The role of human papillomavirus in laryngeal cancer in Southern China.

To delineate the role of human papillomavirus (HPV) in laryngeal cancer in Southern Chinese, a retrospective cross-sectional study was conducted in a major otorhinolaryngology referral center in Hong Kong. Eighty-five Chinese patients with histology-confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed between 2005 and 2010 were examined for the status of HPV by PCR, and the expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings were correlated with clinicopathological features, recurrence and 5-year survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2-6.4%) who had glottic cancer and harbored HPV-6. Overexpression of p16 and p53 were detected in 11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of patients at a median of 13 months. The 5-year overall survival and disease-specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or p53 was not associated with clinicopathological features, recurrence or overall survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate marker for oncogenic involvement of HPV and cannot predict survival in laryngeal cancer.

Use of glucocorticoids in the critical care setting: Science and clinical evidence.

Glucocorticoids (GC) in all its various forms and formulations are likely one of the most commonly used pharmacologic agents in medicine. Their use can be profoundly therapeutic but are also associated with a myriad of acute and chronic side effects. It is fairly well-accepted in the medical community that GC can be life-saving when used in critically ill patients with severe exacerbations of asthma and chronic obstructive pulmonary disease, HIV-associated pneumocystosis, and systemic vasculitides. However, the adjunctive role of GC is much more controversial in acute respiratory distress syndrome (ARDS), septic shock, community-acquired pneumonia, and several other serious medical conditions. Despite such controversies, GC should at least be considered for patients with fulminant manifestations of the following conditions as there is equipoise to indicate that GC may improve outcome with acceptable risks: (i) severe ARDS with refractory hypoxemia despite one to two weeks of state-of-the-art management, (ii) recalcitrant, vasopressor-dependent septic shock, (iii) non-influenza, severe community-acquired pneumonia, and (iv) severe alcoholic hepatitis. The bases for these controversies is likely due to both host factors (e.g., differences in GC resistance and susceptibility to adverse effects) and different phenotypes of any one disease state; e.g., different pathogenesis and pathogens under the rubric of "sepsis." Elucidation of better biomarkers to determine the underlying pathogenic phenotype will significantly advance our understanding and prediction of which critically ill patients will benefit from GC and who would experience a deleterious effect from its use.

Treatment of Non-Tuberculous Mycobacterial Lung Disease.

Treatment of non-tuberculous mycobacterial lung disease (NTM-LD) is challenging for several reasons including the relative resistance of NTM to currently available drugs and the difficulty in tolerating prolonged treatment with multiple drugs. Yet-to-be-done, large, multicenter, prospective randomized studies to establish the best regimens will also be arduous because multiple NTM species are known to cause human lung disease, differences in virulence and response to treatment between different species and strains within a species will make randomization more difficult, the need to distinguish relapse from a new infection, and the difficulty in adhering to the prescribed treatment due to intolerance, toxicity, and/or drug-drug interactions, often necessitating modification of therapeutic regimens. Furthermore, the out-of-state resident status of many patients seen at the relatively few centers that care for large number of NTM-LD patients pose logistical issues in monitoring response to treatment. Thus, current treatment regimens for NTM-LD is largely based on small case series, retrospective analyses, and guidelines based on expert opinions. It has been nearly 10 years since the publication of a consensus guideline for the treatment of NTM-LD. This review is a summary of the available evidence on the treatment of the major NTM-LD until more definitive studies and guidelines become available.

Prevalence, Clinicopathological Characteristics, and Outcome of Human Papillomavirus-Associated Oropharyngeal Cancer in Southern Chinese Patients.

BACKGROUND: Although the global incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing, there is little information on southern Chinese population available. METHODS: We analyzed 207 patients which constituted 63.5% of all newly diagnosed OPSCC in Hong Kong during a 5-year period from 2005 to 2009. RESULTS: We used E6/7 mRNA as a marker of oncogenic involvement and found 20.8% (43/207) of OPSCC and 29.0% (36/124) of tonsillar SCC was associated with HPV. HPV-16 was identified in all cases except one (HPV-18). Patients with HPV-associated OPSCCs were significantly younger than HPV-negative patients (mean age: 59.8 vs. 63.9 years, P = 0.05). Multivariate analysis showed that HPV-associated OPSCC was more likely to occur in nonsmokers (39.5% vs. 15.1%, OR: 2.89, P = 0.05), nondrinkers (52.5% vs. 25.6%, OR: 2.72, P = 0.04), originate from the palatine tonsils (83.7% vs. 53.7%, OR: 3.88, P = 0.01), present with an early primary tumor (T1/2; 79.1% vs. 47.6%, OR: 3.81, P = 0.004), and exhibit basaloid differentiation (33.3% vs. 7.3%, OR: 19.74, P = 0.006). HPV positivity was an independent predictor for better prognosis for both 5-year overall and 5-year disease-specific survivals (DSS; 63.0% vs. 29.7%, HR: 0.33, P < 0.001, and 87.8% vs. 42.6%, HR: 0.16, P < 0.001, respectively). CONCLUSION: The estimated age-standardized incidence of OPSCC in Hong Kong during the period 2005-2009 was 0.12/100,000/year. IMPACT: This study has provided the most comprehensive clinical and pathologic information to date about this newly recognized disease in southern Chinese. In view of the global trend, we should anticipate and prepare for an increase in HPV-related OPSCC in southern China.

Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations.

Pulse oximetry has revolutionized the ability to monitor oxygenation in a continuous, accurate, and non-invasive fashion. Despite its ubiquitous use, it is our impression and supported by studies that many providers do not know the basic principles behind its mechanism of function. This knowledge is important because it provides the conceptual basis of appreciating its limitations and recognizing when pulse oximeter readings may be erroneous. In this review, we discuss how pulse oximeters are able to distinguish oxygenated hemoglobin from deoxygenated hemoglobin and how they are able to recognize oxygen saturation only from the arterial compartment of blood. Based on these principles, we discuss the various conditions that can cause spurious readings and the mechanisms underlying them.

Octreotide: a drug often used in the critical care setting but not well understood.

While the canonical function of somatostatin (SST) is to inhibit the secretion of growth hormone, it has a number of other physiologic effects that are less widely appreciated. Octreotide, an analog of SST, is not uncommonly used in the critical care setting, particularly for the treatment of variceal hemorrhage. Herein, we discuss the biology and pharmacology of SST, octreotide, and other SST analogs. We also review the evidence behind their use in esophageal variceal bleeds, hepatorenal syndrome, hypoglycemia due to sulfonylurea poisoning, and chylous pleural effusions.

Adipokines in children with obstructive sleep apnea and the effects of treatment.

BACKGROUND: The objective of this study was to evaluate circulating adipokines concentration in children with and without obstructive sleep apnea (OSA) and to determine the effects of treatment of OSA on their plasma concentration. METHODS: Children with habitual snoring and symptoms suggestive of OSA were consecutively recruited. Their parents completed a sleep apnea symptom questionnaire, and the subjects underwent physical examination and an overnight polysomnography (PSG). OSA was diagnosed if they had an obstructive apnea index > 1. Fasting serum adiponectin, leptin, and lipid profiles were taken after overnight PSG. The subjects were divided into groups as obese, nonobese, and with and without OSA for comparison. RESULTS: One hundred forty-one children, of whom 96 were boys, with a median (interquartile range) age of 10.8 (8.5-12.8) years were recruited. Forty-three subjects had OSA. Subjects with OSA did not have significantly different adiponectin and leptin concentrations than those without OSA for both the obese and nonobese groups. Stepwise multiple linear regressions revealed that systolic BP, age, high-density lipoprotein cholesterol, and BMI z-score were independently associated with adiponectin, whereas diastolic BP, triglyceride, height, and BMI z-score were independently associated with leptin concentration. Sixteen children with OSA underwent treatment, and there was reduction in their plasma adiponectin concentration after intervention, but such change became insignificant after controlling for change in the BMI z-score. CONCLUSIONS: BMI rather than OSA was the main determinant of adipokines in children.