In the original published version of this article, the middle name for author Mirko H. H. Schmidt is missing.
https://ift.tt/2RcB5s8
Τρίτη 23 Οκτωβρίου 2018
Damage-regulated autophagy modulator 1 in oral inflammation and infection
Abstract
Objectives
Damage-regulated autophagy modulator (DRAM) 1 is a p53 target gene with possible involvement in oral inflammation and infection. This study sought to examine the presence and regulation of DRAM1 in periodontal diseases.
Material and methods
In vitro, human periodontal ligament fibroblasts were exposed to interleukin (IL)-1β and Fusobacterium nucleatum for up to 2 days. The DRAM1 synthesis and its regulation were analyzed by real-time PCR, immunocytochemistry, and ELISA. Expressions of other autophagy-associated genes were also studied by real-time PCR. In vivo, synthesis of DRAM1 in gingival biopsies from rats and patients with and without periodontal disease was examined by real-time PCR and immunohistochemistry. For statistics, ANOVA and post-hoc tests were applied (p < 0.05).
Results
In vitro, DRAM1 was significantly upregulated by IL-1β and F. nucleatum over 2 days and a wide range of concentrations. Additionally, increased DRAM1 protein levels in response to both stimulants were observed. Autophagy-associated genes ATG3, BAK1, HDAC6, and IRGM were also upregulated under inflammatory or infectious conditions. In vivo, the DRAM1 gene expression was significantly enhanced in rat gingival biopsies with induced periodontitis as compared to control. Significantly increased DRAM1 levels were also detected in human gingival biopsies from sites of periodontitis as compared to healthy sites.
Conclusion
Our data provide novel evidence that DRAM1 is increased under inflammatory and infectious conditions in periodontal cells and tissues, suggesting a pivotal role of DRAM1 in oral inflammation and infection.
Clinical relevance
DRAM1 might be a promising target in future diagnostic and treatment strategies for periodontitis.
https://ift.tt/2F1nlvh
Treatment of intrabony defects with modified perforated membranes in aggressive periodontitis: a 12-month randomized controlled trial
Abstract
Objective
The aim of this study was to compare the clinical and radiographic efficacy of guided tissue regeneration with a modified perforated collagen membrane (MPM) or standard collagen membrane (CM) in the treatment of intrabony defects in patients with aggressive periodontitis (AgP).
Materials and methods
Fifteen AgP patients were included in the study. Two single intrabony defects of at least 3 mm depth with ≥ 6 mm probing pocket depth (PPD) from each patient were randomly assigned to either xenogenic graft plus MPM (test group) or xenogenic graft plus CM (control group). PPD, clinical attachment level (CAL), and gingival recession (GR) were recorded at baseline and at 12 months. The radiographic assessments included the measurements of defect depth (DD), change in alveolar crest position (ACP), linear defect fill (LDF), and percentage defect fill (%DF).
Results
After treatment, PPD, CAL, DD, and ACP values improved significantly in both groups, without statistical differences between them. However, with respect to LDF and %DF, the 12-month radiographic analysis at MPM-treated sites showed a significant improvement compared to the 6-month outcomes, that was not observed at control sites (additional LDF of 0.4 ± 0.5 mm, p = 0.010 and %DF of 6.4 ± 7.6%, p = 0.025).
Conclusions
Both strategies proved effective in the treatment of intrabony defects in patients with AgP. Nonetheless, enhanced LDF and %DF 12 months postoperatively at MPM-treated sites may stem from cellular and molecular migration from the periosteum and overlying gingival connective tissue through barrier's pores.
Clinical relevance
Modification of CM may have positive ramifications on periodontal regeneration.
https://ift.tt/2E4VZYb
Oral health-related quality of life is associated with disease specific parameters in patients with ankylosing spondylitis
Abstract
Background
The aim of this cross-sectional study was to investigate oral health-related quality of life (OHRQoL) in patients with ankylosing spondylitis (AS) and its association to oral health as well as AS specific parameters.
Methods
Patients with AS and a healthy control group (HC) were included and examined. The oral examination included decayed-, missing-, and filled-teeth index (DMF-T) as well as assessment of periodontal probing depth and clinical attachment loss to classify patients into healthy/mild, moderate, or severe periodontitis. Furthermore, the German short form of the oral health impact profile (OHIP G14) was used.
Results
A total of 50 patients each group (age: AS, 47.18 ± 15.67; HC, 55.82 ± 10.56; p < 0.01, gender male: AS, 52%; HC, 46%; p = 0.69) was included. AS patients showed worse D-T (p < 0.01) and periodontal condition (p = 0.01). The OHIP G14 score was clinically relevant and statistically significant higher in AS compared to HC (AS, 6.2 [2; 0–10.75]; HC, 1.7 [0; 0–2.0]; < 0.01). Only in HC, an association of OHIP G14 to DMF-T (p = 0.01) and M-T (p = 0.01) was found, while the OHIP G14 in AS group was not associated to oral health parameters. Within the AS group, the majority of investigated AS specific parameters were statistically significant and clinically relevant associated to OHIP G14 scores (pi < 0.05).
Conclusion
Patients with AS show worse OHRQoL compared to HC, irrespective of oral status. The high general disease burden might affect OHRQoL, making an increased attention of these patients in dental care, especially considering psychological aspects, necessary.
Clinical relevance
Increased consideration of psychosocial and disease related aspects in dental care of AS patients appear recommendable.
https://ift.tt/2q6aLEi
A 30-s exposure to ethanol 20% is cytotoxic to human keratinocytes: possible mechanistic link between alcohol-containing mouthwashes and oral cancer
Abstract
Objectives
To provide mechanistic evidence for the epidemiological link between long-term use of alcohol-containing mouthwashes and oral cancer.
Material and methods
Human epithelial keratinocytes were exposed for 30 s to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.
Results
A marked cytotoxic effect was observed for ethanol concentrations of 20% and above.
Conclusions
The cytotoxicity of ethanol may explain the epidemiological association between mouthwash use and oral cancer. Evidence suggests that the risk of developing cancer in a tissue is strongly determined by the number of stem cell divisions accumulated by the tissue during a person's lifetime; cell division is a major source of mutations and other cancer-promoting errors. Since cell death activates the division of stem cells, the possible cytotoxicity of ethanol on the cells lining the oral mucosa will promote the division of the stem cells located in deeper layers to produce new cells to regenerate the damaged epithelium. If we regularly use mouthwashes containing cytotoxic concentrations of ethanol, the stem cells of the oral cavity may need to divide more often than usual and our risk of developing oral cancer may increase.
Clinical relevance
Many mouthwashes contain percentages of ethanol above 20%. Because ethanol is not crucial to prevent and reduce gingivitis and plaque, members of the dental team should consider the potential risk of oral cancer associated with frequent use of alcohol-containing mouthwashes when advising their patients.
https://ift.tt/2RdvWA5
Novel evaluation method of dentin repair by direct pulp capping using high-resolution micro-computed tomography
Abstract
Objectives
We evaluated a novel micro-computed tomography (micro-CT) assessment for quality and quantity of dentin repair, which is difficult to visualize by histological analysis, after direct pulp capping under standardized cavity preparation.
Materials and methods
Standardized cavities were prepared on Wistar rats and direct pulp capping was performed using two commercial bioceramics, ProRoot MTA, and iRoot BP Plus. After 2 or 4 weeks, quality and quantity of tertiary dentin formation were evaluated using high-resolution micro-CT analyses including dentin mineral density, dentin mineral contents, compactness and integrity of tertiary dentin, and dentin volume with/without void space. Reproducibility of micro-CT analyses was confirmed by histological evaluation of the same specimen.
Results
The exposed pulp area sizes were similar between iRoot BP Plus and ProRoot MTA. Micro-CT analysis of 2-week samples showing compactness of tertiary dentin was significantly higher in iRoot BP Plus than ProRoot MTA (p < 0.05). Tertiary dentin volume without void space, dentin mineral contents, and density were not significantly different between the groups. In 4-week samples, a significant increase was observed in dentin mineral density, compactness, and dentin volume with/without void space induced by iRoot BP Plus (p < 0.05). Micro-CT analysis of tertiary dentin integrity demonstrated that some ProRoot MTA specimens had small defects and lacked continuity (6/512 images). No defects were observed with iRoot BP Plus.
Conclusions
Micro-CT analysis was confirmed as an accurate, objective, and inclusive approach for evaluating quality and quantity of dentin repair.
Clinical relevance
These multifaceted approaches to evaluate pulp capping materials may accelerate review processes, ultimately improving vital pulp therapy.
https://ift.tt/2o24h87
Impact of simulated reduced alveolar bone support, increased tooth mobility, and distal post-supported, root-treated abutment tooth on load capability of all-ceramic zirconia-supported cantilever FDP
Abstract
Objectives
The aim of this in vitro study was an analysis of the impact of simulated reduced alveolar bone support and post-restored, endodontically treated distal abutment tooth on load capability of all-ceramic zirconia-based cantilever-fixed dental prosthesis (CFDP).
Material and methods
The roots of human lower sound premolars (n = 80) were divided into five experimental groups to be restored with all-ceramic zirconia-supported three-unit CFDP regarding bone loss (BL) relative to the cement-enamel junction (CEJ): 2 mm below CEJ = 0% BL (control group), group 25% distal BL, group 50% distal BL, group 50% mesial and distal BL, and group 50% distal BL and adhesive post-supported restoration. Specimens were exposed to simulated clinical function by thermo-mechanical loading (6.000 cycles 5°–55°; 1.2 × 106 cycles 0–50 N) and subsequent linear loading until failure.
Results
Tooth mobility increased significantly for groups with simulated bone loss (p < 0.001). Four specimens failed during thermal cycling and mechanical loading (TCML). The maximum load capability ranged from 350 to 569 N, and did not differ significantly between experimental groups (p = 0.095). Groups with simulated bone loss revealed more tooth fractures at distal abutment teeth, whereas technical failures were more frequent in the control group (p = 0.024).
Conclusions
Differences of alveolar bone support and respectively increased tooth mobility between mesial and distal abutments did not influence load capability. A distal adhesively post-and-core-supported, root-treated abutment tooth did not increase risk of three-unit CFDP failure.
Clinical relevance
CFDPs are a treatment option used with caution when reduced alveolar bone support, increased tooth mobility, and distal post-supported, root-treated abutment teeth are involved.
https://ift.tt/2nMwZK1
N -acetyl- l -cysteine protects dental tissue stem cells against oxidative stress in vitro
Abstract
Objectives
The aim of our study was to investigate whether N-acetyl-l-cysteine (NAC) could protect stem cells from exfoliated deciduous teeth (SHED) against oxidative damage, during in vitro cultivation, to preserve regenerative potential of these cells. Accordingly, we examined the potential of cell culture supplementation with NAC in prevention of lipid peroxidation, unfavorable changes of total lipids fatty acid composition, and the effects on the activity of antioxidant enzymes.
Material and methods
We analyzed the extent of oxidative damage in SHED after 48 h treatment with different NAC concentrations. Cellular lipid peroxidation was determined upon reaction with thiobarbituric acid. All enzyme activities were measured spectrophotometrically, based on published methods. Fatty acid methyl esters were analyzed by gas-liquid chromatography.
Results
Concentration of 0.1 mM NAC showed the most profound effects on SHED, significantly decreasing levels of lipid peroxidation in comparison to control. This dose also diminished the activities of antioxidant enzymes. Furthermore, NAC treatment significantly changed fatty acid composition of cells, reducing levels of oleic acid and monounsaturated fatty acids and increasing linoleic acid, n-6, and total polyunsaturated fatty acid (PUFA) proportions.
Conclusion
Low dose of NAC significantly decreased lipid peroxidation and altered fatty acid composition towards increasing PUFA. The reduced oxidative damage of cellular lipids could be strongly related to improved SHED survival in vitro.
Clinical relevance
Low doses of antioxidants, applied during stem cells culturing and maintenance, could improve cellular characteristics in vitro. This is prerequisite for successful use of stem cells in various clinical applications.
https://ift.tt/2o9G0gy
CAD/CAM produces dentures with improved fit
Abstract
Objectives
Resin polymerisation shrinkage reduces the congruence of the denture base with denture-bearing tissues and thereby decreases the retention of conventionally fabricated dentures. CAD/CAM denture manufacturing is a subtractive process, and polymerisation shrinkage is not an issue anymore. Therefore, CAD/CAM dentures are assumed to show a higher denture base congruence than conventionally fabricated dentures. It has been the aim of this study to test this hypothesis.
Materials and methods
CAD/CAM dentures provided by four different manufacturers (AvaDent, Merz Dental, Whole You, Wieland/Ivoclar) were generated from ten different master casts. Ten conventional dentures (pack and press, long-term heat polymerisation) made from the same master casts served as control group. The master casts and all denture bases were scanned and matched digitally. The absolute incongruences were measured using a 2-mm mesh.
Results
Conventionally fabricated dentures showed a mean deviation of 0.105 mm, SD = 0.019 from the master cast. All CAD/CAM dentures showed lower mean incongruences. From all CAD/CAM dentures, AvaDent Digital Dentures showed the highest congruence with the master cast surface with a mean deviation of 0.058 mm, SD = 0.005. Wieland Digital Dentures showed a mean deviation of 0.068 mm, SD = 0.005, Whole You Nexteeth prostheses showed a mean deviation of 0.074 mm, SD = 0.011 and Baltic Denture System prostheses showed a mean deviation of 0.086 mm, SD = 0.012.
Conclusions
CAD/CAM produces dentures with better fit than conventional dentures.
Clinical Relevance
The present study explains the clinically observed enhanced retention and lower traumatic ulcer-frequency in CAD/CAM dentures.
https://ift.tt/2Rgm9JF
Zinc and silica are active components to efficiently treat in vitro simulated eroded dentin
Abstract
Objectives
Biomaterials for treating dentin hypersensitivity and dentin wear were evaluated to efficiently occlude the dentinal tubules and to increase dentin resistance to abrasion.
Materials and methods
Twenty-four dentin surfaces were treated with EDTA to expose dentinal tubules and were (1) non-brushed, (2) brushed with distilled water, or with pastes containing (3) monetite, (4) brushite, (5) Zn-monetite, (6) Zn-brushite, (7) Silica-brushite, and (8) NovaMin®. Topographical, nanomechanical, and chemical analysis were assessed on dentin surfaces (n = 3) after artificial saliva immersion for 24 h, and after citric acid challenge. Twenty-one further dentin specimens were created to evaluate dentin permeability after brushing, saliva storage, and acid application (n = 3). ANOVA, Student-Newman-Keuls (p < 0.05), and Student t test (p < 0.001) were used.
Results
Particles containing major proportion of silica attained intratubular occlusion by carbonate crystals (Raman carbonate peak heights 15.17 and 19.24 au; complex modulus 110 and 140 GPa, at intratubular dentin). When brushing with pastes containing higher proportion of silica or zinc, phosphate calcium compounds were encountered into tubules and over dentin surfaces (Raman intratubular phosphate peak heights 49 to 70 au, and at the intertubular dentin 78 to 92). The formed carbonated apatite and calcium phosphate layer were resistant to citric acid application. Zinc compounds drastically increased tubule occlusion, decreased dentin permeability (up to 30%), and augmented mechanical properties at the intertubular dentin (90–130 GPa); it was maintained after acid challenging.
Conclusions
Zinc-containing pastes occluded dentinal tubules and improved dentin mechanical properties.
Clinical relevance
Using zinc as an active component to treat eroded dentin is encouraged.
https://ift.tt/2BYZBVv
Influence of operator skill level on the clinical outcome of non-surgical periodontal treatment: a retrospective study
Abstract
Objectives
The aim of this study is to evaluate the effect of operators experience and skill on treatment results of initial non-surgical periodontal therapy.
Materials and methods
Initial periodontal treatment was carried out by either second-year periodontal residents (PR) or last year dental students (DS). From the treatment records of patients in each group, plaque and bleeding indices, and pocket depth (PD) at baseline and at re-evaluation were collected retrospectively on each tooth at six locations. Data were separated according to tooth type, area, and probing depth categories, sub-grouped to 1–3, 4–5, and ≥ 6 mm.
Results
Fifty and 49 records of DS and PR patients, accordingly, were analyzed. Initial periodontal treatment improved patient compliance in both groups and reduced signs of inflammation with significantly superior results in the PR group. Significant change in percentage of pockets was recorded in each category. The increase in percentage of sites with PD 1–3 mm and decrease in percentage of PD ≥ 6 mm pockets was significantly (p ≤ 0.001) superior in patients treated by PR. Percentage of 4–5 mm pockets was significantly reduced in both groups (p ≤ 0.01), with a significantly greater reduction in the mandibular molar and anterior teeth in the PR group.
Conclusions
Experience and skill significantly affect the outcome of non-surgical periodontal therapy, with more positive improvement in patient compliance and clinical parameters when performed by a more qualified operator.
Clinical relevance
Improvement of operator skills may decrease the number of residual pockets and increase patient compliance following non-surgical periodontal treatment.
https://ift.tt/2C1fMGa
Study of salivary and serum vaspin and total antioxidants in anorexia nervosa
Abstract
Objectives
Patients with anorexia nervosa (AN) are primarily at high risk of multiple somatic complications, including oral diseases. In recent years, a number of new molecules that may play a potentially important role in AN progress and prognosis have been identified in saliva, but their exact roles are still poorly understood. Two such group of substances are antioxidants and vaspin. The purpose of this observational, cross-sectional study was to measure both the salivary and serum total antioxidant status (TAS), and vaspin (VASP) concentrations of patients with AN in comparison to an average population.
Material and methods
Ninety subjects participated (30 patients with AN, 60 matched healthy control subjects). A clinical examination was made, and blood and salivary samples were taken during the acute stage of AN (BMI < 15 kg/m2) in the first week of hospitalization. Enzyme immunoassay (ELISA) suitable for measuring VASP and colorimetric assay for TAS were used.
Results
Anorexic patients had significant reductions in salivary flow, TAS, and an elevation in VASP levels in their saliva and serum. Significant correlations between TAS, VASP, salivary flow, and nutritional status were detected.
Conclusion
Determination of TAS and VASP in combined biological material confirmed that saliva might be a reliable non-invasive source of information for potent nutritional biomarkers.
Clinical relevance
Our findings suggest that VASP cannot be excluded, as its increased concentration in saliva is an adaptive mechanism in reduced TAS, one resulting from diminished salivary secretion. It is therefore worth conducting further research aimed at recognizing the role of TAS and VASP in the saliva of underweight patients.
https://ift.tt/2BYlXuF
APRT deficiency: the need for early diagnosis
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder which leads to accumulation of poorly soluble 2,8-dihydroxyadenine in kidneys resulting in nephrolithiasis as well as chronic kidney disease from crystal nephropathy. This report describes a 55-year-old previously fit man who presented with shortness of breath and the investigative pathway that eventually led to a diagnosis of APRT deficiency. Early diagnosis has aided in timely institution of allopurinol, thereby improving his renal function and possibility of weaning off renal replacement therapy. Genetic testing has enabled early identification of other family members at risk and prevention of renal failure by commencing xanthine oxidoreductase (XOR) inhibitors. The issues surrounding kidney donation by a member of this family are also discussed. This case represents the importance of awareness and recognition of the signs and symptoms of this rare condition, complications of which can be easily prevented by early institution of XOR inhibitor therapy.
https://ift.tt/2EIgmep
Congenital hypoplasia of depressor anguli oris muscle (CHDAOM): an uncommon cause of asymmetric crying facies in childhood
Description
A 2-year-old developmentally normal girl presented to us with a history of deviation of angle of mouth to right only during crying, persisting from neonatal period. She was born at term by normal vaginal delivery to a primigravida mother with a birth weight of 2.2 kg and smooth perinatal transition. Parents noticed asymmetry of face from neonatal period visible only during crying, which disappeared when she was consoled, without any drooling, regurgitation of feeds or poor sucking. There is no history suggestive of any other neurological or systemic abnormality in index case or in family.
Local examination revealed thinning of lower lip near left angle of mouth on palpation. There was no facial asymmetry while the child was calm (figure 1A), however, on crying there was deviation of the angle of mouth downwards and towards right side (figure 1B). There was no evidence of hypoplasia...
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Brazilian experience with atopy patch tests for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis
The aim of this study was to evaluate the positivity rates of atopy patch tests for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis in patients with respiratory diseases such as ast...
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The Plasma NAD+ Metabolome Is Dysregulated in “Normal” Aging
Rejuvenation Research, Ahead of Print.
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A paediatric case of cutaneous larva migrans acquired in the UK
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2q8QRIM
A paediatric case of cutaneous larva migrans acquired in the UK
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2q8QRIM
Sturz bei der Gartenarbeit mit asymptomatischer penetrierender Halsverletzung
Laryngo-Rhino-Otol
DOI: 10.1055/a-0756-9714
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Aerobe Belastung bei Mundatmung verändert die Wahrnehmungsschwelle für H2S nicht
Laryngo-Rhino-Otol
DOI: 10.1055/a-0753-0367
Hintergrund Während aerober körperlicher Belastung verschlechterte sich in einer früheren Studie bei Nasenatmung die Wahrnehmungsschwelle für H2S. Die Ursache blieb offen. Es soll in dieser Studie geprüft werden, wie sich die Wahrnehmungsschwelle bei alleiniger Mundatmung verändert. Material und Methoden Während einer Ruhephase einer aeroben Belastung und nachfolgender Erholungsphase wurden unterschiedliche H2S-Konzentrationen mittels eines Fluss-Olfaktometers im staircase Verfahren inspirationssynchron intranasal appliziert. Die fehlende Nasenatmung wurde online und offline objektiviert. Es wurden die Reaktionszeiten bestimmt. Parallel sind verschiedene Vitalparameter gemessen worden. Ergebnisse Die passiven Wahrnehmungsschwellen zwischen den Belastungs- und der Erholungsphasen differierten nicht. In der Ruhephase war die H2S Schwelle am höchsten. Die Reaktionszeiten waren in den drei Versuchsphasen nicht different. Schlussfolgerung Eine etwa halbstündige aerobe Belastung veränderte die passive Riechschwelle für H2S bei Mundatmung im Vergleich zur nachfolgenden Erholungsphase nicht. Die hohe Riechschwelle in der Ruhephase wird mit anfänglichen Anpassungsschwierigkeiten an die Versuchsbedingungen erklärt.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Association between atopic dermatitis, depression and suicidal ideation: A systematic review and meta-analysis
This meta-analysis found that atopic dermatitis was associated with increased odds of clinical depression, depressive symptoms, anti-depressant use, suicidality and parental depression. Presence of depression and suicidality should be incorporated into clinical decision-making of atopic dermatitis patients.
https://ift.tt/2q8UVc7
Treatment of primary non-metastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival
Volume-outcome relationships in cancer care have motivated calls for regionalization of care. We demonstrate that high-volume academic facilities achieve improved outcomes for melanoma patients. Increased utilization of those aspects of these centers that increase patient survival, whether by regionalization of care or dissemination of these practices, may improve patient outcomes.
https://ift.tt/2R5u2RQ
Multi-disciplinary evaluation of a 5-month-old with hypertrophic cardiomyopathy related to a functional adrenocortical tumor
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2yDfTVt
Long-term follow-up of gonadal dysfunction in morbidly obese adolescent boys after bariatric surgery
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2JerfmK
Carotid intima media thickness and associations with serum osteoprotegerin and s-RANKL in children and adolescents with type 1 diabetes mellitus with increased risk for endothelial dysfunction
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2yyWbKh
Adolescents with premenstrual syndrome: not only what you eat but also how you eat matters!
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2JdcCA2
Perspectives on Dexmedetomidine Use for Neurosurgical Patients
The α2-adrenergic receptor agonist dexmedetomidine has sedative, anxiolytic, analgesic, and sympatholytic effects. The potential advantages of neuroprotection, minimal impact on neuronal function, stable hemodynamics, opioid and anesthesia sparing effects, and minimal respiratory depression during awake procedures render it an effective anesthetic adjuvant in various neurosurgical settings. However, both the benefits and drawbacks of the use dexmedetomidine in neuroanesthesia should be considered. This narrative review will summarize the applications of dexmedetomidine in various neurosurgical settings, highlighting evidence regarding both its common and controversial uses. Supported by Beijing Municipal Administration of Hospitals' Youth Program (QML20160503) and by the National Natural Science Foundation of China (Grant No.1701038). The authors have no funding or conflicts of interest to disclose. Address correspondence to: Adrian W. Gelb, MB, ChB, Department of Anesthesia & Perioperative Care, University of California San Francisco, 500 Parnassus Ave., MUE 408, San Francisco, CA 94143 (e-mail: adrian.gelb@ucsf.edu). Received March 27, 2018 Accepted September 6, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved
https://ift.tt/2CZG0JS
https://ift.tt/2CZG0JS
A novel hydroxyapatite-binding antimicrobial peptide against oral biofilms
Abstract
Objectives
Novel synthetic antimicrobial peptides which consist of a new immunomodulatory peptide 1018 and two different modifications with hydroxyapatite-binding affinity were developed. We compared the effect(s) of these peptides against oral plaque biofilms and measured their effectiveness in killing biofilm microbes and in reducing biofilm volume.
Materials and methods
The high affinity hydroxyapatite (HA)-binding peptide 1018 (SHABP), the mild affinity HA-binding peptide 1018 (MHABP), and peptide 1018 without additional amino acid sequence (peptide 1018) were synthesized. Oral multispecies biofilms were grown anaerobically for 3 days. The biofilms were exposed to three peptides at two different concentrations (0.65 and 3.25 μmol/L) for 24, 48, and 72 h. The biofilms were also treated for 3 or 9 min with the peptides (3.25 μmol/L). The percentage of killed biofilm bacteria and biofilm volume were determined by using LIVE/DEAD viability staining and confocal laser scanning microscopy.
Results
SHABP was superior to MHABP and peptide 1018 in its killing efficacy of the pre-formed biofilms, especially at concentration of 3.25 μmol/L (p < 0.05). SHABP performed also better than MHABP and peptide 1018 in reducing the overall biofilm volume at both concentrations (p < 0.05). During the 3 days of long-term exposure, MHABP and peptide 1080 killed more bacteria in the top half of the biofilms, compared to bottom half. SHABP killed more bacteria in the bottom half (39%) of the biofilms than in the top half (29%) at day 1 (p < 0.05), whereas more bacteria were killed in the upper layers on days 2 and 3. SHABP killed a much higher percentage of plaque biofilm bacteria when used on 3-day-old biofilms for one or three times for 3 min than MHABP or peptide 1018 at high concentration (p < 0.05).
Conclusions
The modified peptide 1018 with high HA-binding affinity had higher antimicrobial activity against biofilm microbes and reduced biofilm volume more than the other peptides tested.
Clinical relevance
Modified peptide 1018 with high hydroxyapatite-binding affinity is a promising agent for use in oral antibiofilm strategies in the future.
https://ift.tt/2PkKDnm
Androgen-dependent immune modulation in parasitic infection
Abstract
Parasitic infections modulate the immune system of the host, resulting in either immune tolerance or the induction of pro-inflammatory defense mechanisms against the pathogen. In both cases, sex hormones are involved in the regulation of the immune response, as they are present in the systemic circulation and can act on a wide variety of cell types, including immune cells. Men and women have a different milieu of sex hormones, and these hormones play a role in determining immune responses to parasitic infections. Men, who have higher plasma levels of androgens than women, are generally more susceptible to parasitic infections. Many immune cells express the androgen receptor (AR), and the immunologic functions of these cells can be modulated by androgens. In this review, we will highlight the immune cell types that are sensitive to male steroid hormones and describe their roles during three parasitic diseases, amebiasis, leishmaniasis, and helminthiasis.
https://ift.tt/2PMCFR7
A Phase Ib, Open‐Label Study of Dalantercept, an Activin Receptor‐Like Kinase 1 Ligand Trap, plus Sorafenib in Advanced Hepatocellular Carcinoma
Lessons Learned. Patients with hepatocellular carcinoma (HCC) often have limited therapeutic responses to the vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor sorafenib, which is standard of care in advanced HCC. Targeting the activin receptor‐like kinase 1 (ALK1) and VEGF pathways simultaneously by combining the ALK1 ligand trap dalantercept with sorafenib may result in more effective angiogenic blockade and delay tumor progression in patients with advanced HCC.Although the combination was generally well tolerated, there was no additive antitumor activity with the combination of dalantercept plus sorafenib in patients with advanced HCC. No complete or partial responses were observed, and overall survival ranged from 1.9 to 23.3 months.These results suggest that, in this patient population, further development of the possible limited benefits of combination therapy with dalantercept plus sorafenib is not warranted.Background.Targeting the activin receptor‐like kinase 1 (ALK1) and vascular endothelial growth factor (VEGF) pathways may result in more effective angiogenic blockade in patients with hepatocellular carcinoma (HCC).Methods.In this phase Ib study, patients with advanced HCC were enrolled to dose‐escalation cohorts, starting at 0.6 mg/kg dalantercept subcutaneously every 3 weeks plus 400 mg sorafenib orally once daily, or to a dose expansion cohort. The primary objective was to determine the safety and tolerability and the dalantercept maximum tolerated dose (MTD) level. Secondary objectives were to assess the preliminary activity and the association of pharmacodynamic biomarkers with tumor response.Results.A total of 21 patients were enrolled in the study. Five patients received 0.6 mg/kg dalantercept in the first dose escalation cohort. Based on the initial safety results, the dose level was de‐escalated to 0.4 mg/kg in the second cohort (n = 6). The MTD was identified as 0.4 mg/kg and used for the dose expansion cohort (n = 10). At this dose level, the combination was generally well tolerated. Overall survival ranged from 1.9 to 23.3 months, and the best overall response was stable disease.Conclusion.The addition of dalantercept to sorafenib did not improve antitumor activity in patients with HCC. The dalantercept program in this population was discontinued.
https://ift.tt/2NZp47q
A Case of Metastatic Biliary Tract Cancer Diagnosed Through Identification of an IDH1 Mutation
AbstractThe role of next‐generation sequencing from either circulating tumor DNA (ctDNA) or formalin‐fixed paraffin‐embedded (FFPE) tissue to identify therapeutically targetable genomic alterations has been well established. Genomic profiling may also have untapped potential as a diagnostic tool in cases in which traditional immunohistochemistry assays cannot establish a clear histologic diagnosis. Expanding the number of histologies with unique genomic signatures or alterations is critical in this setting. Here we describe a case of a 73‐year‐old man who presented with a duodenal mass extending to the liver and peritoneal carcinomatosis, initially thought to be metastatic duodenal adenocarcinoma. Subsequent genomic profiling of ctDNA and FFPE tissue revealed an IDH1 mutation, which is rare in duodenal adenocarcinoma but common in biliary tract cancers (BTCs). This finding prompted a second biopsy, which revealed pancreaticobiliary adenocarcinoma. The clinical significance of IDH mutations in terms of their molecular specificity to certain histologies is reviewed. Recent and ongoing investigations into IDH inhibitors for advanced and metastatic BTCs are also discussed.Key Points. This case demonstrates a novel use of next‐generation sequencing as a diagnostic tool to modify a primary cancer diagnosis, leading to important changes in therapy.Isocitrate dehydrogenase mutations are rare in solid organ malignancies and are highly specific for biliary tract cancers (BTCs) within the gastrointestinal malignancies.IDH inhibition is an active area of investigation in metastatic BTCs; early results have been promising.
https://ift.tt/2OFIvHz
Phase Angle and the Diagnosis of Impending Death in Patients with Advanced Cancer: Preliminary Findings
AbstractBackground.Phase angle is a prognostic factor in patients with months of survival, but its accuracy has not been examined in patients with weeks/days of survival. We determined the association between phase angle and survival in patients with advanced cancer admitted to an acute palliative care unit (APCU).Subjects, Materials, and Methods.We prospectively assessed phase angle in consecutive patients with advanced cancer admitted to our APCU. We conducted univariate and multivariate survival analyses adjusting for established prognostic factors. Post hoc subgroup analyses examined patients with and without edema.Results.Among 204 patients, the median overall survival was 10 days (95% confidence interval [CI] 8–11 days). Seventy‐four (36%) did not have edema. The median phase angle was 3.7° for the entire cohort, 3.9° for the nonedematous subgroup and 3.6° for the edematous subgroup. In univariate analysis, a low phase angle was associated with decreased survival for the entire cohort (≤3° vs. >3°, median survival 7 vs. 10 days, p = .045) and the nonedematous subgroup (5 vs. 18 days, p < .001) but not the edematous subgroup (9 vs. 9 days, p = .84). In multivariate analysis, phase angle did not reach significance for the entire cohort but remained significant in the nonedematous subgroup (hazard ratio 2.46, 95% CI 1.14–5.31, p < .001). Specifically, phase angle ≤3° had an accuracy of 86% (95% CI 77%–93%) for 3‐day survival in patients without edema.Conclusion.Phase angle had limited prognostic utility in unselected APCU patients but was significant in the nonedematous subgroup. Further studies are required to confirm these preliminary findings.Implications for Practice.In this prospective study involving 204 patients with advanced cancer, phase angle as measured by bioelectric impedance analysis was a significant predictor of mortality independent of known prognostic factors in patients without edema but not patients with edema. Among patients without edema, a phase angle ≤3° had an accuracy of 86% for 3‐day survival, which may inform the diagnosis of impending death and potentially end‐of‐life decision making.
https://ift.tt/2O4YKsE
A stereotaxic MRI template set of mouse brain with fine sub-anatomical delineations: Application to MEMRI studies of 5XFAD mice
Publication date: Available online 22 October 2018
Source: Magnetic Resonance Imaging
Author(s): Binbin Nie, Di Wu, Shengxiang Liang, Hua Liu, Xi Sun, Panlong Li, Qi Huang, Tianhao Zhang, Ting Feng, Songtao Ye, Zhijun Zhang, Baoci Shan
Abstract
Purpose
Manganese-enhanced magnetic resonance imaging (MEMRI) can help us trace the active neurons and neuronal pathway in transgenic mouse AD model. 5XFAD has been widespread accepted as a valuable model system for studying brain dysfunction progresses in the courses of AD. To further understand the development of AD at early stages, an effective and objective data analysis platform for MEMRI studies should be constructed.
Materials and methods
A set of stereotaxic templates of mouse brain in Paxinos and Franklin space, "the Institute of High Energy Physics Mouse Template", or IMT for short, was constructed by iteratively registration and averaging. An atlas image was reconstructed from the Paxinos and Franklin atlas figures and each sub-anatomical segmentation was assigning a unique integer. An analysis SPM plug-in toolbox was further created, that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and statistical analysis for MEMRI scans.
Results
The IMT comprised a T2WI template image, a MEMRI template image, intracranial tissue segmentations, and accompany with a digital mouse brain atlas image, in which 707 sub-anatomical brain regions are delineated. Data analyses were performed on groups of developing 5XFAD mice to demonstrate the usage of IMT, and the results shows that abnormal neuronal activity occurs at early stage in 5XFAD mice.
Conclusion
We have constructed a stereotaxic template set of mouse brain named IMT with fine delineations of sub-anatomical structures, which is compatible with SPM. It will give a widely range of researchers a standardized coordinate system for localization of any mouse brain related data.
https://ift.tt/2Jgj5KI
Lésions auto-provoquées dans un contexte d’hidradénite suppurée : un cas de pathomimicrie
Publication date: Available online 22 October 2018
Source: Annales de Dermatologie et de Vénéréologie
Author(s): A. Marzouki-Zerouali, A. Schoeffler, A.-L. Liegeon, P. Le Vaou, F. Truchetet
Résumé
Introduction
Les troubles factices constituent un domaine complexe de la pathologie. Si le diagnostic est souvent évoqué, il est difficile à poser et la thérapeutique est délicate. La pathomimie cutanée est une expression somatique cutanée d'un désordre psychiatrique souvent grave, provoquée dans un état de conscience claire par le malade lui-même sur son revêtement cutanéomuqueux mais dont la motivation est inconsciente, sans recherche de bénéfices secondaires ; elle se distingue donc de la simulation. Les pathomimicries représentent une entité particulière proche de la pathomimie : il s'agit de l'induction de poussées d'une maladie connue déclenchées par l'exposition volontaire à l'agent responsable. Nous rapportons un cas de pathomimicrie dans un contexte d'hidradénite suppurée.
Observation
Une adolescente ayant pour antécédents principaux une obésité de grade 2 et un épisode d'abcès pubien était vue en consultation pour des lésions axillaires. Elle arrivait dans un état d'incurie, méfiante, agressive et refusait de se déshabiller. Après mise en confiance, l'examen clinique montrait de larges ulcérations à distance des plis sur les zones axillaires, à contours géographiques et à fond propre et bourgeonnant, associées à des lésions typiques d'hidradénite suppurée de grade 2 (Hurley), avec des pertuis purulents et des cicatrices en corde des plis inguinaux. Une hospitalisation était proposée et l'évolution était favorable sous antibiothérapie par doxycycline et soins locaux par pansements alginates et hydrocellulaires. L'avis psychiatrique concluait à une faille narcissique ancienne à type de dysmorphophobie probablement réactionnelle à un harcèlement scolaire récurrent depuis l'enfance. Sous couvert d'une relation de confiance difficilement établie, la patiente reconnaissait la manipulation de ses lésions. Devant les données anamnestiques, cliniques, la négativité du bilan paraclinique, le diagnostic de pathomimicrie était retenu.
Discussion
Plusieurs cas de pathomimicrie de dermatoses (auto-entretien d'un ulcère de cause connue, contact avec un allergène identifié dans l'eczéma ou reprise d'un médicament incriminé dans une toxidermie) ou de maladies systémiques (injections d'insuline chez un patient diabétique) ont été rapportés. Ce cas est le premier décrit, à notre connaissance, de pathomimicrie dans le cadre d'une hidradénite suppurée. Sur le plan thérapeutique, le suivi doit être multidisciplinaire. Il faut éviter l'affrontement avec le patient et ne pas forcer son aveu, ce qui risquerait d'induire une décompensation psychiatrique grave. Une attitude rassurante permet le recours au psychiatre une fois la confiance durablement établie. Le dermatologue a donc une place primordiale dans la prise en charge de ces patients.
Summary
Background
Factitious disorders constitute a complex pathology for the dermatologist. Although a diagnosis is often indicated, it is difficult to confirm and treatment is complicated. Dermatitis artefacta is the somatic expression of an often serious psychiatric disorder consciously created by patients on their own cutaneous-mucosal surfaces but the motivation is unconscious and no secondary benefits are sought (in contrast to simulation). Pathomimicry represent a specific entity: the provocation of outbreaks of a known disease, triggered by voluntary exposure to a causative agent. Herein we report on a case of pathomimicry in a context of hidradenitis suppurativa.
Patients and methods
A teenage girl whose main previous medical history consisted of grade-2 obesity and an episode of pubic abscess was seen at our clinic for axillary lesions. She presented in a state of negligence, was suspicious and aggressive, and refused to undress. After gaining her trust, clinical examination revealed prominent ulcerations (each with a granulated base) at a distance from the folds in the axillary areas, as well as typical hidradenitis lesions of Hurley Grade 2 with purulent openings and rope-like scars from the inguinal folds. Hospitalization was recommended and a positive outcome was achieved under antibiotic therapy with doxycycline, topical alginate and hydrocellular dressings. A psychiatric evaluation concluded that the patient was presenting dysmorphophobic narcissistic weakness, probably in reaction to recurrent harassment at school since childhood. Once she developed trust with us, which was difficult to establish, the patient admitted to having caused the lesions herself. Given the history and clinical data, as well as the negative laboratory tests, a diagnosis of pathomimicry was made.
Discussion
Several cases of dermatological pathomimicry (sustainment by the patient of an ulcer with a known cause, contact with an allergen found in eczema, or renewed use of a medication implicated in toxiderma) or systemic disease (insulin injection in a diabetic patient) have been reported. To the best of our knowledge, this is the first description of pathomimicry associated with hidradenitis suppurativa. Regarding therapy, aftercare should be multidisciplinary. Confessions should not be forced and confrontations, which risk serious psychiatric collapse, should be avoided. A reassuring attitude enables psychiatry to be applied once trust has been sustainably established, hence the crucial role of the dermatologist.
https://ift.tt/2S9uDU9
Sinking Skin Flap Syndrome: Phenomenon of Neurological Deterioration after Decompressive Craniectomy
Sinking skin flap syndrome is rare phenomenon that occurs in patients with large craniectomies. Alteration in normal anatomy and pathophysiology can result in wide variety of symptoms including altered mental status, hemodynamic instability, and dysautonomias. Management is largely conservative. We here present a case of a patient with large craniectomy who was admitted to our hospital with pneumonia. Later on, he developed worsening mental status and CT head revealed sinking skin flap with significant midline shift. This is a very rare case of neurological deterioration after craniectomies, commonly known as sinking skin flap syndrome. To our knowledge, only few cases have been reported so far.
https://ift.tt/2CBjzK9
Adjuvant De-Escalated Radiation + Adjuvant Nivolumab for Intermediate-High Risk P16+ Oropharynx Cancer
Conditions: Carcinoma, Squamous Cell of Head and Neck; Oropharynx Squamous Cell Carcinoma
Interventions: Drug: Nivolumab Injection; Radiation: Radiotherapy (RT)
Sponsors: Robert Ferris; Bristol-Myers Squibb
Not yet recruiting
https://ift.tt/2z0kzUn
Interventions: Drug: Nivolumab Injection; Radiation: Radiotherapy (RT)
Sponsors: Robert Ferris; Bristol-Myers Squibb
Not yet recruiting
https://ift.tt/2z0kzUn
Adjuvant De-Escalated Radiation + Adjuvant Nivolumab for Intermediate-High Risk P16+ Oropharynx Cancer
Conditions: Carcinoma, Squamous Cell of Head and Neck; Oropharynx Squamous Cell Carcinoma
Interventions: Drug: Nivolumab Injection; Radiation: Radiotherapy (RT)
Sponsors: Robert Ferris; Bristol-Myers Squibb
Not yet recruiting
https://ift.tt/2z0kzUn
Interventions: Drug: Nivolumab Injection; Radiation: Radiotherapy (RT)
Sponsors: Robert Ferris; Bristol-Myers Squibb
Not yet recruiting
https://ift.tt/2z0kzUn
IgG Fc N-glycosylation: Alterations in neurologic diseases and potential therapeutic target?
Publication date: Available online 22 October 2018
Source: Journal of Autoimmunity
Author(s): Yannick Kronimus, Richard Dodel, Sebastian P. Galuska, Sascha Neumann
Abstract
Immunoglobulin G (IgG) is the most abundant antibody subclass of the human circulatory system and has important functions in the adaptive immune response. On the one hand, recognition and neutralization of antigens is mediated by the fab fragment, and on the other hand, processes such as phagocytosis, complement activation and inflammatory reactions are triggered by the Fc fragment. Here, the composition of conserved N-glycans attached to asparagine 297 of the IgG CH2 domain is a major critical factor that particularly modulates the effector functions of IgG. Additional attachments of fucoses, galactoses, N-acetylglucosamines, and sialic acids have been identified as factors that influence the affinity to a wide range of complement proteins and receptors and, thus, secondarily induce the secretion of pro- and anti-inflammatory cytokines. Consequently, alterations in the IgG Fc N-glycosylation pattern can provoke disruptions in the immunological state and are accompanied by various diseases, although the involvement of changed IgG glycosylation in disease outbreaks remains unknown. In addition to many autoimmune diseases, which have already been extensively reviewed, there are a number of further disorders related to altered IgG glycosylation patterns. In the present review, we focus on neurologic diseases, as in the last few years, an increasing number of studies have been published in this field. Due to the absence of reliable early biomarkers as well as therapeutic options in many cases, such analyses are of great interest and reveal possible future approaches.
https://ift.tt/2PfLlSX
Hyaluronic acid gel based on CPM® technology with and without lidocaine: Is there a difference?
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2D1BZ7P
Effects of isotretinoin on the hair cycle
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2PU7oMl
Autologous pure platelet‐rich plasma injections for facial skin rejuvenation: Biometric instrumental evaluations and patient‐reported outcomes to support antiaging effects
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2D2qJYX
Hyaluronic acid gel based on CPM® technology with and without lidocaine: Is there a difference?
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2D1BZ7P
Effects of isotretinoin on the hair cycle
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2PU7oMl
Autologous pure platelet‐rich plasma injections for facial skin rejuvenation: Biometric instrumental evaluations and patient‐reported outcomes to support antiaging effects
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2D2qJYX
The brain-structural correlates of mathematical expertise
Publication date: Available online 22 October 2018
Source: Cortex
Author(s): Tudor Popescu, Elie Sader, Marie Schaer, Adam Thomas, Devin B. Terhune, Ann Dowker, Rogier B. Mars, Roi Cohen Kadosh
Abstract
Studies in several domains of expertise have established that experience-dependent plasticity brings about both functional and anatomical changes. However, little is known about how such changes come to shape the brain in the case of expertise acquired by professional mathematicians. Here, we aimed to identify cognitive and brain-structural (grey and white matter) characteristics of mathematicians as compared to non-mathematicians. Mathematicians and non-mathematician academics from the University of Oxford underwent structural and diffusion MRI scans, and were tested on a cognitive battery assessing working memory, attention, IQ, numerical and social skills. At the behavioural level, mathematical expertise was associated with better performance in domain-general and domain-specific dimensions. At the grey matter level, in a whole-brain analysis, behavioural performance correlated with grey matter density in left superior frontal gyrus – positively for mathematicians but negatively for non-mathematicians; in a region of interest analysis, we found in mathematicians greater grey matter density in the right superior parietal lobule but lower grey matter density in the right intraparietal sulcus and the left inferior frontal gyrus. In terms of white matter, there were no significant group differences in fractional anisotropy or mean diffusivity. These results reveal new insights into the relationship between mathematical expertise and grey matter metrics in brain regions previously implicated in numerical cognition, as well as regions that received less attention in this field so far. Further studies, based on longitudinal designs and cognitive training, could examine the conjecture that such cross-sectional findings arise from a bidirectional link between experience and structural brain changes that is itself subject to change across the lifespan.
https://ift.tt/2PkiBs8
Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck
Publication date: December 2018
Source: Oral Oncology, Volume 87
Author(s): Gregory T. Wolf, William Winter, Emily Bellile, Ariane Nguyen, C.R. Donnelly, Jonathan B. McHugh, Dafydd Thomas, Lahin Amlani, Laura Rozek, Yu L. Lei, the Head and Neck SPORE Program
Abstract
Introduction
Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavior. To determine if such changes relate to prognosis or host immune response, expression of these markers and correlations with clinical characteristics, histologic worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TIL) and survival were assessed.
Methods
Immunohistologic expression of markers was determined in tissue microarrays from 274 previously untreated HNSCC patients. Expression was correlated with levels of TILs in microcores and WPOI in biopsy specimens. Correlations were assessed by Kruskal-Wallis testing and Spearman correlation coefficients where appropriate. Overall and relapse-free survival were analyzed with Cox proportional hazards models. Median follow up was 60.0 months.
Results
Loss of E-cadherin expression was significantly associated with low or absent SOX2 expression (R = 0.433, p < 0.0001). SOX2 expression and low grade WPOI were significantly associated with favorable overall (OS) and relapse free (RFS) survival in multivariable analysis. E-cadherin expression did not correlate with TILs, however WPOI score correlated indirectly with CD4, CD8, and FoxP3 levels. When grouped by primary treatment, lower grades (1, 2) of WPOI predicted improved RFS and OS in patients treated with primary surgery but not for patients treated with chemoradiation.
Conclusion
The findings suggest that SOX2 expression and WPOI are significant prognostic factors and that WPOI correlates with decreased T cell infiltration. The combination of markers and TILs might be useful in selecting patients for primary surgery.
https://ift.tt/2PQknyu
Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults
Publication date: December 2018
Source: Oral Oncology, Volume 87
Author(s): Mauricio E. Gamez, Ryan Kraus, Michael L. Hinni, Eric J. Moore, Daniel J. Ma, Stephen J. Ko, Jean Claude M. Rwigema, Lisa A. McGee, Michele Y. Halyard, Matthew R. Buras, Robert L. Foote, Samir H. Patel
Abstract
Objectives
The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger.
Materials and methods
We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980–2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts.
Results
Median patient age was 35 years (range, 19–40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001).
Conclusion
Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.
https://ift.tt/2D3RVGy
Repeated SBRT for in- and out-of-field recurrences in the liver
Abstract
Purpose
To evaluate the feasibility and toxicity profile of repeated stereotactic body radiotherapy (SBRT) for recurrent primary or secondary liver tumors.
Methods
Consecutive patients with primary (hepatocellular carcinoma [HCC] or cholangiocarcinoma [CCC]) or secondary liver cancer (LM), with intrahepatic recurrence or progression after SBRT, underwent re-SBRT in 3 to 12 fractions with a median time of 15 (range 2–66) months between treatments.
Results
In all, 24 patients which were previously treated with SBRT (30 lesions) were retreated with SBRT for "in- and out-of-field" recurrences (2nd SBRT: n = 28, 3rd SBRT: n = 2). The median follow-up after re-irradiation was 14 months. The median prescribed dose for the first SBRT was 46.5 (range 33–66 Gy, EQD210 = 70.5) Gy and 48 (range 27–66 Gy, EQD210 = 71) Gy for the re-SBRT. The median mean liver dose (Dmean, liver) was 6 Gy (range 1–25, EQD22 = 7 Gy) for the first SBRT and 10 Gy (range 1–63 Gy, EQD22 = 9 Gy) for the re-SBRT. Of the 30 re-irradiated lesions 6 were re-irradiated in-field resulting in a median EQD22, maximum of 359 (range 120–500) Gy for both treatments, with an α/β = 2 to account for liver parenchyma. Treatment was well tolerated. Two patients with stent placement before SBRT developed cholangitis 4 and 14 months after re-SBRT. There were no elevations of the serum liver parameters after re-SBRT. One patient developed a grade 3 gastrointestinal bleeding. There was no radiation induced liver disease (RILD) observed.
Conclusions
Repeated liver SBRT is feasible, without excessive liver toxicity, when there is no considerable overlapping with pre-irradiated portions of the stomach or bowel and enough time for the liver to regenerate.
https://ift.tt/2PjTupx
SBRT planning for spinal metastasis: indications from a large multicentric study
Abstract
Background
The dosimetric variability in spine stereotactic body radiation therapy (SBRT) planning was investigated in a large number of centres to identify crowd knowledge-based solutions.
Methods
Two spinal cases were planned by 48 planners (38 centres). The required prescription dose (PD) was 3 × 10 Gy and the planning target volume (PTV) coverage request was: VPD > 90% (minimum request: VPD > 80%). The dose constraints were: planning risk volume (PRV) spinal cord: V18Gy < 0.35 cm3, V21.9 Gy < 0.03 cm3; oesophagus: V17.7 Gy < 5 cm3, V25.2 Gy < 0.03 cm3. Planners who did not fulfil the protocol requirements were asked to re-optimize the plans, using the results of planners with the same technology. Statistical analysis was performed to assess correlations between dosimetric results and planning parameters. A quality index (QI) was defined for scoring plans.
Results
In all, 12.5% of plans did not meet the protocol requirements. After re-optimization, 98% of plans fulfilled the constraints, showing the positive impact of knowledge sharing. Statistical analysis showed a significant correlation (p < 0.05) between the homogeneity index (HI) and PTV coverage for both cases, while the correlation between HI and spinal cord sparing was significant only for the single dorsal PTV case. Moreover, the multileaf collimator leaf thickness correlated with the spinal cord sparing. Planners using comparable delivery/planning system techniques produced different QI, highlighting the impact of the planner's skills in the optimization process.
Conclusion
Both the technology and the planner's skills are fundamentally important in spine SBRT planning optimization. Knowledge sharing helped to follow the plan objectives.
https://ift.tt/2EG12Pd
Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma
Publication date: Available online 23 October 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Sumita Khatri, Wendy Moore, Peter G. Gibson, Richard Leigh, Arnaud Bourdin, Jorge Maspero, Manuel Barros, Roland Buhl, Peter Howarth, Frank C. Albers, Eric S. Bradford, Martyn Gilson, Robert G. Price, Steven W. Yancey, Hector Ortega
Abstract
Background
Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials ≤12 months' duration; however, long-term data are lacking.
Objective
To evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA).
Methods
COLUMBA (NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (NCT01000506). Patients received 100mg subcutaneous mepolizumab every 4 weeks plus standard of care, until a protocol-defined stopping criterion was met. Safety endpoints included frequency of adverse events (AEs), serious AEs (SAEs), and AEs of special interest. Efficacy endpoints included annualized exacerbation rate, changes from baseline in Asthma Control Questionnaire (ACQ)-5 score, and blood eosinophil counts. Immunogenicity was also assessed.
Results
Overall, 347 patients were enrolled for an average of 3.5yrs (maximum: 4.5yrs; total exposure: 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate: 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced ≥1 on-treatment SAE; there were 6 deaths, none assessed as related to mepolizumab. For patients with ≥156 weeks enrollment, the exacerbation rate was 0.74 events/year (Weeks 0–156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first post-baseline assessment, the mean ACQ-5 score was reduced by 0.47 points and blood eosinophil counts by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies.
Conclusion
These data support the long-term safety and efficacy of mepolizumab in patients with SEA.
Clinical Implications
Following long-term use in patients with severe eosinophilic asthma, mepolizumab maintains clinical effectiveness and continues to demonstrate a favorable safety profile, with no evidence of inducing neutralizing antibodies.
Graphical abstract
https://ift.tt/2CAuCDl
Advances in Atopic Dermatitis in 2017
Publication date: Available online 22 October 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Katie Kennedy, Jennifer Heimall, Jonathan M. Spergel
Synopsis
This review encompasses relevant scientific and clinical advances in atopic dermatitis published in 2017. These include articles from the Journal as well as other prominent publications that have contributed to the emerging field of the microenvironment of the skin and molecular patterns guiding biologic treatment strategies. The most commonly questioned and explored themes of the year included the impact of the microbiome on atopic dermatitis development as well as cell signaling and severity of symptoms. Topics also included the description of patient specific molecular endotypes within the larger atopic dermatitis population. All of these factors will create potential opportunities to guide personalized therapy with the broadening array of topical and systemic interventions currently available, as well as provide new insights to guide development of novel, molecularly targeted therapeutics. With recent FDA approval of the first wave of new, targeted therapies for atopic dermatitis (AD), additional information exploring the safety profiles and long-term effects of these medications was also at the forefront of 2017.
https://ift.tt/2AmHQSn
Elevated IgE M1 prime transcripts in nasal tissues in patients with nasal polyps and asthma
Publication date: Available online 22 October 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Heleen Scheerens, Ashley Smith, Olga Li, Lee Honigberg, Jeffrey M. Harris, Gabriele Holtappels, Claus Bachert
https://ift.tt/2CxTcES
Lingual cavernous hemangioma in a Nepalese boy—‘A Difficult Associate!!!’
Abstract
Hemangiomas are benign tumors comprising of ectatic blood vessels. Although common in the head and neck region, those occurring within the oral cavity and tongue are exceedingly rare. We report a 5-year-old boy with a swelling over the anterior third of tongue post failed conservative therapy eventually treated with surgical excision and confirmed histologically as a cavernous hemangioma probably first of its kind reported from Nepal.https://ift.tt/2EEljoh
Risk of recurrence in patients with papillary thyroid carcinoma and minimal extrathyroidal extension not treated with radioiodine
Abstract
Purpose
This study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and minimal extrathyroidal extension (mETE) who had low thyroglobulin (Tg) after total thyroidectomy, and therefore, did not receive radioactive iodine (RAI).
Methods
This was a prospective study including 182 patients with tumors ≤ 4 cm and mETE without aggressive histology or clinically apparent lymph node involvement (cN0pNx). After thyroidectomy, all patients had nonstimulated Tg ≤ 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. Because of these results, the patients were not submitted to RAI.
Results
The time of follow-up ranged from 24 to 132 months (median 72 months). One hundred and seventy-eight patients (97.8%) continued to have nonstimulated Tg ≤ 0.3 ng/ml and negative US. Four patients (2.2%) exhibited an increase in Tg and lymph node metastases (structural recurrence). After surgery, these patients obtained nonstimulated Tg < 1 ng/ml and no apparent tumor was detected by the imaging methods.
Conclusion
The results suggest that patients with mETE and without other adverse features, who have low nonstimulated Tg and negative neck US after thyroidectomy, do not require ablation with RAI.
https://ift.tt/2ywUZqI
JAMA Otolaryngology-Head & Neck Surgery.
JAMA Otolaryngology-Head & Neck Surgery.
JAMA Otolaryngol Head Neck Surg. 2018 Oct 01;144(10):861
Authors:
PMID: 30347055 [PubMed - in process]
https://ift.tt/2EEs6OX
Timely Adjuvant Postoperative Radiotherapy: Racing to a PORT in the Storm.
Timely Adjuvant Postoperative Radiotherapy: Racing to a PORT in the Storm.
JAMA Otolaryngol Head Neck Surg. 2018 Oct 18;:
Authors: Teng MS, Gupta V
PMID: 30347023 [PubMed - as supplied by publisher]
https://ift.tt/2OHEEK0
Association of Facility Volume With Positive Margin Rate in the Surgical Treatment of Head and Neck Cancer.
Association of Facility Volume With Positive Margin Rate in the Surgical Treatment of Head and Neck Cancer.
JAMA Otolaryngol Head Neck Surg. 2018 Oct 18;:
Authors: Nocon CC, Ajmani GS, Bhayani MK
Abstract
Importance: The achievement of complete tumor resection with tumor-free margins is one of the main principles of oncologic surgery for head and neck squamous cell carcinoma (HNSCC). The negative prognostic influence of a positive margin (PM) across all head and neck subsites has been well established. National guidelines recommend the use of adjuvant chemoradiation therapy (CRT) in the setting of PM.
Objective: To determine the incidence of PM in HNSCC across multiple subsites, as well as the factors associated with its occurrence.
Design, Setting, and Participants: This retrospective cohort study used the National Cancer Database to identify patients diagnosed with HNSCC between 2010 and 2014 and who underwent surgical resection (n = 28 840).
Main Outcomes and Measures: Predictors of PM rate and likelihood to receive adjuvant CRT.
Results: Among the 28 840 patients included in this study, 19 727 (68.4 %) were men, and the average age was 62.4 years (range, 40 to ≥90 years). In univariable analysis, a lower PM rate was associated with higher facility volume (26.3% for the lowest volume quartile, 16.5% for the middle 2 quartiles, and 10.8% for the highest volume quartile) and treatment at academic vs nonacademic facilities (14.0% vs 22.7%). In multivariate analysis, those treated at higher-volume facilities remained significantly less likely to have PM (adjusted odds ratio, 0.85; 95% CI, 0.83-0.88). The trend of decreasing PM rate with increasing facility volume was observed in both academic (aOR, 0.88 per 10-case volume increase [95% CI, 0.85-0.91]) and nonacademic (aOR, 0.73 per 10-case volume increase [95% CI, 0.68-0.80]) facilities. There was no association between facility volume and patient likelihood of receiving adjuvant CRT in the setting of PM (compared with CCPs: aOR, 0.98 per 10-case volume increase [95% CI, 0.84-1.14] for CCCPs; and aOR, 1.24 [95% CI, 0.99-1.55] for INCPs).
Conclusions and Relevance: These findings suggest that high-volume facilities are associated with lower rates of PM in the surgical treatment of HNSCC in both academic and nonacademic settings. Facility volume for head and neck oncologic surgeries may be considered a benchmark for quality of care.
PMID: 30347018 [PubMed - as supplied by publisher]
https://ift.tt/2EEs5dR
Association of Care Processes With Timely, Equitable Postoperative Radiotherapy in Patients With Surgically Treated Head and Neck Squamous Cell Carcinoma.
Association of Care Processes With Timely, Equitable Postoperative Radiotherapy in Patients With Surgically Treated Head and Neck Squamous Cell Carcinoma.
JAMA Otolaryngol Head Neck Surg. 2018 Oct 18;:
Authors: Janz TA, Kim J, Hill EG, Sterba K, Warren G, Sharma AK, Day TA, Hughes-Halbert C, Graboyes EM
Abstract
Importance: Delays in initiation of postoperative radiotherapy (PORT) after surgery for head and neck squamous cell carcinoma (HNSCC) are common, predominantly affect racial minorities, and are associated with decreased survival. Details regarding the care processes that contribute to timely, equitable PORT remain unknown.
Objective: To determine care processes associated with timely, equitable PORT.
Design, Setting, and Participants: This retrospective cohort study included patients 18 years or older undergoing surgery for HNSCC at the Medical University of South Carolina (MUSC), Charleston, followed by PORT (at MUSC or elsewhere) with or without chemotherapy from January 1, 2014, through December 31, 2016. Data were analyzed from September 15, 2017, through June 28, 2018.
Main Outcomes and Measures: The main outcome measure was the proportion of timely, guideline-adherent initiation of PORT (≤6 weeks postoperatively). Secondary outcome measures included care processes associated with timely PORT. The association between process variables with timely PORT was explored using multivariable logistic regression analysis. Effect modification of the association between receipt of care processes and timely PORT by race was explored using interaction effects.
Results: A total of 197 patients were included in the analysis; they were predominantly white (157 [79.7%]) and male (136 [69.0%]) with a mean age of 59 years (range, 28-89 years). Overall, 89 patients (45.2%) experienced a delay initiating PORT. African American patients had a 13.5% absolute increase in the rate of delayed PORT relative to white patients (21 of 37 [56.8%] vs 68 of 157 [43.3%]). The adjusted multivariable regression showed that the following care processes were associated with timely PORT: preoperative radiotherapy consultation (odds ratio [OR], 8.94; 95% CI, 1.64-65.53), PORT at MUSC (OR, 6.21; 95% CI, 1.85-24.75), pathology report within 7 postoperative days (OR, 4.14; 95% CI, 1.21-15.86), time from surgery to PORT referral of no longer than 10 days (OR, 12.14; 95% CI, 3.14-63.00), time from PORT referral to consultation of no longer than 10 days (OR, 10.76; 95% CI, 3.01-49.70), and time from PORT consultation to its start of no longer than 21 days (OR, 4.80; 95% CI 1.41-18.44). Analysis of interactions revealed no statistically significant differences between African American and white patients in receipt of key processes associated with timely PORT.
Conclusions and Relevance: Specific care processes are associated with guideline-adherent initiation of PORT. Novel strategies appear to be needed to ensure that these processes are performed for all patients with HNSCC, thereby facilitating timely, equitable PORT.
PMID: 30347012 [PubMed - as supplied by publisher]
https://ift.tt/2OEYYM9
The fragility of statistically significant results in otolaryngology randomized trials
Publication date: Available online 22 October 2018
Source: American Journal of Otolaryngology
Author(s): Mason Skinner, Daniel Tritz, Clayton Farahani, Andrew Ross, Tom Hamilton, Matt Vassar
Abstract
Objectives
The American Academy of Otolaryngology–Head and Neck Surgery regards randomized controlled trials as class A evidence. A novel method to determine the robustness of outcomes in trials is the fragility index. This index represents the number of patients whose status would have to change from a non-event to an event to make a statistically significant result non-significant.
Methods
Investigators included otolaryngology journals listed in the top 10 of one or both of Google Scholar Metrics and Clarivate Analytics' Journal rankings. For inclusion, a randomized controlled trial needed to report a one-to-one random assignment of participants to condition, contain two parallel arms or have used a two-by-two factorial design, and report at least one statistically significant dichotomous outcome.
Results
Sixty-nine trials met inclusion criteria. The median fragility index was three events (interquartile range 1–7.5). Median sample size was 72 (interquartile range 50–102.5). Modest correlations were observed between fragility index and total sample size (r = 0.27) and fragility index and event rate (r = 0.46). Investigators found no correlation between fragility index and impact factor or Science Citation Index. In 39% (27/69) of trials, the number lost to follow-up was equal to or greater than the fragility index.
Conclusion
A median fragility index of 3 indicates that three people, on average, are needed to alter the outcomes in otolaryngology trials. This indicates that the results of two-group randomized controlled trials reporting binary endpoints published in otolaryngology journals may frequently be fragile.
https://ift.tt/2yXzkaL
Resveratrol Represses Tumor Necrosis Factor α/c-Jun N-terminal Kinase Signaling via Autophagy in Human Dental Pulp Stem Cells
Publication date: Available online 22 October 2018
Source: Archives of Oral Biology
Author(s): Feng-Ming Wang, Zhiai Hu, Xiaohua Liu, Jian Q. Feng, Robert. A. Augsburger, James L. Gutmann, Gerald N. Glickman
Abstract
Objectives
To study the effects of polyphenol resveratrol on TNFα-induced inflammatory signaling as well as the underlying mechanism in human dental pulp stem cells (DPSCs).
Materials and Methods
Human DPSCs were cultured and treated by TNFα in the presence or absence of resveratrol. NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways were analyzed by Western blotting and immunofluorescence staining. Interleukin 6 (IL6) and interleukin 8 (IL8) mRNA levels were analyzed by reverse transcription polymerase chain reaction. For the mechanistic study, autophagy was examined and further manipulated by gene silencing of Atg5 using siRNAs. Statistical analysis was performed by Student's t- test, and values of p < 0.05 were considered significant.
Results
Upon TNFα treatments, neither degradation of IκBα nor the phosphorylation and nuclear translocation of p65 NF-κB were inhibited by resveratrol at different concentrations. In contrast, resveratrol dramatically inhibited TNFα-induced phosphorylation of c-Jun N-terminal kinase (JNK) MAPK. Furthermore, resveratrol activated autophagy, as evidenced by the accumulated autophagic puncta formed by lipid bound LC3B in resveratrol-treated cells. Intriguingly, both resveratrol and JNK inhibitor SP600125 suppressed TNFα-induced IL6 and IL8 mRNA expression (P < 0.05). Silencing autophagy gene Atg5 led to the hyper-activation of JNK and augmented TNFα-induced IL6 and IL8 mRNA expression (P < 0.05).
Conclusions
The results suggest that resveratrol suppresses TNFα-induced inflammatory cytokines expressed by DPSCs through regulating the inhibitory autophagy-JNK signaling cascade. Resveratrol might be beneficial to ameliorate pulpal damage during the acute phase of inflammation in vital pulp therapy.
https://ift.tt/2ScoKpd
Poorly differentiated plasmacytoid squamous cell carcinoma: Case report of a rare malignancy
Publication date: Available online 23 October 2018
Source: American Journal of Otolaryngology
Author(s): Gabrielle Rieth, Arminé Kocharyan, Akina Tamaki, Jason Thuener, Freedom Johnson
Abstract
Plasmacytoid squamous cell carcinoma is an especially aggressive variant of squamous cell carcinoma that has previously been described in the literature as a variant of oral cancers and most extensively, in vulvular [3], transitional cell, and urothelial carcinomas [2,13,15–20]. In this case report, we present a 36-year-old man with 6 to 8 weeks of a progressively enlarging mass over the lateral third of his clavicle, acromion process, and deltoid. The mass was resected, and the supraclavicular defect was reconstructed using an anterolateral thigh free flap. Final pathology determined the specimen was an invasive poorly differentiated squamous cell carcinoma with spindle cell and plasmacytoid features of cutaneous origin. Plasmacytoid squamous cell carcinomas have previously been described in the oral cavity, but in no other subsite of the head and neck. This article describes the patient's case and provides a literature review of the available reports related to plasmacytoid variant of squamous cell carcinoma.
https://ift.tt/2SeEjwH
Andrologie bei onkologischen Erkrankungen
Zusammenfassung
In der dermatoonkologischen Behandlung findet sich eine Vielzahl gonadotoxischer Interventionen. Insbesondere alkylierende und hormonell aktive Substanzen sowie gonadale Bestrahlungen sind bekannt für eine fertilitätseinschränkende Wirkung beim Mann. Die zertifizierten Hautkrebszentren in Deutschland haben deshalb seit 2017 die Auflage zur Umsetzung von Beratungen zum Fertilitätserhalt. Gestützt wird dies durch die S2k-Leitlinie zur Fertilitätserhaltung bei onkologischen Therapien. Da die verschiedenen Interventionen von den dermatoonkologischen Leitlinien stadienabhängig empfohlen werden, befürworten die Autoren mindestens die Frage „Ist Kinderwunsch ein Thema für Sie?", wenn Patienten ein entsprechendes Stadium erreichen. Die Fertilitätsprotektion des Mannes über eine Kryokonservierung von Ejakulat oder Hodenmaterial ist dann eine einfache und sichere Möglichkeit. Das Verfahren ist standardisiert und häufig verfügbar. Zudem bietet sich über das neue Projekt Androprotect jetzt die Möglichkeit zur Kryokonservierung von Hodenmaterial präpubertärer männlicher Kinder und Säuglinge. Treten unter Therapie Zeichen eines Hypogonadismus auf, kann in Abwägung der Testosteronwirkungen eine Behandlung erwogen werden, wichtig ist, hier die anabolen und immunmodulierenden Effekte zu beachten.
https://ift.tt/2CAkzhB
Analysis of the role of thyroidectomy and thymectomy in the surgical treatment of secondary hyperparathyroidism
Publication date: Available online 22 October 2018
Source: American Journal of Otolaryngology
Author(s): Mateus R. Soares, Graziela V. Cavalcanti, Ricardo Iwakura, Leandro J. Lucca, Elen A. Romão, Luiz C. Conti de Freitas
Abstract
Purpose
Parathyroidectomy can be subtotal or total with an autograft for the treatment of renal hyperparathyroidism. In both cases, it may be extended with bilateral thymectomy and total or partial thyroidectomy. Thymectomy may be recommended in combination with parathyroidectomy in order to prevent mediastinal recurrence. Also, the occurrence of thyroid disease observed in patients with hyperparathyroidism is poorly understood and the incidence of cancer is controversial. The aim of the present study was to report the experience of a single center in the surgical treatment of renal hyperparathyroidism and to analyse the role of thyroid and thymus surgery in association with parathyroidectomy.
Materials and methods
We analysed parathyroid surgery data, considering patient demographics, such as age and gender, and surgical procedure data, such as type of hyperparathyroidism, associated thyroid or thymus surgery, surgical duration and mediastinal recurrence. Histopathological results of thyroid and thymus samples were also analysed.
Results
Medical records of 109 patients who underwent parathyroidectomy for secondary hyperparathyroidism were reviewed. On average, thymectomy did not have impact on time of parathyroidectomy (p = 0.62) even when thyroidectomy was included (p = 0.91). Intrathymic parathyroids were detected in 7.5% of the thymuses removed and papillary carcinoma was detected in 20,8% of thyroid tissue samples. Two patients showed recurrence of supernumerary intrathymic parathyroids and a single case of mediastinitis was observed.
Conclusions
Parathyroidectomy with thymectomy and/or thyroidectomy has an important role in the treatment of renal hyperparathyroidism since thyroid cancer can frequently occur and require surgery. Thymectomy should be considered to avoid recurrence and a risky re-operation.
https://ift.tt/2S9qDml
SLAM family receptors in natural killer cells – Mediators of adhesion, activation and inhibition via cis and trans interactions
Publication date: Available online 22 October 2018
Source: Clinical Immunology
Author(s): Maren Claus, Doris Urlaub, Frank Fasbender, Carsten Watzl
Abstract
SLAM family receptors are important for the fine-tuning of immune reactions. Their expression is restricted to cells of hematopoietic origin and most SLAM family receptors are their own ligand. Here we review how these receptors are involved in regulating the functions of Natural Killer (NK) cells. We discuss that promoting cellular adhesion may be a main function of SLAM family receptors in NK cells. The homophilic interactions of SLAM family receptors can not only occur in trans between different cells, but also in cis on the surface of the same cell. This cis interaction additionally modulates the function of the receptors and subsequently affects the activities of NK cells. Finally, SLAM-family receptors can also mediate inhibitory signals under certain conditions. These inhibitory signals can contribute to the functional maturation of NK cells during NK cell education. Therefore, SLAM family receptors are critically involved in many aspects of NK cell functionality.
https://ift.tt/2RbP5T1
Imbalance of two main circulating dendritic cell subsets in patients with myasthenia gravis
Publication date: Available online 22 October 2018
Source: Clinical Immunology
Author(s): Pei Chen, Yingkai Li, Hao Huang, Yan Li, Zhenguang Chen, Xiaoxi Liu, Li Qiu, Changyi Ou, Zhidong Huang, Zhongqiang Lin, Hao Ran, Weibin Liu
Abstract
Although it is well documented that circulating dendritic cells (DCs) have specialized features in many kinds of physiological and pathological condition of human, there is still lack reports about the features of DCs in the peripheral blood of myasthenia gravis (MG) patients. We aimed to investigate the quantitative and component features of DCs and their implication in MG. We collected peripheral blood from different kinds of MG patients and recorded their clinical characteristics. Using flow cytometry, we distinguished circulating DC subsets [plasmacytoid DCs (pDCs) and myeloid DCs (mDCs)] and enumerated their densities in peripheral blood. Absolute numbers of circulating pDCs were significantly decreased in naïve MG patients compared with healthy controls, resulting in a markedly lower ratio of pDCs/mDCs (percentage). Thus, there was an imbalance in the proportions of different circulating DC subsets. We did not find clustered pDCs in the hyperplastic thymus of MG patients. The clinical status of MG patients was improved after drug treatment, together with an increased ratio of pDCs/mDCs. In a longitudinal follow-up, we observed that circulating mDCs were significantly reduced after 1 month of therapy with a steroid and immunosuppressant, resulting in recovery of the pDC/mDC ratio. The ratio of circulating DC subsets might reflect the balance between the autoimmune response and immune tolerance of a patient, and ratio changes during treatment could be a promising marker to predict the efficacy of a specific drug used for MG patients.
https://ift.tt/2q8044i
In Response to “Descriptive Survival Study of Nail Melanoma Patients Treated With Functional Surgery vs Distal Amputation”
Publication date: Available online 23 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Brooke Vasicek, Taylor Erickson, Eden Lake
https://ift.tt/2Sb6Raf
High-Throughput Sequencing of the T-cell receptor beta chain gene distinguishes two subgroups of cutaneous T-cell lymphoma
Publication date: Available online 23 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Jie Wang, Bryan Rea, Paul Haun, Ryan Emerson, Ilan Kirsch, Adam Bagg
https://ift.tt/2yX2V49
Dear Dr. Dermatoethicist: Erection Ethics
Publication date: Available online 23 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Paige Norwick, Gillian K. Weston, Jane M. Grant-Kels
https://ift.tt/2Sb6Gf5
Surgical Pearl: Reverse Beveling to Improve Wound Edge Apposition
Publication date: Available online 23 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Kourosh Beroukhim, Lindsay R. Sklar, Daniel B. Eisen
https://ift.tt/2yXwS43
Association between atopic dermatitis, depression and suicidal ideation: A systematic review and meta-analysis
Publication date: Available online 23 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Kevin R. Patel, Supriya Immaneni, Vivek Singam, Supriya Rastogi, Jonathan I. Silverberg
Abstract
Background
Atopic dermatitis (AD) is associated with psychological distress. However, previous studies found conflicting results about whether AD is associated with increased depression or suicidality.
Objectives
To determine the complex relationship between AD and depression.
Methods
A systematic review was performed of all published observational studies in MEDLINE, Pubmed, EMBASE, GREAT, LILACS, Cochrane Library, Scopus and PsychInfo that analyzed depression in AD. Two reviewers performed study title/abstract review and data abstraction. Pooled meta-analysis was performed using random-effects weighting.
Results
Overall, 106 studies met inclusion criteria; 36 had sufficient data for meta-analysis. The prevalence of any depression was higher in persons with vs. without AD (20.1% vs. 14.8%). Similar results were found in sensitivity analyses of studies assessing clinical depression, depressive symptoms, and adults, with healthy controls, low and high study quality. AD was associated with significantly higher depression scales, parental depression, anti-depressant use, and suicidality. No publication bias was detected
Limitations
Individual level data were not available.
Conclusions
AD patients have higher odds of depression and suicidality.
https://ift.tt/2Sb6uMT
The Cost of an Itch: A Nationally Representative Retrospective Cohort Study of Pruritus-Associated Healthcare Expenditure in the United States
Publication date: Available online 23 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Raghav Tripathi, Konrad D. Knusel, Harib H. Ezaldein, Jeremy S. Bordeaux, Jeffrey F. Scott
https://ift.tt/2yWj9ui
Reply
Publication date: Available online 22 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Suelen Montagner
https://ift.tt/2S9O5Qs
The Prognostic Value of Inositol Polyphosphate 5-Phosphatase in Cutaneous Squamous Cell Carcinoma
Publication date: Available online 22 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Helen JL. Cumksy, Collin M. Costello, Nan Zhang, Richard Butterfield, Matthew Buras, Jessica Schmidt, Kevin Drenner, Steven A. Nelson, Shari A. Ochoa, Christian Baum, Mark R. Pittelkow, David J. DiCaudo, Aleksandar Sekulic, Aaron R. Mangold
Abstract
Background
Inositol Phosphate 5-Phosphatase (INPP5A) has been shown to play a role in development and progression of cutaneous squamous cell carcinoma (cSCC). The goal of the current study is to explore the prognostic value of INPP5A expression in cSCC.
Methods
A total of 189 cases of actinic keratoses and SCCs from 174 patients were identified, clinical and outcome data abstracted, histopathology re-rereviewed, and immunohistochemical (IHC) staining and interpretation was performed for INPP5A.
Results
The majority of tumors (89.4%) had an INPP5A score of 2 or 3. No patients had complete loss of INPP5A. Tumors with INPP5A score of 1 were more likely to be intermediate to high risk (BWH stage T2a and above 85.0% vs 23.7%, p < 0.0001), have a larger diameter (2.4 cm vs. 1.3 cm, p = 0.0004), moderate to poor differentiation (86.7% vs. 17.6%, p < 0.0001), and perineural invasion (37.5% vs. 5.3%, p < 0.0001). INPP5A score of 1 has worse 3-year survival of 42.3% (HR = 2.81, p = 0.0006) and local metastatic rates of 48.0% (HR=4.71, p < 0.0001).
Conclusions
Low INPP5A scores are predictive of aggressive tumors and may be a useful adjunct to guide clinical management of cSCC.
https://ift.tt/2yZIKST
Clinicopathologic, immunophenotypic, and molecular analysis of subcutaneous panniculitis‐like T‐cell lymphoma: A retrospective study in a tertiary care center
Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2EFOd7G
Assessment of balance skills and falling risk in children with congenital bilateral profound sensorineural hearing loss
Publication date: Available online 23 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Emre Soylemez, Suha Ertugrul, Erkan Doğan
Abstract
Objective
To evaluate the balance skills and falling risk in children with a congenital bilateral profound sensorineural hearing loss (CBPSNHL)
Methods
25 children with CBPSNHL and healthy 25 children with similar age and gender were included in the study. The flamingo balance test, the tandem stance test, and the one-leg standing test were performed to assess the patients' static balance skills. The pediatric balance scale (PBS) was used to evaluate the dynamic balance. Visual analog scale (VAS) was applied to the patients assess the frequency of falls.
Results
The flamingo balance test, the tandem stance test, and the one-leg standing test in the children with CBPSNHL were all significantly worse than the control group. Although the scores of PBS in patients with CBPSNHL were significantly lower than the control group (p <0.001), the results of both groups were consistent with a low risk of falls. There was no significant difference between the VAS scores indicating the frequency of falls among the groups (p = 0.552).
Conclusion
Static and dynamic balance skills of the children with CBPSNHL are significantly impaired compared to their healthy peers. Children with CBPSNHL also have a lower risk of falling just like their healthy peers and there is no significant difference between their falling frequencies. Balance skills of children with CBPSNHL can be assessed quickly and effectively on a hard floor (eyes closed), with a tandem standing test or a one-leg standing test.
https://ift.tt/2EDRUdX
In response to Letter to the Editor entitled “Cortical mastoidectomy with posterior atticotomy as surgical treatment in cases of acute mastoiditis in children”
Publication date: Available online 23 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Józef Mierzwiński, Karolina Haber, Justyna Tyra, Maria Drela, Anna Sinkiewicz, Michael David Puricelli
https://ift.tt/2PjM2uo
Cortical mastoidectomy with posterior atticotomy as surgical treatment in cases of acute mastoiditis in children
Publication date: Available online 22 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Rafal Zielinski
https://ift.tt/2EFMr6o
Hazardous Noise Exposure From Noisy Toys May Increase After Purchase and Removal From Packaging: A Call for Advocacy
Publication date: Available online 22 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Noel Jabbour, Heather M. Weinreich, James Owusu, Marta Lehn, Bevan Yueh, Samuel Levine
Abstract
Objective
Previous studies identified hazardous noise levels from packaged toys. Sound levels may increase when packaging is removed and therefore, complicate the ability to accurately assess noise levels before purchase. The goal of this study was to evaluate how packaging affects the decibel (dB) level of toys by:
Methods
Thirty-five toys were selected from the 2009-2011 Sight and Hearing Association (SHA) based on availability for purchase. Toys' speakers were categorized as Exposed, Partially Exposed, or Covered, based on its packaging. The dB level of each toy was tested at 0 cm and 25 cm from the speaker using a handheld digital sound meter in a standard audiometric booth. T tests and ANOVA were performed to assess mean change in sound level before and after packaging removal.
Results
Significant dB increases were noted after packaging was removed (mean change 11.9 dB at 0 cm; and 2.5 dB at 25 cm, p<0.001). Sixty-four percentage of Covered toys (n=14) had dB greater than 85 dB when packaged and this increased to 100% when unpackaged.
Conclusion
Many manufactured toys have hazardous sound levels. Caregivers and healthcare providers should be aware that toys tested in the store may actually be louder when brought home and removed from their packaging. Limits on and disclosure of dB level of toys should be considered nationally.
https://ift.tt/2PfK0vC
Prevalence of Bifid Uvula in Primary School Children
Publication date: Available online 22 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Pranvera Feka, Jacqueline Banon, Igor Leuchter, Giorgio C. La Scala
Abstract
Background
A bifid uvula is an anatomic variation that can be predictive of sub-mucous cleft palate, which may cause velopharyngeal insufficiency (VPI). Bifid uvula prevalence in the literature ranges from 0.18% to 10.3%, depending on the population studied. The aim of this study is to determine the prevalence of bifid uvula in the Geneva's school children population.
Methods
A cross-sectional study was conducted in Geneva's primary school children, from September 2014 to June 2015. An examination of the uvula was performed by dentists working for the Scholastic Dental Service, after a specific training in diagnosing bifid uvulas. The dentists recorded their findings on a standardized form.
Results
The total number of school children in Geneva in the school year 2014-2015 was 30,375. 23,961 children had their uvula examined, representing 79% of the total population of school children. Among them, a hundred school children had a cleft uvula. One schoolgirl had no uvula. The prevalence of bifid uvula is 0.42%. Sex ratio (M/F) is 0.96.
Discussion
This large study, the second in literature for number of patients examined, identified a prevalence of bifid uvula of 0.42%. This result is in agreement with previous studies.
https://ift.tt/2EFOiIw
Oral peanut immunotherapy ‐ How much is too much? How much is enough?
Allergy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2CAcRUH
Delayed granulomatous reaction and cutaneous fistula induced by retained electrodes from a cardiac pacemaker in a child
Pediatric Dermatology, EarlyView.
https://ift.tt/2PdLRkw
Issue Information
Head &Neck, Volume 40, Issue 10, Page 2117-2120, October 2018.
https://ift.tt/2AnNjIQ
Issue Information
Journal of Neuroendocrinology, Volume 30, Issue 11, November 2018.
https://ift.tt/2Sen0Mf
Autophagy and its potent modulators from phytochemicals in cancer treatment
Abstract
Autophagy is a ubiquitous catabolic process by which damaged or harmful intracellular components are delivered to the lysosomes for self-digestion and recycling. It is critical in cancer treatment. Therapy-induced autophagy predominantly acts as a pro-survival mechanism, but progressive autophagy can lead to non-apoptotic cell death, also known as autophagic cell death. Plants or herbs contain various natural compounds that are widely used in the treatment of many types of malignancies. Emerging evidence indicates that phytochemicals targeting the autophagic pathway are promising agents for cancer treatment. However, these compounds play different roles in autophagy. In this review, we discussed the role of autophagy in cancer development and therapy, and focussed on elucidating the anti-cancer activities of autophagic modulators, especially phytochemicals. Notably, we described a novel premise that the dynamic role of phytochemicals should be evaluated in regulation of autophagy in cancer.
https://ift.tt/2AnlK2s
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