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     

Giant dermoid associated with foot duplication

After resection at birth of an accessory left foot, a white male infant was followed up for a slowly enlarging posterior calf mass of the same leg. When the patient was 8 years old, the mass was thought to have enlarged sufficiently to warrant excisional biopsy. Histologic examination of the tumor was consistent with the diagnosis of a dermoid cyst, revealing a lesion lined with stratified squamous epithelium and containing cutaneous adnexal structures represented by eccrine sweat glands. A congenital dermoid in the extremities is unusual. The prognosis following removal is good, and recurrence is rare.     

In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.     

Health promotion training needs analysis: an integral role for clinical nurses in Lanarkshire,Scotland*

Training needs analysis is considered essential to professional and organizational development, for continuing education and for incorporation into professional practice. Increasingly, nurses are encouraged to develop their health promotion role. Despite this there has been relatively little research in Scotland into the health promotion role of the hospital nurse. This study describes the results of a health promotion training needs analysis undertaken on qualified, hospital-based nurses in Lanarkshire, Scotland. Information on the nurses' current health promotion practices, their attitudes and beliefs, their views on role development and priorities for further training were collated, analysed and discussed within the framework of the Health Action Model. This model was originally designed to assist understanding of the gap that exists between an individual intention to act and the eventual health action. However, in this study the ways in which ‘cognitive factors’ (knowledge and beliefs) and ‘motivational factors’ (considering values, attitudes and drives) and pressures from social norms and significant others assisted in the understanding of the nurse's orientation to, and beliefs about, health promotion practice. Fifty-seven per cent of nurses in the study considered health promotion activities to be emerging in clinical care and 4% considered them to be advanced. The interest respondents have in role development and the further integration of health promotion activities into nursing practice was explored by ascertaining the nurses' attitudes and beliefs about their own health promotion role. Of 107 respondents, a majority 72 (67%) agreed health promotion interventions to be an important function of the nurse with 29 (27%) strongly agreeing (n=107). Sixty per cent stated they would be interested in developing their role and 30% were very strongly interested. Recommendations are therefore made for future planning and development strategies for the health promotion role of hospital nurses.     

Endarterectomy as an adjunct to coronary artery bypass grafting

Between November 1988 and February 1992, 416 patients required coronary endarterectomy for diffuse coronary artery disease. This constitutes 16.19 per cent of all patients who underwent coronary artery bypass grafting during the same period. A total of 528 endarterectomies were performed. Four-hundred and twenty-two endarterectomies were performed on right coronary system and 106 endarterectomies were performed on left coronary system. One-hundred and twelve (26.92%) patients required more than one endarterectomies. The hospital mortality was 2.16 percent. 3.37 per cent of patients had perioperative infarction. Intraaortic balloon pump was required in 1.92 per cent of patients. 5.77 per cent of the patients had significant arrhythmias. The patients have been followed up for a mean period of 27 months. One-hundred and forty patients were evaluated by exercise multigated radionuclide angiogram. One-hundred and thirty-four (95.71%) patients showed increase in ejection fraction as compared to preoperative value. Six (4.29%) patients did not show any significant change while eight (5.71%) patients had fall in ejection fraction. Postoperative coronary angiogram was done in 44 patients at a mean of 10 months. 89.59 per cent of grafts to the endarterectomised vessels and 91.67% of grafts to nonendarterectomised vessel were patent. The difference between the two groups was not statistically significant.