Approximately 5%–10% of gastric cancers have a fibroblast growth factor receptor-2 (FGFR2) gene amplification. AZD4547 is a selective FGFR-1, 2, 3 tyrosine kinase inhibitor with potent preclinical ...activity in FGFR2 amplified gastric adenocarcinoma SNU16 and SGC083 xenograft models. The randomized phase II SHINE study (NCT01457846) investigated whether AZD4547 improves clinical outcome versus paclitaxel as second-line treatment in patients with advanced gastric adenocarcinoma displaying FGFR2 polysomy or gene amplification detected by fluorescence in situ hybridization.
Patients were randomized 3:2 (FGFR2 gene amplification) or 1:1 (FGFR2 polysomy) to AZD4547 or paclitaxel. Patients received AZD4547 80 mg twice daily, orally, on a 2 weeks on/1 week off schedule of a 21-day cycle or intravenous paclitaxel 80 mg/m2 administered weekly on days 1, 8, and 15 of a 28-day cycle. The primary end point was progression-free survival (PFS). Safety outcomes were assessed and an exploratory biomarker analysis was undertaken.
Of 71 patients randomized (AZD4547n = 41, paclitaxel n = 30), 67 received study treatment (AZD4547n = 40, paclitaxel n = 27). Among all randomized patients, median PFS was 1.8 months with AZD4547 and 3.5 months with paclitaxel (one-sided P = 0.9581); median follow-up duration for PFS was 1.77 and 2.12 months, respectively. The incidence of adverse events was similar in both treatment arms. Exploratory biomarker analyses revealed marked intratumor heterogeneity of FGFR2 amplification and poor concordance between amplification/polysomy and FGFR2 mRNA expression.
AZD4547 did not significantly improve PFS versus paclitaxel in gastric cancer FGFR2 amplification/polysomy patients. Considerable intratumor heterogeneity for FGFR2 gene amplification and poor concordance between FGFR2 amplification/polysomy and FGFR2 expression indicates the need for alternative predictive biomarker testing. AZD4547 was generally well tolerated.
Research has revealed that exercise is effective for reducing symptoms of depression and anxiety. The mechanisms by which these reductions occur, however, have not been widely studied. To examine ...several potential theories, a prospective, randomized, 7‐week exercise intervention was conducted. Untrained participants were randomly assigned to an aerobic exercise group or to a stretching‐control group. Participants completed several questionnaires to assess psychological variables, including measures of depression and anxiety, and blood was drawn at pre‐ and post‐test to measure serum serotonin levels. A mixed‐design ANOVA revealed that the exercise group had lower levels of depression than the stretching‐control group after the intervention. The exercise group also showed a larger percentage decrease in serotonin than the stretching‐control group. This reduction in blood serotonin after exercise is similar to the effects of selective serotonin reuptake inhibitors. Additionally, percent change in serotonin was found to partially mediate the relationship between exercise and depression.
We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 ...receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment. Two partial responses (PR) and 19 stable disease (SD) patients were observed at the 12-week time point. At 28 weeks, according to centrally reviewed Response Evaluation Criteria in Solid Tumours (RECIST) criteria, five PR and 8 SD patients were observed in 50 assessable cases. Overall, objective response rate (5 PR) was of 10%, meeting the pre-specified endpoint. Fourteen patients discontinued due to adverse events. Eleven patients had retinal pigment epithelial detachments which was asymptomatic and reversible in all but one patient. Exploratory ribonucleic acid sequencing (RNA-Seq) analysis was done on patients' samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547.
Since one of the costs in the commercial egg industry is that of replacement pullets, commercial egg layer managers have opted to induce molt older hens in order to extend their productive life for ...additional egg laying cycles. Conventional molt induction involves the complete removal of feed for several days. However, this management practice can lead to deleterious physiological responses by the hen and subsequent susceptibility to infection by pathogens. Consequently less stressful molting regimens involving the feeding of low energy diets such as alfalfa have been developed. In this study, 80 week old laying hens that were deprived of feed or fed alfalfa meal during a nine day induced molt. Full fed hens were used as the control. On day 8 serum triglycerides were quantified and on day 9 hens were euthanized and the liver, spleen, heart, intestine, pancreas, ovary, and kidney were collected and weighed. Intestinal weight were highest in the non-molted hens, lower in the hens fed alfalfa, and lower still in the hens deprived of feed. Molted hens exhibited reduced weights of liver, heart, ovary, and pancreas compared to the non-molted hens. Serum triglycerides were highest in the non-molted hens, less in feed deprived hens, and the lowest in alfalfa fed hens. These results suggest that a comparable molt could be achieved with feeding alfalfa meal to 80 week hens compared to feed deprivation.
ABSTRACT
Introduction
Prolonged field care for junctional wounds is challenging and involves limb movement to facilitate transport. No studies to date have explored the efficacy of gauze products to ...limit rebleeding in these scenarios.
Materials and Methods
We randomly assigned 48 swine to QuikClot Combat Gauze, ChitoGauze, NuStat Tactical, or Kerlix treatment groups (12 each) and then inflicted a severe groin injury by utilizing a modified Kheirabadi model of a 6-mm femoral artery punch followed by unrestricted bleeding for 60 seconds. We reassessed rebleed following limb movement at 30 minutes of stabilization and 4 hours after stabilization.
Results
Swine treated with Combat Gauze proved to have the lowest incidence of rebleeding, and conversely, NuStat Tactical had the highest incidence of rebleeding at wounds after limb movement. Importantly, rebleeds occurred at a rate of 25%-58% across all swine treatment groups at 30 minutes postinjury and 0%-42% at 270 minutes postinjury demonstrating that limb movements universally challenge hemostatic junctional wounds.
Conclusions
Our findings highlight the difficulty of controlling hemorrhage from junctional wounds with hemostatic gauze in the context of prolonged field care and casualty transport. Our research can guide selection of hemorrhage control gauze when patients have prolonged field extraction or difficult transport. Our data demonstrates the frequency of junctional wound rebleeding after movement and thus the importance of frequent patient reassessment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
To evaluate whether bacterial vaginosis predicts the acquisition of sexually transmitted diseases (STDs), we studied 255 nonpregnant female subjects aged 15–30 who reported recent sexual contact with ...a male partner in whom either gonococcal or chlamydial urethritis or nongonococcal urethritis was diagnosed. Compared to subjects with normal vaginal flora, subjects with bacterial vaginosis were more likely to test positive for Neisseria gonorrhoeae (odds ratio OR, 4.1; 95% confidence interval CI, 1.7–9.7) and Chlamydia trachomatis (OR, 3.4; 95% CI, 1.5–7.8). Subjects colonized vaginally by hydrogen peroxide–producing lactobacilli were less likely to receive a diagnosis of chlamydial infection or gonorrhea than subjects without such lactobacilli. Bacterial vaginosis was a strong predictor of gonorrhea and chlamydial infection among subjects who reported recent exposure to a male partner with urethritis. These data support the importance of vaginal flora in the defense against STD acquisition.
Fluoroquinolones are widely prescribed antibiotics with well-known, mostly transient adverse effects, the most common of which are gastrointestinal disturbances, headaches, dizziness, rash, etc. ...However, a less recognized yet profoundly debilitating complication exists known as fluoroquinolone-associated disability (FQAD), operationally defined as impacting at least two systems (neurological, musculoskeletal, psychiatric, and/or cardiovascular) for at least 30 days post-cessation of a fluoroquinolone and with an outcome reported as disability. Unfortunately, this syndrome has yet to be formally recognized by the medical community. As such, FQAD patients are rarely diagnosed and undergo extensive diagnostic testing, leading to unnecessary costs to the patient and our healthcare system. Herein, we present the case of a 41-year-old male patient who developed acute bilateral numbness and tingling in his upper and lower extremities after just two doses of ciprofloxacin for epididymitis. Despite extensive evaluations from various specialists and therapists over the following 18 months, his symptoms continued to progress without any clear insight into the cause of his symptoms. He eventually reached out to an FQAD specialist due to his own suspicions and began therapy with hyperbaric oxygen, IV magnesium, and IV glutathione. Mild improvement was noted from these therapies, but he was unable to undergo regular treatments due to the financial debt acquired from his extensive medical workups and ultimately stopped treatment completely without any further improvements. Our case report highlights the importance of early recognition of FQAD to start prompt treatment and avoid costly testing. Overall, we aim to raise awareness of FQAD among clinicians as a potential complication of fluoroquinolone use.
The practice of induced molting involves the restriction of light, feed removal and optionally water for 5–14 days. However, there is growing concern regarding feed removal and animal welfare issues. ...With this in mind, alternative diets have been developed to produce similar molting effects as that of feed deprivation. Alfalfa, which largely consists of insoluble fiber, can be used as a molting diet. In this study, heterophil and lymphocyte counts, serum chemistry, and organ weight parameters were evaluated in hens that were deprived of feed or fed alfalfa during a nine day induced molt. Full-fed hens were used as the control. Blood serum parameters assessed included calcium, magnesium, glucose, total protein, ketone bodies, uric acid, and cholesterol. White blood cells were counted and categorized by cell type. On the ninth day of the trial, the hens were euthanized and the liver, spleen, heart, intestine, pancreas, ovary, oviduct, and kidney were collected and weighed. On day 8 birds molted with alfalfa or by feed deprivation had significantly higher (
P
<
0.05) levels of ketone bodies and cholesterol and lower levels of calcium, and magnesium compared to the full-fed hens while birds molted by feed deprivation exhibited significantly lower levels of uric acid. Birds molted by both methods exhibited significant reductions in ovary, oviduct, liver and pancreas weights and increased spleen weights when compared to the non-molted hens. On days 0, 2, and 6 there were no significant differences (
P
>
0.05) in either heterophil or lymphocyte percentages. However, heterophil percentages were higher in feed withdrawal birds than full-fed birds on day 4 but lymphocyte percentages were higher in full-fed birds compared to feed withdrawal birds. On day 8 of the induced molt lymphocyte percentages were higher from full-fed birds when compared to feed withdrawal birds but no significant differences were detectable for heterophil percentages. Based on reproductive organ weight loss and changes in serum and immunological responses of birds during molt, it appears that alfalfa meal can be an effective molt induction alternative.
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