Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?

The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.

Does reproductive stage impact cardiovascular disease risk factors? Results from a population-based cohort in Lausanne (CoLaus study).

CONTEXT: Menopause has been associated with adverse cardiovascular disease (CVD) risk profile, yet it is unclear whether the changes in CVD risk factors differ by reproductive stage independently of underlying ageing trajectories. DESIGN: The CoLaus study is a prospective population-based cohort study in Lausanne, Switzerland. PATIENTS: We used data from women at baseline and follow-up (mean: 5.6 ± 0.5 years) from 2003 to 2012 who did not use hormone therapy. We classified women into (i) premenopausal, (ii) menopausal transition, (iii) early (≤5 years) and (iv) late (>5 years) postmenopausal by comparing their menstruation status at baseline and follow-up. MEASUREMENTS: We measured fasting lipids, glucose and cardiovascular inflammatory markers. We used repeated measures (linear mixed models) for longitudinal analysis, using premenopausal women as a reference category. We adjusted analyses for age, medications and lifestyle factors. RESULTS: We used the data from 1710 women aged 35-75 years. Longitudinal analysis showed that the changes in CVD risk factors were not different in the other three menopausal categories compared to premenopausal women. When age was used as a predictor variable and adjusted for menopause status, most CVD risk factors increased, while interleukin-6 and interleukin-1ß decreased with advancing age. CONCLUSION: The current study suggests that women have a worsening cardiovascular risk profile as they age, and although menopausal women may have higher levels of cardiovascular risk factors compared to premenopausal women at any given time, the 5-year changes in cardiovascular risk factors may not depend on the reproductive stage.

Evaluating the effect of a water exercise routine on the postural stability of the elderly / Evaluación del efecto de una rutina de ejercicios acuáticos sobre la estabilidad postural de adultos mayores

Abstract Background: Postural stability enables humans to maintain the center of mass of their body within their base of support. Nevertheless, over time, such stability is affected by different factors such as age, repetitive strain, and accidents. Although studies in this field have investigated the effectiveness of hydrotherapy, only a few of them have explored its influence on postural stability, which is reflected in a lack of research that estimates its impact on rehabilitation. Aim: To determine the immediate and final effects of an aquatic routine protocol on the postural stability of elderly subjects. Methods: The postural stability of 20 adults over 60 years of age was analyzed using electromyographic and baropodometric methods. Electromyographic signals were obtained from the tibialis anterior, soleus, both gastrocnemius, vastus medialis, and biceps femoris to calculate the coactivation percentage of the muscles in charge of postural stability. The baropodometric data were collected to analyze the area of the stabilometric ellipse, mean plantar pressure, and weight distribution percentage. Results: The outcome of both methods revealed improvements in the elderly patients after the aquatic routine protocol was applied, which indicates that the type of water exercises implemented in this study has positive effects on their postural stability. Conclusion: The postural stability of the elderly participants was improved after each session because their stability index decreased along with the electrical activity of some muscle pairs, their body weight was better distributed, and the area of body oscillation was reduced. However, this effect was immediate and not final.

Resumen Antecedentes: La estabilidad postural permite a los humanos mantener el centro de masa de su cuerpo dentro de su base de apoyo. Sin embargo, con el tiempo, dicha estabilidad se ve afectada por diferentes factores como la edad, el esfuerzo repetitivo y los accidentes. Si bien los estudios en este campo han investigado la efectividad de la hidroterapia, solo algunos de ellos han explorado su influencia en la estabilidad postural, lo que se refleja en la falta de investigaciones que estimen su impacto en la rehabilitación. Objetivo: Determinar los efectos inmediatos y finales de un protocolo de rutina acuática sobre la estabilidad postural de adultos mayores. Métodos: Se analizó la estabilidad postural de 20 adultos mayores de 60 años mediante métodos electromiográficos y baropodométricos. Se obtuvieron señales electromiográficas del tibial anterior, sóleo, gastrocnemio, vasto interno y bíceps femoral para calcular el porcentaje de coactivación de los músculos encargados de la estabilidad postural. Los datos baropodométricos se recolectaron para analizar el área de la elipse estabilométrica, la presión plantar media y el porcentaje de distribución del peso corporal. Resultados: Ambos métodos mostraron mejoras en los pacientes luego de la aplicación del protocolo de rutina acuática, lo que indica que el tipo de ejercicios acuáticos implementados en este estudio tiene efectos positivos en su estabilidad postural. Conclusión: La estabilidad postural de los participantes mejoró después de cada sesión porque su índice de estabilidad disminuyó junto con la actividad eléctrica de algunos pares de músculos, su peso corporal se distribuyó mejor y se redujo el área de oscilación corporal. Sin embargo, este efecto fue inmediato y no definitivo.

Preoperative assessment of CD44-mediated depth of invasion as predictor of occult metastases in early oral squamous cell carcinoma.

BACKGROUND: Epithelial-mesenchymal transition and cancer stem-like cells (CSC) have been linked to increased metastatic potential. We evaluated the prognostic impact of CD44, a CSC biomarker, on depth of invasion (DOI) and outcome in oral squamous cell carcinoma (OSCC). METHODS: Using a multivariable logistic regression model, we evaluated in early OSCCs the relationship between CD44 expression at the invasive tumor front, DOI, sentinel lymph node biopsy, extension of nodal involvement, and survival. We also assessed whether CT and/or MRI could predict DOI preoperatively. RESULTS: CD44 expression was associated with increased DOI (P = .018), worse disease-specific survival (P = .041) but not with positive sentinel lymph node biopsy (P > .05). Each millimeter increase in DOI was associated with a 31.1% higher risk for positive sentinel lymph node biopsy (95% CI: 5.8%-62.4%, P = .013) and with higher metastatic ratio (P = .015). Preoperative estimation of DOI by CT and/or MRI and histopathological DOI showed a strong correlation (P < .0001). CONCLUSIONS: CD44 expression correlates with DOI, which predicts occult lymph node metastasis. Preoperative CT and/or MRI provides an accurate estimation of histopathological DOI. Both pieces of information gained preoperatively can help surgeons tailor their operation in regard to the surgical management of the neck.

Histopathologic Effects of Onabotulinum Toxin A Treatment in Pediatric Submandibular Glands.

Onabotulinum toxin A (OBTXA) is an effective treatment for drooling. Our objective was to determine if there are histologic changes in the submandibular glands (SMGs) after repetitive OBTXA injections. The study included blinded histologic analysis and comparison of SMGs with ≥4 OBTXA injections versus controls who never received OBTXA. The number of acinar cells were counted, and the morphology of the cells was evaluated within each histologic sample of the SMGs. Thirty-one glands were analyzed (14 control, 17 cases). No physical differences were observed between the 2 acinar cell groups. There was no significant difference in the number acinar cells per surface area in the control group as compared with the OBTXA group (1.29 ± 0.13 vs 1.17 ± 0.11 cells/µm2, respectively). To conclude, no significant histologic findings were established in this first human study on SMGs post-OBTXA treatment.

Cricothyroid onabotulinum toxin A injection to avert tracheostomy in bilateral vocal fold paralysis.

IMPORTANCE: More than half of children with bilateral vocal fold paralysis require a tracheostomy for airway management. We report an innovative, minimally invasive approach consisting of onabotulinum toxin A injection into the cricothyroid muscles. OBSERVATIONS: Onabotulinum toxin A was injected under direct vision into the cricothyroid muscles of 6 pediatric patients with bilateral abductor vocal fold paralysis. None of the patients had fold fixation on laryngoscopy performed at the time of the injection. All patients had a documented increase in airway patency as visualized on flexible laryngoscopy within days after injection. This procedure successfully averted a tracheostomy in 5 patients and permitted decannulation of the sixth patient. CONCLUSIONS AND RELEVANCE: Onabotulinum toxin A injection into the cricothyroid muscles leads to an increase in the glottic space, providing an adequate airway. Onabotulinum toxin A injection in the cricothyroid muscles could be offered as a safe, effective, noninvasive first-line option for patients with bilateral vocal fold paralysis.

Acute mastoiditis in children with cochlear implants: is explantation required?

OBJECTIVE: Acute mastoiditis is an uncommon but challenging condition when it occurs in children with cochlear implant. The literature is scarce as to the management of this condition with regards to explantation. The objective of the study is to determine the need for explantation in patients with cochlear implants who suffer from acute mastoiditis. DATA SOURCES: Online medical databases-PubMed, Ovid Medline, Ovid Medline in process, Embase, Cochrane Library, CINAHL, Biosis, Google Scholar, and Scopus. REVIEW METHODS: A systematic review of all publications addressing the treatment of mastoiditis in cochlear implant children prior to November 2013 was conducted. Data were collected from online medical databases-PubMed, Ovid Medline, Ovid Medline in process, Embase, Cochrane Library, CINAHL, Biosis, Google Scholar, and Scopus. The review was performed in 3 phases; an initial screening review of abstracts was performed, followed by a detailed review of full articles based on inclusion and exclusion criteria, and lastly a final review to extract data from selected articles. RESULTS: Twelve articles were found eligible for this systematic review including a total of 43 patients. Subperiosteal abscess was present in 14.3%. All patients received intravenous antibiotics as an initial treatment, and if needed, surgical intervention was performed. Only 1 patient required explantation (2.3%). CONCLUSION: Prompt, aggressive medical and if needed surgical therapy can help in saving the implant and result in a favorable outcome.

Intake and home use of olive oil or mixed oils in relation to healthy lifestyles in a Mediterranean population. Findings from the prospective Pizarra study.

Discordances exist in epidemiological studies regarding the association between the intake of nutrients and death and disease. We evaluated the social and health profile of persons who consumed olive oil in a prospective population cohort investigation (Pizarra study) with a 6-year follow-up. A food frequency questionnaire and a 7 d quantitative questionnaire were administered to 538 persons. The type of oil used in food preparation was determined by direct measurement of the fatty acids in samples obtained from the kitchens of the participants at baseline and after follow-up for 6 years. The fatty acid composition of the serum phospholipids was used as an endogenous marker of the type of oil consumed. Total fat intake accounted for a mean 40 % of the energy (at baseline and after follow-up). The concordance in intake of MUFA over the study period was high. The fatty acid composition of the serum phospholipids was significantly associated with the type of oil consumed and with fish intake. The concentration of polar compounds and polymers, indicative of degradation, was greater in oils from the kitchens where sunflower oil or refined olive oil was used, in oils used for deep frying and in oils that had been reused for frying five times or more. Consumption of olive oil was directly associated with educational level. Part of the discordance found in epidemiological studies between diet and health may be due to the handling of oils during food preparation. The intake of olive oil is associated with other healthy habits.

Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test.

Recent studies suggest that measuring the free-fatty acids (FFA) during an intravenous glucose tolerance test (IVGTT) may provide information about the metabolic associations between serum FFA and carbohydrate and insulin metabolism. We evaluated the FFA profile during an IVGTT and determined whether this test changes the composition and concentration of FFA. An IVGTT was given to 38 severely obese persons before and 7 months after undergoing bariatric surgery and also to 12 healthy, nonobese persons. The concentration and composition of the FFA were studied at different times during the test. The concentration of FFA fell significantly faster during the IVGTT in the controls and in the severely obese persons with normal-fasting glucose (NFG) than in the severely obese persons with impaired-fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) (P < 0.05). Significant differences were found in the time to minimum serum concentrations of FFA (control = NFG < IFG < T2DM) (P < 0.001). These variables improved after bariatric surgery in the three groups. The percentage of monounsaturated and n-6 polyunsaturated FFA in the control subjects and in the obese persons, both before and after surgery, decreased significantly during the IVGTT. In conclusion, during an IVGTT, severely obese persons with IFG or T2DM experienced a lower fall in the FFA than the severely obese persons with NFG and the controls, becoming normal after bariatric surgery.

Improved carbohydrate metabolism after bariatric surgery raises antioxidized LDL antibody levels in morbidly obese patients.

OBJECTIVE: Antioxidized LDL (anti-oxLDL) antibodies have recently been suggested to be protective against the development of diabetes. We measured the changes in anti-oxLDL antibody levels in the inverse situation of improvement in carbohydrate metabolism. RESEARCH DESIGN AND METHODS: The study was undertaken in 73 morbidly obese individuals, 21 of whom had type 2 diabetes, before and 7 months after they underwent bariatric surgery and in 11 healthy, nonobese individuals. Measurements were made of the area under the curve of glucose (AUC(Glu)) by an intravenous glucose tolerance test and of oxidized LDL (oxLDL) and IgG and IgM anti-oxLDL antibodies. RESULTS: The morbidly obese patients with diabetes had significantly higher levels of oxLDL compared with the morbidly obese patients with normal fasting glucose and the control subjects and significantly lower levels of IgM anti-oxLDL antibodies. An inverse correlation was found between the levels of oxLDL and IgM anti-oxLDL antibodies (r = -0.352, P = 0.012). Although the levels of IgG and IgM anti-oxLDL antibodies rose after surgery, this increase was only significant in the diabetic patients, who experienced an improvement in their metabolic profile. Different multiple linear regression models showed that the AUC(Glu) was the main factor explaining the behavior of the levels of oxLDL and anti-oxLDL antibodies. CONCLUSIONS: We found a close association between carbohydrate metabolism and IgM anti-oxLDL antibodies, which were significantly reduced in the morbidly obese patients with diabetes. The improvement in carbohydrate metabolism after bariatric surgery led to a significant increase in the levels of IgG and IgM anti-oxLDL antibodies.

Morbidly obese individuals with impaired fasting glucose have a specific pattern of insulin secretion and sensitivity: effect of weight loss after bariatric surgery.

BACKGROUND: Obesity is often associated with hyper-secrection of insulin. Impaired fasting glucose (IFG) has recently been redefined as a fasting plasma glucose of 5.6-6.9 mmol/L. The aim of this study was to determine whether changes in insulin secretion in morbidly obese persons also commence with normal serum glucose levels. METHODS: 32 morbidly obese subjects were studied before and after bariatric surgery. Measurements were made of glucose tolerance (K(G)), insulin sensitivity (SI), first-phase insulin release and the disposition index (DI) from a frequently sampled intravenous glucose tolerance test. RESULT: In morbidly obese subjects, the SI (P<0.01), DI (P<0.01) and first-phase insulin release (P<0.02) started changing with serum glucose levels considered to be normal (5.00-5.28 mmol/L). K(G) showed a clear slope according to the baseline glycemia status (P<0.05), and it was significantly related with the DI, both before (r=0.76, P<0.001) and after (r=0.57, P=0.002) surgery. Following surgery, all the variables significantly associated with insulin secretion and insulin sensitivity recovered significantly. The most significant changes occurred in morbidly obese individuals with IFG. CONCLUSIONS: Morbidly obese subjects show slopes of insulin sensitivity and insulin secretion in accordance with their baseline serum glucose levels. The fall in first-phase insulin release begins when serum glucose values are considered normal. Morbidly obese persons with the IFG phenotype have a specific pattern of insulin sensitivity and insulin secretion. K(G) clearly discriminates the clinical phenotypes, depending on baseline serum glucose levels.