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- Jurrius, Patriek, et al.
(author)
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Invasive breast cancer over four decades reveals persisting poor metastatic outcomes in treatment resistant subgroup - the "ATRESS" phenomenon
- 2020
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In: Breast. - : CHURCHILL LIVINGSTONE. - 0960-9776 .- 1532-3080. ; 50, s. 39-48
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Journal article (peer-reviewed)abstract
- Background: Major advances in breast cancer treatment have led to a reducuction in mortality. However, there are still women who are not cured. We hypothesize there is a sub-group of women with treatment-resistant cancers causing early death.Methods: Between 1975 and 2006, 5392 women with invasive breast cancer underwent surgery at Guy's Hospital, London. Data on patient demographics, tumour characteristics, treatment regimens, local recurrence, secondary metastasis, and death were prospectively recorded. We considered four time periods (1975-1982, 1983-1990, 1991-1998, 1999-2006). Risks and time to event analysis were performed with Cox proportional hazards model and Kaplan-Meier estimation.Results: Unadjusted hazard ratios for developing metastasis and overall mortality relative to the 1975-1982 cohort decreased steadily to 0.23 and 0.63, respectively in 1999-2006. However, metastasis-free interval shortened, with the proportion of women developing metastasis <= 5 years increasing from 73.9% to 83.0%. Furthermore, median post-metastatic survival decreased from 1.49 years to 0.94 years. Applying our risk criteria identified the presence of +/- 200 patients in each cohort who developed metastasis early and died within a much shorter time frame.Conclusions: Advances in treatment have decreased the risk of metastasis and improved survival in women with invasive breast cancer over the last 40 years. Despite this, a subpopulation with shorter metastasis-free and post-metastatic survival who are unresponsive to available treatment remains. This may be due to the ATRESS phenomenon (adjuvant therapy-related shortening of survival) secondary to preselection inherent in adjuvant therapy, successful treatment of less malignant tumour cells and treatment-induced resistance in the remaining tumour clones.
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- Kraus, Stefan, et al.
(author)
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Planet Formation Imager (PFI) : Science vision and key requirements
- 2016
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In: Optical and Infrared Interferometry and Imaging V. - : SPIE. - 9781510601932 ; 9907
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Conference paper (peer-reviewed)abstract
- The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the "Hill Sphere" of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs.
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3. |
- Leta, Tesfaye H., et al.
(author)
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Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement
- 2024
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In: JAMA Network Open. - 2574-3805. ; 7:5
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Journal article (peer-reviewed)abstract
- Importanc eDespite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.
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4. |
- Leta, Tesfaye H., et al.
(author)
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The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania
- 2023
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In: Acta Orthopaedica. - 1745-3674 .- 1745-3682. ; 94, s. 416-425
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Journal article (peer-reviewed)abstract
- Background and purpose — Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods — This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Den-mark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results — ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion — The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.
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