Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab

Background Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.Methods Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.Results Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).Conclusions High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registration Registered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).Subject terms: Tumour biomarkers, Head and neck cancer, Tumour biomarkers, Head and neck cancer, Predictive markers     

On modelling the kinestatic charge detector for digital radiographic diagnostic and portal imaging

The kinestatic charge detection (KCD) principle has been a digital radiography technique for more than a decade. The advances of the KCD technique have gone from diagnostic imaging to portal imaging. However, little work has been done on understanding the selection of key KCD parameters and relationships between them. In the present study, an engineering model was established that could be used to optimize the placements of key parameters in terms of KCD system mechanical design. In the proposed KCD engineering model, the basic energy conservation law was applied to the process of ion transmission. It allows for the computation of the KCD design parameters such as the optimum grid placement, high voltage board tilt angle and grid wire space, as well as to provide recommendations on high voltage board and electric potentials and their ratio.     

Fibrous dysplasia of the mastoid

A rare case of fibrous dysplasia involving the mastoid bone is reported. Its histopathological characteristics are also described.     

Imaging in isolated sacral tuberculosis: a review of 15 cases

Objective. To review imaging studies of isolated involvement of the sacrum due to tuberculosis and determine the role of imaging in the diagnosis and management of these patients. Design and patients. A retrospective analysis of 15 cases of isolated sacral tuberculosis imaged with MR imaging was performed. The CT images were also reviewed where available, and the various lesion characteristics were identified. We also reviewed the medical records in an attempt to determine the impact of the imaging studies on the management of these patients. Results. Fifteen patients (5 male, 10 female) presented with symptoms of 3–15 months’ duration. Chronic localized backache with muscle spasm was the commonest presenting symptom; discharging sinuses with abscess formation was found in six patients, five of whom were children. MR imaging of the sacrum revealed a hypointense marrow signal on T1-weighted images and hyperintense signal on T2-weighted images in 14 of 15 patients, the S2 vertebra being always involved. CT revealed osteolytic changes in the sacrum in all the five patients in whom CT was performed. All patients showed marked clinical improvement within 1 year of anti-tuberculous chemotherapy. Conclusion. Isolated tuberculosis of the sacrum is uncommon but should be suspected in patients presenting with chronic low backache or children with discharging sinuses/abscesses and showing sacral destruction on CT or MR imaging. MR imaging can identify cases and enables early institution of anti- tuberculous chemotherapy. Received: 31 August 1999 Revision requested: 1 November 1999 Revision received: 27 March 2000 Accepted: 14 April 2000     

Tumor like swellings arising from Hoffa's fat pad: A report of three patients

We report three rare cases of tumor-like conditions arising from Hoffa''s fat pad (HFP). Patients were having persistent knee pain, the cause of which was not diagnosed by the general physician, and then were referred to us for knee pain. Magnetic resonance imaging revealed the lesions to be arising from HFP (ganglion cysts and hemangioma), as was suggested by clinical findings. Anatomy, pathology, and radiological features of the Hoffa''s disease are described here to increase awareness in orthopedic community of this rare but interesting disease which is often misdiagnosed as meniscal pathology. These cases illustrate that increased cognizance can facilitate timely intervention which will prevent morbidity of the patient.     

Selenium reducing Citrobacter fruendii strain KP6 from Mandovi estuary and its potential application in selenium nanoparticle synthesis

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The present study foregrounds the isolation of selenium tolerant bacteria from Mandovi estuary of Goa, India,...     

Associations of pain catastrophizing with pain-related brain structure in individuals with or at risk for knee osteoarthritis: Sociodemographic considerations

Compelling evidence exists that non-Hispanic blacks (NHB) engage in pain catastrophizing (negatively evaluate one’s ability to cope with pain) more often than non-Hispanic whites (NHW). Functional neuroimaging studies revealed that individuals with high levels of trait pain catastrophizing show increased cerebral responses to pain in several pain-related brain regions (e.g., insula, primary somatosensory cortex [S1]), but associations between brain structure and catastrophizing remain largely unexplored. The current investigation was conducted at the University of Florida and the University of Alabama at Birmingham. Participants were 129 community-dwelling adults with or at risk of knee osteoarthritis (OA). Participants completed the pain catastrophizing subscale of the Coping Strategies Questionnaire-Revised and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain intensity subscale. Magnetic Resonance Imaging data were obtained. MANOVA and Chi-Square analyses assessed sociodemographic/clinical differences stratified by ethnicity/race. Multivariate regression analyses with insula and somatosensory cortical thickness entered as dependent variables with catastrophizing and the interaction between catastrophizing and ethnicity/race as the independent variables. Covariates include education, body mass index, study site, and WOMAC pain (ethnicity/race was an additional covariate in non-stratified analyses). There were significant interactions between ethnicity/race, pain catastrophizing, and brain structure. Higher pain catastrophizing was associated with thinner S1 bilaterally (ps < .05) in NHW, but not NHB participants with or at risk for knee OA. These results suggest that pain catastrophizing might have differing effects on pain-related central pathways and may contribute to ethnic/race group differences in individuals with or at risk for knee OA.