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1.
Usha Patel Manish Pandey Sadhana Kannan Tanuja A. Samant Poonam Gera Neha Mittal Swapnil Rane Asawari Patil Vanita Noronha Amit Joshi Vijay M. Patil Kumar Prabhash Manoj B. Mahimkar 《British journal of cancer》2020,123(12):1757
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
2.
Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease
Abhinav Sharma Adrian Coles Nishant K. Sekaran Neha J. Pagidipati Michael T. Lu Daniel B. Mark Kerry L. Lee Hussein R. Al-Khalidi Udo Hoffmann Pamela S. Douglas 《Journal of the American College of Cardiology》2019,73(8):893-902
Background
The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.Objectives
The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.Methods
PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.Results
Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).Conclusions
In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550) 相似文献3.
4.
The effects of morphine tolerance-dependence and abstinence on 5-HT1A receptors in brain regions and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact (tolerant-dependent) and in the other they were removed (abstinent). Rats were killed, and spinal cords and brains were excised. Brain was dissected into seven regions (amygdala, hippocampus, hypothalamus, striatum, midbrain, pons + medulla and cortex). 5-HT1A receptors were characterized by using [3H]8-hydroxy-di-n-propylaminotetralin [( 3H]DPAT) as the ligand and unlabelled 5-HT to determine the non-specific binding. In morphine and placebo tolerant-dependent rats the binding of [3H]DPAT to 5-HT1A receptors in brain regions and spinal cord did not differ. The Bmax value of [3H]DPAT in the hypothalamus of morphine abstinent rats was decreased by 61.9%. No change in Bmax value was observed in other brain regions and spinal cord. The Kd values were unaffected. Subcutaneous administration of DPAT produced hypothermia in rats from which pellets had been removed. The intensity of DPAT-induced hypothermic response was greater in morphine abstinent rats as compared to placebo abstinent rats. Since DPAT is believed to have a major action on the presynaptic 5-HT neurons, it is concluded that in morphine abstinent rats 5-HT1A receptors are down-regulated in hypothalamus, but in morphine tolerant-dependent rats they are unaffected. 相似文献
5.
A 32-year-old male presented with progressive weakness and numbness of both upper limbs of one-month duration. The patient had weakness and wasting of small muscles of both hands with weak grip. Sensory system revealed graded sensory loss to pain, temperature and touch in C5 to T1 distribution and vibration and joint position sense from C5 to C8 in the both upper limbs. There was areflexia in the upper limbs while there was no motor or sensory deficit in the lower limbs. The cortical potential on stimulation of posterior tibial nerve was prolonged on both sides. On MR imaging of the cervical spine there was iso to low intense lesion which was hyperintense on T2-weighted imaging along the dorsal aspect of the cord extending from C2 to C6 level. The axial images showed involvement of the posterior column. The serum vitamin B12 level was found to be low. The patient responded to parenteral cyanocobalamine therapy and the radiological lesion subsequently resolved. 相似文献
6.
Xanthotoxol (XT), 8-hydroxypsoralen, exhibited dose-graded sedative activity in dogs, cats, rats, mice and hamsters. At doses of 5-20 mg/kg intraperitoneally (i.p.) in cats and 3-100 mg/kg orally (p.o.) in dogs, XT blocked predatory mouse/rat killing behavior. In mice, XT (10-300 mg/kg i.p.) exhibited a dose-dependent reduction in locomotor activity but was less potent in this regard than reference diazepam (10-100 mg/kg i.p.). XT in mice (0.1-10.0 mg/kg i.p.) and in hamsters (0.1-10.0 mg/kg p.o.) antagonized amphetamine-induced hypermobility but was less potent than diazepam. XT elevated the electrical threshold in foot-shock-induced fighting behavior in rats. XT (0.1-30.0 mg/kg p.o.) potentiated pentobarbital-induced narcosis in hamsters at otherwise subeffective doses of pentobarbital. Conditioned avoidance responses in rats were not significantly altered with 1-3 mg/kg i.p. and 30-100 mg/kg p.o. doses of XT but 300 mg/kg p.o. blocked both conditioned and unconditioned response. Doses of 100-1000 mg/kg i.p. of XT in mice were used to study 48-h acute toxicity of XT and its LD50 was estimated to be 468 mg/kg. Doses of 10, 40 and 80 mg/kg p.o. were used to study the chronic toxicity of XT in rats for 6 months and no side effects or abnormalities in reproductive activity or endocrine integrity were noted. The F1 generation of rats from 6-month XT-treated parents were free of teratogenic effects. 相似文献
7.
8.
A case of fat embolism syndrome is reported following an uncomplicated bone marrow harvest. The presenting symptoms were restlessness, shortness of breath and arterial hypoxemia. A lung perfusion scan ruled out the presence of a lung thromboembolism. The patient received supportive therapy and recovered within a few hours. We speculate that the larger gauge needle (13 vs 15) used to aspirate the bone marrow may have represented increased trauma to the iliac crest leading to fat embolism. 相似文献
9.
P. Arora V. Kher P. K. Rai M. K. Singhal S. Gulati A. Gupta 《Pediatric nephrology (Berlin, Germany)》1997,11(2):153-155
Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic
factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P <0.05) and associated with cardiac surgery (90.9%, P <0.01). Anuria (67.6% vs. 43.5%, P <0.05), need for dialysis (85.3% vs. 56.5%, P <0.05), neurological complications (50% vs. 6.3%, P <0.01), and respiratory complications (35.2% vs. 2.1%, P <0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological
and respiratory complications to be poor prognostic factors.
Received May 2, 1995; received in revised form August 28, 1996; accepted September 13, 1996 相似文献
10.