| 1. |
- Jensen, Lars Henrik, et al.
(författare)
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Phase III randomized clinical trial comparing the efficacy of neoadjuvant chemotherapy and standard treatment in patients with locally advanced colon cancer: The NeoCol trial.
- 2023
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 41:17_SUPPL
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Tidskriftsartikel (refereegranskat)abstract
- LBA3503Background: Locally advanced colon cancer presents a therapeutic challenge regarding improving survival and minimizing side effects by optimizing the timing of surgical and systemic treatments. Neoadjuvant chemotherapy is a widely accepted approach in numerous cancers as it aims to eliminate micrometastases and reduce tumor size. Our study aimed to assess the impact of neoadjuvant chemotherapy on locally advanced colon cancer compared to standard initial surgery. Methods: This was a randomized, controlled, phase III clinical trial. Patients aged 18 years or older with biopsy-proven colon cancer were eligible for inclusion if staged as T4 or T3 with invasion depth >= 5 mm, N0-2, and M0 according to CT scan evaluation. Patients were randomly assigned to either standard upfront surgery or surgery after neoadjuvant chemotherapy with either 3 cycles of CAPOX (oxaliplatin, capecitabine every 3 weeks) or 4 cycles of FOLFOX (oxaliplatin, 5FU every 2 weeks). Adjuvant chemotherapy was chosen based on the pathological stage of the cancer according to guidelines. The primary endpoint, disease-free survival (DFS), was analyzed on an intent-to-treat basis. The sample size was set at 125 patients per arm, based on a projected increase in two-year disease-free survival from 80% to 90%, with a two-sided significance level of 5%, power of 80%, 3 years of inclusion, 2 years of follow-up, and a 10% drop-out rate. Results: Nine centers in 3 countries included 122 patients in the standard group and 126 patients in the neoadjuvant group from 10/2013 to 11/2021. Forty-four % were female, the median age was 66 years, and 91% had a performance status (PS) of 0, while 9% had a PS of 1. Seventy-three % of the tumors were classified as T3, with a median outgrowth of 11 mm, while 26% were classified as T4 on the baseline CT scan. There were no significant differences in baseline characteristics. The median number of chemotherapy cycles was lower in the neoadjuvant group, 3 (IQR 1-7) vs. 4 (0-8). There were slightly more postoperative complications in the standard group regarding ileus, anastomotic leakage, and length of stay. Postoperatively, more patients in the standard arm had an indication of adjuvant chemotherapy, 88 vs. 72 (p = 0.02). DFS at 2 years was similar in the two arms (p = 0.95, logrank), as was overall survival (OS) (p = 0.95, logrank). Conclusions: Neoadjuvant chemotherapy and standard upfront surgery showed no significant difference in DFS and OS in patients with colon cancer. However, neoadjuvant chemotherapy seemed to have more favorable outcomes in terms of chemotherapy cycles, postoperative complications, and downstaging. CT scan alone may not be sufficient in identifying high-risk patients preoperatively. These findings suggest that neoadjuvant chemotherapy could be considered a viable treatment option for patients with locally advanced colon cancer. Clinical trial information: NCT01918527.
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| 2. |
- Laisk, Triin, et al.
(författare)
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The genetic architecture of sporadic and multiple consecutive miscarriage.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P=3.2 × 10-8, odds ratio (OR)=1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF=6.4%, P=1.3 × 10-8, OR=1.7; rs143445068, MAF=0.8%, P=5.2 × 10-9, OR=3.4; rs183453668, MAF=0.5%, P=2.8 × 10-8, OR=3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.
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| 3. |
- Mortensen, Camilla B., et al.
(författare)
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Mortality and HRQoL in ICU patients with delirium : Protocol for 1-year follow-up of AID-ICU trial
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:10, s. 1519-1525
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intensive care unit (ICU)-acquired delirium is frequent and associated with poor short- and long-term outcomes for patients in ICUs. It therefore constitutes a major healthcare problem. Despite limited evidence, haloperidol is the most frequently used pharmacological intervention against ICU-acquired delirium. Agents intervening against Delirium in the ICU (AID-ICU) is an international, multicentre, randomised, blinded, placebo-controlled trial investigates benefits and harms of treatment with haloperidol in patients with ICU-acquired delirium. The current pre-planned one-year follow-up study of the AID-ICU trial population aims to explore the effects of haloperidol on one-year mortality and health related quality of life (HRQoL). Methods : The AID-ICU trial will include 1000 participants. One-year mortality will be obtained from the trial sites; we will validate the vital status of Danish participants using the Danish National Health Data Registers. Mortality will be analysed by Cox-regression and visualized by Kaplan-Meier curves tested for significance using the log-rank test. We will obtain HRQoL data using the EQ-5D instrument. HRQoL analysis will be performed using a general linear model adjusted for stratification variables. Deceased participants will be designated the worst possible value. Results: We expect to publish results of this study in 2022. Conclusion: We expect that this one-year follow-up study of participants with ICU-acquired delirium allocated to haloperidol vs. placebo will provide important information on the long-term consequences of delirium including the effects of haloperidol. We expect that our results will improve the care of this vulnerable patient group.
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| 4. |
- Schwabe, Joachim, et al.
(författare)
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The Baltic Sea Chart Datum 2000 (BSCD2000) : Implementation of a common reference level in the Baltic Sea
- 2020
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Ingår i: The international hydrographic review. - Monaco : International Hydrographic Organization. - 0020-6946. ; :23, s. 63-83
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Baltic Sea Chart Datum 2000 (BSCD2000) is a geodetic reference system adopted for Baltic Sea hydrographic surveying, hydrographic engineering, nautical charts, navigational publications and water level information. It is based on the common geodetic standards for the height system (EVRS) and the spatial reference system (ETRS89) in Europe. In particular, the zero level of BSCD2000 is in accordance with the Normaal Amsterdams Peil (NAP). BSCD2000 is about to be adopted as unified chart datum by all the countries around the Baltic Sea. It agrees with most national height realizations used on land. BSCD2000 will facilitate effective use of GNSS methods like GPS, GLONASS and Galileo for accurate navigation and hydrographic surveying in the future.
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