| 61. |
- Powles, T, et al.
(författare)
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Plain language summary of results from the JAVELIN Bladder 100 study: avelumab maintenance treatment for advanced urothelial cancer
- 2022
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Ingår i: Future oncology (London, England). - : Future Medicine Ltd. - 1744-8301 .- 1479-6694. ; 18:19, s. 2361-2371
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Tidskriftsartikel (refereegranskat)abstract
- This is a plain language summary of an article originally published in The New England Journal of Medicine. It is about initial results (collected in October 2019) from the JAVELIN Bladder 100 study (a clinical trial), which looked at avelumab maintenance treatment in people with advanced urothelial cancer. Urothelial cancer is the most common type of bladder cancer. People with advanced urothelial cancer often receive chemotherapy. If this is the first treatment people with advanced disease are given, it is called first-line treatment. If the cancer stops growing or shrinks with first-line chemotherapy, people can be given different treatment to try to prevent the cancer from growing again. This is called maintenance treatment. It may help people live longer. What happened in the JAVELIN Bladder 100 study? In the JAVELIN Bladder 100 study, researchers wanted to find out if maintenance treatment with avelumab would help people with advanced urothelial cancer live longer. Avelumab is a type of medicine called immunotherapy. Immunotherapy helps the body's immune system fight cancer. 700 people took part in the study. To take part, they must have already been treated with first-line chemotherapy. Also, their cancer must have shrunk or not grown with this treatment. They were then treated with either avelumab maintenance treatment plus best supportive care or best supportive care alone. Best supportive care means treatments that help improve symptoms and quality of life. These treatments do not affect the cancer directly and can include medicines to relieve pain. What were the results? Researchers found that people treated with avelumab maintenance treatment plus best supportive care lived, on average, 7 months longer than people who received best supportive care alone. People treated with avelumab had more side effects than those not treated with avelumab, but most were not severe. Common side effects with avelumab included persistent tiredness, itchy skin, urinary tract infection, and diarrhea. What do the results of the study mean? Results from the JAVELIN Bladder 100 study support the use of avelumab as maintenance treatment for people with advanced urothelial cancer whose cancer has shrunk or not grown with first-line chemotherapy. ClinicalTrials.gov NCT number: NCT02603432
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| 62. |
- Robba, Chiara, et al.
(författare)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 63. |
- Robba, Chiara, et al.
(författare)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 64. |
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| 66. |
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| 67. |
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| 68. |
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| 69. |
- Ullen, A., et al.
(författare)
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Additive/synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 644-50
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Tidskriftsartikel (refereegranskat)abstract
- Once bone metastasized and androgen independent, prostate cancer is often associated with skeletal morbidity and disability. New treatment modalities that can palliate symptoms from the skeleton and inhibit further progression are warranted. In this study, the antitumoral effects following treatment with a combination of docetaxel and the new generation bisphosphonate, zoledronic acid, were investigated on two hormone-refractory prostate cancer cell lines: PC3 and DU145. The prostate cancer cells were treated with increasing concentrations of zoledronic acid in the absence or presence of docetaxel. Toxicity was measured using fluorometric microculture cytotoxic assay technique. A concentration of 25 microM, zoledronic acid reduced the viable cell number to 68% and 98% for PC3 and DU145 cells respectively. Docetaxel, on the other hand, at a concentration of 0.1 ng/ml, had no effect on the viability. However, a combination of zoledronic acid and docetaxel reduced the cell number to 60% and 81% respectively. Furthermore, zoledronic acid in the concentration range 12.5 microM-50 microM enhanced the antitumoral effects of docetaxel (0.01-1 ng/ml) in an additive and/or synergistic manner for both cell lines. These data support the hypothesis that zoledronic acid, in addition to having bone resorption inhibiting properties, also exhibits anti-tumoral effects. It also appears that combined treatment with docetaxel causes additive and/or synergistic cytostatic effects on prostate cancer cells.
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| 70. |
- Ullen, A., et al.
(författare)
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Prostate cancer cell lines lack amplification: overexpression of HER2
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:5, s. 490-5
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Tidskriftsartikel (refereegranskat)abstract
- The potential overexpression of HER2 in prostate cancer cells has attended significant interest during the past few years, both as potential target for HER2 pathway focused therapy and as a mechanism involved in the progression to androgen independence. Conflicting results have been reported concerning HER2 status on clinical material, differences which generally have been attributed to methodological differences. Nevertheless, HER2 has been utilized for targeted therapy of prostate cancer in a number of preclinical studies and is still regarded as an exciting target molecule. In this study, the HER2 status of three widely used prostate cancer cell lines and corresponding xenografts has been analysed. By use of validated and FDA approved analytical staining techniques none of these cell lines or xenografts were shown to overexpress/amplify HER2, as demonstrated by immunohistochemistry and fluorescence in situ hybridization. These findings are important for the interpretation and understanding of the therapeutic effects when developing drugs targeting HER2 in prostate cancer cell lines and also emphasize the importance of using broad and validated analytical techniques.
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