Contributing Determinants to Hearing Loss in Elderly Men and Women: Results from the Population-Based Rotterdam Study

To contribute to a better understanding of the etiology in age-related hearing loss, we carried out a cross-sectional study of 3,315 participants (aged 52-99 years) in the Rotterdam Study, to analyze both low- and high-frequency hearing loss in men and women. Hearing thresholds with pure-tone audiometry were obtained, and other detailed information on a large number of possible determinants was collected. Hearing loss was associated with age, education, systolic blood pressure, diabetes mellitus, body mass index, smoking and alcohol consumption (inverse correlation). Remarkably, different associations were found for low- and high-frequency loss, as well as between men and women, suggesting that different mechanisms are involved in the etiology of age-related hearing loss

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma

Objective MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution. Methods Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (= 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM. Results Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05). Conclusion MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DO

The impact of ambient NO on online measurements of exhaled and nasal NO:The PIAMA study

The guidelines of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) for standardized measurements of exhaled nitric oxide (NO) state that for online measurements the inhaled air should be free of NO. As it is not always possible to create an NO-free environment, inhalation through an NO-scrubber is used. To describe the relationship between ambient NO and measurements of fractional exhaled NO (FENO) and nasal NO (nNO) investigated according to the ATS-ERS guidelines in a large population of children. The present work makes use of data collected during the 8-yr follow-up of the Dutch PIAMA birth cohort study. FENO and nNO were measured in three hospitals in a total of 1005 children with a NIOX chemiluminescence analyser. In two hospitals, almost half of the measured ambient NO levels exceeded 5 p.p.b. Maximum levels were > 100 p.p.b. in all hospitals. Despite its large variation, ambient NO did not have an effect on FENO, but it did have a significant impact on nNO in two of the three centres. The currently recommended technique including inhalation through an NO scrubber effectively deals with variable levels of ambient NO on FENO. In contrast, ambient NO has an effect on measurements of nNO

A new prediction model for giant cell arteritis in patients with new onset headache and/or visual loss

Objective: The gold standard for diagnosis of giant cell arteritis (GCA) is a temporal artery biopsy (TAB). We sought for a clinical useful model to predict when an invasive TAB is not necessary to confirm GCA. Methods: A prospective cohort study was conducted with patients > 50 years with possible GCA, presenting with newly onset headache and/or visual loss. Demographical, clinical, laboratory findings and histological data were collected. Results: Fifty-six (70%) of the 94 patients showed 1 or more halos of the superficial temporal artery branches. Ultrasound-guided biopsy was positive in 28 patients (30%). Four independent variables predicted a positive TAB: weight loss, bilateral headache, positive halo sign and thrombocytosis. The ROC of the model had an area under the curve of 0.932 with a PPV of 83% and a NPV of 94%. Conclusions: Weight loss, bilateral headache, a positive halo sign with duplex and thrombocytosis are the most important clinical and laboratory predictors for GCA in a selected group of patients. Significance: In patients > 50 years presenting with new onset headache or visual loss with 3 or more of the above mentioned risk factors, a biopsy of the temporal artery is not needed to confirm the diagnosis GCA.KEY MESSAGES In our study biopsy of the temporal artery was positive in 30% of the patients with possible GCA Weight loss, bilateral headache, a positive halo sign on duplex and thrombocytosis are predictors for GCA The halo sign had a high sensitivity but a low specificity for a biopsy proven GCA

A novel immunohistochemical scoring system reveals associations of C-terminal MET, ectodomain shedding, and loss of E-cadherin with poor prognosis in oral squamous cell carcinoma

Using tissue microarrays, it was shown that membranous C-terminal MET immunoreactivity and ectodomain (ECD) shedding are associated with poor prognosis in oral cancer. Seen the potential diagnostic value, extrapolation of these results to whole-tissue sections was investigated. Because MET orchestrates epithelial-to-mesenchymal transition (EMT), the results were benchmarked to loss of E-cadherin, a readout for EMT known to be associated with poor prognosis. C-terminal MET, N-terminal MET, and E-cadherin immunoreactivities were examined on formalin-fixed paraffin-embedded parallel sections of 203 oral cancers using antibody clones D1C2, A2H2-3, and NCH-38. Interantibody and intra-antibody relations were examined using a novel scoring system, nonparametric distribution, and median tests. Survival analyses were used to examine the prognostic value of the observed immunoreactivities. Assessment of the three clones revealed MET protein status (no, decoy, transmembranous C-terminal positive), ECD shedding, and EMT. For C-terminal MET-positive cancers, D1C2 immunoreactivity is independently associated with poor overall survival (hazard ratio [HR] = 2.40; 95% confidence interval [CI] = 1.25 to 4.61; and P = 0.008) and disease-free survival (HR = 1.83; 95% CI = 1.07-3.14; P = 0.027). For both survival measures, this is also the case for ECD shedding (43.4%, with HR = 2.30; 95% CI = 1.38 to 3.83; and P = 0.001 versus HR = 1.87; 95% CI = 1.19-2.92; P = 0.006) and loss of E-cadherin (55.3%, with HR = 2.21; 95% CI = 1.30 to 3.77; and P = 0.004 versus HR = 1.90; 95% CI = 1.20-3.01; P = 0.007). The developed scoring system accounts for MET protein status, ECD shedding, and EMT and is prognostically informative. These findings may contribute to development of companion diagnostics for MET-based targeted therapy