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     

Dry mouth: saliva substitutes which adsorb and modify existing salivary condition films improve oral lubrication

Clinical Oral Investigations - The aims of this study are to assess different saliva substitutes for their efficacy to lubricate the oral cavity, and to relate this oral lubrication to the ability...     

Genomic Dissection of Travel-Associated Extended-Spectrum-Beta-Lactamase-Producing Salmonella enterica Serovar Typhi Isolates Originating from the Philippines: a One-Off Occurrence or a Threat to Effective Treatment of Typhoid Fever?

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring bla_SHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi.     

Wooden stick penetration from the perineal region up to the thorax

BACKGROUND: Penetrating injuries of the perineum are rare but very dangerous. Since the genitourinary and colorectal organs may be injured, how to evaluate surgical management of the injury is very important.METHODS: The present report presents a case of penetrating injury of the perineum by a wooden stick when the patient fell on the upright wooden stick from a tree. The three feet long stick entered the perineal region just left lateral to the anal opening. Upon reaching the thoracic cavity, it broke and only a foot stick was left in the subcutaneous plane. These injuries are potentially serious with risk of damage to multiple organs. Exploratory laprotomy was done, and bladder injury was repaired. The entry wound and the track of stick was thoroughly washed and allowed for secondary intention healing.RESULTS: The post operative period was uneventful and the patient recovered fully.CONCLUSION: Meticulous evaluation and surgical management of perineal injuries are the key to prevent devastating complications.     

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.     

Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.     

Efficacy of nasal cytology

Nasal Cytogram is a simple, economical and reliable investigation. Although its utility was recognised as early s1927, it has not gained much popularity. Here an attempt is madeto assess the efficacy of nasal cytology in the light of histology, to diagnose various nasal conditions.127 cases of common rhinological problem were studied at Govt. Medical College, Nagpur. This investigation was found to be simple, reliable & economical.