Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively ...preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity.
This was a phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) study of the safety, efficacy and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for treatment-naive extensive-stage small-cell lung cancer patients. Patients received trilaciclib or placebo before E/P on days 1–3 of each cycle. Select end points were prespecified to assess the effect of trilaciclib on myelosuppression and antitumor efficacy.
A total of 122 patients were enrolled, with 19 patients in part 1 and 75 patients in part 2 receiving study drug. Improvements were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, P = 0.3831); median PFS 6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107).
Trilaciclib demonstrated an improvement in the patient’s tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib’s myelopreservation benefits.
NCT02499770.
Abstract Sulfated polysaccharides from 11 species of tropical marine algae (one edible specie of Rhodophyta, six species of Phaeophyta and four species of Chlorophyta) collected from Natal city coast ...(Northeast of Brazil) were evaluated for their anticoagulant, antioxidant and antiproliverative in vitro activities. In the activated partial thromboplastin time (APTT) test, which evaluates the intrinsic coagulation pathway, seven seaweeds presented anticoagulant activity. Dictyota cervicornis showed the highest activity, prolonging the coagulation time to double the baseline value in the APTT with only 0.01 mg/100 μl of plasma, 1.4-fold lesser than Clexane® , a low molecular weight heparin. In the protrombin time (PT) test, which evaluates the extrinsic coagulation pathway, only Caulerpa cupresoides showed anticoagulant activity. All species collected showed antioxidant activities. This screening emphasized the great antioxidant potential (total capacity antioxidant, power reducing and ferrous chelating) of four species: C. sertularioide ; Dictyota cervicornis; Sargassum filipendula and Dictyopteris delicatula . After 72 h incubation, HeLa cell proliferation was inhibited ( p < 0.05) between 33.0 and 67.5% by S. filipendula ; 31.4 and 65.7% by D. delicatula ; 36.3 and 58.4% by Caulerpa prolifera and 40.2 and 61.0% by Dictyota menstrualis at 0.01–2 mg/mL algal polysaccharides. The antiproliferative efficacy of these algal polysaccharides were positively correlated with the sulfate content ( r = 0.934). Several polysaccharides demonstrated promising antioxidant, antiproliferative an/or anticoagulant potential and have been selected for further studies on bioguided fractionation, isolation and characterization of pure polysaccharides from these species as well as in vivo experiments are needed and are already in progress.
We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a ...randomized phase 2 trial in patients with metastatic pancreatic cancer.
Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m2 (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks Q2W), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate.
In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41–70) in the ganitumab arm, 59% (42–73) in the conatumumab arm, and 50% (33–64) in the placebo arm. The grade ≥3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%).
Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate.
There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and ...the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.
Bed management team with Kanban web-based application ROCHA, HERMANO ALEXANDRE LIMA; DA CRUZ SANTOS, ANA KELLY LIMA; DE CASTRO ALCÂNTARA, ANTÔNIA CELIA ...
International journal for quality in health care,
11/2018, Letnik:
30, Številka:
9
Journal Article
Recenzirano
Odprti dostop
To measure the effectiveness of the bed management process that uses a web-based application with Kanban methodology to reduce hospitalization time of hospitalized patients.
Before-after study was ...performed.
The study was conducted between July 2013 and July 2017, at the Unimed Regional Hospital of Fortaleza, which has 300 beds, of which 60 are in the intensive care unit (ICU). It is accredited by International Society for Quality in Healthcare.
Patients hospitalized in the referred period.
Bed management with an application that uses color logic to signal at which stage of high flow the patients meet, in which each patient is interpreted as a card of the classical Kanban theory. It has an automatic user signaling system for process movement, and a system for monitoring and analyzing discharge forecasts.
Length of hospital stay, number of customer complaints related to bed availability.
After the intervention, the hospital's overall hospital stay time was reduced from 5.6 days to 4.9 days (P = 0.001). The units with the greatest reduction were the ICUs, with reduction from 6.0 days to 2.0 (P = 0.001). The relative percentage of complaints regarding bed availability in the hospital fell from 27% to 0%.
We conclude that the use of an electronic tool based on Kanban methodology and accessed via the web by a bed management team is effective in reducing patients' hospital stay time.
In poison frogs (Dendrobatoidea), usually the males are territorial, care for terrestrial nests and later transport their offspring to waterbodies where they complete larval development. In some ...species, mothers care for their offspring or may exhibit flexible care to compensate for father absence. We conducted a multi-season field experiment with the Amazonian species Allobates paleovarzensis, in which it was possible to study the joint impact of paternal care and the El Niño climatic anomaly on offspring survival. The experiment consisted of two treatments: non-removal, and removal of the father from their territories. We observed that parental care was performed exclusively by the father, and none of the mothers of the 21 monitored nests transported the tadpoles. We also observed that the severe drought in a year under the influence of the El Niño event caused such a high mortality in all pre-metamorphic stages, that the role of parental care became irrelevant for offspring survival during that season. We found that pre-metamorphic Allobates paleovarzensis are highly vulnerable to the loss of paternal care. In addition, we showed that paternal care, when present, does not prevent offspring death under these increasingly frequent climatic anomalies.
Trend between the docking scores (PPARγ receptor) and the anti-inflammatory activity of eight new synthesized 5-arylidene-3-benzyl-thiazolidine-2,4-diones compounds. The compound
11 exhibited an ...anti-inflammatory activity slightly higher than the reference drug, rosiglitazone, a well-known potent agonist of the PPARγ.
Eight new 5-arylidene-3-benzyl-thiazolidine-2,4-diones with halide groups on their benzyl rings were synthesized and assayed in vivo to investigate their anti-inflammatory activities. These compounds showed considerable biological efficacy when compared to rosiglitazone, a potent and well-known agonist of PPARγ, which was used as a reference drug. This suggests that the substituted 5-arylidene and 3-benzylidene groups play important roles in the anti-inflammatory properties of this class of compounds. Docking studies with these compounds indicated that they exhibit specific interactions with key residues located in the site of the PPARγ structure, which corroborates the hypothesis that these molecules are potential ligands of PPARγ. In addition, competition binding assays showed that four of these compounds bound directly to the ligand-binding domain of PPARγ, with reduced affinity when compared to rosiglitazone. An important trend was observed between the docking scores and the anti-inflammatory activities of this set of molecules. The analysis of the docking results, which takes into account the hydrophilic and hydrophobic interactions between the ligands and the target, explained why the 3-(2-bromo-benzyl)-5-(4-methanesulfonyl-benzylidene)-thiazolidine-2,4-dione compound had the best activity and the best docking score. Almost all of the stronger hydrophilic interactions occurred between the substituted 5-arylidene group of this compound and the residues of the binding site.
Sesbania virgata (Cav.) Pers. seeds are protein sources with health and environmental benefits. In this research, proteins with lectin activity were identified in a protein fraction from S. virgata ...seeds (PFLA), as well its antioxidant and antimicrobial potentials, in addition to cytotoxic effects. To obtain PFLA, seed flour was homogenized in Glycine-NaOH (100 mM; pH 9.0; NaCl 150 mM) and precipitated in ammonium sulfate. PFLA concentrates bioactive lectins (32 HU/mL, 480 HU/gFa, 18.862 HU/mgP) and essential amino acids (13.36 g/100g protein). PFLA exerts antioxidant activity, acting as a promising metal chelating agent (~77% of activity). Analyzes of cell culture assay results suggest that antioxidant activity of PFLA may be associated with the recruitment of essential molecules to prevent the metabolic impairment of cells exposed to oxidative stress. PFLA (256 - 512 µg/mL) also exhibits antifungal activity, inhibiting the growth of Aspergillus flavus, Candida albicans, Candida tropicalis and Penicillium citrinum. Cytotoxic analysis indicates a tendency of low interference in the proliferation of 3T3 and HepG2 cells in the range of PFLA concentrations with biological activity. These findings support the notion that PFLA is a promising adjuvant to be applied in current policies on the management of metal ion chelation and fungal infections.
The detection and mapping of surface water resources for South America (DMSWSA) in Remote sensing context is a highly relevant issue from a scientific point of view due to the impact on the ...understanding of changes in the hydrological cycle, water availability, and climate in global terms since 45% of all water resources available on the globe are present on this continent. This study presents a new approach to evaluating the scientific literature of the last 21 years focused on DMSWSA in a Remote sensing scientific literature. Our study aims to carry out a bibliometric analysis on the application of the DMSWSA in a Remote sensing dominium to assess researchers, countries, and trends. We used the Scopus database for the literature search. Then we used bibliometric tools to access information and reveal quantification patterns of literature. Our results show that the most relevant contributions involved Brazil and Argentina. DMSWSA has only shown an expansion in recent years regarding the number of articles published and citations. It was possible to show that the DMSWSA in a Remote sensing scientific area needs further collaboration expansion between countries within South America and beyond this continental border. We reveal aspects of great importance and interest in the literature using bibliometric approaches to give a clear view of research trends for DMSWSA.
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