Spare Roof Technique Versus Component Dorsal Hump Reduction: A Randomized Prospective Study in 250 Primary Rhinoplasties, Aesthetic and Functional Outcomes.

BACKGROUND: Most Caucasian aesthetic rhinoplasty patients complain about having a noticeable hump in profile view. Taking the integrity of the middle vault into consideration, there are 2 ways to dehump a nose: the structured technique and the preservation technique. OBJECTIVES: The aim of this study was to compare the aesthetic and functional outcomes of 2 reduction rhinoplasty techniques. METHODS: We performed a prospective, randomized, interventional, and longitudinal study on 250 patients randomly divided into 2 groups: the component dorsal hump reduction group (CDRg) (n = 125) and the spare roof technique group (SRTg) (n = 125). We utilized the Utrecht Questionnaire for Outcome Assessment in Aesthetic Rhinoplasty. Patients answered the questionnaire before the surgery, and at 3 and 12 months after surgery. In addition, we utilized a visual analog scale (VAS) to score nasal patency for each side. RESULTS: Analyses of the preoperative and postoperative aesthetic VAS scores showed a significant improvement in both groups, from 3.66 to 7.00 (at 3 months) to 7.35 (at 12 months) in the CDRg, and from 3.81 to 8.14 (at 3 months) to 8.45 (at 12 months) in the SRTg. Analyses of postoperative means of aesthetic VAS scores showed a significant improvement in both groups over time. However, aesthetic improvement was higher in the SRTg than in the CDRg at both 3 (P < 0.001) and 12 months (P < 0.001) postsurgery. Analyses of the mean functional VAS scores showed a significant improvement with both techniques, with a better result for the SRTg. CONCLUSIONS: The SRT is a reliable technique that can help deliver consistently better aesthetic and functional results than CDR for reduction rhinoplasty in Caucasian patients with a dorsal hump.

Rhinoplasty-Do Patients and Surgeons See the Same? A Double-Blind Study with 100 Randomized Patients.

One of the key points of a successful rhinoplasty is communication between the patient and surgeon. The surgeon needs to get a clear understanding of the patient's motivation for surgery and expectations of the procedure. This information is mandatory in formulating an optimal surgical plan and managing realistic expectations of the procedures. Ideally, surgeons and patients see, discuss, and quantify the same nasal defects. In reality, the subjective nature of perceiving aesthetics can cause variability of inter-rating nasal appearance. Therefore, one might question how well surgeons understand their patients. Do they see what patients see? The aim of this study is to assess the level of agreement on the evaluation of nasal appearance between patients, surgeons, and nonphysicians observers, and try to find predictive factors that cause high interobserver variability. This prospective, observational, and cross-sectional study was performed on a total of 100 randomized patients undergoing rhinoplasty. All patients were photographed before surgery and asked to rate the appearance of their nose on a 10 cm visual analogue scale (VAS) with 0 indicating very ugly and 10 indicating very nice. Subsequently, the photographs of each patient were, independently, rated by two panels: one constituted by two rhinoplasty surgeons and the other by four nonmedical raters. Both panels included European raters from the north (The Netherlands) and south (Portugal). Data regarding age, gender, skin type, and major nasal deformity were also collected. The authors found that there is no statistical agreement between the aesthetical evaluation of the nose between patients and surgeons or patients and nonmedical raters. Based exclusively on the VAS for subjective evaluation of nasal appearance, the authors' findings show that surgeons and patients do not "see the same" and generally, the score attributed by the surgeon is more favorable (almost 1 point higher) than the auto-assessment's score. This is important to realize when communicating about nasal appearance before rhinoplasty.

Curcumin and Rutin Down-regulate Cyclooxygenase-2 and Reduce Tumor-associated Inflammation in HPV16-Transgenic Mice.

AIM: Cyclo-oxygenase-2 (COX2) plays a prominent role in carcinogenesis. This study addresses the effects of two nutraceutical compounds on the expression of COX2 and tumor-associated inflammation in human papillomavirus type 16 (HPV16)-transgenic mice. MATERIALS AND METHODS: Six-week-old FVB/n mice were supplemented with rutin or curcumin for 24 weeks: HPV16-/- no treatment, n=12; HPV16+/- no treatment, n=13; HPV16+/- rutin, n=12; HPV16+/- curcumin, n=13. HPV16-induced skin lesions and their inflammatory infiltrates were studied histologically. COX2 expression was assessed immunohistochemically. RESULTS: Rutin reduced COX2 expression in the dermis (immunostaining score 7.83 versus 11.25 in untreated HPV16-transgenic mice) and epidermis (4.5 versus 10.0). Curcumin led to dermal and epidermal scores of 10.5 and 4.5. Both compounds reduced leukocytic infiltration, but neither prevented epidermal dysplasia. CONCLUSION: COX2 expression in HPV16-induced lesions may be modulated by nutraceuticals, reducing tumor-associated inflammation. However, this was not sufficient to block carcinogenesis, calling for additional studies focused on combination therapies.

Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice.

PURPOSE: Persistent human papillomavirus (HPV) infection is associated with the development of certain types of cancer and the dysregulation of microRNAs has been implicated in HPV-associated carcinogenesis. This is the case of microRNA-146a (miR-146a), which is thought to regulate tumor-associated inflammation. We sought to investigate the expression levels of miR-146a during HPV16-mediated carcinogenesis using skin samples from K14-HPV16 transgenic mice which develop the consecutive phases of the carcinogenesis process. METHODS: Female transgenic (HPV+/-) and wild-type (HPV-/-) mice were sacrificed at 24-26 weeks-old or 28-30 weeks-old. Chest and ear skin samples from HPV+/- and HPV-/- mice were histologically classified and used for microRNA extraction and quantification by qPCR. RESULTS: Chest skin samples from 24 to 26 weeks-old HPV+/- mice presented diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while at 28-30 weeks-old all (100.0%) HPV+/- animals showed epidermal dysplasia. All HPV+/- ear skin samples showed carcinoma in situ (CIS). MiR-146a expression levels were higher in HPV+/- compared to HPV-/- mice (p = 0.006). There was also an increase in miR-146a expression in dysplastic skin lesions compared with hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease in miR-146a expression when compared to samples showing epidermal hyperplasia (p = 0.018) and epidermal dysplasia (p = 0.009). CONCLUSIONS: These results suggest that HPV16 induces the overexpression of miR-146a in the initial stages of carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at later stages (CIS). Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis.

[Stapedo-Vestibular Ankylosis: Retrospective Study of Five Cases in São Tomé e Príncipe]. / Anquilose Estapedo-Vestibular: Estudo Retrospetivo de Cinco Casos em São Tomé e Príncipe.

INTRODUCTION: Otosclerosis is a common form of conductive hearing loss characterized by abnormal bone remodeling exclusively in the otic capsule. The prevalence of otosclerosis varies in racial populations and is described as being rare in black African populations. In this paper we aim to report five cases of clinical, and surgically confirmed, otosclerosis in black individuals, in São Tomé and Príncipe. MATERIAL AND METHODS: Since February 2011, Ear, Nose and Throat consultations and surgeries specialty have been carried out at Dr. Ayres de Menezes Hospital in cooperation with the project 'Health for all'. A retrospective analysis was undertaken of the records of all patients subjected either to stapedectomy or partial stapedectomy until February 2014. Information regarding clinical presentation, audiometric data and surgery reports was recorded. RESULTS: Five adult patients underwent stapedectomy or partial stapedectomy. All of them presented with normal otoscopy, conductive or mixed hearing loss on audiogram and normal tympanometry with absent stapedial reflexes. None of the patients had signs of infection or history of head trauma. Three cases showed improvement in the air-bone gap after surgery. The other two were lost to follow-up. DISCUSSION: We documented and surgically confirmed five cases of clinical otosclerosis in this population. A thematic review was carried out and concluded that, despite being described as a rare event in this race, available literature on this topic is not enough to state that there is lower prevalence of otosclerosis amongst the African population. CONCLUSION: Even if not common, otosclerosis cannot be disregarded as a possible cause for conductive hearing loss among the population of São Tomé and Principe.

Introdução: A otosclerose é uma causa frequente de hipoacusia de condução caracterizada pela alteração da remodelação óssea localizada exclusivamente à cápsula ótica. Diferenças rácicas são evidentes na literatura e, ao contrário dos caucasianos, as descrições na população de origem africana são raras. Neste trabalho pretende-se reportar cinco casos observados, e cirurgicamente confirmados, de otosclerose em indivíduos de raça negra, em São Tomé e Príncipe. Material e Métodos: Desde fevereiro de 2011, efetuam-se consultas e cirurgias de Otorrinolaringologia no Hospital Ayres de Menezes, em São Tomé e Príncipe, inseridas no projeto 'Saúde para todos ­ Especialidades'. Neste trabalho realizou-se um estudo retrospetivo dos doentes submetidos a estapedotomia ou estapedectomia parcial durante estas missões até fevereiro de 2014. Recolheu-se informação relativa à apresentação clínica, resultados audiométricos e relatórios cirúrgicos. Resultados: Cinco doentes, adultos, foram submetidos a procedimento cirúrgico. Todos apresentavam otoscopia normal, ausência de história de traumatismo cranioencefálico ou quadro infecioso, audiograma com hipoacusia mista ou de condução e timpanograma tipo A, sem reflexos estapédicos. Em três doentes foi possível realizar audiograma pós-operatório, verificando-se melhoria do gap aero-ósseo. Discussão: Neste trabalho documentam-se cinco casos de otosclerose clínica, e cirurgicamente confirmada, na população negra de São Tomé e Príncipe. Efetuada uma revisão temática, constata-se que, apesar de a otosclerose ser considerada rara nesta raça, os dados disponíveis parecem insuficientes para determinar se, de facto, diferentes raças têm diferentes incidências da doença. Conclusão: Apesar de rara, a otosclerose não pode ser ignorada como uma possível causa de hipoacusia de condução em São Tomé e Príncipe.

Regulation of miRNA-146a and miRNA-150 Levels by Celecoxib in Premalignant Lesions of K14-HPV16 Mice.

BACKGROUND/AIM: Human papillomavirus type 16 (HPV16) induces various types of cancer in several locations. Microenvironmental microRNAs (miRNAs) such as miRNA-146a and miRNA-150 regulate cancer-associated inflammation and are involved in HPV-induced carcinogenesis. We studied the effects of celecoxib on the expression of these two miRNAs in HPV16-induced lesions. MATERIALS AND METHODS: Female transgenic (HPV16+/-) and wild-type (HPV16-/-) mice were administered 75 mg/kg/day celecoxib orally (treatment groups) or placebo (control groups) for four weeks. Skin samples were classified histologically, or used for miRNA analysis by quantitative real-time PCR. RESULTS: HPV16+/- mice showed higher miRNA-146a and miRNA-150 expression levels compared to wild-type animals. Celecoxib further increased miRNA-150 (p<0.05) and miRNA-146a levels in treated animals. Celecoxib-treated HPV16+/- animals also showed reduced incidence of epidermal dysplasia and reduced inflammation, compared to untreated mice. CONCLUSION: In this model, celecoxib may be able to regulate tumour-associated inflammation, through mechanisms involving the regulation of miRNA-146a and miRNA-150.

Intermediate osteotomies in rhinoplasty: a new perspective.

The nasal dorsum framework plays a major role in nasal and facial harmony. This study presents a new approach to an already known technique, intermediate osteotomies, which can be used routinely in patients with cosmetically unpleasant changes in eyebrow-tip line features, allowing the acquisition of a natural, aesthetically agreeable and harmonious dorsum contour, while preserving nasal function. The approach was evaluated retrospectively in 50 consecutive patients at a tertiary referral hospital. Patients were asked to complete a survey to rate their satisfaction with the cosmetic outcome on a 5-point visual analog scale (VAS) and to compare the impact of nasal obstruction on their quality of life, pre- and postoperatively, by completing the validated Nasal Obstruction Symptom Evaluation (NOSE) scale. Satisfaction was scored as excellent (satisfaction level VAS average score, 4.4), with more than 50% of the patients completely satisfied with the aesthetic result, while NOSE scale scores demonstrated preservation of nasal function postoperatively. Typical complications of the upper third of the nose following osteotomies were not observed.

Dysregulated expression of microRNA-150 in human papillomavirus-induced lesions of K14-HPV16 transgenic mice.

AIMS: High-risk human papillomavirus (HPV) infection is one of the major causes of infection-related cancers worldwide. MicroRNAs (miRNAs) are a family of non-coding RNAs (ncRNAs), whose dysregulated levels may cause an aberrant expression of genes involved in oncogenic pathways and consequently lead to cancer development. This is the case of the miRNA-150 (miR-150), whose expression in HPV-induced lesions remains unclear and the present work aims to clarify it. We employed K14-HPV16 mice, which express the early genes of HPV16 in basal keratinocytes, leading to the development of hyperplastic and dysplastic skin lesions and squamous cell carcinomas, and are a representative model of HPV-induced cancers. MAIN METHODS: In order to evaluate the expression of miR-150 in HPV-induced lesions, we performed qPCR in wild-type mice (HPV-/-) and in skin lesions of K14-HPV16 transgenic mice (HPV+/-). Matched skin samples were analyzed histologically. KEY FINDINGS: 24-26weeks-old HPV+/- mice showed diffuse epidermal hyperplasia and focal dysplasia in a hyperplastic background (31.8% incidence), but 28-30weeks-old HPV+/- mice presented higher incidence of dysplasia (100.0%). MiR-150 was upregulated in HPV+/- mice when compared with HPV-/- mice (p<0.001). MiR-150 was also overexpressed in diffuse dysplastic lesions when compared with hyperplastic lesions (p=0.005). SIGNIFICANCE: The present results suggest that miR-150 is overexpressed in HPV-induced lesions in this model and its expression seems to increase with lesion progression, along the process of multi-step carcinogenesis.

HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition.

Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-κB were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-κB canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-κB inhibitors may be useful resources for treating this syndrome.

The posterosuperior quadrant of the tympanic membrane.

OBJECTIVE: To document the anatomic relationship of the posterosuperior segment of the tympanic membrane. STUDY DESIGN: Point-prevalence study of postmortem material. SUBJECTS AND MATERIALS: One hundred seventy temporal bones from adults without history of otologic pathology were studied. The anatomic details of the tympanic membrane were observed, histology was documented on 30 sectioned bones, and, with the use of the scanning electron microscope, lamina propria was studied in 40 bones. RESULTS: We established that the posterosuperior quadrant was the largest, representing 28.7 percent of the total area of the eardrum. This feature implies that this quadrant is more likely than are the other quadrants to exhibit changes prompted by pressure challenges. We also verified that the posterosuperior part of tympanic sulcus, above the chorda tympanic nerve, lost its depth in an unexpected way in 60 percent of the cases. In association, we established that at this level there was a decrease in annulus caliber. In 25 percent of cases, by the absence of the circular fibers of lamina propria, the posterosuperior quadrant had only the radial fiber layer. CONCLUSIONS: Anatomic and morphologic details in posterosuperior quadrant were newly described and may explain the greater incidence of retraction pockets and marginal perforations that provide origin for the cholesteatoma.