor inhibitor (e.g., cetuximab or panitumumab) if the tumor contains a wild-type
RAS
gene, represents contemporary standard therapy and has extended . . .
Journal Article
Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study
Purpose
To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.
Methods
The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1–2 who received invasive mechanical ventilation.
Results
2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO
2
/FiO
2
ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.
Conclusions
Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.
Trial Registration: ClinicalTrials.gov NCT02010073.
Journal Article
Fitness after 40 : your strong body at 40, 50, 60, and beyond
\"Includes a 6-week total-body workout program.\"
Book
Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer
In women with hormone-receptor–positive metastatic breast cancer that had progressed after endocrine therapy, palbociclib plus fulvestrant was associated with progression-free survival of more than 9 months, as compared with less than 4 months with fulvestrant alone.
Approximately 80% of breast cancers express estrogen receptors, progesterone receptors, or both. Endocrine therapies are the mainstay of treatment for these hormone-receptor–positive cancers, substantially reducing the relapse rate after presentation with early-stage cancer.
1
Despite advances in endocrine therapy, many women have a relapse during or after completing adjuvant therapy. The care of these women remains a considerable clinical challenge. Single-agent treatment with an aromatase inhibitor or tamoxifen has shown limited clinical benefit.
2
,
3
The selective estrogen-receptor degrader fulvestrant has modest activity in this population of patients,
4
,
5
and the development of effective therapies that can reverse resistance to endocrine therapy . . .
Journal Article
Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source
In a randomized trial involving patients who had a first stroke from an embolus of unknown source, rivaroxaban at a daily dose of 15 mg did not result in a lower incidence of recurrent stroke than aspirin at a dose of 100 mg. Bleeding rates were higher with rivaroxaban.
Journal Article
Beauty 40+ : 24 looks to feel beautiful
A guide to beauty for mature women covers age-appropriate makeup looks, with twenty-five step-by-step, illustrated instructions, and offers beauty advice, essential tools, and helpful tips for beauty care from head to toe.
Book
Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis
In this randomized, placebo-controlled trial, treatment with nintedanib, an intracellular inhibitor of multiple tyrosine kinases, led to a reduced rate of loss of forced vital capacity in patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is a fatal lung disease characterized by worsening dyspnea and progressive loss of lung function.
1
A decline in forced vital capacity (FVC) is consistent with disease progression and is predictive of reduced survival time.
1
–
6
Idiopathic pulmonary fibrosis is believed to arise from an aberrant proliferation of fibrous tissue and tissue remodeling due to the abnormal function and signaling of alveolar epithelial cells and interstitial fibroblasts.
7
The activation of cell-signaling pathways through tyrosine kinases such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of . . .
Journal Article