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Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAFV600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer  相似文献   
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Background

There is continued debate regarding retention versus sacrificing of the posterior cruciate ligament (PCL) in total knee arthroplasty (TKA). We sought to determine if there was a difference in range of motion (ROM) after TKA between patients with PCL sacrifice versus PCL retention when using a highly congruent polyethylene insert.

Methods

We conducted an Institutional Review Board approved retrospective study of consecutive patients receiving TKA using the same implant with a highly congruent polyethylene component implanted by one surgeon from November 2013 to January 2016. Patients were placed in 2 groups based on whether the PCL was intact or released at the time of surgery. Patient charts were reviewed for age, body mass index, PCL status at surgery (incompetent, kept intact, or released), and preoperative/postoperative knee ROM.

Results

Both groups were similar in average age (60.5 vs 60.6, respectively) and body mass index (33.3 vs 32.6, respectively). Postoperative tibial slope (5.5° PCL release, 6.6° PCL retained, P = .028) was the only alignment variable reaching significance; all other alignment and motion variables were similar.

Conclusion

Results indicate that the PCL can be successfully retained with the use of a congruent bearing design, with no evident limitation in postoperative ROM or loss of stability due to the bearing in comparison to patients who undergo PCL release.  相似文献   
4.
While colorectal cancer (CRC) screening rates have been increasing in the general population, rates are considerably lower in Federally Qualified Health Centers (FQHCs), which serve a large proportion of uninsured and medically vulnerable patients. Efforts to screen eligible patients must be accelerated if we are to reach the national screening goal of 80% by 2018 and beyond. To inform this work, we conducted a survey of key informants at FQHCs in eight states to determine which evidence-based interventions (EBIs) to promote CRC screening are currently being used, and which implementation strategies are being employed to ensure that the interventions are executed as intended. One hundred and forty-eight FQHCs were invited to participate in the study, and 56 completed surveys were received for a response rate of 38%. Results demonstrated that provider reminder and recall systems were the most commonly used EBIs (44.6%) while the most commonly used implementation strategy was the identification of barriers (84.0%). The mean number of EBIs that were fully implemented at the centers was 2.4 (range 0–7) out of seven. Almost one-quarter of respondents indicated that their FQHCs were not using any EBIs to increase CRC screening. Full implementation of EBIs was correlated with higher CRC screening rates. These findings identify gaps as well as the preferences and needs of FQHCs in selecting and implementing EBIs for CRC screening.  相似文献   
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Abstract:  Aims:  A single-centre, randomized single-blind parallel study was undertaken to compare staining seen with three brushing regimens and to determine subject perception of side effects such as staining and effects on taste. Methods:  This 6-week parallel study used 157 volunteers who were randomized into one of three treatment groups: (i) brushing in the morning and evening with a normal dose of a 1% chlorhexidine gel, (ii) brushing with a low dose of chlorhexidine gel in the evening and a whitening dentifrice in the morning, and (iii) brushing with a standard fluoride paste in the morning and evening. Following home usage of their allocated products, the study volunteers returned after 3 and 6 weeks to record the amount of stain present. After the 6-week period, subject perception of taste and stain acceptability was determined using a questionnaire. Results:  After 6 weeks of use of the low-dose chlorhexidine gel and whitening dentifrice, significantly more stain was seen compared with the use of a standard dentifrice ( P  < 0.0001). Similarly, significantly more stain was seen with use of the normal-dose chlorhexidine gel compared with the low-dose gel and whitening dentifrice ( P  = 0.0007). Approximately 30% of individuals on the low-dose chlorhexidine gel regimen found the amount of stain unacceptable and 10% noted an effect on their taste perception. Conclusions:  The use of low dose of chlorhexidine gel at night and a whitening paste in the morning produced a significant amount of stain that 30% of subjects considered unacceptable.  相似文献   
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The recent guidelines issued by the DHSS and the BDS recommend that to prevent cross-infection gloves should be worn by dentists and their assistants whilst treating all patients. Little information is available on the permeability of the various types of glove available; this pilot study was therefore conducted, to test five commonly used brands of gloves for permeability to air, electrolytes, dye and bacteria. Tests were carried out before and after using the gloves for varying periods. From these studies it was found that only one brand of glove passed all the tests before wearing. After wearing the gloves for up to 3 hours, between 20% and 50% of the gloves, depending on type, allowed bacteria to pass across the glove. The visual test was less critical than the ion passage and bacterial tests, in that some gloves without obvious perforations allowed ions and bacteria to pass through.  相似文献   
9.
A total of 22 cases that were diagnosed as having space discrepancy problems in the deciduous and early mixed dentitions showed that treatment by early expansion therapy with Crozat appliances had eliminated the need for extraction of deciduous canines or permanent premolars.  相似文献   
10.
It is important to give the patient a denture that is clean and free from cross-contamination. This study was made to determine if Clorox could be used as a rapid, safe, and clinically effective way to sterilize complete dentures. The data obtained from this study indicate that a 5-minute immersion of dentures in undiluted Clorox accomplished sterilization against a variety of microorganisms, including a spore-forming bacteria and C. albicans.  相似文献   
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