| 1. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 2. |
- Geelen, Inge G. P., et al.
(författare)
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Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response : clinical and immunological effects
- 2023
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Ingår i: Annals of Hematology. - : Springer. - 0939-5555 .- 1432-0584. ; 102:6, s. 1395-1408
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Tidskriftsartikel (refereegranskat)abstract
- In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.
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| 3. |
- Enajat, Morteza, et al.
(författare)
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Aesthetic Refinements and Reoperative Procedures Following 370 Consecutive DIEP and SIEA Flap Breast Reconstructions : Important Considerations for Patient Consent
- 2010
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Ingår i: Aesthetic Plastic Surgery. - : Springer Science and Business Media LLC. - 0364-216X .- 1432-5241. ; 34:3, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- Breast reconstruction often requires multiple operations. In addition to potential complications requiring reoperation, additional procedures are frequently essential in order to complete the reconstructive process, with aesthetic outcome and breast symmetry shown to be the most important factors in patient satisfaction. Despite the importance of these reoperations in decision-making and the consent process, a thorough review of the need for such operations has not been definitively explored. A review of 370 consecutive autologous breast reconstructions (326 patients) was undertaken, comprising 365 deep inferior epigastric artery perforator (DIEP) flaps and 5 superficial inferior epigastric artery (SIEA) flaps. The need for additional procedures for either complications or aesthetic refinement following initial breast reconstruction was assessed. Overall, there was an average of 1.06 additional interventions for every patient carried out after primary reconstructive surgery. Of 326 patients, 46 underwent early postoperative operations for surgical complications (0.17 additional operations per patient as a consequence of complications). Procedures for aesthetic refinement included those performed on the reconstructed breast, contralateral breast, or abdominal donor site. Procedures for aesthetic refinement included nipple reconstruction, nipple-areola complex tattooing, dog-ear correction, liposuction, lipofilling, scar revision, mastopexy, and reduction mammaplasty. While DIEP flap surgery for breast reconstruction provides favorable results, patients frequently require additional procedures to improve aesthetic outcomes. The need for reoperation is an important part of the consent process prior to reconstructive surgery, and patients should recognize the likelihood of at least one additional procedure following initial reconstruction.
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| 4. |
- Smit, Jeroen M., et al.
(författare)
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Multilayer reconstructions for defects overlying the Achilles tendon with the lateral-arm flap : Long-term follow-up of 16 cases
- 2012
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 32:6, s. 438-444
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Tidskriftsartikel (refereegranskat)abstract
- Defects of the Achilles tendon and the overlying soft tissue are challenging to reconstruct. The lateral-arm flap has our preference in this region as it provides thin pliable skin, in addition, the fascia and tendon can be included in the flap as well. The aim of this report is to share the experience the authors gained with this type of reconstruction. The authors report the largest series in the published reports today. Patients and methods: A retrospective review was performed of all patients treated between January 2000 and January 2009 with a lateral-arm flap for a soft-tissue defect overlying the Achilles tendon. Results: In the reviewed period, 16 soft-tissue defects overlying the Achilles tendon were reconstructed, with a mean follow-up of 63 months. In three cases, tendon was included into the flap and in two, a sensory nerve was coapted. Fifteen cases (94%) were successful, one failed. In seven cases, a secondary procedure was necessary for thinning of the flap. Conclusion: The lateral-arm flap is a good and safe option for the reconstruction of defects overlying the Achilles tendon. (c) 2012 Wiley Periodicals, Inc. Microsurgery, 2012.
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| 5. |
- Acosta, Rafael, et al.
(författare)
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A Clinical Review of 9 Years of Free Perforator Flap Breast Reconstructions : An Analysis of 675 Flaps and the Influence of New Techniques on Clinical Practice
- 2011
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Ingår i: Journal of reconstructive microsurgery. - : Georg Thieme Verlag KG. - 0743-684X .- 1098-8947. ; 27:2, s. 91-98
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Forskningsöversikt (refereegranskat)abstract
- The aim of this study is to review our 9-year experience with deep inferior epigastric perforator (DIEP) breast reconstructions to help others more easily overcome the pitfalls we experienced. A chart review was conducted for all 543 patients who had 622 DIEP breast reconstructions in our clinic between January 2000 and January 2009. In this time, there were an additional 28 superior gluteal artery perforator and 25 superficial inferior epigastric artery reconstructions, bringing the total free flap reconstructions to 675. In the early years, the success rate was 90.7%, the average operative time was 7 hours and 18 minutes, and the complication rate was 33.3%; these have improved to 98.2%, 4 hours and 8 minutes, and 19.3%, respectively. We describe our selection criteria, preoperative vascular mapping, surgical techniques, and postoperative monitoring as they relate to these improvements in outcome, operative time, and complications. The DIEP flap is a safe and reliable option in breast reconstructions. By acquiring experience with the flap and introducing new and improving existing techniques we have improved the ease of the procedure and the success rate and have shortened the operative time.
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| 6. |
- Acosta, Rafael, et al.
(författare)
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Performing two DIEP flaps in a working day : an achievable and reproducible practice
- 2010
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Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 63:4, s. 648-654
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Tidskriftsartikel (refereegranskat)abstract
- Background: While the deep inferior epigastric artery perforator (DIEP) flap is a reliable technique for autologous breast reconstruction, the meticulous dissection of perforators may require lengthy operative times. In our unit, we have performed 600 free flaps for breast reconstruction over 8 years and have reduced operative times with a combination of preoperative computed tomographic angiography (CTA), various anastomotic techniques and the Cook-Swartz implantable Doppler probe for perfusion monitoring. We sought to assess the feasibility of performing two DIEP flaps within the working hours of a single day. Methods: A review of 101 consecutive patients undergoing DIEP flap breast reconstruction in a 12-month period was performed, comparing one DIEP flap per day (n=43) to two DIEP flaps per day (n=58). Complications, outcomes and techniques used were critically analysed. For cases of two DIEP flaps per day, a comparison was made between the use of two separate operating theatres (n=44) and a single consecutive theatre (n=14). Results: Complications did not increase when two DIEP flaps were performed in a single working day. The use of vascular closure staple (VCS) sutures and ring couplers resulted in statistically significant reductions in anastomotic times. The use of two separate theatres for performing two DIEP flaps resulted in a reduction of 59 min in operative time per case (p=0.004). Conclusion: Two DIEP flaps can be safely and routinely performed within the hours of a single working day. By minimising operative times, these techniques can improve productivity and substantially decrease surgeon fatigue.
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| 7. |
- Darcy, Catharine M., et al.
(författare)
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Surgical technique : The intercostal space approach to the internal mammary vessels in 463 microvascular breast reconstructions
- 2011
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Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 64:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- The internal mammary vessels are one of the most frequently used recipient sites for microsurgical free-flap breast reconstruction, and an accepted technique to expose these vessels involves removal of a segment of costal cartilage of the rib. However, in some patients, cartilage removal may result in a visible medial chest-wall depression that requires corrective procedures. We, therefore, use an intercostal space approach to the internal mammary vessels, as there is minimal disturbance of the costal cartilage with this technique. We have developed and performed our technique over an 8-year period in 463 microvascular breast reconstructions, and present it here as it contains modifications not previously described that may be of interest to other surgeons. There was no serious morbidity associated with the intercostal space approach, the internal mammary vessels were reliably and safely exposed in all these cases and the flap success rate was 95.8%.
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| 8. |
- Enajat, Morteza, et al.
(författare)
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A single center comparison of one versus two venous anastomoses in 564 consecutive diep flaps : Investigating the effect on venous congestion and flap survival
- 2010
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 30:3, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Background: Venous complications have been reported as the more frequently encountered vascular complications seen in the transfer of deep inferior epigastric artery (DIEA) perforator (DIEP) flaps, with a variety of techniques described for augmenting the venous drainage of these flaps to minimize venous congestion. The benefits of such techniques have not been shown to be of clinical benefit on a large scale due to the small number of cases in published series. Methods: A retrospective study of 564 consecutive DIEP flaps at a single institution was undertaken, comparing the prospective use of one venous anastomosis (273 cases) to two anastomoses (291 cases). The secondary donor vein comprised a second DIEA venae commitante in 7.9% of cases and a superficial inferior epigastric vein (SIEV) in 92.1%. Clinical outcomes were assessed, in particular rates of venous congestion. Results: The use of two venous anastomoses resulted in a significant reduction in the number of cases of venous congestion to zero (0 vs. 7, P = 0.006). All other outcomes were similar between groups. Notably, the use of a secondary vein did not result in any significant increase in operative time (385 minutes vs. 383 minutes, P = 0.57). Conclusions: The use of a secondary vein in the drainage of a DIEP flap can significantly reduce the incidence of venous congestion, with no detriment to complication rates. Consideration of incorporating both the superficial and deep venous systems is an approach that may further improve the venous drainage of the flap.
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| 9. |
- Enajat, Morteza, et al.
(författare)
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The deep inferior epigastric artery perforator flap for autologous reconstruction of large partial mastectomy defects
- 2011
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Ingår i: Microsurgery. - : Wiley. - 0738-1085 .- 1098-2752. ; 31:1, s. 12-17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast conservation surgery in the treatment of early stage breast cancer has become increasingly utilized as a means to avoiding mastectomy. While partial mastectomy defects (PMDs) may often be cosmetically acceptable, some cases warrant consideration of reconstructive options, and while several reconstructive options have been described in this role, a series of deep inferior epigastric perforator (DIEP) flaps has not been reported to date. Methods: A cohort of 18 patients undergoing PMD reconstruction with a DIEP flap were included. Patient-specific data, operation details, cosmetic results, and complication rates were assessed. Oncologic outcomes, in particular recurrence rates, were also evaluated. Results: In our series there were no cases of partial or total flap necrosis, and overall complications were low. There were two cases of wound infection (both had undergone radiotherapy), managed conservatively, and one case of reoperation due to hematoma. There were no cancer recurrences or effect on oncologic management. Cosmetic outcome was rated as high by both patients and surgeon. The results were thus comparable with other reconstructive options. Conclusion: Although autologous reconstruction has an established complication rate, our results suggest that the DIEP flap may be of considerable value for delayed reconstruction of selected larger partial mastectomy defects.
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| 10. |
- Marschall, Tobias, et al.
(författare)
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Computational pan-genomics : status, promises and challenges
- 2018
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 19:1, s. 118-135
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Tidskriftsartikel (refereegranskat)abstract
- Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.
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