Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment 1,2. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease 3. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines 4,5. We identified a whole blood 393 transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment. A subset of latent TB patients had signatures similar to those in active TB patients. We also identified a specific 86-transcript signature that discriminated active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-γ and Type I IFNαβ signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis, suggest that this TB signature reflects both changes in cellular composition and altered gene expression. Although an IFN signature was also observed in whole blood of patients with Systemic Lupus Erythematosus (SLE), their complete modular signature differed from TB with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto under-appreciated role of Type I IFNαβ signalling in TB pathogenesis, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.

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The robotic approach is feasible for performing targeted parathyroidectomy that avoids a neck scar. The clinical efficacy and cost-effectiveness of the robotic approach compared with conventional targeted parathyroidectomy warrant further evaluation to establish if this represents a viable alternative to the existing targeted techniques.

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With the cases described, we strive to introduce single photon emission computerized tomography in combination with conventional computer tomography (SPECT/CT) to shoulder surgeons, illustrate the possible clinical value it may offer as new diagnostic radiologic modality, and discuss its limitations. SPECT/CT may facilitate the establishment of diagnosis, process of decision making, and further treatment for complex shoulder pathologies. Some of these advantages were highlighted in cases that are frequently seen in most shoulder clinics.

METHOD:The TAX 324 trial showed that the proportion of HPV positive oropharyngeal tumors was nine times higher in white versus black patients. HPV positive tumors exhibited a dramatically improved overall survival leading to an overall improved survival rate in white versus black patients. To confirm the racial disparity observed in Tax324 we performed a retrospective analysis in a larger sample size of 480 patients with oropharyngeal cancer treated at a single institution between 1995 and 2007. HPV-16 status was evaluated by PCR of DNA extracted from pretreatment biopsies embedded in paraffin. RESULTS: Among the 480 patients, detailed clinical information is available for 288 patients, and HPV status is known for 155 patients. 56% of patients are white and 44% are black. 84% of the patients are male. Median age is 56. The majority of patients (64%) are stage IV. Of patients with informative HPV samples, 40/95 (42%) of white patients are HPV positive while only 7 of 60 black patients (12%) are HPV positive (pϽ0.0001). CONCLUSION: This independent data set confirms the Tax324 trial observation that the prevalence of HPV positive oropharyngeal cancers is much lower in blacks than in whites. Together with the markedly favorable prognosis of HPV positive compared to HPV negative patients, this difference contributes significantly to overall racial survival disparities in oropharyngeal cancer.