Cardiovascular risk in chronic myeloid leukaemia: A multidisciplinary consensus on screening and management.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for chronic myeloid leukaemia (CML), but cardiovascular (CV) risk and exacerbation of underlying risk factors associated with TKIs have become widely debated. Real-world evidence reveals little application of CV risk factor screening or continued monitoring within UK CML management. This consensus paper presents practical recommendations to assist healthcare professionals in conducting CV screening/comorbidity management for patients receiving TKIs. METHODS: We conducted a multidisciplinary panel meeting and two iterative surveys involving 10 CML specialists: five haematologists, two cardio-oncologists, one vascular surgeon, one haemato-oncology pharmacist and one specialist nurse practitioner. RESULTS: The panel recommended that patients commencing second-/third-generation TKIs undergo formal CV risk assessment at baseline, with additional investigations and involvement of cardiologists/vascular surgeons for those with high CV risk. During treatment, patients should undergo CV monitoring, with the nature and frequency of testing dependent on TKI and baseline CV risk. For patients who develop CV adverse events, decision-making around TKI interruption, cessation or change should be multidisciplinary and balance CV and haematological risk. CONCLUSION: The panel anticipates these recommendations will support healthcare professionals in implementing CV risk screening and monitoring, broadly and consistently, and thereby help optimise TKI treatment for CML.

Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Incidence and Risk Factors of Velopharyngeal Insufficiency Postadenotonsillectomy.

OBJECTIVES: To evaluate the incidence and risk factors of velopharyngeal insufficiency (VPI) postadenoidectomy, posttonsillectomy, and postadenotonsillectomy. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary care center (2007-2014). SUBJECTS AND METHODS: Retrospective review of patients who underwent adenoidectomies, tonsillectomies, or adenotonsillectomies by 1 pediatric otolaryngologist. Patient's age, sex, type of surgery, indication for surgery, medical syndromes, tonsil grade, adenoid size, and pre- and postoperative nasal air emissions were obtained. RESULTS: The VPI risk at 3 weeks postoperatively was 13.6% (95% CI: 9.0%, 18.2%) for adenotonsillectomies, 3.2% (95% CI: 1.2%, 7.6%) for adenoidectomies, and 2.2% (95% CI: 2.1%, 6.5%) for tonsillectomies. There was a significantly higher risk of VPI with combined procedures in comparison with adenoidectomies (P = .02) or tonsillectomies alone (P = .03). There was no significant difference in risk of VPI between adenoidectomies and tonsillectomies (P = .78); between surgical indication groups (sleep-disordered breathing vs other; P = .15); or in terms of sex (P = .80), age (P = .11), tonsil grade (P = .96), or adenoid size (P = .15). There was no qualitative difference in postoperative nasal air emissions between patients with and without medical syndromes. CONCLUSION: Our data are consistent with the literature that most VPI after adenotonsillectomy is temporary in nature and resolves by 5 months postoperatively. Combined procedures were shown to have a significantly higher risk of VPI. Our rates of VPI were much higher than that previously cited and may be indicative of subclinical cases of VPI, which were accounted for due to this study's unique methodology.

The aesthetic unit principle of facial aging.

IMPORTANCE: In youth, facial aesthetic units flow together without perceptible division. The face appears as a single dynamic structure with a smooth contour and very little if any shadowing between different anatomical regions. As one ages, facial aesthetic units slowly become distinct. This process may be a consequence of differences in skin thickness, composition of subcutaneous tissue, contour of the facial skeleton, and location of facial ligaments. Although the impact of aesthetic unit separation is clinically apparent, its fundamental role in perceived facial aging has not yet been defined empirically. OBJECTIVES: To evaluate and define the effect of aesthetic unit separation on facial aging and to empirically validate the rationale for the blending of aesthetic units as a principle for facial rejuvenation. DESIGN, SETTING, AND PARTICIPANTS: We prepared the photographs of 7 women for experimental evaluation of the presence or absence of facial aesthetic unit separation. Photographic stimuli were then presented to 24 naive observers in a blinded paired comparison. For each stimulus pair, observers were asked to select the facial photograph that they considered to be more youthful in appearance. Each stimulus was compared with all others. MAIN OUTCOMES AND MEASURES: We calculated a preference score for the total number of times any photograph was chosen to be more youthful compared with all others. Paired t tests were used to compare the preference scores between the facial stimuli with and without aesthetic unit separation. RESULTS: We generated 4032 responses for analysis. Photographs without facial aesthetic unit separation were consistently judged to be more youthful than their aged original or modified counterparts, with mean preference scores of 0.66 and 0.33, respectively (P ≤ .047). When we selected the paired stimulus that directly compared one photograph with aesthetic unit separation with another with blended aesthetic units (2015 pairs), observers indicated that the photograph with the blended aesthetic unit was younger 95% of the time. Within-rater reliability was found to be very good (r = 0.88). CONCLUSIONS AND RELEVANCE: Our data support the hypothesis that facial aesthetic unit separation influences perceived facial youthfulness among photographs of women. The presence of facial aesthetic unit separation results in a less youthful appearance. Based on these empirical data, the concept of facial aesthetic unit separation appears to play a significant role in perceived facial aging. LEVEL OF EVIDENCE: NA.

High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer.

IMPORTANCE: Large-scale whole-exome sequencing studies of head and neck squamous cell carcinoma (HNSCC) have established that the disease is dominated by frequent mutations in tumor suppressor genes with rare activating mutations in oncogenes that would be easily targetable with molecular agents. There was evidence in these reports, however, that activating mutations in phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) were common in patients with human papillomavirus (HPV)-positive tumors. We set out to test this prediction in oropharyngeal patient samples from our institution. OBJECTIVE: To confirm whether activating mutations in PIK3CA are frequent in HPV-positive HNSCC because this mutated oncogene represents a potential therapeutic target. DESIGN, SETTING, AND PARTICIPANTS: A retrospective search of the London Health Sciences Centre pathology database was performed to identify oropharyngeal cancer samples. DNA from pretreatment primary site biopsy samples from 87 patients were tested for high-risk HPV types 16 and 18 by real-time polymerase chain reaction. MAIN OUTCOMES AND MEASURES: Samples were tested for activating mutations at the 3 mutational hot spots (codons 542, 545, and 1047) by polymerase chain reaction followed by Sanger sequencing using forward and reverse primers. RESULTS: Only 4 of 41 HPV-negative tumors (10%) demonstrated PIK3CA hot spot mutations, including 3 at codon 1047 and 1 at codon 542. Of 46 HPV-positive tumors, 13 (28%) demonstrated activating PIK3CA mutations, including 7 at codon 542, 5 at codon 545, and 1 at codon 1047. The difference in PIK3CA mutation frequency was significantly different between HPV-positive and HPV-negative cancers (P = .03). CONCLUSIONS AND RELEVANCE: Although there has been a suggestion that activating PIK3CA mutations are common in HPV-positive HNSCC, to our knowledge, this is the first study to clearly identify this phenomenon. Targeting PIK3CA with molecular agents in HPV-positive patients may be a mechanism to improve cure rates and decrease treatment toxic effects in this rapidly growing cohort of patients.

Functional outcomes after lateral crural J-flap repair of external nasal valve collapse.

OBJECTIVES: We evaluated the lateral crural J-flap technique in the surgical repair of external nasal valve collapse with standardized and validated outcome measurements. METHODS: Prospective data were gathered on consecutive cases, performed by a single surgeon between 2007 and 2010, of adult patients who underwent a lateral crural approach to repair of external nasal valve collapse. Data were collected on diagnosis, surgical outcomes, and complications. Outcome measures included the Nasal Obstructive Symptom Evaluation and the Rhinoplasty Outcome Evaluation. RESULTS: Fifteen patients were included in the study. Their follow-ups ranged from 9 to 13 months. All patients had statistically significant improvements in Nasal Obstructive Symptom Evaluation scores. There was no significant change in perceived nasal appearance after surgery as measured by the Rhinoplasty Outcome Evaluation. There were no surgical complications. CONCLUSIONS: The lateral crural J-flap approach to repair of external nasal valve collapse is a technically straightforward and relatively safe procedure. The efficacy is excellent at the 1-year follow-up examination.

Superiorly based pharyngeal flap for velopharyngeal insufficiency: intermediate and longer-term perceptual speech and nasometric outcomes.

OBJECTIVE: To evaluate the intermediate and longer-term perceptual and objective speech outcomes in velopharyngeal insufficiency (VPI) patients treated with a superiorly based pharyngeal flap. DESIGN: Retrospective review. SETTING: Tertiary care centre, London, Ontario. METHODS: Forty consecutive VPI patients (mean age 14.5 years) from 2004 to 2008 who had a first time superiorly based pharyngeal flap were included. The modified Hogan flap and lateral port control technique was used with a 70° endoscope to provide intraoperative coaxial and magnified lateral port visualization. MAIN OUTCOME MEASURES: The American Cleft Palate-Craniofacial Association (ACPA) perceptual speech assessment and nasalance measured via nasometry using the MacKay-Kummer Simplified Nasometric Assessment Procedures Revised (SNAP-R). A comparison of mean outcomes from the pretreatment versus an intermediate (ACPA 4.3 months; SNAP-R 4.0 months) and longer-term (ACPA 19.5 months) posttreatment time point was performed, and the distribution of successful outcomes was assessed. RESULTS: Mean perceptual scores improved significantly early after surgery (p < .0001; n  =  33) and in the longer term (p < .01; n  =  21), with high success rates for hypernasality (87.9% and 80.9%; p < .0001), audible nasal emission (90.9% and 90.5%; p < .0001), overall intelligibility (75.7% and 81.0%; p < .01), and compensatory articulation (81.8% and 85.7%; p < .01). Likewise, significant improvements were observed in posttreatment nasal (n  =  38; p < .01) and mean oral SNAP-R scores (n  =  39; p < .001), which demonstrated success rates of 100% (p < .0001) and 73% (p < .0001), respectively. Overcorrection was not observed in perceptual and nasometric testing. CONCLUSION: The modified Hogan flap and lateral port control technique with the use of a 70° endoscope is highly successful in treating VPI. These results indicate that speech outcome improvement occurs early after surgery and is maintained over time.

Recognition and treatment of oncologic emergencies.

An oncologic emergency is a clinical condition resulting from a structural or metabolic change caused by cancer or its treatment that requires immediate medical intervention to prevent loss of life or quality of life. Five oncologic emergencies (septic shock, syndrome of inappropriate antidiuretic hormone, tumor lysis syndrome, disseminated intravascular coagulopathy, and spinal cord compression) are defined and described physiologically and clinically. Also, appropriate treatment of each oncologic emergency is discussed.