Chemical Senses by Alexandros G. Sfakianakis: Αυγούστου 2016

Τρίτη 30 Αυγούστου 2016

Dengue and Chikungunya

Management and Treatment of Dengue and Chikungunya - Natural Products to the Rescue: Neglected tropical diseases (NTDs) flourish mostly in impoverished developing nations of the world. It is estimated that NTDs plague up to 1 billion people every year thereby inducing a massive economic and health burden worldwide. Following explosive outbreaks mostly in Asia, Latin America, Europe and the Indian Ocean, two common NTDs namely, Chikungunya and Dengue both transmitted by an infected mosquito vector principally Aedes aegypti have emerged as a major public health threat. Given the limitations of conventional medicine in specifically targeting the Chikungunya and Dengue virus (CHIKV and DENV), natural products present an interesting avenue to explore in the quest of developing novel anti; mosquito, CHIKV and DENV agents. In this endeavor, a number of plant extracts, isolated phytochemicals, essential oils and seaweeds have shown promising larvicidal and insecticidal activity against some mosquito vectors as well as anti CHIKV and DENV activity invitro. Other natural products that have depicted good potential against these diseases include; the symbiotic bacterial genus Wolbachia which can largely reduce the life span and infectivity of mosquito vectors and the marine Cyanobacterium Trichodesmium erythraeum which has shown anti- CHIKV activity at minimal cytotoxic level. The impetus of modern drug discovery approaches such as high throughput screening, drug repositioning, synthesis and computer-aided drug design will undeniably enhance the process of developing more stable lead molecules from natural products which have shown promising antiviral activity in-vitro.

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Orbito-Masticatory Syndrome : Bilobed lesion connecting the temporal fossa to the orbit through a defect in the lateral orbital wall

Orbito-Masticatory Syndrome:

Abstract: We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double vision and oscillopsia after a right fronto-temporal-orbito-zygomatic craniotomy with osteotomy of the lesser wing of the sphenoid for a complex invasive pituitary adenoma. Proptosis of the right globe was present only during mastication. Computed tomography (CT) revealed a bony defect in the right lateral orbital wall. A 48-year-old man presented with transient diplopia and scotoma in the right eye elicited by chewing. CT and magnetic resonance imaging demonstrated a bilobed lesion connecting the temporal fossa to the orbit through a defect in the right lateral orbital wall. The regional neuroanatomy and pathophysiology as pertaining to these cases are discussed.

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Orbito-Masticatory Syndrome : Intermittent double vision and oscillopsia after a right fronto-temporal-orbito-zygomatic craniotomy with osteotomy of the lesser wing of the sphenoid for a complex invasive pituitary adenoma

Orbito-Masticatory Syndrome:

Suprasellar Primitive Neuroectodermal Tumor

in an Adult:

Abstract: Primitive neuroectodermal tumors (PNET) of the central nervous system (CNS) are a heterogeneous group of embryonal malignancies that are composed of undifferentiated or poorly differentiated neuroepithelial cells. Supratentorial PNET is the second most common CNS embryonal malignancy in children, but it is rare in adults. We report the case of a 31-year-old woman with bilateral vision loss and a bitemporal hemianopia. Neuroimaging revealed a suprasellar mass, and pathology was consistent with PNET. After surgical debulking of the tumor followed by radiation therapy and chemotherapy, the patient had significant visual recovery and remained stable over 14 months of follow-up.

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Unilateral nonarteritic anterior ischemic optic neuropathy (NAION)

Can Corneal Biomechanical Properties Give Clues About Elasticity of Optic Nerve Scleral Component in Nonarteritic Anterior Ischemic Optic Neuropathy?:

Abstract

Objective: To investigate corneal biomechanical properties among individuals with unilateral nonarteritic anterior ischemic optic neuropathy (NAION) compared to healthy gender- and age-matched subjects.

Methods: The study subjects were separated into 2 groups: 66 eyes of 33 patients with unilateral NAION (study group) and 33 eyes of 33 healthy individuals (control group). Reichert ocular response analyzer (Reichert Ophthalmic Instruments) was used to assess corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure values. Also, central corneal thickness was measured using Scheimpflug camera combined with a Placido disc corneal topographer (Sirius; Costruzioni Strumenti Oftalmici).

Results: Mean CH and median CRF values were significantly lower in the affected eyes (8.8 ± 1.8 mm Hg, 9.4 mm Hg, respectively) and contralateral unaffected eyes (9.1 ± 1.6 mm Hg, 9.8 mm Hg, respectively) of NAION patients than those in the control group (9.9 ± 1.3 mm Hg, 10.4 mm Hg, respectively; all P < 0.017). Mean IOPcc was significantly higher in the affected eyes of NAION patients (19.2 ± 3.5 mm Hg) than in the eyes of control group (17.1 ± 3.6 mm Hg; P = 0.002).

Conclusions: CH and CRF are significantly reduced in patients with NAION, possibly indirectly reflecting structural weakness in the lamina cribrosa.

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Interferon-Related Depression

A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem: Background: Depression is among the commonest of psychiatric disorders, and inflammatory mechanisms have been suggested to play a role in its pathophysiology. Interferons are a superfamily of proinflammatory cytokines that play a role in host defence mechanisms. Interferons are used in the treatment of a variety of autoimmune (e.g. multiple sclerosis), viral (e.g. chronic hepatitis B and C), and malignant (e.g. malignant melanoma, hairy cell leukemia) disorders; depression, however, is a notable and clinically troublesome adverse effect. Objective: This article seeks to present a simple explanation and update for the reader about what interferons are, how interferons are classified, the clinical conditions in which interferons are used, the occurrence of depression as a clinical adverse effect of interferon therapy, possible mechanisms that explain interferon-related depression, the treatment of interferon-related depression, and the prevention of interferon-related depression. Methods: A qualitative literature review is presented. Results and Conclusions: Irrespective of the indication for IFN therapy, IFNs are associated with a 30- 70% risk of treatment-emergent depression. This risk could be due to the IFN, or to an interaction between the IFN and the indication for which it was prescribed. Various neurohormonal, neurochemical, neurohistological, and other mechanisms have been put forth to explain IFN-related depression. Prophylactic treatment with antidepressants reduces the risk of IFN-related depression; antidepressants also effectively treat the condition. Recent alternatives to IFNs have shown to decrease the risk of treatment-emergent depression. 

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Subcutaneous melanocytoma mimicking a lipoma:

A rare presentation of a rare neoplasm with histological, immunohistochemical, cytogenetic and molecular characterization:

Abstract

Melanocytoma are the melanocytic tumors originating from leptomeningeal melanocytes. Melanocytomas are commonly seen in the central nervous system (CNS) and are often associated with neurocutaneous melanosis (NCM). However, simultaneous presentation of intra-axial and extra-cranial melanocytoma is a very rare event. Here we report a unique case of 21-year-old male with intermediate grade subcutaneous melanocytoma, mimicking lipoma, occurred synchronously with an intracranial melanocytoma, not associated with NCM.

A 21-year old Caucasian male presented to the emergency department (ED) with severe vertigo and vomiting. A magnetic resonance imaging (MRI) of the brain was performed at the ED, which revealed a subcutaneous (SC) mass in the right occipital scalp and a right cerebellopontine angle (CPA) mass. Excision of the SC mass revealed a well-circumscribed highly pigmented melanocytic tumor.

The SC mass tumor cells were positive for melanocytic lineage markers. The histopathological features were between benign melanocytomas and malignant melanomas. The Ki67 and PHH3 IHCs confirm the intermediate grade of the tumors. An array-CGH (Comparative Genome Hybridization) and next-generation sequencing analysis of the tumor DNA extracted from the formalin fixed paraffin embedded tissue reveals chromosome 6p gain and p.Q209P mutation in the GNAQ gene, respectively, consistent with the diagnosis of intermediate grade melanocytoma.

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Oral Exposure to Bisphenol A (BPA)

Impact of Low Dose Oral Exposure to Bisphenol A (BPA) on the Neonatal Rat Hypothalamic and Hippocampal Transcriptome: A CLARITY-BPA Consortium Study: Endocrinology, Early Release.

Sheryl E. Arambula1,2,3, Scott M. Belcher1,3, Antonio Planchart1,3, Stephen D. Turner4, and Heather B. Patisaul1,2,3

Address all correspondence and requests for reprints to: Corresponding author and person to whom reprint requests should be addressed: Heather B. Patisaul, PhD,

Department of Biological Sciences, NC State University, Raleigh, NC 27695, USA

, Phone: 919–513-7567, e-mail: hbpatisa@ncsu.edu.

DOI: http://ift.tt/2bOQyyA

Abstract

Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the No Observed Adverse Effect Level (NOAEL) can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain including estrogen receptors (ERs). The present studies, conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights of BPA Toxicity) program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 (PND1) with the hypothesis that genes sensitive to estrogen and/or sexually dimorphic in expression would be altered by prenatal BPA exposure. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (0, 2.5, 25, 250, 2500, or 25000 μ g/kg body weight (bw) /day). Ethinyl estradiol (EE) was used as a reference estrogen (0.05 or 0.5 μ g/kg bw/day). PND1 brains were microdissected and gene expression was assessed with RNA-seq (0, 2.5 and 2500 μ g/kg bw BPA groups only) and/or qRT-PCR (all exposure groups). BPA-related transcriptional changes were mainly confined to the hypothalamus. Consistent with prior observations, BPA induced sex-specific effects on hypothalamic ERα and ERβ (Esr1 and Esr2) expression and hippocampal and hypothalamic oxytocin (Oxt) expression. These data demonstrate prenatal BPA exposure, even at doses below the current NOAEL, can alter gene expression in the developing brain.

Affiliations

1Department of Biological Sciences, NC State University, Raleigh, NC 27695;

2Keck Center for Behavioral Biology, NC State University, Raleigh, NC 27695;

3Center for Human Health and the Environment, NC State University, Raleigh, NC 27695;

4Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908.

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Phytochemicals as Adjunctive with Conventional Anticancer Therapies

Phytochemicals as Adjunctive with Conventional Anticancer Therapies: Background: Cancer is defined as the abnormal proliferations of cells which could occur in any tissue and can cause life-threatening malignancies with high financial costs for both patients and health care system. Plant-derived secondary metabolites are shown to have positive role in various diseases and conditions. The aim of the present study is to summarize clinical evidences on the benefits of phytochemicals as adjuvant therapy along with conventional anticancer therapies. Methods: Electronic databases including Pubmed, Scopus and Cochrane library were searched with the keywords “chemotherapeutic”, “anticancer”, “antineoplastic” or “radiotherapy” with “plant”, “extract”, “herb”, or “phytochemical”, until July 2015. Only clinical studies were included in this review. Results: The findings showed that positive effects of phytochemicals are due to their direct anticarcinogenic activity, induction of relief in cancer complications, as well as their protective role against side effects of conventional chemotherapeutic agents. Results obtained from current review demonstrated that numerous phytochemical agents from different chemical categories including alkaloid, benzopyran, coumarin, carotenoid, diarylheptanoid, flavonoid, indole, polysaccharide, protein, stilbene, terpene, and xanthonoid possess therapeutic effect in patients with different types of cancer. Polyphenols are the most studied components. Curcumin, ginsenosides, lycopene, homoharringtonine, aviscumine, and resveratrol are amongst the major components with remarkable volumes of clinical evidence indicating their direct anticancer activities in different types of cancer including hepatocarcinoma, prostate cancer, leukemia and lymphoma, breast and ovarian cancer, and gastrointestinal cancers. Cannabinoids, cumarin, curcumin, ginsenosides, epigallocatechin gallate, vitexin, and salidroside are phytochemicals with significant alleviative effect on synthetic chemotherapy- induced toxicities. Conclusion: There is lack of evidence from clinical trials in case of a large number of phytochemicals and further human studies are recommended to confirm the role of plant metabolites in the management of cancer.

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Fluorine-18 fluorodeoxyglucose avid thyroid incidentalomas on PET/CT scan in cancer patients: how sinister are they?

Fluorine-18 fluorodeoxyglucose avid thyroid incidentalomas on PET/CT scan in cancer patients: how sinister are they?

Nucl Med Commun. 2016 Oct;37(10):1069-1073

Authors: Hassan A, Riaz S, Zafar W

Abstract
OBJECTIVE: To evaluate the prevalence of malignancy in incidental thyroidal uptake on PET with fluorine-18 deoxyglucose integrated with computed tomography (F-FDG PET/CT) in Pakistani cancer patients and to assess the role of standardized uptake value (SUV) in deciding which lesions to investigate further.
METHOD: We retrospectively reviewed all patients who underwent F-FDG PET/CT scans over a period of 59 months and further analysed those with visually increased thyroidal uptake. Uptake was classified as focal or diffuse.
RESULTS: Out of 10 012 F-FDG PET/CT scans done for evaluation of known, nonthyroid malignancies, 173 (1.7%) showed incidental thyroid uptake. Of these, 29 were malignant (33%; 24 focal, five diffuse) and 58 were benign (67%; 26 focal, 32 benign) cases. The prevalence of malignancy was significantly higher in cases of focal uptake (P=0.002). After controlling for sex, age, and SUV those with focal uptake were 6.5 times more likely to have malignancy compared with those with diffuse uptake. Odds ratio 6.5; 95% confidence interval 2.0-20.9; P less than 0.01. We found no correlation of SUV with the incidence or type of malignancy.
CONCLUSION: Focal thyroid uptake on F-FDG PET/CT imaging should be sonographically correlated and if indicated with cytological analysis. Although diffuse uptake is usually benign, lymphoma is the leading malignant differential. Nonavid lesions have a low likelihood of malignancy.

PMID: 27571130 [PubMed - as supplied by publisher]

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Profile and prevalence of hearing complaints in the elderly.

Profile and prevalence of hearing complaints in the elderly.

Braz J Otorhinolaryngol. 2016 Jul 31;

Authors: Bauer MA, Zanella ÂK, Filho IG, Carli G, Teixeira AR, Bós ÂJ

Abstract
INTRODUCTION: Hearing is essential for the processing of acoustic information and the understanding of speech signals. Hearing loss may be associated with cognitive decline, depression and reduced functionality.
OBJECTIVE: To analyze the prevalence of hearing complaints in elderly individuals from Rio Grande do Sul and describe the profile of the study participants with and without hearing complaints.
METHODS: 7315 elderly individuals interviewed in their homes, in 59 cities in the state of Rio Grande do Sul, Brazil, participated in the study. Inclusion criteria were age 60 years or older and answering the question on auditory self-perception. For statistical purposes, the chi-square test and logistic regression were performed to assess the correlations between variables.
RESULTS: 139 elderly individuals who did not answer the question on auditory self-perception and 9 who self-reported hearing loss were excluded, totaling 7167 elderly participants. Hearing loss complaint rate was 28% (2011) among the elderly, showing differences between genders, ethnicity, income, and social participation. The mean age of the elderly without hearing complaints was 69.44 (±6.91) and among those with complaint, 72.8 (±7.75) years. Elderly individuals without hearing complaints had 5.10 (±3.78) years of formal education compared to 4.48 (±3.49) years among those who had complaints. Multiple logistic regression observed that protective factors for hearing complaints were: higher level of schooling, contributing to the family income and having received health care in the last six months. Risk factors for hearing complaints were: older age, male gender, experiencing difficulty in leaving home and carrying out social activities.
CONCLUSIONS: Among the elderly population of the state of Rio Grande do Sul, the prevalence of hearing complaints reached 28%. The complaint is more often present in elderly men who did not participate in the generation of family income, who did not receive health care, performed social and community activities, had a lower level of schooling and were older.

PMID: 27569691 [PubMed - as supplied by publisher]

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Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes.

Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20161649

Authors: Rickels MR, Pelekis AJ, Markmann E, Dalton-Bakes C, Kong SM, Teff KL, Naji A

Abstract
CONTEXT: Islet transplantation has been shown to improve glucose counterregulation and hypoglycemia symptom recognition in patients with type 1 diabetes (T1D) complicated by severe hypoglycemia episodes and symptom unawareness, but long-term data are lacking.
OBJECTIVE: To assess the long-term durability of glucose counterregulation and hypoglycemia symptom responses 18 months after intrahepatic islet transplantation, and associated measures of glycemic control during a 24 month follow-up period.
DESIGN, SETTING, AND PARTICIPANTS: Ten patients with T1D disease duration ∼27 years were studied longitudinally before and 6 and 18 months post-transplant in the Clinical & Translational Research Center of the University of Pennsylvania, and compared to 10 nondiabetic control subjects.
INTERVENTION: All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania.
MAIN OUTCOME MEASURES: Counterregulatory hormone, endogenous glucose production, and autonomic symptom responses derived from stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose.
RESULTS: Near-normal glycemia (HbA1c ≤6.5%; time 70 - 180 mg/dl ≥95%) was maintained for 24 months in all patients with one returning to low-dose insulin therapy. In response to insulin-induced hypoglycemia, glucagon secretion was incompletely restored at 6 and 18 months, epinephrine was improved at 6 and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months post-transplant.
CONCLUSIONS: In patients with T1D experiencing problematic hypoglycemia, intrahepatic islet transplantation can lead to long-term improvement of glucose counterregulation and hypoglycemia symptom recognition, physiologic effects that likely contribute to glycemic stability post-transplant.

PMID: 27571180 [PubMed - as supplied by publisher]

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Oral health and human papillomavirus-associated head and neck squamous cell carcinoma.

Oral health and human papillomavirus-associated head and neck squamous cell carcinoma.

Cancer. 2016 Aug 29;

Authors: Mazul AL, Taylor JM, Divaris K, Weissler MC, Brennan P, Anantharaman D, Abedi-Ardekani B, Olshan AF, Zevallos JP

Abstract
BACKGROUND: Indicators of poor oral health, including smoking, have been associated with increased risk of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC), yet few studies have examined whether this association is modified by human papillomavirus (HPV) status.
METHODS: Data from interviews and tumor HPV status from a large population-based case-control study, the Carolina Head and Neck Cancer Study (CHANCE), were used to estimate the association between oral health indicators and smoking among 102 HPV-positive patients and 145 HPV-negative patients with OPSCC and 1396 controls. HPV status was determined by p16INK4a (p16) immunohistochemistry. Unconditional, multinomial logistic regression was used to estimate odds ratios (ORs) for all oral health indictors adjusting for important covariates.
RESULTS: Routine dental examinations were associated with a decreased risk of both HPV-negative OPSCC (OR, 0.52; 95% confidence interval [CI], 0.35-0.76) and HPV-positive OPSCC (OR, 0.55; 95% CI, 0.36-.86). Tooth mobility (a proxy for periodontal disease) increased the risk of HPV-negative disease (OR, 1.70; 95% CI, 1.18-2.43) slightly more than the risk for HPV-positive disease (OR, 1.45; 95% CI, 0.95-2.20). Ten or more pack-years of cigarette smoking were strongly associated with an increased risk of HPV-negative OPSCC (OR, 4.26; 95% CI, 2.85-6.37) and were associated less with an increased risk of HPV-positive OPSCC (OR, 1.62; 95% CI, 1.10-2.38).
CONCLUSIONS: Although HPV-positive and HPV-negative HNSCC differ significantly with respect to etiology and tumorigenesis, the current findings suggest a similar pattern of association between poor oral health, frequency of dental examinations, and both HPV-positive and HPV-negative OPSCC. Future research is required to elucidate interactions between poor oral health, tobacco use, and HPV in the development of OPSCC. Cancer 2016. © 2016 American Cancer Society.

PMID: 27571516 [PubMed - as supplied by publisher]

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Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated with Pembrolizumab.

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated with Pembrolizumab.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162300

Authors: de Filette J, Jansen Y, Schreuer M, Everaert H, Velkeniers B, Neyns B, Bravenboer B

Abstract
CONTEXT: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 receptor (PD-1) monoclonal antibody (mAb), remains to be fully characterized.
OBJECTIVE: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction.
DESIGN AND SETTING: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. (18)Fluorodeoxyglucose uptake on positron emission tomography/computed tomography ((18)FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis.
PATIENTS: 99 patients with advanced melanoma (aged 26.3-93.6 years; 63.6% females) who received at least 1 administration of pembrolizumab.
MAIN OUTCOME MEASURES: Patient characteristics, thyroid function (TSH, fT4), thyroid autoantibodies and (18)FDG-PET/CT.
RESULTS: 18 adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients of which 9 evolved to hypothyroidism. Isolated hypothyroidism was present in 6 patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in 4 of 10 cases. Diffuse increased (18)FDG uptake by the thyroid gland was observed in all 7 thyrotoxic patients who progressed to hypothyroidism.
CONCLUSIONS: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 mAb therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased (18)FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated together with the histopathological correlates.

PMID: 27571185 [PubMed - as supplied by publisher]

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Osteopontin is BMI-independently related to early endothelial dysfunction in children.

Osteopontin is BMI-independently related to early endothelial dysfunction in children.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162238

Authors: Schreier M, Schwartze JT, Landgraf K, Scheuermann K, Erbs S, Herberth G, Pospisilik JA, Kratzsch J, Kiess W, Körner A

Abstract
CONTEXT: Osteopontin (OPN) has been proposed to predict adverse cardiac events in adult type 2 diabetes patients.
OBJECTIVE: We investigated potential associations of circulating OPN and OPN expression in adipose tissue (AT) with obesity and early metabolic and cardiovascular dysfunction in children. Furthermore, we assessed the functional relevance of OPN on primary human endothelial cells.
DESIGN: Serum OPN was determined in healthy lean (n=65) and obese (n=100) children by ELISA. Expression levels were assessed in subcutaneous AT samples from healthy lean (n=33) and overweight and obese (n=31) children by qRT-PCR. Direct effects of recombinant (rh) OPN on adhesion molecule and ENOS expression were assessed in human coronary arterial endothelial cells (HCAEC's).
RESULTS: OPN serum concentrations decreased with pubertal development in lean children. The degree of obesity was negatively associated with OPN serum levels. Multiple regression analysis revealed that BMI SDS, next to pubertal status, was the strongest independent predictor for OPN serum concentrations. Metabolically, the HOMA-index and circulating plasma insulin were negatively correlated with OPN serum levels secondary to obesity. In contrast, independent from BMI, OPN was positively related to VCAM-1 levels, intima media thickening, and negatively associated with endothelial function. Functionally, full-length rhOPN did not affect adhesion molecule and ENOS mRNA expression in primary HCAEC's. Additionally, OPN expression levels in AT positively correlated with BMI SDS, AT inflammation, and markers of metabolic dysfunction but were not related to OPN serum levels.
CONCLUSION: Our findings suggest that OPN levels are BMI-independently related to markers of early endothelial dysfunction in children.

PMID: 27571184 [PubMed - as supplied by publisher]

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Efficacy of brachytherapy concomitant with chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in unresectable head and neck squamous cell carcinoma.

Efficacy of brachytherapy concomitant with chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in unresectable head and neck squamous cell carcinoma.

J BUON. 2016 May-Jun;21(3):588-93

Authors: Wang X, Meng J

Abstract
PURPOSE: Brachytherapy is a form of targeted radiation therapy and has shown good short-term efficacy in clinical practice. The purpose of this clinical trial was to determine the feasibility and safety of radioactive iodine 125 seeds implantation concomitantly with chemotherapy with docetaxel, cisplatin, 5-fluorouracil (TPF) in patients with head and neck squamous cell carcinoma (HNSCC).
METHODS: A total of 23 previously untreated patients with histologically documented advanced unresectable HNSCC underwent percutaneous interstitial implantation of radioactive iodine 125 seeds, and simultaneously received 3 cycles of chemotherapy every 21 days (75 mg/m(2) docetaxel D1, 75 mg/m(2) cisplatin D1, and 750 mg/m(2) 5-fluorouracil D2-5). The treatment efficacy was evaluated based on tumor size and clinical symptoms of the patients.
RESULTS: The overall response rate was 78.3%. No acute complications and treatment-related radiation damages occurred. Two-year progression-free survival (PFS) 60.9% and overall survival (OS) 52.2% were achieved. Four patients (17.4%) died of cardiovascular causes and local disease recurrence.
CONCLUSION: Brachytherapy based on iodine 125 seeds implantation given concomitantly with chemotherapy is a mildly invasive, effective and safe therapeutic approach for advanced HNSCC.

PMID: 27569077 [PubMed - in process]

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Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage In Normal Weight Polycystic Ovary Syndrome Women.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage In Normal Weight Polycystic Ovary Syndrome Women.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162586

Authors: Dumesic DA, Akopians AL, Madrigal VK, Ramirez E, Margolis DJ, Sarma MK, Thomas AM, Grogan TR, Haykal R, Schooler TA, Okeya BL, Abbott DH, Chazenbalk GD

Abstract
CONTEXT: Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction.
OBJECTIVE: This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia.
DESIGN: This is a prospective cohort study Setting: The setting was an academic medical center.
PATIENTS: Six normal weight PCOS women and fourteen age- and body mass index-matched normoandrogenic ovulatory (NL) women.
INTERVENTION(S): All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and subcutaneous (SC) abdominal fat biopsy.
MAIN OUTCOME MEASURE(S): Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women.
RESULTS: Circulating luteinizing hormone and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride and non-HDL cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women.
CONCLUSION: Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction.

PMID: 27571186 [PubMed - as supplied by publisher]

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The maxillary artery as a recipient vessel option for complex midface and anterior skull base microsurgical repair: A cadaveric study.

The maxillary artery as a recipient vessel option for complex midface and anterior skull base microsurgical repair: A cadaveric study.

Microsurgery. 2016 Aug 29;

Authors: Assam JH, Quinn TH, Militsakh ON

Abstract
INTRODUCTION: Variations in the operative situation for complex head and neck defect reconstructions resulting from mechanisms such as trauma, oncologic resection, and prior radiation exposure can result in situations of a vessel-depleted neck. This requires an awareness of alternate, innovative options for use in reconstructive repairs. The purpose of this study was to provide characterization of the third segment of the maxillary artery necessary to consider its use as a recipient vessel in free flap repair of complex midface defects.
MATERIALS AND METHODS: Seventeen cadaver hemifaces were used for anatomic demonstration of the maxillary artery third segment by a transmaxillary approach to obtain descriptive measures for statistical analysis.
RESULTS: The average artery intraluminal cross-section diameter was obtained for the sphenopalatine (1.39 ± 0.12 mm) descending palatine (0.94 ± 0.10 mm), and terminal maxillary (1.68 ± 0.17 mm) arterial vessels. The mean transmaxillary depth with was (43 ± 1.2 mm). Mean mobilizable lengths for sphenopalatine, descending palatine, and terminal maxillary arteries were (30 ± 2 mm), (29 ± 2 mm), and (20 ± 2 mm), accordingly. Vessel patterns were characterized using Morton and Kahn classification for sphenopalatine-descending palatine bifurcation as well as the Kwak classification for maxillary artery third segment morphology.
CONCLUSIONS: In situations where primary recipient vessel sites are unavailable, the maxillary artery represents an innovative option to be considered with suitable recipient artery characteristics.

PMID: 27571583 [PubMed - as supplied by publisher]

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Papillary Thyroid Carcinoma With Rare exon 15 BRAF Mutation Has Indolent Behavior: A Single-Institution Experience.

Papillary Thyroid Carcinoma With Rare exon 15 BRAF Mutation Has Indolent Behavior: A Single-Institution Experience.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20161775

Authors: Torregrossa L, Viola D, Sensi E, Giordano M, Piaggi P, Romei C, Materazzi G, Miccoli P, Elisei R, Basolo F

Abstract
CONTEXT: Approximately 40% of papillary thyroid carcinomas (PTC) harbor the BRAF V600E mutation, which is significantly associated with the advanced clinico-pathological features of PTC at diagnosis, higher recurrence rate and disease-related mortality. BRAF alterations other than V600E are less common in PTC, and their clinical significance remains to be established.
OBJECTIVE: The aim of the study was to describe a large cohort of rare exon 15 BRAF alterations (r-BRAF), the clinico-pathological features of PTC harboring these alterations and to clarify their clinical significance.
METHODS: A total of 2,961 PTCs were collected from 2006 to 2013 and screened for exon 15 BRAF alterations.
RESULTS: Exon 15 BRAF alterations were found in 1,186 of 2,961 PTC cases (40.0%). In particular, we found the BRAF V600E mutation in 95.3% (1,131/1,186) and r-BRAF in 4.7% (55/1,186) of the 1,186 cases. r-BRAF were found in 18 microcarcinomas, 33 follicular variants, 1 classic variant and 1 trabecular/solid variant. The most frequent r-BRAF was BRAF K601E (35/55, 63.6%) followed by BRAF V600_K601delinsE (7/55, 12.7%) and BRAF T599I-V600_R603del (2/55, 3.6%). The remaining 11 alterations were found in one case only. The large majority of these tumors were unifocal (34/55, 61.8%), completely encapsulated (46/55, 83.6%) and intrathyroidal (53/55, 96.4%) with a low prevalence of lymph node metastases (1/55, 1.8%) and a less advanced tumor stage at diagnosis (AJCC stage I/II: 51/55, 92.7%).
CONCLUSIONS: r-BRAF are very uncommon in PTC and are found almost exclusively in PTC with low-risk clinico-pathological features.

PMID: 27571181 [PubMed - as supplied by publisher]

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Ten-Year Follow-up on Tumor Growth and Hearing in Patients Observed With an Intracanalicular Vestibular Schwannoma.

Ten-Year Follow-up on Tumor Growth and Hearing in Patients Observed With an Intracanalicular Vestibular Schwannoma.

Neurosurgery. 2016 Aug 26;

Authors: Kirchmann M, Karnov K, Hansen S, Dethloff T, Stangerup SE, Caye-Thomasen P

Abstract
BACKGROUND: Reports on the natural history of tumor growth and hearing in patients with a vestibular schwannoma (VS) are almost exclusively short-term data. Long-term data are needed for comparison with results of surgery and radiotherapy.
OBJECTIVE: To report the long-term occurrence of tumor growth and hearing loss in 156 patients diagnosed with an intracanalicular VS and managed conservatively.
METHOD: In this longitudinal cohort study, diagnostic and follow-up magnetic resonance imaging and audiometry were compared.
RESULTS: After a follow-up of 9.5 years, tumor growth had occurred in 37% and growth into the cerebellopontine angle had occurred in 23% of patients. Conservative treatment failed in 15%. The pure tone average had increased from 51- to 72-dB hearing level, and the speech discrimination score (SDS) had decreased from 60% to 34%. The number of patients with good hearing (SDS > 70%) was reduced from 52% to 22%, and the number of patients with American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A hearing was reduced from 19% to 3%. Hearing was preserved better in patients with 100% SDS at diagnosis than in patients with even a small loss of SDS. Serviceable hearing was preserved in 34% according to AAO-HNS (class A-B) and in 58% according to the word recognition score (class I-II). Rate of hearing loss was higher in patients with growing tumors.
CONCLUSION: Tumor growth occurred in only a minority of patients diagnosed with an intracanalicular VS during 10 years of observation. The risk of hearing loss is small in patients with normal discrimination at diagnosis. Serviceable hearing is preserved spontaneously in 34% according to AAO-HNS and in 58% according to the word recognition score.
ABBREVIATIONS: AAO-HNS, American Academy of Otolaryngology-Head and Neck SurgeryHL, hearing levelPTA, pure tone averageSDS, speech discrimination scoreWRS, word recognition score.

PMID: 27571523 [PubMed - as supplied by publisher]

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Development of Spontaneous Activity in the Avian Hindbrain.

Development of Spontaneous Activity in the Avian Hindbrain.

Front Neural Circuits. 2016;10:63

Authors: Momose-Sato Y, Sato K

Abstract
Spontaneous activity in the developing central nervous system occurs before the brain responds to external sensory inputs, and appears in the hindbrain and spinal cord as rhythmic electrical discharges of cranial and spinal nerves. This spontaneous activity recruits a large population of neurons and propagates like a wave over a wide region of the central nervous system. Here, we review spontaneous activity in the chick hindbrain by focusing on this large-scale synchronized activity. Asynchronous activity that is expressed earlier than the above mentioned synchronized activity and activity originating in midline serotonergic neurons are also briefly mentioned.

PMID: 27570506 [PubMed - in process]

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A follow-up study of the prevalence of valvular heart abnormalities in hyperprolactinemic patients treated with cabergoline.

A follow-up study of the prevalence of valvular heart abnormalities in hyperprolactinemic patients treated with cabergoline.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162224

Authors: Drake WM, Stiles CE, Bevan JS, Karavitaki N, Trainer PJ, Rees DA, Richardson TI, Baldeweg SE, Stojanovic N, Murray RD, Toogood AA, Martin NM, Vaidya B, Han TS, Steeds RP, Baldeweg FC, Sheikh UE, Kyriakakis N, Parasuraman S, Taylor L, Butt N, Anyiam S, UK Cabergoline valvulopathy study group

Abstract
CONTEXT Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease; and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate.
OBJECTIVE: To provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors; and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used.
DESIGN: Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalised estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group.
SETTING: Thirteen centers of secondary/tertiary endocrine care across the United Kingdom.
RESULTS: There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97mg (20-377) and 232mg (91-551) respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality.
CONCLUSION: This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.

PMID: 27571182 [PubMed - as supplied by publisher]

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In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary ovarian insufficiency Patients.

In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary ovarian insufficiency Patients.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20161589

Authors: Zhai J, Yao G, Dong F, Bu Z, Cheng Y, Sato Y, Hu L, Zhang Y, Wang J, Dai S, Li J, Sun J, Hsueh AJ, Kawamura K, Sun Y

Abstract
CONTEXT: Recently, two Primary ovarian insufficiency (POI) patients delivered healthy babies after IVA (In Vitro Activation) treatment followed by auto-transplantation of frozen-thawed ovarian tissues.
OBJECTIVE: To report the first case of live birth after IVA treatment following fresh ovarian tissue grafting in POI patients, together with monitoring of follicle development and serum hormonal changes.
DESIGN: Prospective observational cohort study.
SETTING: We performed IVA treatment in 14 POI patients with mean age of 29 years, mean duration since last menses of 3.8 years, and average basal FSH level of 94.5 mIU/mL.
INTERVENTIONS: Prior to IVA treatment, all patients received routine hormonal treatments with no follicle development. We removed one ovary from POI patients and treated them with Akt stimulators. We improved upon early procedures by grafting back fresh tissues using a simplified protocol.
MAIN OUTCOME MEASURES: In six of the 14 patients (43%), a total of 15 follicle development waves were detected, and 4 patients had successful oocyte retrieval to yield 6 oocytes. For 2 patients showing no spontaneous follicle growth, HMG treatment induced follicle growth at 6-8 months after grafting. After IVF of oocyte retrieved, 4 early embryos were derived. Following embryo transfer, one patient became pregnant and delivered a healthy baby boy, with three other embryos under cryopreservation.
CONCLUSION: IVA technology can effectively activate residual follicles in some POI patients and allow them to conceive their own genetic offspring. IVA may also be useful for treating patients with ovarian dysfunction including aging women and cancer survivors.

PMID: 27571179 [PubMed - as supplied by publisher]

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upper respiratory tract infection; +55 new citations

55 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2016/08/30

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma.

Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma.

Oncotarget. 2016 Aug 23;

Authors: Eberhardt A, Hansen JN, Koster J, Lotta LT, Wang S, Livingstone E, Qian K, Valentijn LJ, Zheng YG, Schor NF, Li X

Abstract
Amplification or overexpression of MYCN is associated with poor prognosis of human neuroblastoma. We have recently defined a MYCN-dependent transcriptional signature, including protein arginine methyltransferase 1 (PRMT1), which identifies a subgroup of patients with high-risk disease. Here we provide several lines of evidence demonstrating PRMT1 as a novel regulator of MYCN and implicating PRMT1 as a potential therapeutic target in neuroblastoma pathogenesis. First, we observed a strong correlation between MYCN and PRMT1 protein levels in primary neuroblastoma tumors. Second, MYCN physically associates with PRMT1 by direct protein-protein interaction. Third, depletion of PRMT1 through siRNA knockdown reduced neuroblastoma cell viability and MYCN expression. Fourth, we showed that PRMT1 regulates MYCN stability and identified MYCN as a novel substrate of PRMT1. Finally, we demonstrated that mutation of putatively methylated arginine R65 to alanine decreased MYCN stability by altering phosphorylation at residues serine 62 and threonine 58. These results provide mechanistic insights into the modulation of MYCN oncoprotein by PRMT1, and suggest that targeting PRMT1 may have a therapeutic impact on MYCN-driven oncogenesis.

PMID: 27571165 [PubMed - as supplied by publisher]

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Long-term Outcome in Levothyroxine Treated Patients with Subclinical Hypothyroidism and Concomitant Heart Disease.

Long-term Outcome in Levothyroxine Treated Patients with Subclinical Hypothyroidism and Concomitant Heart Disease.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162226

Authors: Andersen MN, Olsen AS, Madsen JC, Kristensen SL, Faber J, Torp-Pedersen C, Gislason GH, Selmer C

Abstract
CONTEXT: Subclinical hypothyroidism is a common condition that may lead to impaired cardiac function.
OBJECTIVE: To examine the effects of levothyroxine treatment in patients with subclinical hypothyroidism and heart disease.
DESIGN: Register-based historical cohort study.
SETTING AND PARTICIPANTS: Danish primary care patients and hospital outpatients aged 18 years and older with established heart disease who were diagnosed with subclinical hypothyroidism in 1997 - 2011. Patients were stratified according to whether or not they claimed a subsequent prescription of levothyroxine. Event rates and incidence rate ratios (IRR) were calculated by use of time-dependent multi-variable Poisson regression models.
MAIN OUTCOME MEASURES: All-cause mortality, MACE (major adverse cardiac events) defined as cardiovascular death, fatal or non-fatal MI and stroke, and all-cause hospital admissions.
RESULTS: Of 61,611 patients with a diagnosis of cardiac disease having their first time thyroid function testing, 1,192 patients with subclinical hypothyroidism (mean age 73.6 [SD ± 13.3] years, 63.8% female) were included, of whom 136 (11.4%) were treated with levothyroxine. During a median follow-up time of 5.6 years (IQR 6.5), 694 (58.2%) patients died. Patients treated with levothyroxine displayed no significantly increased risk of all-cause mortality (adjusted IRR 1.17 [95% CI: 0.90-1.52]), MACE (adjusted IRR 1.08 [95% CI: 0.80-1.45]), or hospital admission (adjusted IRR 0.94 [95% CI: 0.71-1.24]), when compared to patients not treated with levothyroxine.
CONCLUSION: Levothyroxine treatment in patients with subclinical hypothyroidism and heart disease was not associated with a significant benefit nor risk of all-cause mortality, MACE or hospital admission in this large real-world cohort study.

PMID: 27571183 [PubMed - as supplied by publisher]

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Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage In Normal Weight Polycystic Ovary Syndrome Women.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage In Normal Weight Polycystic Ovary Syndrome Women.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162586

Authors: Dumesic DA, Akopians AL, Madrigal VK, Ramirez E, Margolis DJ, Sarma MK, Thomas AM, Grogan TR, Haykal R, Schooler TA, Okeya BL, Abbott DH, Chazenbalk GD

PMID: 27571186 [PubMed - as supplied by publisher]

} http://ift.tt/2bOGvYY

http://ift.tt/2c1OQqY

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Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated with Pembrolizumab.

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated with Pembrolizumab.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162300

Authors: de Filette J, Jansen Y, Schreuer M, Everaert H, Velkeniers B, Neyns B, Bravenboer B

PMID: 27571185 [PubMed - as supplied by publisher]

} http://ift.tt/2c7sfbL

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Osteopontin is BMI-independently related to early endothelial dysfunction in children.

Osteopontin is BMI-independently related to early endothelial dysfunction in children.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20162238

Authors: Schreier M, Schwartze JT, Landgraf K, Scheuermann K, Erbs S, Herberth G, Pospisilik JA, Kratzsch J, Kiess W, Körner A

PMID: 27571184 [PubMed - as supplied by publisher]

} http://ift.tt/2bOFDU6

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Carcinoma cervix presenting with clivus metastasis.

Carcinoma cervix presenting with clivus metastasis.

J Cancer Res Ther. 2015 Jul-Sep;11(3):662

Authors: Rao AS, Nandennavar M, Narayanan GS

Abstract
We present an unusual case of a large metastatic lesion from carcinoma cervix located in the clivus. Patient presented with severe headache and vomiting, mimicking an intracranial pathology. Radiological imaging suggested metastatic origin of the lesion and later on investigations revealed primary in the uterine cervix. The anatomic importance of extradural neural axis component in the process of metastasis of carcinoma cervix to the clivus is highlighted in this case report.

PMID: 26458683 [PubMed - indexed for MEDLINE]

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The maxillary artery as a recipient vessel option for complex midface and anterior skull base microsurgical repair: A cadaveric study.

The maxillary artery as a recipient vessel option for complex midface and anterior skull base microsurgical repair: A cadaveric study.

Microsurgery. 2016 Aug 29;

Authors: Assam JH, Quinn TH, Militsakh ON

PMID: 27571583 [PubMed - as supplied by publisher]

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via IFTTT

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Maternally Inherited Diabetes and Deafness

Is Phenotypically and Genotypically Heterogeneous: Response

http://ift.tt/2bO7plh

Hypoxic-Ischemic Encephalopathy : The vulnerable brain areas in hypoxic-ischemic encephalopathy (HIE) following systemic hypotension are typically the neocortex, deep cerebral gray nuclei, hippocampus, cerebellum, and the parieto-occipital arterial border zone region. The visual cortex is not commonly recognized as a target in this setting.

Hypoxic-Ischemic Encephalopathy With Clinical and Imaging Abnormalities Limited to Occipital Lobe: Background: The vulnerable brain areas in hypoxic-ischemic encephalopathy (HIE) following systemic hypotension are typically the neocortex, deep cerebral gray nuclei, hippocampus, cerebellum, and the parieto-occipital arterial border zone region. The visual cortex is not commonly recognized as a target in this setting.

Methods: Single-institution review from 2007 to 2015 of patients who suffered cortical visual loss as an isolated clinical manifestation following systemic hypotension and whose brain imaging showed abnormalities limited to the occipital lobe.

Results: Nine patients met inclusion criteria. Visual loss at outset ranged from hand movements to 20/20, but all patients had homonymous field loss at best. In 1 patient, imaging was initially normal but 4 months later showed encephalomalacia. In 2 patients, imaging was initially subtle enough to be recognized as abnormal only when radiologists were advised that cortical visual loss was present.

Conclusions: The occipital lobe may be an isolated target in HIE with cortical visual loss as the only clinical manifestation. Imaging performed in the acute period may appear normal or disclose abnormalities subtle enough to be overlooked. Radiologists informed of the clinical manifestations may be more attune to these abnormalities, which will become more apparent months later when occipital volume loss develops.

http://ift.tt/2bFeJfB

Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder of the central nervous system (CNS) with predilection for the optic nerves and spinal cord.

Finding NMO: The Evolving Diagnostic Criteria of Neuromyelitis Optica:

Abstract: Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder of the central nervous system (CNS) with predilection for the optic nerves and spinal cord. Since its emergence in the medical literature in the late 1800's, the diagnostic criteria for NMO has slowly evolved from the simultaneous presentation of neurologic and ophthalmic signs to a relapsing or monophasic CNS disorder defined by clinical, neuroimaging, and laboratory criteria. Due to the identification of a specific autoantibody response against the astrocyte water channel aquaporin-4 (AQP4) in the vast majority of affected individuals, the clinical spectrum of NMO has greatly expanded necessitating the development of new international criteria for the diagnosis of NMO spectrum disorder (NMOSD). The routine application of new diagnostic criteria for NMOSD in clinical practice will be critical for future refinement and correlation with therapeutic outcomes.

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Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor

r in Human Rhabdomyosarcoma Cells: To test the role of STAT3 in human rhabdomyosarcoma cells, genetic approaches were used to either knockdown the expression of STAT3 and GP130, an upstream activator of STAT3 using short hairpin RNA (shRNA) or express persistently active STAT3 protein. Knockdown expression of GP130 or STAT3 sensitized cells to anti-cancer drugs doxorubicin, cisplatin, and MEK inhibitor AZD6244. On the other hand, expression of the constitutively active STAT3 protein reduced the sensitivity of rhabdomyosarcoma cells to those drugs. In addition, we tested a small molecule STAT3 inhibitor LY5 and a GP130 inhibitor bazedoxifene in rhabdomyosarcoma cells. Our data demonstrated that the combination of LY5 or bazedoxifene with doxorubicin, cisplatin, and AZD6244 showed stronger inhibitory effects than single agent alone. In summary, our results demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments.

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Assessing the Impact of Atopic Dermatitis on the Patients' Parents with the Visual Instrument ‘Caregiver-PRISM'

Assessing the Impact of Atopic Dermatitis on the Patients' Parents with the Visual Instrument ‘Caregiver-PRISM': Background: There is a need to improve the quality of communication between clinicians and parents of young patients with atopic eczema (AE). Objective: To create a tool to measure the suffering that caregivers experience in association with their child's AE (Caregiver Pictorial Representation of Illness and Self-Measure, Caregiver-PRISM), assess the validity and reliability, and identify factors associated with caregiver suffering. Methods: Caregiver-PRISM was administered to 45 parents of patients from an AE outpatient service (Padua, Italy). Results: Caregiver-PRISM had a good test-retest reliability (r = 0.85; t₇ = 4.13; p Conclusion: Our results support the use of Caregiver-PRISM in parents of AE patients to assess suffering associated with patients' illness.

Dermatology

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Therapeutic activity of radioiodine in Graves’ disease

Calculation of therapeutic activity of radioiodine in Graves’ disease by means of Marinelli’s formula, using technetium ( 99m Tc) scintigraphy:

Abstract

The therapeutic activity of ¹³¹I administered to patients with Graves’ disease can be calculated by means of Marinelli’s formula. The thyroidal iodine uptake (¹³¹IU_max) needed for the calculation is usually determined with the use of ¹³¹I. The purpose of the paper was to estimate ¹³¹IU_max on the basis of technetium uptake in the thyroid at 20 min (^99mTcU_20min). Eighty patients suffering from Graves’ disease were qualified for radioiodine therapy with measurement of fT₄, fT₃, thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. ¹³¹IU_max for each patient was determined according to the levels of ¹³¹I after 24 h (¹³¹IU_24h), while effective half-life (T
_eff) according to the measurements of ¹³¹IU_24h and ¹³¹I uptake after 48 h (¹³¹IU_48h). Additionally, on the day before measuring ¹³¹IU_24h, ^99mTcU_20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p < 0.05, between the following pairs of values: TRAb and ¹³¹IU_24h, TRAb and ^99mTcU_20min, and ^99mTcU_20min and ¹³¹IU_24h. The interdependence between ¹³¹IU_24h and ^99mTcU_20min at the level of significance p < 0.05 is described by the following algorithms: ¹³¹IU_24h = 17.72 × ln (^99mTcU_20min) + 30.485, if TRAb < 10 IU/ml, and ¹³¹IU_24h = 18.03 × ln (^99mTcU_20min) + 38.726, if TRAb > 10 IU/ml. It is possible to predict thyroid iodine uptake ¹³¹IU_24h in Graves’ disease on the basis of measuring the uptake of ^99mTcU_20min. This shortens the time necessary for diagnosis and enables the calculation of ¹³¹I activity using Marinelli’s formula.

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Methylene blue (MB) on preventing postoperative pain

Pain and functional improvement effects of methylene blue injection on the soft tissue around fusion site after traumatic thoracolumbar fixation: A double-blind, randomized placebo-controlled study

via Clinical Neurology and Neurosurgery

Publication date: November 2016
Source:Clinical Neurology and Neurosurgery, Volume 150
Author(s): Majid Reza Farrokhi, Hamed Yazdanpanah, Mehrnaz Gholami, Farnaz Farrokhi, Amir Reza Mesbahi
ObjectiveFractures of the thoracolumbar spine can cause pain, long-term reductions in quality of life (QOL), and neural deficits. The aim of this study was to investigate the effects of methylene blue (MB) on preventing postoperative pain and improving QOL in patients with throracolumbar fractures undergoing posterior pedicle screw fixation.MethodsFifty patients underwent standard posterior pedicular screw fixation for stabilization of the thoracolumbar fractures: 25 received 1ml of MB solution at a concentration of 0.5% and 25 received normal saline on the soft tissue around fusion site. Primary outcomes were the control of pain, evaluated at 48h, 2 and 6 months after surgery with the use of a visual analog scale (VAS), and the improvement of QOL, assessed 2 and 6 months postoperatively by means of Oswestry Disability Index (ODI) questionnaire.ResultsThe mean VAS scores for pain were significantly lower in the MB group compared with the control group at 2 months (1.30±0.45 vs. 2.60±1.19, P<0.001) and 6 months (1.17±0.37 vs. 1.60±0.87; P=0.028) after treatment. At 2 months after the surgery, the mean ODI score was significantly lower in the MB-treated patients than the control group (20.4±10.92 vs. 34.8±15.11; P=0.001). The ODI score in the MB-treated patients was better than the control group at 6 months after the surgery (12.2±11.66 vs. 20.8±11.14; P=0.016).ConclusionA single dose of MB on the soft tissue around fusion site shows promising results in terms of safety, reduction of postoperative pain, and functional results when compared with placebo 6 months after surgery.

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Helicobacter suis (H. suis) is the most prevalent gastric non-H. pylori Helicobacter species in humans.

Comparative virulence of in vitro-cultured primate- and pig-associated Helicobacter suis strains in a BALB/c mouse and a Mongolian gerbil model:

Abstract

Background

Helicobacter suis (H. suis) is the most prevalent gastric non-H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of nonhuman primates. The aim of this study was to obtain better insights into potential differences between pig- and primate-associated H. suis strains in virulence and pathogenesis.

Materials and Methods

In vitro-isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis), and rhesus monkeys (Macaca mulatta) were used for intragastric inoculation of BALB/c mice and Mongolian gerbils. Nine weeks and six months later, samples of the stomach of inoculated and control animals were taken for PCR analysis and histopathological examination.

Results

The cynomolgus monkey-associated H. suis strain only colonized the stomach of mice, but not of Mongolian gerbils. All other H. suis strains colonized the stomach in both rodent models. In all colonized animals, severe gastric inflammation was induced. Gastric lymphoid follicles and destruction of the antral epithelium were observed in infected gerbils, but not in mice. Infection with both pig- and primate-associated H. suis strains evoked a similar marked Th17 response in mice and gerbils, accompanied by increased CXCL-13 expression levels.

Conclusions

Apart from the cynomolgus monkey-associated strain which was unable of colonizing the stomach of Mongolian gerbils, no substantial differences in virulence were found in rodent models between in vitro-cultured pig-associated, cynomolgus monkey-associated and rhesus monkey-associated H. suis strains. The experimental host determines the outcome of the immune response against H. suis infection, rather than the original host.

http://ift.tt/2bFebGN

Oropharyngeal squamous cell carcinoma treated with definitive transoral robotic surgery versus definitive chemoradiation

Oncologic outcomes and patient-reported quality of life in patients with

via ScienceDirect Search: ESOPHAGEAL CANCER

Publication date: October 2016
Source:Oral Oncology, Volume 61
Author(s): D.C. Ling, B.V. Chapman, J. Kim, G.W. Choby, P. Kabolizadeh, D.A. Clump, R.L. Ferris, S. Kim, S. Beriwal, D.E. Heron, U. Duvvuri
ObjectiveIt has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality of life (QOL) outcomes between definitive CRT and definitive TORS.Materials and methodsAn observational comparison study was performed on 92 patients treated with TORS±adjuvant therapy and 46 patients treated with definitive CRT between July 2005 and January 2016. The Kaplan Meier method was used for survival analyses, and the Mann-Whitney test was used to compare QOL scores between groups.ResultsAll patients had T0-T2 and N0-N2 disease, although CRT patients had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was 22.1months (range: 0.33–83.4). There were no significant differences in locoregional control or overall survival between CRT and TORS groups. Definitive TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and 24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067, p=0.008).ConclusionDefinitive CRT and definitive TORS offer similar rates of locoregional control, overall survival, and disease-free survival in patients with early stage OPSCC. TORS resulted in significantly better short and long-term saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and taste-related QOL compared to TORS alone.

http://ift.tt/2bO7Trn

miR-144 has potential benefits in protecting against myocardial ischemia and suppression of tumor growth

Time Dependent Distribution of MicroRNA 144 after Intravenous Delivery: Background: miR-144 has potential benefits in protecting against myocardial ischemia and suppression of tumor growth. We have previously shown that a single intravenous injection of miR-144 provides potent cardioprotection, but its kinetics and distribution are not known. Methods: Single stranded mature miR-144 or Cy3-labelled-miR-144 was delivered into C57/B6 mice by tail vein injection. Results: After intravenous injection, the signal of Cy3-labelled-miR-144 in the kidney, brain, heart and liver peaks at 60 minutes, and is predominantly localised to the endothelium at that stage. In the kidney and heart, Cy3-labelled-miR-144 signal is detectable within the parenchymal tissues for at least 3 days, after which it starts to decrease, but brain Cy3-miR-144 signal rapidly decreases after 1 hour, and is lost at day 1, with no parenchymal uptake detected. Cy3-miR-144 signal can be detected until day 28 in the liver. Stem loop RTPCR confirmed the temporal pattern shown by miR-144 in kidney, brain and heart, but in liver there was a continuous rise following the initial injection until day 28 with no signs of decrease, suggesting de-novo synthesis. Conclusion: There is early endothelial uptake of injected miR-144 followed by organ-specific distribution and kinetics. In the liver, there appears to be a positive feedback process that leads to continued accumulation of miR-144 that persists for at least 28 days. These observations should be taken into account when designing experiments utilizing parenteral miR-144 and assessing the biology of its actions. 

http://ift.tt/2bFeCkf

SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy, systemic disease, hypertension, or undetermined)

Pathogenesis and Subtype of Intracerebral Hemorrhage (ICH) and ICH Score Determines Prognosis: Whether original intracerebral hemorrhage (ICH) score can be used to predict clinical outcomes in patients with SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy, systemic disease, hypertension, or undetermined) classification remains an open question. This study obtained data related to consecutive acute patients with ICH from 21 tertiary hospitals in China during January 2012 to December 2014. Using the SMASH-U method, patients were classified into 6 subtypes. Favorable functional outcome and mortality was obtained after ICH at the 3 months. We used logistic regression to evaluate the effectiveness of each risk model in predicting clinical outcome and under the receiver operating characteristic curves (ROC) to assess performance. A total of 3475 patients were included, the most common cause was hypertensive angiopathy (n=1279, 36.81%), followed by undetermined (n=1168, 33.61%), cerebral amyloid angiopathy (CAA) (n=507, 14.59%), structural vascular lesions (n=368, 10.59%), medication (n=96, 2.76%), and systemic disease (n=57, 1.64%). For good clinical outcome (mRS≤2), the ROC values of original ICH score were 0.781, 0.701, 0.718, 0.722, 0.788, and 0.771, while for the mortality in 3-month, the ROC values of original ICH score were 0.840, 0.734, 0.836, 0.722, 0.785, 0.820, and 0.734 according to SMASH-U pathogenic classification, respectively. The ability of original ICH score may be well differentiated among the 6 ICH pathogeneses. Thus, physicians should select different risk score according to different etiological ICH.

http://ift.tt/2bO9cqe

Migraine and Central Sensitization

Clinical Features, Main Comorbidities and Therapeutic Perspectives: Migraine is a very common neurologic disorder, characterized by recurrent attacks of severe headache, autonomic nervous system dysfunction and in some patients by an aura. Background: Migraine is a very common neurologic disorder of neuro-vascular origin, being amongst the 20 most disabling diseases. Migraine attacks are characterized by severe headache, associated to autonomic nervous system dysfunction and in some patients by aura. Pathophysiology and Role of Central Sensitization: Abnormal neuronal excitability may subtend altered processing of sensory stimuli, leading to cortical spreading depression and trigeminal activation. A dysfunction of pain modulation enhances central sensitization phenomena, contributing to acute allodynia and headache persistence. The peculiarity of migraine pain facilitates the use of analgesics, and causes an adjunctive invalidating tendency toward drug over-use. Comorbidity: Chronic migraine patients are frequently affected by diffuse pain, framed in fibromyalgia diagnosis. This comorbidity seems to be supported by common pathophysiological mechanisms. It may aggravate migraine invalidity being worth of consideration for therapeutic management. Migraine Management: Acute and preventive treatments need to be tailored to single cases. Main comorbidity and factors facilitating central sensitization should be taken into account. The management of migraine patients should include a link between headache centers and general practitioner, in order to provide for a better patient information and treatment just at the onset of the disease. Conclusions: Despite its high epidemiologic impact, migraine is frequently underestimated and destined to evolve into chronic form and drugs abuse. A more focused attention to factors facilitating central sensitization and invalidating comorbidities, should reduce the global burden of the disease. Key words: migraine, pathophysiology, central sensitization, fibromyalgia comorbidity, acute and preventive therapy, patients – centered approach. 

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Influence of short-term selenium supplementation on the natural course of Hashimoto’s thyroiditis

s: clinical results of a blinded placebo-controlled randomized prospective trial:

Abstract

Background

The real efficacy of selenium supplementation in Hashimoto’s thyroiditis (HT) is still an unresolved issue.

Objectives

We studied the short-term effect of l-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of l-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels.

Methods

In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive l-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T₄ (FT₄), free T₃ (FT₃), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis.

Results

TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT₄ levels were significantly decreased (P < 0.03) after 3 months, while FT₃ increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT₃ decreased after 3 and 6 months (P < 0.02) compared to baseline.

Conclusion

The short-term l-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term l-selenomethionine supplementation in HT.

http://ift.tt/2bO81HC

OPHELIA (OlaParib in patients with HEad and neck squamous-celL carcInomA) trial : Preoperative Administration of Olaparib With or Without Cisplatin in Patients Who Are Candidates for Surgery of Carcinoma of Head and Neck

Preoperative Administration of Olaparib With or Without Cisplatin in Patients Who Are Candidates for Surgery of Carcinoma of Head and Neck: Condition: Squamous Cell Carcinoma of the Head and Neck

Interventions: Drug: Olaparib; Drug: Cisplatin; Drug: Olaparib

Sponsors: Hellenic Cooperative Oncology Group; AstraZeneca; Pfizer

OPHELIA (OlaParib in patients with HEad and neck squamous-celL carcInomA) trial is a Greek, investigator-initiated, randomized open-label window-of-opportunity phase II study. Patients with operable histologically documented squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx will be randomized between combination with cisplatin and olaparib, monotherapy with olaparib or no treatment, before standard treatment.

Condition	Intervention	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Olaparib Drug: Cisplatin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase ΙΙ (Window) Preoperative Study of Olaparib With or Without Cisplatin or no Treatment in Patients With Histologically Proven Squamous Cell Carcinoma of the Head and Neck Who Are Candidates for Surgery

Resource links provided by NLM:

Genetics Home Reference related topics: head and neck squamous cell carcinoma

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Olaparib

U.S. FDA Resources

Further study details as provided by Hellenic Cooperative Oncology Group:

Primary Outcome Measures:

Investigation of the change between initial and post-treatment Ki67 measured on Formalin- Fixed Parafin-Embedded collected tumour biopsy or surgical sample, before and after treatment with the combination of olaparib + cisplatin or olaparib monotherapy. [ Time Frame: At baseline and at the day of the surgery or 2nd biopsy (at days 23-29 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective response rate according to RECIST 1.1 criteria [ Time Frame: Imaging studies will be performed at baseline and on week 4 ] [ Designated as safety issue: No ]
Pathologic complete response rate [ Time Frame: On week 4 only for operable patients ] [ Designated as safety issue: No ]
Metabolic response rate assessed by FDG-PET/CT scan (optional) [ Time Frame: At baseline, on week 4 ] [ Designated as safety issue: No ]
Number of participants with tolerability to the treatment. [ Time Frame: From the 1st day of therapy and every week for 4 weeks maximum and 30 days after last therapy administration ] [ Designated as safety issue: No ]
Surgical complication rate [ Time Frame: Up to 30 days after surgery or the day of initiation of the next anticancer therapy ] [ Designated as safety issue: No ]
Mutations in genes associated with DNA repair [ Time Frame: At baseline, on day of surgery or the 2nd biopsy (at days 23-29) ] [ Designated as safety issue: No ]
Expression of tissue biomarker: PARP1 [ Time Frame: At baseline, on day of surgery or the 2nd biopsy (at days 23-29) ] [ Designated as safety issue: No ]
Expression of tissue biomarker: BRACA1,2 [ Time Frame: At baseline, on day of surgery or the 2nd biopsy (at days 23-29) ] [ Designated as safety issue: No ]
Expression of tissue biomarker: ERCC1 [ Time Frame: At baseline, on day of surgery or the 2nd biopsy (at days 23-29) ] [ Designated as safety issue: No ]
Plasma methylation biomarker: PARP1 methylation in plasma cell-free DNA [ Time Frame: At baseline, a day before surgery and 30 days after surgery ] [ Designated as safety issue: No ]
Plasma methylation biomarker: BRCA1,2 methylation in plasma cell-free DNA [ Time Frame: At baseline, a day before surgery and 30 days after surgery ] [ Designated as safety issue: No ]
Plasma methylation biomarker: ERCC1 methylation in plasma cell-free DNA [ Time Frame: At baseline, a day before surgery and 30 days after surgery ] [ Designated as safety issue: No ]
Plasma methylation biomarker: RAD51C methylation in plasma cell-free DNA [ Time Frame: At baseline, a day before surgery and 30 days after surgery ] [ Designated as safety issue: No ]
Single-nucleotide polymorphisms: PARP-1 Val762Ala [ Time Frame: Sample will be collected once at baseline ] [ Designated as safety issue: No ]
Single-nucleotide polymorphisms: ERCC1 Asn118Asn (C/T), ERCC2 Lys751Gln (T/G), GSTP1 Ile105Val (A/G), XPD Lys751Gln (A/C, C/C), XRCC1 Arg399Gln (G/A) [ Time Frame: Sample will be collected once at baseline ] [ Designated as safety issue: No ]
Circulating tumor cells (CTCs) evaluated for DNA repair biomarkers [ Time Frame: At baseline, a day before surgery and 30 days after surgery ] [ Designated as safety issue: No ]
Circulating tumor cells (CTCs) evaluated for PD-L1 [ Time Frame: At baseline, a day before surgery and 30 days after surgery ] [ Designated as safety issue: No ]


Estimated Enrollment:	39
Study Start Date:	September 2016
Estimated Study Completion Date:	June 2018
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Monotherapy with olaparib Patients in the monotherapy arm will be treated with olaparib until the 21st -28th day depending on the day of surgery, will be reassessed by imaging (tumour objective response by RECIST) on the 22nd -28th day and then have a second biopsy or be operated on the 23rd - 29th day. If surgery is delayed, olaparib will be continued until the day before surgery.	Drug: Olaparib 300 mg BD x 21-28 days. Other Name: Lynparza
Experimental: Combination of cisplatin and olaparib Patients in the combination arm will receive treatment until the 5th day, will be reassessed by imaging (tumour objective response by RECIST) on the 22nd -28th day and then will have a second biopsy or be operated on the 23rd - 29th day.	Drug: Olaparib 50/25 mg BD split x 5 days Other Name: Lynparza Drug: Cisplatin 60 mg/m^2 d1-d5 Other Name: Platamine
No Intervention: No treatment arm Patients in the "no treatment" arm will wait to be operated or have a second biopsy on the 23rd - 29th day.Optionally, patients who have a baseline FDG-PET/CT scan may be re-examined on the 22nd -28th day by the same modality to assess metabolic response.

Detailed Description:

OPHELIA is a window-of-opportunity phase II study randomized between combination with cisplatin and olaparib, monotherapy with olaparib or no treatment, before standard treatment.

Although patients will be randomized between the 3 arms, no formal comparison between the 3 arms will be performed. Patients allocated to the olaparib monotherapy arm will serve as a proof-of-concept to interpret the mechanism of action of olaparib. Patients allocated in the "no treatment" group will be used as control.

Primary endpoint will be the change in tumour Ki67 (ΔKi67) that is caused by the investigational treatment. Secondary endpoints will be early tumour response by RECIST criteria, pathologic complete response rate, tolerability to treatment and surgical complications rate, and optionally, metabolic response assessed by FDG-PET/CT scan. Translational correlates will be tested in tumour tissue, plasma and germline DNA.

All the endpoints will be analyzed by an "as treated analysis" since the trial does not include a formal comparison of the treatment arms.

Administration of olaparib monotherapy has been associated with reports of the following laboratory findings and/or clinical diagnoses, generally of mild or moderate severity (CTCAE Grade 1 or 2) and generally not requiring treatment discontinuation.

http://ift.tt/2bFf164

Anti-tumor Specific Immune Response in Head and Neck Cancers

Anti-tumor Specific Immune Response in Head and Neck Cancers: Condition: Head and Neck Squamous Cell Carcinoma

Intervention: Other: Blood sample

Sponsor: Central Hospital, Nancy, France

The purpose is the description of anti-tumor immune responses in general and according to clinical stage and disease free survival (DFS: survival without recurrence (local or distant)) in patients with Head & Neck Squamous Cell Carcinoma

Secondary purposes are:

Study of relationship between anti-tumor immune response and qualitative (yes/no) and quantitative (number) presence of circulating tumor cells (CTCs);
Study of relationship between qualitative (yes/no) and quantitative (number) presence of CTCs and clinical stage as well as DFS
Study of relationship between anti-tumor immune response and clinical stage as well as DFS.

Condition	Intervention
Head and Neck Squamous Cell Carcinoma	Other: Blood sample


Study Type:	Observational
Study Design:	Observational Model: Case-Only Time Perspective: Prospective
Official Title:	Anti-tumor Specific Immune Response in Head and Neck Cancers

Resource links provided by NLM:

Genetics Home Reference related topics: head and neck squamous cell carcinoma

MedlinePlus related topics: Cancer Head and Neck Cancer

U.S. FDA Resources

Further study details as provided by Central Hospital, Nancy, France:

Primary Outcome Measures:

Presence or absence of spontaneous responses against tumor-associated antigens (TAA) according to tumor stage [ Time Frame: day 0 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Functional signature of T cell responses (polyfunctionality index of lymphocytes) according to tumor stage [ Time Frame: day 0 ] [ Designated as safety issue: No ]
Effector functions and phenotypes of T cells
Number of CTCs according to tumor stage [ Time Frame: day 0 ] [ Designated as safety issue: No ]
Polyfunctionality index of lymphocytes according to number of CTCs [ Time Frame: day 0 ] [ Designated as safety issue: No ]
Disease free survival (survival without local or distant recurrence) according to Presence pr absence of CTCs at diagnosis [ Time Frame: 2 years after diagnosis ] [ Designated as safety issue: No ]
Disease free survival (survival without local or distant recurrence) according to Presence or absence of spontaneous responses against TAA [ Time Frame: 2 years after diagnosis ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Blood sample


Estimated Enrollment:	154
Study Start Date:	September 2016
Estimated Study Completion Date:	March 2020
Estimated Primary Completion Date:	March 2020 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
squamous cell carcinoma Patients affected by Head & Neck Squamous Cell Carcinoma. Blood sample at diagnosis, before any antitumor treatment	Other: Blood sample Blood sample with 6 tube of blood (40 mL), after diagnosis and before any specific anticancer treatment

http://ift.tt/2bO7ohd

Πληροφορίες

Τρίτη 30 Αυγούστου 2016

Abstract

Abstract

Abstract

Abstract

Background

Materials and Methods

Results

Conclusions

Abstract

Background

Objectives

Methods

Results

Conclusion

Δημοφιλείς αναρτήσεις

Αγευσία

Ανοσμία

Απώλεια ακοής