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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  相似文献   
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The value of ultrasound in the diagnosis of a large rapidly growing thyroid mass was assessed in a study of 42 patients with a large (> 3 cm) rapidly growing (< two months) solitary mass. Haemorrhage into a thyroid nodule was present in 31 patients and thyroid malignancy in 11. Ultrasound of haemorrhage into a thyroid nodule revealed a large cystic mass in all 31 patients containing internal debris (22), septations (three), or a combination of both (six). The malignant causes of a large rapidly growing mass were lymphoma (two), anaplastic carcinoma (four) and metastasis (five). Ultrasound of these thyroid malignancies revealed a mass with a smooth, well-defined margin and strikingly low homogeneous echogenicity in all cases. Patients with thyroid metastases had evidence of widespread metastatic disease elsewhere. Lymphoma was differentiated from anaplastic carcinoma on fine-needle aspiration cytology or surgical biopsy. Ultrasound was of value in differentiating between a benign haemorrhagic nodule and a malignant tumour. The various malignant tumours had similar appearances, however, and could not be distinguished on ultrasound.  相似文献   
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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.  相似文献   
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The optimal conditions for inactivation of Bordetella pertussis organisms with glutaraldehyde for the production of a safe and potent whole cell pertussis vaccine were investigated. Two bacterial harvests from B. pertussis strain 10536 were treated with glutaraldehyde, each with 0.025, 0.05 and 0.1% concentrations of glutaraldehyde for 10, 60 and 120 min. The nine types of glutaraldehyde-inactivated pertussis vaccine (GIPV) and conventional heat-inactivated pertussis vaccine (HIPV) preparations made from two bacterial harvests were comparatively evaluated for the mouse weight gain test (MWGT), potency, and the histamine-sensitization (HS) and leucocytosis-promoting-factor (LPF) tests. The minimum period for killing the B. pertussis organisms with glutaraldehyde was>10 min for 0.025%, 10 min for 0.05% and 5 min for 0.1% concentration. The average loss in opacity varied from 5 to 10% for GIPV preparations and was 14% for HIPV preparations. The GIPV preparations except those inactivated with 0.025% glutaraldehyde for 10 min (GIPV-A) were much less toxic than the HIPV preparations in the MWGT. The GIPV-A preparations did not pass the MWGT. The GIPV preparations were also much less toxic in HS and LPF tests than the HIPV preparation. The potency of GIPV preparations inactivated with 0.05% glutaraldehyde for 10 min (GIPV-D) was similar to that of HIPV preparations. The prolonged treatments with glutaraldehyde reduced the potency. The GIPV-D preparation with good potency and less toxicity was found to be inactivated with glutaraldehyde under optimal conditions. All the preparations were innocuous in the abnormal toxicity test.  相似文献   
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Background: Ingestion of coins is a common clinical problem in children. Many of the coins are ferromagnetic and can be retrieved with the help of a magnet. We describe the use of a novel endoscopic accessory for removing ferromagnetic coins. Material and methods: Two magnet discs of 1.5 cm diameter were joined to a 200 cm steel wire of 0.75 mm thickness with a terminal 5 cm spring. A Teflon tube (160 cm, 7 F) was used along with this instrument as a sleeve. The use of this accessory was analyzed prospectively in subjects presenting with a history of coin ingestion. The time taken for removal of coins, complications during the procedure and failure rate was noted. Effect of the magnet on cardiac rhythm was also noted during the procedure. Results: A total of 55 children (mean age 5.1 ± 2.3 years) with coin ingestion presented over a period of 1 year. Forty‐four coins were ferromagnetic. All ferromagnetic coins were removed successfully. Mean time for removal was 68 ± 22 s. No complications were encountered. Conclusion: The novel magnetic instrument is precise, safe and quick for the removal of ferromagnetic coins under direct vision.  相似文献   
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Teratomas are true neoplasms composed of tissues from all three germinal layers and may exhibit variable levels of maturity. They have an unknown origin and eccentric microscopic appearance. Teratomas arising from the oral cavity are rare in the newborn; only 22 cases have been reported in the literature. We describe a female neonate with an oral teratoma originating from the tongue that was successfully treated with surgery.  相似文献   
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