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     

Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Oropalatal band (maxillo-mandibular band). off.

A rare case of a maxillo-mandibular band in a 21 year female patient is reported. Possibility of its being a remnant of buccaphary geal membrane is discussed in the light of clinical and histological findings.     

Bladder stone disease in children in Afghanistan

Of 132 children with bladder stones seen in 1 year, 94% were boys and 73% were aged between 1 and 5 years. Significant malnutrition and evidence of vitamin deficiency were absent. Wheat bread was the dietary staple, while the intake of milk and dairy products, eggs and meat was very low. Analysis of 29 stones showed them to consist mainly of calcium oxalate and uric acid, with small amounts of calcium phosphate and magnesium ammonium phosphate in some cases. The composition of the surface and central parts of the stones, examined in 20 cases, was usually different. The nucleus was formed almost entirely of calcium oxalate and uric acid in four and three cases respectively, whereas the surface layers were composed of other ingredients. In another case the nucleus was composed entirely of xanthine, which indicated a diagnosis of xanthinuria.     

Comparison of stress transmission in the IMZ implant system with polyoxymethylene or titanium intramobile element: a finite element stress analysis.

Using the finite element method, this study modeled a 4.0 x 13.0-mm IMZ implant, restored with a cast gold crown, to examine the influence of the polyoxymethylene (POM) intramobile element (IME) on the transmission of vertical and oblique forces. Stress concentrations in the bone and in components of the implant system were much greater under a 30-degree load than under an equal vertical load. Stress transmission to bone occurred chiefly in the crestal region, and these stresses were not reduced when the IME was modeled in POM rather than in titanium. Maximum stress concentrations occurred in the fastening screw.     

Postoperative cerebellar herniation in a large intrapetrous aneurysmal bone cyst.

An 18-year old boy presented with a tumour involving a large part of the petrous bone. A radical resection of a petrous bone 'aneurysmal bone cyst' was achieved. A large defect in the dura adjoining the posterior surface of the petrous bone was made during surgery. Post-operative MR imaging showed complete tumour resection but herniation of cerebellum into the operative defect, a phenomenon probably assisting to seal the site of cerebrospinal fluid fistula.     

Dynamic response of the occipito-atlanto-axial (C0-C1-C2) complex in right axial rotation.

The torque-angular deformation in right axial rotation until failure of the ligamentous occipito-atlanto-axial complex subjected to variable loading rate (dynamic) axial torque was characterized using a biaxial MTS system. A special fixture and gear box that permitted right axial rotation of the specimen until failure without imposing any additional constraints were used to obtain the data. The specimens were divided into three groups and tested until failure at three different dynamic loading rates: 50, 100, and 400 degrees/s. A previous study by the authors provided data for quasi-static (4 degrees/s) loading conditions. The torque versus rotation curves can be divided into two straight regions and two transition zones. The plots clearly indicated that at loading rates higher than 4 degrees/s, the specimens became stiffer in the region of steadily increasing resistance prior to failure. The increase in stiffness was maximum at 100 degrees/s. The stiffness decreased somewhat at 400 degrees/s in comparison with 100 degrees/s, but this decrease was not significant. The resulting torque-right axial rotation curves were also examined to estimate the magnitude of maximum resistance (torque) and the corresponding angular rotation value. The average maximum resistance torque increased from 13.6 Nm at 4 degrees/s to 27.8 Nm at 100 degrees/s. The corresponding right angular rotation data (65-78 degrees), however, did not show any significant variation with loading rate. Posttest dissection of the specimens indicated that the type of injury observed was related to the rate of axial loading imposed on a specimen during testing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of single and repeated electroconvulsive therapy sessions on plasma ACTH, prolactin, growth hormone and cortisol concentrations.

To study the effects of electroconvulsive therapy (ECT) on hormone release, we measured circulating concentrations of adrenocorticotropic hormone (ACTH), prolactin (PRL), growth hormone (GH) and cortisol (CORT) immediately before and at 2 min, 5 min, 15 min, and 30 min following ECT. Compared to pre-ECT concentrations, there were significant increases in post-ECT plasma ACTH, PRL and CORT. GH did not change consistently. No significant difference between unilateral and bilateral ECT was observed. Compared to the first ECT, repeated treatments were associated with a significant decrease in the magnitude of hormone surge. These hormonal changes induced by ECT may reflect changes at the neurotransmitter level.