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.

Differential control of band 3 lateral and rotational mobility in intact red cells.

Measurements of integral membrane protein lateral mobility and rotational mobility have been separately used to investigate dynamic protein--protein and protein-lipid interactions that underlie plasma membrane structure and function. In model bilayer membranes, the mobilities of reconstituted proteins depend on the size of the diffusing molecule and the viscosity of the lipid bilayer. There are no direct tests, however, of the relationship between mechanisms that control protein lateral mobility and rotational mobility in intact biological membranes. We have measured the lateral and rotational mobility of band 3 in spectrin-deficient red blood cells from patients with hereditary spherocytosis and hereditary pyropoikilocytosis. Our data suggest that band 3 lateral mobility is regulated by the spectrin content of the red cell membrane. In contrast, band 3 rotational mobility is unaffected by changes in spectrin content. Band 3 lateral mobility and rotational mobility must therefore be controlled by different molecular mechanisms.     

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

1. Download : Download high-res image (177KB)
2. Download : Download full-size image

     

The restorative effect of naps on perceptual deterioration

Human performance on visual texture discrimination tasks improves slowly (over days) in the absence of additional training. This 'slow learning' requires nocturnal sleep after training and is limited to the region of visual space in which training occurred. Here, we tested human subjects four times in one day and found that with repeated, within-day testing, perceptual thresholds actually increased progressively across the four test sessions. This performance deterioration was prevented either by shifting the target stimuli to an untrained region of visual space or by having the subjects take a mid-day nap between the second and third sessions.     

Use of ivabradine for treatment of junctional ectopic tachycardia in post congenital heart surgery

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis are mainly responsible for junctional ectopic tachycardia (JET). Diversified antiarrhythmic agents have been used in an impressive way to treat JET but showed suboptimal efficacy and varied associated adverse effects. But, ivabradine has proved as final crusader for its treatment. We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine.     

Guidelines for gastrostomy tube placement and enteral nutrition in patients with severe,refractory hypoglycemia after gastric bypass

BackgroundPostbariatric hypoglycemia (PBH) affects up to 38% of Roux-en-Y gastric bypass (RYGB) patients. Severe cases are refractory to diet and medications. Surgical treatments including bypass reversal and pancreatectomy are highly morbid and hypoglycemia often recurs. We have developed a highly effective method of treatment by which enteral nutrition administered through a gastrostomy (G) tube placed in the remnant stomach replaces oral diet: if done correctly this reverses hyperinsulinemia and hypoglycemia, yielding substantial health and quality of life benefits for severely affected patients.ObjectivesTo provide clinical guidelines for placement of a G-tube to treat postRYGB hypoglycemia, including candidate selection, preoperative evaluation, surgical considerations, and post-RYGB management.SettingStanford University Hospital and Clinics.MethodsBased on our relatively large experience with placing and managing G-tubes for PBH treatment, an interdisciplinary task force developed guidelines for practitioners.ResultsA team approach (endocrinologist, dietitian, surgeon, psychologist) is recommended. Appropriate candidates have a history of RYGB, severe hypoglycemia refractory to medical-nutrition therapy, and significantly affected quality of life. Preoperative requirements include education and expectation setting, determination of initial enteral feeding program, and establishing service with a home enteral provider. Close postoperative follow-up is needed to ensure success and may require adjustments in formula and mode/rate of delivery to optimize tolerance and meet nutritional goals. G-tube nutrition must fully replace oral nutrition to prevent hypoglycemia.ConclusionsG-tube placement in the remnant stomach represents a relatively well-tolerated and effective treatment for severe, refractory hypoglycemia after RYGB.