| 1. |
- van Thuijl, Hinke F., et al.
(författare)
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Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment
- 2015
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Ingår i: Acta Neuropathologica. - : Springer Verlag (Germany). - 0001-6322 .- 1432-0533. ; 129:4, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-na less than ve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.
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| 2. |
- Yang, Liyun, 1992-, et al.
(författare)
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Impact of Procedure Type, Case Duration, and Adjunctive Equipment on Surgeon Intraoperative Musculoskeletal Discomfort
- 2020
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Ingår i: Journal of the American College of Surgeons. - : ELSEVIER SCIENCE INC. - 1072-7515 .- 1879-1190. ; 230:4, s. 554-560
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgeons are at high risk of developing musculoskeletal disorders. STUDY DESIGN: This study was designed to identify risk factors and assess intraoperative physical stressors using subjective and objective measures, including type of procedure and equipment used. Wearable sensors and pre- and postoperation surveys were analyzed. RESULTS: Data from 116 cases (34 male and 19 female surgeons) were collected across surgical specialties. Surgeons reported increased pain in the neck, upper, and lower back both during and after operations. High-stress intraoperative postures were also revealed by the real-time measurement in the neck and back. Surgical duration also impacted physical pain and fatigue. Open procedures had more stressful physical postures than laparoscopic procedures. Loupe usage negatively impacted neck postures. CONCLUSIONS: This study highlights the fact that musculoskeletal disorders are common in surgeons and characterizes surgeons' intraoperative posture as well as surgeon pain and fatigue across specialties. Defining intraoperative ((C) 2020 The Author(s). Published by Elsevier Inc. on behalf of the American College of Surgeons.
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| 3. |
- Yang, Liyun, 1992-, et al.
(författare)
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Intraoperative musculoskeletal discomfort and risk for surgeons during open and laparoscopic surgery.
- 2020
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Ingår i: Surgical Endoscopy. - : Springer Nature. - 0930-2794 .- 1432-2218.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgeon workload is significant both mentally and physically and may differ by procedure type. When comparing laparoscopic surgery and open surgery, studies have reported contrasting results on the physical and mental workload assessed.METHODS: Wearable posture sensors and pre-/post-surgical questionnaires were employed to assess intraoperative workload and to identify risk factors for surgeons using objective and subjective measures.RESULTS: Data from 49 cases (27 open and 22 laparoscopic surgeries performed by 13 male and 11 female surgeons) were assessed. More than half the surgeons reported a clinically relevant post-surgical fatigue score. The surgeons also self-reported a significant increase in pain for the neck, upper back, and lower back during/after surgery. Procedural time had significant impacts on fatigue, body part pain, and subjective (NASA-TLX) workload. The objectively assessed intraoperative work postures using wearable sensors showed a high musculoskeletal risk for neck and lower back based on their posture overall. Open surgeries had significantly larger neck angles (median [IQR]: 40 [28-47]°) compared with laparoscopic surgeries (median [IQR]: 23 [16-29]°), p < 0.001) and torso (median [IQR]: 17 [14-22]° vs. 13 [10-17]°, p = 0.006).CONCLUSION: Surgeons reported significantly higher levels of fatigue and pain in the neck and lower back during or after performing a surgical case. Longer procedural time resulted in more self-rated fatigue, pain, and subjective workload. Open surgery had higher postural risk. Overall, surgeons spent a disturbingly high percentage of time during surgery in high-risk musculoskeletal postures, especially the neck. These results show that intraoperative postural risk is very high and that interventions are necessary to protect surgeon musculoskeletal health for optimal surgeon performance and career longevity.
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| 5. |
- Hooke, Alexander W., et al.
(författare)
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Mechanical Assessment of Tissue Properties During Tourniquet Application
- 2021
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Ingår i: Military medicine. - : OXFORD UNIV PRESS. - 0026-4075 .- 1930-613X. ; 186, s. 378-383
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Successful tourniquet application increases survival rate of exsanguinating extremity hemorrhage victims. Tactile feedback during tourniquet application training should reflect human tissue properties in order to increase success in the field. This study aims to understand the mechanical properties of a human limb during tourniquet application. Method: Six cadaveric extremities-three uppers and three lowers-were tested from three body mass index groups: low (<19) healthy (19-24), and overweight (>24). Each specimen donned with a tourniquet and mounted to a servo-hydraulic testing machine, which enabled controlled tightening of the tourniquet while recording the tourniquet tension force and strap displacement. A thin-film pressure sensor placed between the specimen and the tourniquet recorded contact pressure. Each limb was tested with the tourniquet applied at two different sites resulting in testing at the upper arm, forearm, thigh, and shank. Results: The load displacement curves during radial compression were found to be nonlinear overall, with identifiable linear regions. Average contact pressure under the tourniquet strap at 200N and 300N of tension force was 126.3 (sigma= 41.2) mm Hg and 205.3 (sigma = 75.3) mm Hg, respectively. There were no significant differences in tissue stiffness or contact pressure at 300N of tension force between limb (upper vs. lower) or body mass index. At 200N of tension, the upper limb had significantly higher contact pressure than the lower limb (P= 0.040). Relative radial compression was significantly different between upper (16.74, sigma = 4.16%) and lower (10.15, sigma = 2.25%) extremities at 200N tension (P= 0.005). Conclusions: Simulation of tissue compression during tourniquet application may be achieved with a material exhibiting elastic properties to mimic the force-displacement behavior seen in cadaveric tissue or with different layers of material. Different trainers for underweight, healthy, and overweight limbs may not be needed. Separate tourniquet training fixtures should be created for the upper and lower extremities.
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| 6. |
- Lowndes, Bethany, et al.
(författare)
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Preliminary Investigation of Civilian Clinician Perspectives & Just-in-Time Guidance for Tourniquet Use to "Stop the Bleed"
- 2019
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Ingår i: Military medicine. - : Oxford University Press. - 0026-4075 .- 1930-613X. ; 184:3-4, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe American College of Surgeons (ACS) encourages clinicians to provide training to laypeople on tourniquet application. It is unclear whether clinicians are confident in their abilities and equipped with adequate knowledge, skills, and resources. This study aimed to determine surgical trainee knowledge and attitudes regarding tourniquet application and compare the effectiveness of instructions.MethodsThirty surgical trainees performed a tourniquet application simulation using a Combat Application Tourniquet and one of the three instructions sets developed by ACS, Department of Homeland Security, and the tourniquet manufacturer. Participants reported tourniquet knowledge, attitudes, and confidence and discussed the instructions. One instruction set was updated and compared to the original set with 20 new trainees.ResultsParticipants with ACS instructions passed the greatest number of steps (p < 0.01) and completed the task significantly faster compared to those with manufacturer instructions (p < 0.01). Participants (80%) reported favorable views toward tourniquets but 30–60% did not align with to ACS tourniquet guidelines. Focus group participants suggested revisions to the ACS instructions. Comparing the original and revised version of these instructions resulted in no significant improvements.ConclusionsACS instructions provide guidance; however, improvements to tourniquet instruction are needed for success in controlling exsanguinating hemorrhage.
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| 7. |
- Wells, Antonia C., et al.
(författare)
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Operating hurts : a study of EAES surgeons
- 2019
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Ingår i: Surgical Endoscopy. - : SPRINGER. - 0930-2794 .- 1432-2218. ; 33:3, s. 933-940
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWork-related pain and discomfort experienced by surgeons is widely reported in the literature. A survey was, therefore, conducted to explore this issue among members of the European Association for Endoscopic Surgery (EAES).MethodsThe survey was emailed to 2980 EAES members in 2017 enquiring about their working practice, musculoskeletal (MSK) pain and burnout.ResultsA total of 569 (19%) surgeons responded, of whom 556 were practicing surgeons; 86% were consultants, 84% were male, and 94% were right-handed. Respondents operated on average 3.3days/week with 27% of their procedures lasting longer than 3h. The 386 endoscopists surveyed reported performing an average of 5.3 procedures/day with 83% performing endoscopy at least once per week. Over half of practicing surgeons (62%) reported their worst pain score was 3 or higher (10-point scale) in the past 7 working days, encompassing 71% of their open, 72% laparoscopic, 48% robot-assisted cases and 52% of their endoscopies. Of the 120 surgeons who had ever sought medical help for aches, pain or discomfort, 38% were currently in pain and 16% had considered leaving surgery due to their MSK pain, 26% had reported work-related pain to their employer, 26% had been on short-term disability during their career and 4% long-term disability due to MSK disorders. A significant proportion of the respondents (49%) felt their physical discomfort would influence the ability to perform or assist with surgical procedures in the future. These surgeons reported significantly lower satisfaction from their work (p=0.024), higher burnout (p=0.005) and significantly higher callousness toward people (p<0.001) than those not fearing loss of career longevity.ConclusionThe results show that MSK pain is prevalent amongst EAES members. Nearly half the respondents had career longevity fears from pain/discomfort which, in turn, correlated with more prevalent feelings of burnout. More emphasis should be placed on the aetiology, prevention and management of musculoskeletal pain in the surgical workforce.
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