The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence

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 BRAF^V600, 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     

Screening for enteroviral meningitis in infants and children—Is it useful in clinical practice?

Enteroviral meningitis in infants and children commonly leads to hospital admission. Diagnosing viral meningitis can be difficult clinically. We examined the usefulness of enteroviral polymerase chain reaction (PCR) testing using cerebrospinal fluid (CSF) samples on clinical practice by comparing positive enteroviral CSF PCR cases (n = 39/136) to negative controls using both clinical outcomes and laboratory parameters. A positive result correlated with a reduced admission to high dependency unit, reduced the duration of antibiotics and a shorter length of stay (P < .05). Adjusted CSF white cell count > 5/μL correlated with positive PCR (P < .05) but would have missed 32% of cases of enteroviral meningitis. Following these findings, an algorithm for the management of suspected viral meningitis has been introduced.     

Microleakage of temporary endodontic restorations in teeth restored with amalgam

Microleakage of seven temporary restorative materials was evaluated in endodontic access preparations made in teeth restored with amalgam. Ten teeth were used for each of the seven materials: Cavit, Cavit-G, TERM, zinc phosphate cement, polycarboxylate cement, glass ionomer cement, and IRM. A class I amalgam was placed in the occlusal surface of each experimental tooth and an endodontic access preparation was made entirely within the amalgam. Then the access preparation was restored with one of the temporary restorative materials, and microleakage was evaluated using a fluid filtration technique. The amount of microleakage was quantitated by measuring the fluid flow at 15 min, 1 h, 24 h, 1 wk, and 2 wk after insertion of the temporary restoration. Cavit, Cavit-G, TERM, IRM, and glass ionomer cement all provided excellent seals while zinc phosphate cement and polycarboxylate cement provided less effective seals.     

Assessing the quality of life in infants with deformational plagiocephaly

This was a parent-reported outcome study on the impact of helmet therapy on the quality of life of infants with deformational plagiocephaly and their caregivers. Using survey-based analysis, we compared the quality of life in infants with deformational plagiocephaly with a cohort of their healthy peers. In addition, we compared infant quality of life before and after helmet therapy to evaluate the impact of this mainstay therapy for deformational plagiocephaly.Our results demonstrated that infants with plagiocephaly and their caregivers had a significantly decreased quality of life compared with healthy controls. This reframes our understanding of deformational plagiocephaly and emphasizes the need for therapeutic intervention in these individuals. A common therapeutic option — helmet remolding therapy — was shown to have no negative impact on quality of life, underscoring this as an appropriate therapeutic option. These data will allow us to counsel our future parents more effectively regarding the impact of deformational plagiocephaly and helmet therapy.     

A comparison of Shepard's osteotome versus trapdoor flap technique to harvest iliac crest bone for secondary alveolar bone grafting

OBJECTIVE: To compare the postoperative donor site morbidity and alveolar bone graft results following two different techniques for iliac crest bone graft harvest: a closed (Shepard's osteotome) and an open (trapdoor flap) technique. DESIGN: A retrospective review of two cohorts of alveolar bone grafts performed from 1998 to 2004 in Birmingham Children's Hospital by two surgeons using different harvest techniques. Medical and nursing anesthetic notes and medication charts were reviewed. Alveolar bone graft results were assessed using preoperative and postoperative radiographic studies. PATIENTS: A total of 137 patients underwent an operation. Of these, 109 patients were compatible with the inclusion criteria (data available, first operation, no multiple comorbidities). Sixty-four patients had iliac bone harvested using the open trapdoor technique, while 45 had the same procedure using the closed osteotomy technique. RESULTS: Maximum bone graft volumes harvested were similar with both techniques. The mean length of hospital stay was 50.9 hours for the osteotome and 75.5 hours for the open technique group (p < .0001). The postoperative analgesia requirement was higher and the postoperative mobilization was delayed and more difficult for the open technique patients (p < .0005). Kindelan scores performed by two independent orthodontists were similar for both techniques. CONCLUSION: The findings demonstrate that harvesting bone from the iliac crest using an osteotome technique reduces time in hospital, analgesia requirements, and postoperative donor site morbidity with no detrimental outcome.     

Short-term clinical outcomes and patient compliance with temporomandibular disorder treatment recommendations

AIMS: To evaluate short-term patient compliance with 5 conservative temporomandibular disorder (TMD) treatments (jaw relaxation, jaw stretching, heat application, cold application, and occlusal splint use) and the association of compliance with changes in pain intensity, pain-related activity interference, and jaw use limitations. METHODS: Eighty-one TMD patients were given 1 to 5 treatment recommendations as part of usual care in a TMD specialty clinic. Compliance with each recommendation and pain, pain-related activity interference, and jaw use limitation measures were calculated from electronic interviews conducted 3 times daily for 2 weeks. RESULTS: Median compliance with individual treatment modalities ranged from 7.7% for heat application to 92.7% for jaw relaxation; median overall compliance was 54.8%. Participants with higher initial pain intensity and jaw use limitations were significantly more compliant with their recommended treatment regimen (P < .05). The authors controlled for age, gender, education, and initial jaw use limitations. Overall compliance was associated significantly and positively with 2-week jaw use limitations (P = .03). A trend toward a statistically significant positive association was found between compliance and 2-week pain intensity (P = .09). CONCLUSION: Compliance varied widely across patients and therapies. Patients with higher initial pain and jaw use limitation levels were more compliant with treatment recommendations. Although compliance was associated with slight increases in pain and jaw use limitations in this preliminary study, further research is needed to evaluate the longer-term effects of compliance with recommended therapies.     

Effect of pH on element release from dental casting alloys

Statement of problem. Dental casting alloys are subjected to transient acidity in the oral environment, yet most studies have not investigated the effects of these transient environments on elemental release from alloys. Elemental release is important because it plays a significant role in alloy biocompatibility. Purpose. It was hypothesized that acidic environments would increase elemental release from dental alloys during exposure and after the acidic environment was removed. This hypothesis was based on the known increase in release of nickel from nickel-based alloys in an acidic environment. Material and methods. High-noble, noble, and base metal casting alloys were exposed for 30 minutes to solutions with pH ranging from 1 to 7. Elemental release of representative elements was measured by means of atomic absorption spectrometry during the exposure and in the week after the exposure. This release was compared with elemental release in the week before the exposure. Results. High-noble and noble alloys were resistant to acidic environments. A pH of 4 did not increase elemental release during or after exposure. A pH 1 environment slightly elevated release of Ag, Cu, and Pd in some alloys. However, a Ni-based alloy released large amounts of Ni during the acidic exposure of pH 1 or 4, and more importantly, in the week after the exposure as well. Increased time of exposure to acid did not alter elemental release from noble or high-noble alloys, but markedly increased release from the Ni-based alloy. Conclusions. Transient exposure of casting alloys to an acidic oral environment is likely to significantly increase elemental release from Ni-based alloys, but not from high-noble or noble alloys. (J Prosthet Dent 1998;80:691-8.)     

Primary oral infection of infants with Streptococcus mutans

Strep. mutans was not detected in 16 normal predentate infants, but was isolated from $\text{3}\text{43}$ infants with 1 to 5 primary incisor teeth and $\text{12}\text{42}$ infants with 6 to 8 incisors. The salivary level of Strep. mutans was determined for the 42 mothers of the infants with only 6 to 8 incisors. The difference in the distribution of the salivary levels of Strep. mutans within the maternal populations of infected versus non-infected infants was statistically significant (p = 0.03). Ten mothers harboured greater than 10⁵ colony-forming units (CFUs) of Strep. mutans per ml. saliva. The organism was detected in 6 of their infants. Of 13 mothers with levels less than 10³ CFUs per ml. saliva only 2 of their infants harboured the organism.