Background The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. Methods Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. Findings Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. Interpretation Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes. Received for publication September 5, 2018; and accepted for publication, after revision, October 9, 2018. Conflicts of interest and sources funding: none declared. Correspondence to: Alexander Radbruch, MD, JD, Department of Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. E-mail: a.radbruch@dkfz.de. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Κυριακή 25 Νοεμβρίου 2018
Negligible Risk of Acute Renal Failure Among Hospitalized Patients After Contrast-Enhanced Imaging With Iodinated Versus Gadolinium-Based Agents
Introduction The potential adverse renal outcome among patients undergoing iodine-based contrast-enhanced computerized tomography (CT) has been questioned recently, given the caution undertaken in patients' selection, hydration protocols, and the low radiocontrast volume, used with advanced imaging equipment. Materials and Methods This study is a retrospective assessment of renal outcome in 12,580 hospitalized patients undergoing contrast-enhanced CT, compared with 754 patients subjected to gadolinium-based magnetic resonance imaging, with subsequent propensity matching for clinical characteristics and potential risk factors. Results The risk of postcontrast acute kidney injury (PC-AKI) was found to be negligible as compared with patients undergoing enhanced magnetic resonance imaging studies, before and after propensity matching (8% vs 7.3% rate of AKI in the nonmatched iodine-based contrast agents [IBCAs] and gadolinium-based contrast agents [GBCAs], respectively, P = 0.3, and 7% in the matched IBCA group, P = 0.9), including comparisons among subgroups with well-defined risk factors such as chronic renal failure, diabetes, older age, and hypertension. However, lower systolic blood pressure before imaging was associated with higher risk to develop PC-AKI after IBCA administration but not with GBCA (for systolic blood pressure lower than 110 mm Hg, odds ratio for AKI after IBCA was 1.49; 95% confidence interval, 1.16–1.88, and after GBCA; odds ratio, 0.12; 95% confidence interval, 0.003–0.73). Conclusions With the current precautions undertaken, the real-life risk of PC-AKI among inpatients undergoing CT is insignificant. Possible reasons for the diverse impact of blood pressure on the propensity to develop acute kidney failure after iodine-based but not gadolinium-based enhancement imaging are discussed. Received for publication September 24, 2018; and accepted for publication, after revision, October 17, 2018. Conflicts of interest and sources of funding: none declared. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (https://ift.tt/2kq7jVD). Correspondence to: Samuel N. Heyman, MD, Department of Medicine, Hadassah Hebrew University Hospital, Mt Scopus, PO Box 24035, Jerusalem 91240, Israel. E-mail: Heyman@cc.huji.ac.il. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted
Background The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. Methods Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. Findings Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. Interpretation Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes. Received for publication September 5, 2018; and accepted for publication, after revision, October 9, 2018. Conflicts of interest and sources funding: none declared. Correspondence to: Alexander Radbruch, MD, JD, Department of Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. E-mail: a.radbruch@dkfz.de. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Negligible Risk of Acute Renal Failure Among Hospitalized Patients After Contrast-Enhanced Imaging With Iodinated Versus Gadolinium-Based Agents
Introduction The potential adverse renal outcome among patients undergoing iodine-based contrast-enhanced computerized tomography (CT) has been questioned recently, given the caution undertaken in patients' selection, hydration protocols, and the low radiocontrast volume, used with advanced imaging equipment. Materials and Methods This study is a retrospective assessment of renal outcome in 12,580 hospitalized patients undergoing contrast-enhanced CT, compared with 754 patients subjected to gadolinium-based magnetic resonance imaging, with subsequent propensity matching for clinical characteristics and potential risk factors. Results The risk of postcontrast acute kidney injury (PC-AKI) was found to be negligible as compared with patients undergoing enhanced magnetic resonance imaging studies, before and after propensity matching (8% vs 7.3% rate of AKI in the nonmatched iodine-based contrast agents [IBCAs] and gadolinium-based contrast agents [GBCAs], respectively, P = 0.3, and 7% in the matched IBCA group, P = 0.9), including comparisons among subgroups with well-defined risk factors such as chronic renal failure, diabetes, older age, and hypertension. However, lower systolic blood pressure before imaging was associated with higher risk to develop PC-AKI after IBCA administration but not with GBCA (for systolic blood pressure lower than 110 mm Hg, odds ratio for AKI after IBCA was 1.49; 95% confidence interval, 1.16–1.88, and after GBCA; odds ratio, 0.12; 95% confidence interval, 0.003–0.73). Conclusions With the current precautions undertaken, the real-life risk of PC-AKI among inpatients undergoing CT is insignificant. Possible reasons for the diverse impact of blood pressure on the propensity to develop acute kidney failure after iodine-based but not gadolinium-based enhancement imaging are discussed. Received for publication September 24, 2018; and accepted for publication, after revision, October 17, 2018. Conflicts of interest and sources of funding: none declared. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (https://ift.tt/2kq7jVD). Correspondence to: Samuel N. Heyman, MD, Department of Medicine, Hadassah Hebrew University Hospital, Mt Scopus, PO Box 24035, Jerusalem 91240, Israel. E-mail: Heyman@cc.huji.ac.il. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Association between asthma, rhinitis and conjunctivitis multimorbidities with molecular IgE sensitization in adults
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Association between asthma, rhinitis and conjunctivitis multimorbidities with molecular IgE sensitization in adults
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MKSAP: 82-year-old woman with a 1-week history of urinary incontinence
Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians. An 82-year-old woman is evaluated for a 1-week history of urinary incontinence with lower abdominal discomfort. She reports no dysuria, fever, or back pain. Medical history is significant for hypertension and allergic reacti on to sulfa drugs, which cause a generalized rash. […]Find jobs at Careers by KevinMD.com. Search thousands of physician, PA, NP, and CRNA jobs now. Learn more. (Source: Kevin, M.D. - Medical Weblog)
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MKSAP: 82-year-old woman with a 1-week history of urinary incontinence
Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians. An 82-year-old woman is evaluated for a 1-week history of urinary incontinence with lower abdominal discomfort. She reports no dysuria, fever, or back pain. Medical history is significant for hypertension and allergic reacti on to sulfa drugs, which cause a generalized rash. […]Find jobs at Careers by KevinMD.com. Search thousands of physician, PA, NP, and CRNA jobs now. Learn more. (Source: Kevin, M.D. - Medical Weblog)
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Accidental ingestion of aspirin and non-steroidal anti-inflammatory drugs is common in patients with aspirin-exacerbated respiratory disease
Publication date: Available online 24 November 2018
Source: The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Adedapo Kiladejo, Marina Palumbo, Tanya M. Laidlaw
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Accidental ingestion of aspirin and non-steroidal anti-inflammatory drugs is common in patients with aspirin-exacerbated respiratory disease
Publication date: Available online 24 November 2018
Source: The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Adedapo Kiladejo, Marina Palumbo, Tanya M. Laidlaw
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Perinatal probiotic intervention prevented allergic disease in a Caesarean‐delivered subgroup at 13‐year follow‐up
Abstract
Background
The long‐term effects of probiotic intervention for primary prevention of allergic diseases are not well known. We previously reported less eczema until 10 years in our probiotic intervention trial.
Objective
To investigate the effect of early probiotic intervention on the prevalence of allergic diseases up to 13 years of age.
Methods
Pregnant women (n=1223) carrying a child at a high risk of allergy (at least one parent with allergic disease) were randomised to receive a mixture of probiotics (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii) or placebo in a double‐blind manner from 36 weeks of gestation until birth. Their infants received the same product for the first six months (registration number NCT00298337). At 13‐year follow‐up the participants were requested to return a questionnaire and to provide a blood sample.
Results
A questionnaire was returned by 642 participants (63.1% of intention‐to‐treat infants) and 459 provided a blood sample. In the whole cohort there were no statistically significant differences in doctor‐diagnosed allergic disease (55.2% and 59.0%, probiotic and placebo group, respectively) or allergic disease (47.9% and 51.6%) based on the ISAAC questionnaire data. Inhalant‐specific IgE‐sensitisation (>0.7 kU/L) was 59.3% in the probiotic group and 49.8% in the placebo group (p=0.040). In a post hoc analysis made in Caesarean‐delivered subgroup allergy was reported in 41.5% of the probiotic group and 67.9% of the placebo group (p=0.006), and eczema in 18.9% and 37.5% respectively (p=0.031). In the whole cohort 8.5% of the probiotic group had suffered from wheezing attacks during the previous 12 months vs. 14.7% in the placebo group (p=0.013). There was no statistically significant differences discovered between the characteristics of the participating group and the dropout‐group.
Conclusions
Probiotic intervention protected Caesarean‐delivered subgroup from allergic disease and eczema, but not the total cohort.
This article is protected by copyright. All rights reserved.
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Perinatal probiotic intervention prevented allergic disease in a Caesarean‐delivered subgroup at 13‐year follow‐up
Abstract
Background
The long‐term effects of probiotic intervention for primary prevention of allergic diseases are not well known. We previously reported less eczema until 10 years in our probiotic intervention trial.
Objective
To investigate the effect of early probiotic intervention on the prevalence of allergic diseases up to 13 years of age.
Methods
Pregnant women (n=1223) carrying a child at a high risk of allergy (at least one parent with allergic disease) were randomised to receive a mixture of probiotics (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii) or placebo in a double‐blind manner from 36 weeks of gestation until birth. Their infants received the same product for the first six months (registration number NCT00298337). At 13‐year follow‐up the participants were requested to return a questionnaire and to provide a blood sample.
Results
A questionnaire was returned by 642 participants (63.1% of intention‐to‐treat infants) and 459 provided a blood sample. In the whole cohort there were no statistically significant differences in doctor‐diagnosed allergic disease (55.2% and 59.0%, probiotic and placebo group, respectively) or allergic disease (47.9% and 51.6%) based on the ISAAC questionnaire data. Inhalant‐specific IgE‐sensitisation (>0.7 kU/L) was 59.3% in the probiotic group and 49.8% in the placebo group (p=0.040). In a post hoc analysis made in Caesarean‐delivered subgroup allergy was reported in 41.5% of the probiotic group and 67.9% of the placebo group (p=0.006), and eczema in 18.9% and 37.5% respectively (p=0.031). In the whole cohort 8.5% of the probiotic group had suffered from wheezing attacks during the previous 12 months vs. 14.7% in the placebo group (p=0.013). There was no statistically significant differences discovered between the characteristics of the participating group and the dropout‐group.
Conclusions
Probiotic intervention protected Caesarean‐delivered subgroup from allergic disease and eczema, but not the total cohort.
This article is protected by copyright. All rights reserved.
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N.I.S of AIT in Adult Patients With House Dust Mite Allergy in Real Practice in France
Conditions: Allergic Rhinitis Due to House Dust Mite; Allergic Asthma Due to Dermatophagoides Farinae; Allergic Asthma Due to Dermatophagoides Pteronyssinus Intervention: Drug: Tablet, Dispersible Sponsors: ALK-Abelló A/S; ITEC Services Recruiting (Source: ClinicalTrials.gov)
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BPF Genetics of ILD Study
Conditions: Lung; Disease, Interstitial, With Fibrosis; Alveolitis, Extrinsic Allergic; Bird Fancier's Lung; Idiopathic Interstitial Pneumonias; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis Intervention: Diagnostic Test: Genetic profiling Sponsors: NHS Forth Valley; University of Leicester; University of Glasgow; Newcastle University; British Lung Foundation; British Pigeon Fanciers Medical Research Not yet recruiting (Source: ClinicalTrials.gov)
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BPF Genetics of ILD Study
Conditions: Lung; Disease, Interstitial, With Fibrosis; Alveolitis, Extrinsic Allergic; Bird Fancier's Lung; Idiopathic Interstitial Pneumonias; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis Intervention: Diagnostic Test: Genetic profiling Sponsors: NHS Forth Valley; University of Leicester; University of Glasgow; Newcastle University; British Lung Foundation; British Pigeon Fanciers Medical Research Not yet recruiting (Source: ClinicalTrials.gov)
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Seal, Stopping Atopic Dermatitis and Allergy Study
Conditions: Eczema, Infantile; Eczema; Atopic Dermatitis Eczema; Atopic Dermatitis Interventions: Combination Product: Tri-lipid skin barrier cream (Epiceram); Combination Product: Fluticasone propionate Cream 0.05% Sponsors: Stanford University; King's College London; National Jewish Health Not yet recruiting (Source: ClinicalTrials.gov)
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Seal, Stopping Atopic Dermatitis and Allergy Study
Conditions: Eczema, Infantile; Eczema; Atopic Dermatitis Eczema; Atopic Dermatitis Interventions: Combination Product: Tri-lipid skin barrier cream (Epiceram); Combination Product: Fluticasone propionate Cream 0.05% Sponsors: Stanford University; King's College London; National Jewish Health Not yet recruiting (Source: ClinicalTrials.gov)
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Pay-it-forward RCT for Gonorrhea and Chlamydia Testing
Conditions: Gonorrhea Male; Chlamydia;M Interventions: Other: Pay-it-forward testing; Other: Pay as you want Sponsors: University of North Carolina, Chapel Hill; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA) Recruiting (Source: ClinicalTrials.gov)
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Pay-it-forward RCT for Gonorrhea and Chlamydia Testing
Conditions: Gonorrhea Male; Chlamydia;M Interventions: Other: Pay-it-forward testing; Other: Pay as you want Sponsors: University of North Carolina, Chapel Hill; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA) Recruiting (Source: ClinicalTrials.gov)
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N.I.S of AIT in Adult Patients With House Dust Mite Allergy in Real Practice in France
Conditions: Allergic Rhinitis Due to House Dust Mite; Allergic Asthma Due to Dermatophagoides Farinae; Allergic Asthma Due to Dermatophagoides Pteronyssinus Intervention: Drug: Tablet, Dispersible Sponsors: ALK-Abelló A/S; ITEC Services Recruiting (Source: ClinicalTrials.gov)
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BPF Genetics of ILD Study
Conditions: Lung; Disease, Interstitial, With Fibrosis; Alveolitis, Extrinsic Allergic; Bird Fancier's Lung; Idiopathic Interstitial Pneumonias; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis Intervention: Diagnostic Test: Genetic profiling Sponsors: NHS Forth Valley; University of Leicester; University of Glasgow; Newcastle University; British Lung Foundation; British Pigeon Fanciers Medical Research Not yet recruiting (Source: ClinicalTrials.gov)
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BPF Genetics of ILD Study
Conditions: Lung; Disease, Interstitial, With Fibrosis; Alveolitis, Extrinsic Allergic; Bird Fancier's Lung; Idiopathic Interstitial Pneumonias; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis Intervention: Diagnostic Test: Genetic profiling Sponsors: NHS Forth Valley; University of Leicester; University of Glasgow; Newcastle University; British Lung Foundation; British Pigeon Fanciers Medical Research Not yet recruiting (Source: ClinicalTrials.gov)
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Seal, Stopping Atopic Dermatitis and Allergy Study
Conditions: Eczema, Infantile; Eczema; Atopic Dermatitis Eczema; Atopic Dermatitis Interventions: Combination Product: Tri-lipid skin barrier cream (Epiceram); Combination Product: Fluticasone propionate Cream 0.05% Sponsors: Stanford University; King's College London; National Jewish Health Not yet recruiting (Source: ClinicalTrials.gov)
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Seal, Stopping Atopic Dermatitis and Allergy Study
Conditions: Eczema, Infantile; Eczema; Atopic Dermatitis Eczema; Atopic Dermatitis Interventions: Combination Product: Tri-lipid skin barrier cream (Epiceram); Combination Product: Fluticasone propionate Cream 0.05% Sponsors: Stanford University; King's College London; National Jewish Health Not yet recruiting (Source: ClinicalTrials.gov)
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Pay-it-forward RCT for Gonorrhea and Chlamydia Testing
Conditions: Gonorrhea Male; Chlamydia;M Interventions: Other: Pay-it-forward testing; Other: Pay as you want Sponsors: University of North Carolina, Chapel Hill; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA) Recruiting (Source: ClinicalTrials.gov)
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Pay-it-forward RCT for Gonorrhea and Chlamydia Testing
Conditions: Gonorrhea Male; Chlamydia;M Interventions: Other: Pay-it-forward testing; Other: Pay as you want Sponsors: University of North Carolina, Chapel Hill; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Aging (NIA) Recruiting (Source: ClinicalTrials.gov)
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Simultaneous Translabyrinthine Surgery of Vestibular Schwannoma and Cochlear Implantation With Intraoperative eBERA and Correlation to Hearing Results
Conditions: Vestibular Schwannoma; Hearing Loss Intervention: Sponsor: Christoph Arnoldner Recruiting (Source: ClinicalTrials.gov)
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Audiological Benefit and Quality of Life With Two Bone Conduction Systems: ADHEAR vs. Contact Mini
Condition: Conductive Hearing Loss Interventions: Device: Adhear; Device: Contact Mini (CM) Sponsor: Dominik Riss Recruiting (Source: ClinicalTrials.gov)
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Cochlear Implantation After Gamma Knife Radiosurgery With eABR and Correlation to Postoperative Hearing Results - a Pilot Study
Conditions: Vestibular Schwannoma; Hearing Loss Intervention: Other: eABR Sponsor: Christoph Arnoldner Recruiting (Source: ClinicalTrials.gov)
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Audiological Benefit and Quality of Life With Two Bone Conduction Systems: ADHEAR vs. Contact Mini
Condition: Conductive Hearing Loss Interventions: Device: Adhear; Device: Contact Mini (CM) Sponsor: Dominik Riss Recruiting (Source: ClinicalTrials.gov)
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Simultaneous Translabyrinthine Surgery of Vestibular Schwannoma and Cochlear Implantation With Intraoperative eBERA and Correlation to Hearing Results
Conditions: Vestibular Schwannoma; Hearing Loss Intervention: Sponsor: Christoph Arnoldner Recruiting (Source: ClinicalTrials.gov)
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Alcohol-related attentional bias in a gaze contingency task: Comparing appetitive and non-appetitive cues
Publication date: Available online 24 November 2018
Source: Addictive Behaviors
Author(s): Adam Qureshi, Rebecca L. Monk, Charlotte R. Pennington, Thomas D.W. Wilcockson, Derek Heim
Abstract
Background
Non-problem drinkers attend automatically to alcohol-related cues compared to non-alcohol related cues on tests of inhibitory control. Moreover, attentional bias for alcohol-related cues varies between problem and non-problem drinkers.
Aim
To examine attentional bias towards alcoholic and non-alcoholic appetitive cues between problem and non-problem drinkers.
Method
Forty-one university students (9 male, 32 female; Mage = 21.50) completed an eye-tracking gaze contingency paradigm, measuring the number of times participants looked at peripherally and centrally located stimuli (break frequency) when instructed to maintain focus on a target object. Stimuli consisted of appetitive alcohol-related (e.g., wine), appetitive non-alcohol-related (e.g., cola) and non-appetitive (e.g., fabric softener) stimuli. Participants were split using the Alcohol Use Disorders Identification Test (AUDIT) into non-problem (M AUDIT = 3.86) and problematic drinkers (M AUDIT = 11.59).
Results
Problematic drinkers had higher break frequencies towards peripheral appetitive stimuli than towards non-appetitive stimuli, while break frequency was equivalent between appetitive cues presented centrally (alcohol and non-alcohol-related). In contrast, there were no differences in break frequency across stimuli type or cue presentation location (central or peripheral) for non-problem drinkers.
Conclusion
In contrast to non-problem drinkers, people displaying more problematic consumption practices may find it more difficult to inhibit eye movements towards appetitive stimuli, particularly when in peripheral vision. This may suggest that attentional biases, as measured in terms of overt eye movements, in problem drinkers may be most powerful when the alcoholic and appetitive stimuli are not directly in field of view. An uncertainty reduction process in the allocation of attention to appetitive cues may help explain the patterns of results observed.
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Simultaneous Translabyrinthine Surgery of Vestibular Schwannoma and Cochlear Implantation With Intraoperative eBERA and Correlation to Hearing Results
Conditions: Vestibular Schwannoma; Hearing Loss Intervention: Sponsor: Christoph Arnoldner Recruiting (Source: ClinicalTrials.gov)
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Audiological Benefit and Quality of Life With Two Bone Conduction Systems: ADHEAR vs. Contact Mini
Condition: Conductive Hearing Loss Interventions: Device: Adhear; Device: Contact Mini (CM) Sponsor: Dominik Riss Recruiting (Source: ClinicalTrials.gov)
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Cochlear Implantation After Gamma Knife Radiosurgery With eABR and Correlation to Postoperative Hearing Results - a Pilot Study
Conditions: Vestibular Schwannoma; Hearing Loss Intervention: Other: eABR Sponsor: Christoph Arnoldner Recruiting (Source: ClinicalTrials.gov)
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Audiological Benefit and Quality of Life With Two Bone Conduction Systems: ADHEAR vs. Contact Mini
Condition: Conductive Hearing Loss Interventions: Device: Adhear; Device: Contact Mini (CM) Sponsor: Dominik Riss Recruiting (Source: ClinicalTrials.gov)
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Simultaneous Translabyrinthine Surgery of Vestibular Schwannoma and Cochlear Implantation With Intraoperative eBERA and Correlation to Hearing Results
Conditions: Vestibular Schwannoma; Hearing Loss Intervention: Sponsor: Christoph Arnoldner Recruiting (Source: ClinicalTrials.gov)
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Alcohol-related attentional bias in a gaze contingency task: Comparing appetitive and non-appetitive cues
Publication date: Available online 24 November 2018
Source: Addictive Behaviors
Author(s): Adam Qureshi, Rebecca L. Monk, Charlotte R. Pennington, Thomas D.W. Wilcockson, Derek Heim
Abstract
Background
Non-problem drinkers attend automatically to alcohol-related cues compared to non-alcohol related cues on tests of inhibitory control. Moreover, attentional bias for alcohol-related cues varies between problem and non-problem drinkers.
Aim
To examine attentional bias towards alcoholic and non-alcoholic appetitive cues between problem and non-problem drinkers.
Method
Forty-one university students (9 male, 32 female; Mage = 21.50) completed an eye-tracking gaze contingency paradigm, measuring the number of times participants looked at peripherally and centrally located stimuli (break frequency) when instructed to maintain focus on a target object. Stimuli consisted of appetitive alcohol-related (e.g., wine), appetitive non-alcohol-related (e.g., cola) and non-appetitive (e.g., fabric softener) stimuli. Participants were split using the Alcohol Use Disorders Identification Test (AUDIT) into non-problem (M AUDIT = 3.86) and problematic drinkers (M AUDIT = 11.59).
Results
Problematic drinkers had higher break frequencies towards peripheral appetitive stimuli than towards non-appetitive stimuli, while break frequency was equivalent between appetitive cues presented centrally (alcohol and non-alcohol-related). In contrast, there were no differences in break frequency across stimuli type or cue presentation location (central or peripheral) for non-problem drinkers.
Conclusion
In contrast to non-problem drinkers, people displaying more problematic consumption practices may find it more difficult to inhibit eye movements towards appetitive stimuli, particularly when in peripheral vision. This may suggest that attentional biases, as measured in terms of overt eye movements, in problem drinkers may be most powerful when the alcoholic and appetitive stimuli are not directly in field of view. An uncertainty reduction process in the allocation of attention to appetitive cues may help explain the patterns of results observed.
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Can we study 3D grid codes non-invasively in the human brain? Methodological considerations and fMRI findings
Publication date: Available online 24 November 2018
Source: NeuroImage
Author(s): Misun Kim, Eleanor A. Maguire
Abstract
Recent human functional magnetic resonance imaging (fMRI) and animal electrophysiology studies suggest that grid cells in entorhinal cortex are an efficient neural mechanism for encoding knowledge about the world, not only for spatial location but also for more abstract cognitive information. The world, be it physical or abstract, is often high-dimensional, but grid cells have been mainly studied on a simple two-dimensional (2D) plane. Recent theoretical studies have proposed how grid cells encode three-dimensional (3D) physical space, but it is unknown whether grid codes can be examined non-invasively in humans. Here, we investigated whether it was feasible to test different 3D grid models using fMRI based on the direction-modulated property of grid signals. In doing so, we developed interactive software to help researchers visualize 3D grid fields and predict grid activity in 3D as a function of movement directions. We found that a direction-modulated grid analysis was sensitive to one type of 3D grid model – a face-centred cubic (FCC) lattice model. As a proof of concept, we searched for 3D grid-like signals in human entorhinal cortex using a novel 3D virtual reality paradigm and a new fMRI analysis method. We found that signals in the left entorhinal cortex were explained by the FCC model. This is preliminary evidence for 3D grid codes in the human brain, notwithstanding the inherent methodological limitations of fMRI. We believe that our findings and software serve as a useful initial stepping-stone for studying grid cells in realistic 3D worlds and also, potentially, for interrogating abstract high-dimensional cognitive processes.
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Can we study 3D grid codes non-invasively in the human brain? Methodological considerations and fMRI findings
Publication date: Available online 24 November 2018
Source: NeuroImage
Author(s): Misun Kim, Eleanor A. Maguire
Abstract
Recent human functional magnetic resonance imaging (fMRI) and animal electrophysiology studies suggest that grid cells in entorhinal cortex are an efficient neural mechanism for encoding knowledge about the world, not only for spatial location but also for more abstract cognitive information. The world, be it physical or abstract, is often high-dimensional, but grid cells have been mainly studied on a simple two-dimensional (2D) plane. Recent theoretical studies have proposed how grid cells encode three-dimensional (3D) physical space, but it is unknown whether grid codes can be examined non-invasively in humans. Here, we investigated whether it was feasible to test different 3D grid models using fMRI based on the direction-modulated property of grid signals. In doing so, we developed interactive software to help researchers visualize 3D grid fields and predict grid activity in 3D as a function of movement directions. We found that a direction-modulated grid analysis was sensitive to one type of 3D grid model – a face-centred cubic (FCC) lattice model. As a proof of concept, we searched for 3D grid-like signals in human entorhinal cortex using a novel 3D virtual reality paradigm and a new fMRI analysis method. We found that signals in the left entorhinal cortex were explained by the FCC model. This is preliminary evidence for 3D grid codes in the human brain, notwithstanding the inherent methodological limitations of fMRI. We believe that our findings and software serve as a useful initial stepping-stone for studying grid cells in realistic 3D worlds and also, potentially, for interrogating abstract high-dimensional cognitive processes.
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Detection and quantification of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in bacteremia induced by interdental brushing in periodontally healthy and periodontitis patients
Publication date: Available online 24 November 2018
Source: Archives of Oral Biology
Author(s): Nagore Ambrosio, María José Marín, Estefanía Laguna, David Herrera, Mariano Sanz, Elena Figuero
Abstract
Objective
This study was aimed to compare the presence and amounts of bacteremia induced by interdental brushing in healthy (H) and periodontitis (P) individuals using culture based (direct culture [DC]) and molecular based techniques (real-time quantitative polymerase chain reaction [qPCR]) in a cross-sectional study model.
Materials and Methods
After a full mouth periodontal evaluation, blood samples were taken before and 1 min after professionally-administered interdental tooth brushing. These samples were analyzed by DC and qPCR, targeting Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Subgingival samples were also collected and analyzed. Student t-test, chi-square tests correlations were used for analyzing the data.
Results
Thirty individuals per group were included. P. gingivalis and A. actinomycetemcomitans were detected with qPCR methods, but not with DC. At baseline, bacteremia was observed in 5 P patients (16.7%) and in 2 H individuals (6.6%) (p = 0.421). After interdental tooth brushing, bacteremia was only observed in 2 P patients (6.6%) (p = 0.901). A positive correlation between subgingival and blood levels of A. actinomycetemcomitans was observed (r = 0.3; p = 0.013).
Conclusion
Bacteremia related to A. actinomycetemcomitans and P. gingivalis did not significantly increase after a single session of use of interdental brushes.
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Detection and quantification of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in bacteremia induced by interdental brushing in periodontally healthy and periodontitis patients
Publication date: Available online 24 November 2018
Source: Archives of Oral Biology
Author(s): Nagore Ambrosio, María José Marín, Estefanía Laguna, David Herrera, Mariano Sanz, Elena Figuero
Abstract
Objective
This study was aimed to compare the presence and amounts of bacteremia induced by interdental brushing in healthy (H) and periodontitis (P) individuals using culture based (direct culture [DC]) and molecular based techniques (real-time quantitative polymerase chain reaction [qPCR]) in a cross-sectional study model.
Materials and Methods
After a full mouth periodontal evaluation, blood samples were taken before and 1 min after professionally-administered interdental tooth brushing. These samples were analyzed by DC and qPCR, targeting Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Subgingival samples were also collected and analyzed. Student t-test, chi-square tests correlations were used for analyzing the data.
Results
Thirty individuals per group were included. P. gingivalis and A. actinomycetemcomitans were detected with qPCR methods, but not with DC. At baseline, bacteremia was observed in 5 P patients (16.7%) and in 2 H individuals (6.6%) (p = 0.421). After interdental tooth brushing, bacteremia was only observed in 2 P patients (6.6%) (p = 0.901). A positive correlation between subgingival and blood levels of A. actinomycetemcomitans was observed (r = 0.3; p = 0.013).
Conclusion
Bacteremia related to A. actinomycetemcomitans and P. gingivalis did not significantly increase after a single session of use of interdental brushes.
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Intermodel Disagreement of Myocardial Blood Flow Estimation from Dynamic CT Perfusion Imaging
Publication date: Available online 24 November 2018
Source: European Journal of Radiology
Author(s): Marly van Assen, Gert Jan Pelgrim, Carlo N. De Cecco, J. Marco A. Stijnen, Beatrice M. Zaki, Matthijs Oudkerk, Rozemarijn Vliegenthart, U. Joseph Schoepf
Abstract
Purpose
To assess the intermodel agreement of different tracer kinetic models to determine myocardial blood flow (MBF) and their diagnostic accuracy in coronary artery disease (CAD) at dynamic CT myocardial perfusion imaging (CTMPI).
Methods
Three porcine hearts perfused in Langendorff mode and 15 patients with suspected CAD and perfusion single photon emission CT (SPECT) were included. Dynamic CTMPI was performed in shuttle-mode (70 kVp, 350mAs/rot) on 3rd generation dual-source CT. In porcine hearts and patients, myocardial segments (AHA-16-segment model) were drawn. Tissue attenuation curves were constructed per segment and arterial input functions were derived from the aorta. True MBF was calculated with input flow and weight of the porcine hearts. In patients, ischemic segments were based on SPECT results. MBF quantification was performed using the VPCT-software, Upslope, Extended Toft (ET), Two-compartment (TC) and Fermi models.
Results
In porcine hearts, true MBF was 1.88 (interquartile range [IQR]:1.80-2.80)mL/g/min. Diagnostic accuracy was similar for all models: 0.96, 0.99, 0.92, 0.93 and 0.96 for VPCT software, Upslope method, Fermi, ET and TC model. The VPCT software and Upslope method resulted in lower MBF (median 1.44 [1.29-1.58] and 1.39 [1.25-1.59]mL/g/min) compared to the Fermi, ET, and TC model (median values of 1.76 mL/g/min [1.36-2.44], 2.55 mL/g/min [2.20-2.92], and 1.98 mL/g/min [1.60-2.60], respectively [p < 0.001]). In patients, all models showed a significant difference in MBF between the 34 ischemic and 206 non-ischemic segments (p-value<0.001).
Conclusion
Absolute MBF values are significantly different between the models and a uniform threshold could not be determined; however, diagnostic accuracy for detecting ischemia is similar.
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Effects of menstrual cycle on background parenchymal enhancement and detectability of breast cancer on dynamic contrast-enhanced breast MRI: A multicenter study of an Asian population
Publication date: Available online 24 November 2018
Source: European Journal of Radiology
Author(s): Takeshi Kamitani, Hidetake Yabuuchi, Yoshihide Kanemaki, Mitsuhiro Tozaki, Tetsuo Sonomura, Waka Mizukoshi, Waka Nakata, Taro Shimono, Misugi Urano, Toshiko Yamano, Fumi Kato, Megumi Kuchiki, Nobuyuki Shiragami, Hisami Yanagita, Eisuke Katsuda, Masako Kataoka, Ken Yamaguchi, Takuro Horikoshi, Tatsuya Gomi, Miwako Nozaki
Abstract
Purpose
To evaluate the effect of the menstrual cycle on BPE and cancer detectability in an Asian population.
Material and Methods
266 premenopausal patients with regular menstrual cycles from 24 centers were included, and 176 of them were diagnosed by pathology as having breast cancer. Thirty-five patients were examined in the menstrual phase (days 1–4), 105 in the proliferative phase (days 5–14), and 126 in the secretory phase (days 15–30).
Measurement of the following signal intensities (SIs) were obtained: breast tissue on the unaffected side on a pre-contrast image (SI1) and an early-phase image (SI2); the SIs of breast tissue on the affected side on a pre-contrast image (SI3) and an early-phase image (SI4); and the SIs of breast cancer on a pre-contrast image (SI5) and an early-phase image (SI6). We calculated the BPE ratio, i.e., (SI2– SI1)/SI1 and the cancer/background enhancement ratio (C/B) ratio, i.e., (SI6– SI5) / (SI4– SI3). The BPE was classified as minimal, mild, moderate, or marked, and the cancer detectability was classified as excellent, good, or poor independently by two radiologists.
Results
The average C/B ratio was 20.1, 15.7, and 9.1 at the menstrual, proliferative, and secretory phases (p < 0.001). BPE was determined as moderate or marked in 0% and 5.4% at the menstrual phase, 10.3% and 11.0% at the proliferative phase, and 17.5% and 21.7% at the secretory phase by the two observers, respectively (p = 0.01, p = 0.01). The detectability of breast cancer was classified as poor in 0% and 0%, 1.4% and 13.0%, and 8.0% and 22.1% at the menstrual, proliferative, and secretory phases by the two observers, respectively (p = 0.07, p = 0.02).
Conclusion
The menstrual phase and the proliferative phase seem to be suitable for breast MRI of Asian women.
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Intermodel Disagreement of Myocardial Blood Flow Estimation from Dynamic CT Perfusion Imaging
Publication date: Available online 24 November 2018
Source: European Journal of Radiology
Author(s): Marly van Assen, Gert Jan Pelgrim, Carlo N. De Cecco, J. Marco A. Stijnen, Beatrice M. Zaki, Matthijs Oudkerk, Rozemarijn Vliegenthart, U. Joseph Schoepf
Abstract
Purpose
To assess the intermodel agreement of different tracer kinetic models to determine myocardial blood flow (MBF) and their diagnostic accuracy in coronary artery disease (CAD) at dynamic CT myocardial perfusion imaging (CTMPI).
Methods
Three porcine hearts perfused in Langendorff mode and 15 patients with suspected CAD and perfusion single photon emission CT (SPECT) were included. Dynamic CTMPI was performed in shuttle-mode (70 kVp, 350mAs/rot) on 3rd generation dual-source CT. In porcine hearts and patients, myocardial segments (AHA-16-segment model) were drawn. Tissue attenuation curves were constructed per segment and arterial input functions were derived from the aorta. True MBF was calculated with input flow and weight of the porcine hearts. In patients, ischemic segments were based on SPECT results. MBF quantification was performed using the VPCT-software, Upslope, Extended Toft (ET), Two-compartment (TC) and Fermi models.
Results
In porcine hearts, true MBF was 1.88 (interquartile range [IQR]:1.80-2.80)mL/g/min. Diagnostic accuracy was similar for all models: 0.96, 0.99, 0.92, 0.93 and 0.96 for VPCT software, Upslope method, Fermi, ET and TC model. The VPCT software and Upslope method resulted in lower MBF (median 1.44 [1.29-1.58] and 1.39 [1.25-1.59]mL/g/min) compared to the Fermi, ET, and TC model (median values of 1.76 mL/g/min [1.36-2.44], 2.55 mL/g/min [2.20-2.92], and 1.98 mL/g/min [1.60-2.60], respectively [p < 0.001]). In patients, all models showed a significant difference in MBF between the 34 ischemic and 206 non-ischemic segments (p-value<0.001).
Conclusion
Absolute MBF values are significantly different between the models and a uniform threshold could not be determined; however, diagnostic accuracy for detecting ischemia is similar.
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Effects of menstrual cycle on background parenchymal enhancement and detectability of breast cancer on dynamic contrast-enhanced breast MRI: A multicenter study of an Asian population
Publication date: Available online 24 November 2018
Source: European Journal of Radiology
Author(s): Takeshi Kamitani, Hidetake Yabuuchi, Yoshihide Kanemaki, Mitsuhiro Tozaki, Tetsuo Sonomura, Waka Mizukoshi, Waka Nakata, Taro Shimono, Misugi Urano, Toshiko Yamano, Fumi Kato, Megumi Kuchiki, Nobuyuki Shiragami, Hisami Yanagita, Eisuke Katsuda, Masako Kataoka, Ken Yamaguchi, Takuro Horikoshi, Tatsuya Gomi, Miwako Nozaki
Abstract
Purpose
To evaluate the effect of the menstrual cycle on BPE and cancer detectability in an Asian population.
Material and Methods
266 premenopausal patients with regular menstrual cycles from 24 centers were included, and 176 of them were diagnosed by pathology as having breast cancer. Thirty-five patients were examined in the menstrual phase (days 1–4), 105 in the proliferative phase (days 5–14), and 126 in the secretory phase (days 15–30).
Measurement of the following signal intensities (SIs) were obtained: breast tissue on the unaffected side on a pre-contrast image (SI1) and an early-phase image (SI2); the SIs of breast tissue on the affected side on a pre-contrast image (SI3) and an early-phase image (SI4); and the SIs of breast cancer on a pre-contrast image (SI5) and an early-phase image (SI6). We calculated the BPE ratio, i.e., (SI2– SI1)/SI1 and the cancer/background enhancement ratio (C/B) ratio, i.e., (SI6– SI5) / (SI4– SI3). The BPE was classified as minimal, mild, moderate, or marked, and the cancer detectability was classified as excellent, good, or poor independently by two radiologists.
Results
The average C/B ratio was 20.1, 15.7, and 9.1 at the menstrual, proliferative, and secretory phases (p < 0.001). BPE was determined as moderate or marked in 0% and 5.4% at the menstrual phase, 10.3% and 11.0% at the proliferative phase, and 17.5% and 21.7% at the secretory phase by the two observers, respectively (p = 0.01, p = 0.01). The detectability of breast cancer was classified as poor in 0% and 0%, 1.4% and 13.0%, and 8.0% and 22.1% at the menstrual, proliferative, and secretory phases by the two observers, respectively (p = 0.07, p = 0.02).
Conclusion
The menstrual phase and the proliferative phase seem to be suitable for breast MRI of Asian women.
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Extranodal extension is a criterion for poor outcome in patients with metastatic nodes from cancer of the nasopharynx
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Qi-Yong Ai, Ann D. King, Darren M.C. Poon, Frankie K.F. Mo, Edwin P. Hui, Macy Tong, Anil T. Ahuja, Brigette B.Y. Ma, Anthony T.C. Chan
Abstract
Purpose
Extranodal extension (ENE) is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. Our aim was to determine if ENE should be a staging criterion for nasopharyngeal carcinoma (NPC).
Materials & methods
MRI of 546 NPC patients were reviewed retrospectively and in 404/546 (74.0%) with metastatic nodes, the nodes were assessed for ENE (grade 0 = absent; grade 1 = infiltration of surrounding fat; grade 2 = infiltration of muscle/skin), size (total volume), site (unilateral/bilateral and upper/lower neck) and necrosis. Associations between nodal features and regional relapse free survival (RRFS), distant metastases free survival (DMFS) and overall survival (OS) were assessed using cox regression. Differences of survival rates were compared using log-rank test. A p-value of < 0.05 indicates statistical significance.
Results
ENE grade was the only determinant of RRFS (p = 0.014) and only independent determinant of DMFS (p = 0.003) and OS (p < 0.001). Grade 2 ENE was associated with significantly poorer RRFS, DMFS and OS compared to grade 0 and 1 (p < 0.05). Addition of grade 2 ENE to N1 and N2 disease showed similar poor RRFS, DMFS and OS to N3 disease (p > 0.05). Compared to the current stage N3 disease, inclusion of grade 2 ENE increased the number of N3 patients from 53/546 (9.7%) to 82/546 (15.0%) with similar hazard ratios for DMFS (6.855 and 7.125, respectively) and OS (3.614 and 4.085, respectively).
Conclusion
Grade 2 ENE (into muscle and/or skin and/or salivary glands) is an independent indicator of poor outcome and may be considered as a new criterion for N3 nodal disease in NPC.
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Reciprocal activation of cancer-associated fibroblasts and oral squamous carcinoma cells through CXCL1
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Ling-Ying Wei, Jang-Jaer Lee, Chiou-Yueh Yeh, Chia-Ju Yang, Sang-Heng Kok, Jenq-Yuh Ko, Feng-Chiao Tsai, Jean-San Chia
Abstract
Objectives
Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) is known to be involved in various aspects of tumor biology, including during invasion. Using oral squamous cell carcinoma (OSCC) cells as a model, we examined whether and how CAFs respond to inflammatory signals to influence cancer cell migration and invasion.
Materials and methods
Chemokine signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed together with tissue assessment using immunohistochemical staining (IHC) and real-time PCR. A co-culture system was used to identify reciprocal effects exerted by CAFs and cancer cells upon one another. Recombinant CXCL1, CXCL1 neutralizing antibodies, and CXCR2 antagonist were used to confirm CXCL1/CXCR2 axis-mediated cell behaviors.
Results
Analysis of the TCGA dataset revealed that CXCL1 is associated with poor survival, and IHC demonstrated CXCL1 is highly expressed in OSCC stromal cells. Moreover, real-time PCR showed that in addition to CXCL1, IL-1β and CXCR2 are also highly expressed in OSCC and IL-1β mRNA levels positively correlate with CXCL1 expression. Furthermore, CAFs co-cultured with SAS, a poorly differentiated OSCC cell line, or stimulated with IL-1β exhibit increased CXCL1 secretion in an NF-κB-dependent manner. Treatment of SAS cells with CAF-conditioned medium or CXCL1 increased their invasion and migration capabilities, indicating a reciprocal activation between CAFs and cancer cells. Moreover, CXCL-1 upregulated matrix metalloprotease-1 (MMP-1) expression and activity in CAFs.
Conclusion
The induction of IL-1β following CXCL1 stimulation of CAFs mediates cancer cell invasion, and there is a reciprocal dependency between CAFs and cancer cells in the OSCC microenvironment.
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Extranodal extension is a criterion for poor outcome in patients with metastatic nodes from cancer of the nasopharynx
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Qi-Yong Ai, Ann D. King, Darren M.C. Poon, Frankie K.F. Mo, Edwin P. Hui, Macy Tong, Anil T. Ahuja, Brigette B.Y. Ma, Anthony T.C. Chan
Abstract
Purpose
Extranodal extension (ENE) is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. Our aim was to determine if ENE should be a staging criterion for nasopharyngeal carcinoma (NPC).
Materials & methods
MRI of 546 NPC patients were reviewed retrospectively and in 404/546 (74.0%) with metastatic nodes, the nodes were assessed for ENE (grade 0 = absent; grade 1 = infiltration of surrounding fat; grade 2 = infiltration of muscle/skin), size (total volume), site (unilateral/bilateral and upper/lower neck) and necrosis. Associations between nodal features and regional relapse free survival (RRFS), distant metastases free survival (DMFS) and overall survival (OS) were assessed using cox regression. Differences of survival rates were compared using log-rank test. A p-value of < 0.05 indicates statistical significance.
Results
ENE grade was the only determinant of RRFS (p = 0.014) and only independent determinant of DMFS (p = 0.003) and OS (p < 0.001). Grade 2 ENE was associated with significantly poorer RRFS, DMFS and OS compared to grade 0 and 1 (p < 0.05). Addition of grade 2 ENE to N1 and N2 disease showed similar poor RRFS, DMFS and OS to N3 disease (p > 0.05). Compared to the current stage N3 disease, inclusion of grade 2 ENE increased the number of N3 patients from 53/546 (9.7%) to 82/546 (15.0%) with similar hazard ratios for DMFS (6.855 and 7.125, respectively) and OS (3.614 and 4.085, respectively).
Conclusion
Grade 2 ENE (into muscle and/or skin and/or salivary glands) is an independent indicator of poor outcome and may be considered as a new criterion for N3 nodal disease in NPC.
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Reciprocal activation of cancer-associated fibroblasts and oral squamous carcinoma cells through CXCL1
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Ling-Ying Wei, Jang-Jaer Lee, Chiou-Yueh Yeh, Chia-Ju Yang, Sang-Heng Kok, Jenq-Yuh Ko, Feng-Chiao Tsai, Jean-San Chia
Abstract
Objectives
Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) is known to be involved in various aspects of tumor biology, including during invasion. Using oral squamous cell carcinoma (OSCC) cells as a model, we examined whether and how CAFs respond to inflammatory signals to influence cancer cell migration and invasion.
Materials and methods
Chemokine signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed together with tissue assessment using immunohistochemical staining (IHC) and real-time PCR. A co-culture system was used to identify reciprocal effects exerted by CAFs and cancer cells upon one another. Recombinant CXCL1, CXCL1 neutralizing antibodies, and CXCR2 antagonist were used to confirm CXCL1/CXCR2 axis-mediated cell behaviors.
Results
Analysis of the TCGA dataset revealed that CXCL1 is associated with poor survival, and IHC demonstrated CXCL1 is highly expressed in OSCC stromal cells. Moreover, real-time PCR showed that in addition to CXCL1, IL-1β and CXCR2 are also highly expressed in OSCC and IL-1β mRNA levels positively correlate with CXCL1 expression. Furthermore, CAFs co-cultured with SAS, a poorly differentiated OSCC cell line, or stimulated with IL-1β exhibit increased CXCL1 secretion in an NF-κB-dependent manner. Treatment of SAS cells with CAF-conditioned medium or CXCL1 increased their invasion and migration capabilities, indicating a reciprocal activation between CAFs and cancer cells. Moreover, CXCL-1 upregulated matrix metalloprotease-1 (MMP-1) expression and activity in CAFs.
Conclusion
The induction of IL-1β following CXCL1 stimulation of CAFs mediates cancer cell invasion, and there is a reciprocal dependency between CAFs and cancer cells in the OSCC microenvironment.
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