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     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Primary exophytic laryngeal amyloidosis presenting as sudden airway obstruction

Primary amyloidosis of larynx is an uncommon phenomenon, the precise etiopathogenesis of which is not yet clear. It can present with slowly increasing hoarseness or difficulty in breathing. It presents more commonly as infiltrative lesion, exophytic presentation is a rare occurrence.     

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.     

pH-adjusted periocular anaesthesia for primary vitreoretinal surgery

PURPOSE: To evaluate the efficacy of pH-adjusted bupivacaine in conjunction with medial orbital periconal block (periocular anaesthesia). METHODS: Sixty consecutive patients undergoing primary vitreoretinal surgery were enrolled prospectively. RESULTS: Adequate anaesthesia and akinesia with no intraoperative supplementation was achieved in 53 eyes (88.3%). Factors influencing intraoperative supplementation were combined vitrectomy with scleral buckling (p = 0.005) and duration of surgery of more than 2 hours (p = 0.001). No ocular or systemic complication resulted. CONCLUSION: pH-adjusted periocular anaesthesia is safe and effective in patients undergoing primary vitreoretinal surgery.     

Fibrous dysplasia of the mastoid

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

Prevalence of asthma in urban school children in Jaipur, Rajasthan

A cross sectional survey of 3321 school going children (5–15 years) using modified ISAAC questionnaire in Jaipur city showed 7.59% children to have asthma (in last 12 months) and 8.4% wheezing in last 12 months. Only 5.3 % children had “physician diagnosed asthma ever” suggesting under diagnoses.     

Microbial keratitis following vegetative matter injury

The purpose of the present study was to analyze the microbiological profile of cases of keratitis following trauma with vegetative matter in a tertiary care center. A retrospective review of the medical records of 49 patients with keratitis following vegetative matter injury over a 3-month period was performed. All patients underwent corneal scraping for smears and inoculation onto various culture media. The microbiological profile was based on the smear and culture reports. For patients who were culture-negative, outcome after standard empirical antibacterial therapy as per hospital protocol was analyzed. Thirteen patients with corneal ulcers had fungal etiology, eight had bacterial etiology, and two had protozoal etiology, while 13 patients were polymicrobial and 13 were culture-negative. Polymicrobial infections were mainly bacterial (eight cases), and the remaining five cases had coexistent fungal and bacterial etiology. The treatment was directed to the specific organism and patients improved with medical or surgical therapy. Only a third of culture-negative cases showed fungal etiology on biopsy or histopathology after keratoplasty while a third showed improvement with therapy. Corneal infections following vegetative matter trauma show a varied etiological profile; however, bacterial and polymicrobial infections are more prevalent. Empirical anti-fungal therapy, as commonly practiced, must be avoided in cases with vegetative matter injury.