Epigenetics, Inflammation, and Periodontal Disease

Abstract

Purpose of the Review

The purpose is to provide current knowledge and recent development and understanding of periodontal disease dysbiosis in the perspective of epigenetic changes. Epigenetic changes, where environmental factors modify the gene expression network without changing the DNA sequence, may influence inflammatory diseases such as chronic periodontitis. These chemical modifications of DNA and histone proteins cause epigenetic changes that alter cellular function and host defenses.

Recent Findings

Findings suggest that the methylation of cytosine residues on DNA particularly at CpG Islands is commonly associated with gene silencing, and covalent modifications on histones are associated with chromatin structural integrity and function that play crucial roles in gene expression. In periodontal immune dysbiosis, aberrant DNA methylation and/or histone modifications could potentially play a role in disease state.

Summary

We broadly discuss epigenetic modifications related to immune regulation and comprehensively discuss recent developments in the dynamics of epigenetic changes pertaining to chronic inflammatory periodontal disease.

http://bit.ly/2sxXlCB

Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18 F-FDG PET and MRI radiomics features

Abstract

Purpose

Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15–30% of cases, therefore it would be useful to assess if pretreatment of ¹⁸F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC.

Methods

Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models.

Results

In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index).

Conclusions

If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

http://bit.ly/2RozDqZ

Healthcare utilization and management of actinic keratosis in primary and secondary care: a complementary database analysis

Summary

Background

The high prevalence of actinic keratosis (AK) requires optimal use of healthcare resources.

Objectives

To gain insight in health care utilization and management of AK, by describing the healthcare utilization of people with AK in a population‐based cohort and in a primary and secondary care setting.

Methods

A retrospective cohort study using three complementary data sources was conducted to describe the use of care, diagnosis, treatment, and follow‐up of AK patients in the Netherlands. Data sources consisted of a population‐based cohort study (Rotterdam Study, RS), routine general practitioner (GP) records (Integrated Primary Care Information, IPCI), and nationwide claims data (DBC Information System, DIS).

Results

In the population‐based cohort (RS), 69% (918/1,322) of participants diagnosed with AK during a skin screening visit had no prior AK‐related visit in their GP record. This proportion was 50% for participants with extensive AK (i.e.,≥10 AKs; n=270). Cryotherapy was the most used AK treatment by both GPs (78%) and dermatologists (41‐56%). Topical agents were the second most used treatment by dermatologists (13‐21%) but was rarely applied in primary care (2%). During the first AK related GP visit, 31% (171/554) was referred to a dermatologist, with likelihood of being referred comparable between low and high‐risk patients, which is inconsistent with the guidelines. Annually, 40·000 new claims representing 13% of all dermatology claims were labelled as cutaneous premalignancy. Extensive follow‐up rates (56%) in secondary care were registered, while only 18% received a claim for a subsequent cutaneous malignancy in 5 years.

Conclusions

AK management seems to diverge from guidelines in both primary and secondary care. Underutilization of field treatments, inappropriate treatments and high referral rates without proper risk stratification in primary care, combined with extensive follow‐up in secondary care result in inefficient use of healthcare resources and overburdening in secondary care. Efforts directed to better risk differentiation and guideline adherence may prove useful in increasing the efficiency in AK management.

This article is protected by copyright. All rights reserved.

http://bit.ly/2D6F45c

Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer’s disease and mild cognitive impairment

Abstract

Purpose

We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI).

Methods

We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50–78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43–75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)".

Results

The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43–0.99), 0.86 (range 0.64–0.98), and 0.95 (range 0.65–1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18–0.98), 0.70 (range 0.48–0.81), and 0.84 (range 0.75–0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI.

Conclusion

Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions.

http://bit.ly/2D6A9RS

Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice

Abstract

Purpose

REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy.

Methods

Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated.

Results

This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group.

Conclusions

The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.

http://bit.ly/2TKrjig

Tiger man sign in sarcoid myopathy

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The evolving Editorial Board

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Take a look at the eyes in Systemic Lupus Erythematosus: A novel point of view

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Conigliaro Paola, Cesareo Massimo, Chimenti Maria Sole, Triggianese Paola, Canofari Claudia, Barbato Carmen, Giannini Clarissa, Salandri Ada Giorgia, Nucci Carlo, Perricone Roberto

Abstract

Systemic lupus erythematosus (SLE) is a connective tissue disease that involves multiple organs. Ocular structures and visual pathways can be affected in SLE because of disease-related eye involvement or drug toxicity. All the part of the eye may be interested with an external, anterior involvement, responsible of the dry eye disease, or posterior (retina) and neuro-ophtalmic manifestations. Retinopathy in SLE is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival. The early diagnosis is thus the key to a better management and successful treatment. Antimalarial drugs are the cornerstone of SLE treatment and recently the American Academy of Ophthalmology updated the recommendations for hydroxychloroquine retinal toxicity screening which includes the standard automated visual fields and the spectral domain optical coherent tomography. More recently new imaging techniques have been investigated to assess retinal function and reveal subclinical eye involvement. In this review we focalize on the evidence of eye manifestations in SLE, the eye drug toxicity related to antimalarial agents and steroids, and the methods employed for the eye screening. Moreover, the future perspectives on new techniques, such as the optical coherence tomography angiography, are dissected giving new insights on evaluation of microvasculature of the retina and choroid in SLE.

http://bit.ly/2Fp4ygp

Mechanisms of action and historical facts on the use of intravenous immunoglobulins in systemic lupus erythematosus

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Tatiana Martínez, Juan Esteban Garcia-Robledo, Ilich Plata, Maria-Alejandra Urbano, Ivan Posso-Osorio, Lady J. Rios-Serna, María Claudia Barrera, Gabriel J. Tobón

Abstract

The current existing therapies for severe cases of systemic lupus erythematosus (SLE) patients are still limited. Intravenous immunoglobulin (IVIGs), which are purified from the plasma of thousands of healthy human donors, have been profiled as efficacious and life-saving options for SLE patients refractory to conventional therapy. The specific mechanism of action by which IVIGs generate immunomodulation in SLE is not currently understood. In this manuscript, we reviewed some of the hypothesis that have been postulated to explain the IVIG effects, including those on T and B cell intracellular signalling and activation, as well as the interferon signalling pathways involved in the detection of nucleic acids and the defective removal of immune complexes and debris.

http://bit.ly/2Fuo4aw

The impact of self-replicating proteins on inflammation, autoimmunity and neurodegeneration—An untraveled path

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Dana Butnaru, Joab Chapman

Abstract

The central nervous system (CNS) in neurodegenerative diseases is a battlefield in which microglia fight a highly atypical battle. During the inflammatory process microglia themselves become dysfunctional and even with all the available immune arsenal including cytokine or/and antibody production, the battle is eventually lost. A closer look into the picture will reveal the fact that this is mainly due to the atypical characteristics of the infectious agent. The supramolecular assemblies of misfolded proteins carry unique features not encountered in any of the common pathogens. Through misfolding, proteins undergo conformational changes which make them become immunogenic, neurotoxic and highly infective. The immunogenicity appears to be triggered by the exposure of previously hidden hydrophobic portions in proteins which act as damage-associated molecular patters (DAMPs) for the immune system. The neurotoxicity and infectivity are promoted by the small oligomeric forms of misfolded proteins/peptides. Oligomers adopt conformations such as tubular-like, beta-barrel-like, etc., that penetrate cell membranes through their hydrophobic surfaces, thus destabilizing ionic homeostasis. At the same time, oligomers act as a seed for protein misfolding through a prion/prion-like mechanism. Here, we propose the hypothesis that oligomers have catalytic surfaces and exercise their capacity to infect native proteins through specific characteristics such as hydrophobic, electrostatic and π-π stacking interactions as well as the specific surface area (SSA), surface curvature and surface chemistry of their nanoscale supramolecular assemblies. All these are the key elements for prion/prion-like mechanism of self-replication and disease spreading within the CNS. Thus, understanding the mechanism of prion's templating activity may help us in the prevention and development of novel therapeutic strategies for neurodegenerative diseases

http://bit.ly/2FmSJYd

Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Jan Damoiseaux, Jean-Baptiste Vulsteke, Chih-Wei Tseng, Anouk C.M. Platteel, Yves Piette, Ora Shovman, Carolien Bonroy, Dörte Hamann, Ellen De Langhe, Lucille Musset, Yi-Hsing Chen, Yehuda Shoenfeld, Yves Allenbach, Xavier Bossuyt

Abstract

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by immune-mediated muscular lesions that may be associated with extra-muscular manifestations involving skin, lungs, heart or joints. Four main groups of IIM can be distinguished: dermatomyositis (DM), overlap myositis including mainly anti-synthetase syndrome (ASS), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Myositis-specific autoantibodies (MSA) are increasingly recognized as valuable tools for diagnosis, classification and prognosis of IIM. For example, ASS is associated with anti-aminoacyl tRNA synthetase antibodies (anti-Jo-1, PL-7, PL-12, …), IMNM with anti-SRP and anti-HMGCR; IBM with anti-cytosolic 5'nucleotidase 1A (cN1A), and DM with anti-Mi-2, anti-MDA-5, anti-TIF-1γ, anti-NXP-2 and anti-SAE. Moreover, anti-MDA-5 is associated with amyopathic myositis and interstitial lung disease and anti-TIF-1γ and anti-NXP-2 with juvenile DM as well as malignancy in patients >40 years. Most MSA have initially been discovered by immunoprecipitation. In routine laboratories, however, MSA are screened for by indirect immunofluorescence and identified by (automated) monospecific immunoassays or by multispecific immunoassays (mainly line/dot immunoassays). Validation of these (multispecific) assays is a challenge as the antibodies are rare and the assays diverse. In this review, we give an overview of the (clinical) performance characteristics of monospecific assays as well as of multispecific assays for detection of MSA. Although most assays are clinically useful, there are differences between techniques and between manufacturers. We discuss that efforts are needed to harmonize and standardize detection of MSA.

http://bit.ly/2Fqt6VI

Complex regional pain syndrome – False hopes and miscommunications

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Christopher Chang, Patrick McDonnell, M. Eric Gershwin

Abstract

Complex regional pain syndrome (CRPS) has been considered to be an autoimmune disease and there have been clinical trials with intravenous immunoglobulin. Often the etiology of the so-called CRPS diagnosis cannot be discerned and there are no validated instruments that provide functional metrics. The term complex regional pain syndrome (CRPS), coined in 1994 to describe patients in whom the pain is out of proportion to the injury, was actually a diagnosis proposed during the American Civil War, but was originally known as causalgia. Physicians have long observed similar sensitivity and inflammatory symptoms following periods of immobilization and disuse, which generally resolve within a few months of remobilization. Following the original description, persistent disproportionate pain would come to be known under many other names until researchers theorized that it was related to dysfunction in the sympathetic nervous system, after which it acquired the moniker, Reflex Sympathetic Dystrophy ("RSD"). In the latter quarter of the twentieth century, after researchers failed to prove the connection between the pain and the sympathetic nervous system, a small cadre of physicians–without rigorous science—invented CRPS. This new descriptor, CRPS, has become not only a diagnosis without objective data but with proposed criteria involving ambiguous signs and symptoms with low specificity. It has led to patients being treated erroneously with sympatholytic drugs, with or without pharmaceutical or surgical blockade of the sympathetic nervous system, unwarranted use of ketamine infusions, inappropriate use of narcotics and nerve stimulation. Intravenous immunoglobulin infusions have not been effective in the treatment of chronic pain. The indiscriminate use of pain medications to treat subjective symptoms of unclear diagnoses can be a risk factor for opioid and analgesic misuse or abuse.

http://bit.ly/2FmSJaF

Review: Myositis-specific autoantibodies, a cornerstone in immune-mediated necrotizing myopathy

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Céline Anquetil, Olivier Boyer, Nadège Wesner, Olivier Benveniste, Yves Allenbach

Abstract

Over the past few years, myositis-specific autoantibodies played an increasing role in the inflammatory idiopathic myositis definition. They became the critical immunological marker for immune-mediated necrotizing myopathy diagnosis (IMNM) since the paradigm switch from histological to serological criteria.

This review is focused on the key role of the anti-signal recognition particle (anti-SRP) and the anti-3-Hydroxy-3-MethylGlutaryl-Coenzyme A Reductase (anti-HMGCR) antibodies in immune-mediated necrotizing myopathy.

Anti-SRP and anti-HMGCR antibodies are robust diagnostic tools in case of both the classical subacute form and the slowly progressive form of IMNM that may mimic muscular dystrophy. Anti-SRP and anti-HMGCR patients share clinical, biological and histological features with some antibody-associated specificity. Anti-SRP patients harbour more severe muscle weakness and atrophy with severe muscle damage on magnetic resonance imaging study. Approximately 10–20% of anti-SRP patients develop extramuscular symptoms, especially lung interstitial disease. Conversely, anti-HMGCR patients are often associated with statin exposure. In both cases, patients have a poor outcome with frequent relapse and the use of combined immunotherapy. Of note, various data suggest a direct pathogenic role of these antibodies reinforcing the interest in targeted therapeutic strategy.

http://bit.ly/2FwWvxg

Autoimmunity in celiac disease: Extra-intestinal manifestations

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Lerner Aaron, Matthias Torsten, Wusterhausen Patricia

Abstract

Celiac disease is an autoimmune condition of the small intestine caused by prolamins in genetically susceptible individuals evoked by multiple environmental factors. The pathological luminal intricate eco-events produce multiple signals that irradiate the entire body, resulting in a plethora of extra-intestinal manifestations. Nutrients, dysbiosis, dysbiotic components and their mobilome, post-translational modification of naive proteins, inter-enterocyte's tight junction dysfunction resulting in a leaky gut, microbial lateral genetic transfer of virulent genes, the sensing network of the enteric nervous systems and the ensuing pro-inflammatory messengers are mutually orchestrating the autoimmune interplay. Genetic-environmental-luminal events-mucosal changes are driving centrifugally the remote organs autoimmunity, establishing extra-intestinal multi organ injury. Exploring the underlying intestinal eco-events, the sensing and the delivery pathways and mechanisms that induce the peripheral tissues' damages might unravel new therapeutical strategies to prevent and help the gluten affected patients.

http://bit.ly/2FvaaVY

F18-choline/C11-choline PET/CT thyroid incidentalomas

Abstract

Introduction

Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a non-thyroid disease. Aim of this review is to evaluate the prevalence and clinical significance of focal incidental radiolabelled choline uptake in the thyroid gland (CTI) revealed by PET or PET/CT.

Methods

A comprehensive computer literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles about the prevalence and clinical significance of CTIs detected by PET or PET/CT in patients studied for other oncologic purposes.

Results

Fifteen articles (14 case reports, one retrospective study on a larger population sample) were included in the systematic review. Considering the case reports, 7/14 CTIs were benign and 7/14 malignant. In the retrospective study on a larger population sample, 14/15 CTIs which underwent further investigations were benign.

Conclusion

Despite very rare but probably underestimated, CTIs frequently signal in the presence of unexpected lesions in the thyroid that differ from the indicated reason for which the patient was initially scanned, and the risk of malignancy is not negligible.

http://bit.ly/2AHvAvs

F18-choline/C11-choline PET/CT thyroid incidentalomas

Abstract

Introduction

Thyroid incidentaloma is defined as a thyroid lesion incidentally and newly detected by imaging techniques performed for an unrelated purpose and especially for a non-thyroid disease. Aim of this review is to evaluate the prevalence and clinical significance of focal incidental radiolabelled choline uptake in the thyroid gland (CTI) revealed by PET or PET/CT.

Methods

A comprehensive computer literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles about the prevalence and clinical significance of CTIs detected by PET or PET/CT in patients studied for other oncologic purposes.

Results

Fifteen articles (14 case reports, one retrospective study on a larger population sample) were included in the systematic review. Considering the case reports, 7/14 CTIs were benign and 7/14 malignant. In the retrospective study on a larger population sample, 14/15 CTIs which underwent further investigations were benign.

Conclusion

Despite very rare but probably underestimated, CTIs frequently signal in the presence of unexpected lesions in the thyroid that differ from the indicated reason for which the patient was initially scanned, and the risk of malignancy is not negligible.

http://bit.ly/2AHvAvs

Mechanisms of anionic surfactant penetration into human skin: Investigating monomer, micelle, and submicellar aggregate penetration theories

Abstract

Objective

Once penetrated into the stratum corneum, anionic surfactants bind to and denature stratum corneum proteins as well as intercalate into and extract intercellular lipids. With repeated exposures, this leads to skin dryness and irritation, compromising barrier function and skin health. The mechanisms of anionic surfactant penetration into the skin, however, are still widely debated. The objective of this study was to evaluate current theories of surfactant penetration into human skin.

Methods

A test set comprising 15 anionic surfactant systems and one nonionic surfactant, all having either dodecyl or lauryl alkyl chains, was tested for surfactant penetration into split‐thickness human cadaver skin in vitro using radiolabeled sodium dodecyl sulfate (¹⁴C‐SDS). Select physical properties of these formulations thought to be associated with skin penetration including critical micelle concentration, micelle diameter, filtrate concentration, and zeta potential were also measured.

Results

¹⁴C‐SDS penetration into human cadaver skin from surfactant systems in vitro was found to correlate well with CMC (R ²=0.34, p<0.05), filtrate concentration (R ²=0.36, p<0.05), and zeta potential (R ²=0.76, p<0.001), but poorly with micelle diameter (R ²=0.12). Furthermore, the latter measure correlated inversely with penetration compared to what would be expected based on the micelle penetration theory.

Conclusion

Neither monomer nor micelle penetration theories are sufficient to explain anionic surfactant penetration into human skin. Submicellar (or premicellar) aggregate penetration theory is difficult to defend at relevant surfactant concentrations. We propose a new hypothesis for this mechanism in which short‐term penetration is based on monomer concentration and longer‐term penetration is based on surfactant‐induced damage to the skin barrier.

This article is protected by copyright. All rights reserved.

http://bit.ly/2FnHbUr

Hypocellular Medallion‐like Dermal Dendrocyte Hamartoma on the Abdomen of a 25 year old Male

Medallion‐like dermal dendrocyte hamartoma is a rare congenital lesion that is more commonly seen in females. It often presents at birth on the neck or upper trunk as a well‐circumscribed, atrophic patch with wrinkling of the overlying skin. Clinically, the differential diagnosis includes atrophoderma, anetoderma, and congenital atrophic dermatofibrosarcoma protuberans. Histologic findings show epidermal atrophy and dermal spindle cell proliferation that is CD34 positive, along with Factor XIIIa in the original reports. Due to this CD34 positivity, another name for the lesion is plaque‐like CD34+ dermal fibroma. We present a unique patient case as he is male and the lesion is located on his abdomen. Further reports and studies need to be done for thorough understanding of this neoplasm.

This article is protected by copyright. All rights reserved.

http://bit.ly/2CjPH35

Cutaneous myxomas and a psammomatous melanotic schwannoma in a patient with Carney complex

http://bit.ly/2TKr5rg

Issue Information

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Precalcaneal Congenital Fibrolipomatous Hamartoma: Rare or under‐reported ?

Precalcaneal congenital fibrolipomatous hamartoma (PCFH) is a benign under reported condition of infancy characterized by the presence of soft nodules on precalcaneal plantar surface of the heel. These lesions are usually bilateral solitary and asymptomatic. We present a 2‐month‐old infant with solitary skin colored nodules present on precalcaneal plantar aspect of bilateral heels.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TQC5Uf

RANK deletion in NPY neurons attenuates estrogen deficiency related bone loss

Abstract

The RANKL pathway is known to be an important aspect of the pathogenesis of estrogen‐deficiency induced bone loss. RANK deletion specifically in NPY neurons has been shown to enhance the ability of the skeleton to match increases in body weight caused by high fat diet feeding, likely via the modulation of NPY levels. Here, we use ovariectomy in female mice to show that RANK deletion in NPY neurons attenuates bone loss caused by long‐term estrogen deficiency, particularly in the vertebral compartment. Ovariectomy led to a reduction in NPY expression levels in the arcuate nucleus of NPY ^cre/+ ;RANK ^lox/lox mice compared to NPY ^cre/+ ;RANK ^lox/+ controls. As NPY deficient mice also displayed a similar protection against ovariectomy induced bone loss, modulation of hypothalamic NPY signalling is the likely mechanism behind the protection from bone loss in the NPY ^cre/+ ;RANK ^lox/lox mice.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TOow7L

NO acutely modulates hypothalamic and neurohypophyseal CO and H2S production to control AVP, OT and ANP release in rats

Abstract

NO negatively modulates the secretion of vasopressin (AVP), oxytocin (OT) and atrial natriuretic peptide (ANP) induced by the increase in extracellular osmolality, whereas CO and H₂S act potentiating it; however, little information about whether and how such gaseous systems modulate each other is available for the osmotic challenge model. Therefore, using an acute ex vivo model of hypothalamic and neurohypophyseal explants (obtained from male 6/7‐week‐old Wistar rats) under conditions of extracellular iso‐ and hypertonicity, we determined the effects of NO (600 μM SNP), CO (100 μM CORM3) and H₂S (10 mM Na₂S) donors and NOS (300 μM LNMMA), HO (200 μM ZnDPBG) and CBS (100 μM AOA) inhibitors on the release of hypothalamic ANP and hypothalamic and neurohypophyseal AVP and OT, and on the activities of nitric oxide synthase (NOS), heme oxygenase (HO) and cystathionine β‐synthase (CBS). LNMMA reversed hyperosmolality‐induced NOS activity, and enhanced hormonal release by the hypothalamus and neurohypophysis, besides increasing CBS and hypothalamic HO activity. AOA decreased hypothalamic and neurohypophyseal CBS activity and hormonal release; while, ZnDPBG inhibited HO activity and hypothalamic hormone release; however, in both cases, neither AOA modulated NOS and HO activity, nor ZnDPBG affected NOS and CBS activity. Thus, our data indicate that, although endogenous CO and H₂S positively modulate AVP, OT and ANP release, only NO plays, in fact, a concomitant role of modulator of hormonal release and CBS activity in the hypothalamus and neurohypophysis and HO activity in the hypothalamus during an acute osmotic stimulus, which suggests that NO is a key gaseous controller of the neuroendocrine system.

This article is protected by copyright. All rights reserved.

http://bit.ly/2D5kbaF

Local hyperthermia cleared multifarious viral warts in a patient with Cushing's syndrome

Abstract

A female Cushing's syndrome patient had been suffering from extensive viral warts for months. She was diagnosed with flat warts, common warts and plantar warts. The plantar warts on her right foot were initially treated using local hyperthermia at 44°C for 30 minutes according to a defined protocol, followed by treatment targeting a common wart on her left thumb. In response to hyperthermia, the flat warts on her eyelid dissipated within 12 weeks, and when combined with a one week administration of imiquimod, the common warts and plantar warts completely disappeared within 8 weeks. There were no signs of recurrence and during this treatment her Cushing's syndrome was alleviated. This pioneer trial suggests that local hyperthermia may serve as an effective mean for treating multiple cutaneous warts under the conditions of a systemic immuno‐compromised disease.

This article is protected by copyright. All rights reserved.

http://bit.ly/2SQQi34

Identification of a closed cutaneous injury after mechanical trauma caused by collision

Abstract

Purpose

Robotics has evolved rapidly in terms of mechanical design and control in the past few years. Collaborative robots that have direct contact with humans are being introduced in various fields, including industrial and medical services. Because collaborative robot systems are being introduced rapidly, the safety of the humans who work with them is becoming an important issue. In this study, we investigated skin injuries resulting from a collision between robots and humans using a freefall experiment system.

Methods

We particularly focused on closed skin injuries caused by a collision. To induce a closed injury, we struck mini‐pigs with cubic‐edge square and semi‐sphere impactors at collision speeds of 1 and 3 m/s. We did not observe any open injuries with those conditions. Closed injuries were observed in the dermal layer of the skin after the collision test at both speeds and with both impactors.

Results

The collagen fiber in the dermal layer was separated and fragmented, and the subcutaneous fat layer became dense as a result of the collision.

Conclusions

We closely observed and analyzed the histopathologic changes in the dermal and subcutaneous layers with intact epidermis after mechanical trauma to the inner skin layers.

http://bit.ly/2QHG4QM

Patients with Negative Patch Tests: Retrospective Analysis of North American Contact Dermatitis Group (NACDG) Data 2001-2016

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Erin M. Warshaw, Amy J. Zhang, Donald V. Belsito, Joseph F. Fowler, James S. Taylor, Howard I. Maibach, Toby Mathias, Denis Sasseville, James G. Marks, Vincent A. DeLeo, Anthony F. Fransway, Kathryn A. Zug, Melanie D. Pratt, Matthew J. Zirwas, Joel G. DeKoven

Abstract

Background

Little is known regarding characteristics of patients with negative patch tests (NPTs).

Objective

To characterize patients with NPTs.

Methods

Retrospective cross-sectional analysis of 34,822 patch tested patients. NPTs were defined as negative or irritant final interpretations of all North American Contact Dermatitis Group (NACDG) screening allergens and no relevant allergens on supplemental series.

Results

Almost one-third (n=10,888, 31.3%) of patients had negative results. NPT patients were significantly more likely to be male (p<0.0001), aged ≤40 years (p=0.0054), non-Caucasian (p=0.0005), and have dermatitis primarily involving the following body sites: scattered generalized (p=0.0007), lips (p=0.0214), or eyelids (p=0.0364). However, absolute differences in age, race, and site were small and may not be clinically meaningful. NPT patients were significantly less likely to have occupationally related skin disease (p<0.0001). Overall, 8.3% of NPT patients had occupationally related skin disease with precision production workers/machine operators (28.5%), healthcare workers (17.0%), and mechanics/repairers (7.5%) being the most commonly related occupations. 22.9% of NPT patients had relevant irritants and 41.6% of irritants were occupationally related; cosmetics/health care products and soaps were common sources for both occupationally related and non-occupationally related irritants.

Limitations

Retrospective cross-sectional study of tertiary referral population.

Conclusions

Patients with NPTs have distinct characteristics.

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Bupivacaine infiltration in children for postoperative analgesia after tonsillectomy: A randomised controlled study

BACKGROUND Adenotonsillectomy is a frequently performed procedure in paediatric day-case surgery. Postoperative pain can be significant and standard analgesia protocols are often insufficient. OBJECTIVE Our primary objective was to investigate if infiltration of the peritonsillar space with bupivacaine would reduce the need for postoperative opioids compared with pre-emptive intravenous tramadol. DESIGN A prospective, double-blind, randomised controlled trial. SETTING Ambulatory surgical day care centre, University Hospitals of Leuven, Belgium, from January 2012 to September 2016. PATIENTS Two hundred children, between 4 and 10 years old, undergoing elective adenotonsillectomy were included in the study. INTERVENTION Children were randomly allocated to receive either a bolus of 3 mg kg−1 intravenous tramadol or infiltration of the tonsillar lodge with 5-ml bupivacaine 0.25%. Reasons for exclusion were American Society of Anesthesiologists classification greater than 2, allergies to the investigated products, psychomotor retardation, bleeding disorders and lack of proficiency in Flemish. MAIN OUTCOME MEASURES The primary endpoint was the number of children in need of piritramide postoperatively. Secondary outcomes included the cumulative dose of postoperative piritramide, pain scores and the incidence of postoperative nausea and vomiting during the first 24 postoperative hours, time to discharge and adverse effects. RESULTS The proportion of children in need of postoperative piritramide was significantly lower in the tramadol group than in children with peritonsillar infiltration (57 vs. 81%, P 

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Epidemiology and incidence of severe respiratory critical events in ear, nose and throat surgery in children in Europe: A prospective multicentre observational study

BACKGROUND Ear, nose and throat (ENT) surgery, the most frequently performed surgical procedure in children, is a strong predictor for peri-operative respiratory complications. However, there is no clear information about peri-operative respiratory severe critical events (SCEs) associated with anaesthesia management of ENT children in Europe. OBJECTIVE To characterise the epidemiology and incidence of respiratory SCEs during and following ENT surgery in Europe and to identify the risk factors for their occurrence. DESIGN A secondary analysis of the Anaesthesia PRactice In Children Observational Trial, a prospective observational multicentre cohort trial. SETTING The study included 261 centres across 33 European countries and took place over a consecutive 2-week recruitment period between April 2014 and January 2015. PATIENTS We extracted data from 5592 ENT surgical procedures that were performed on 5572 children aged 6.0 (3.6) years (mean (SD)) from the surgical database and compared these with data from 15 952 non-ENT surgical children aged 6.7 (4.8) years. MAIN OUTCOME MEASURES The primary outcome was the incidence of respiratory SCEs (laryngospasm, bronchospasm and new onset of postoperative stridor). Secondary outcomes were the differences in epidemiology between ENT children and non-ENT surgical children and the risk factors for the occurrence of respiratory SCEs. RESULTS The incidence (95% confidence interval) of any respiratory SCE (laryngospasm, bronchospasm and postoperative stridor) was 3.93% (3.46 to 4.48) and was significantly higher than that observed in non-ENT surgical children [2.61% (2.37 to 2.87)], with a relative risk of 1.51 (1.28 to 1.77), P less than 0.0001. Younger age (14% decrease in critical events by increasing year, P 

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A comparison of the analgesic efficacy of local infiltration analgesia vs. intrathecal morphine after total knee replacement: A randomised controlled trial

BACKGROUND Local infiltration analgesia (LIA) is an effective pain management technique following total knee arthroplasty (TKA). OBJECTIVE To investigate if LIA provides better analgesia for patients undergoing unilateral TKA than intrathecal morphine. DESIGN Randomised controlled trial. SETTING Single tertiary referral centre. PATIENTS Consecutive American Society of Anesthesiologists Physical Status I to III patients scheduled to undergo unilateral TKA were randomised to two groups. INTERVENTION The control group received spinal anaesthesia with intrathecal bupivacaine and preservative-free morphine 0.3 mg. The intervention group received opioid-free spinal anaesthesia with bupivacaine, followed by intra-operative infiltration of the knee with levobupivacaine 2 mg kg−1 and adrenaline 0.5 mg diluted to a volume of 100 ml with 0.9% saline. An intra-articular catheter was placed during surgery and used to give a bolus of 15 ml of levobupivacaine 0.5% on the morning of the first postoperative day. MAIN OUTCOME MEASURES Visual analogue scale (VAS) scores for pain were assessed repeatedly for 48 h postoperatively, at rest and on passive knee flexion to 30°. The primary outcome was VAS scores for pain at rest and on movement at 24 postoperative hours. Secondary outcomes were VAS scores at rest and on movement at 2, 6, 12 and 48 postoperative hours, opioid consumption, degree of active flexion of operative knee achieved in the first 48 h and the incidence of opioid-related side effects. RESULTS Forty three patients completed the study. Mean (± SD) VAS scores for pain at 24 h were lower in the intervention group than the control group at rest; 16.43 (± 20.3) vs. 37.2 (± 33.6), (P = 0.029). VAS scores for pain at 24 h on movement were also lower in the intervention group vs. the control group; 39.1 (± 22.8) vs. 57.0 (± 30.9), (P = 0.037). VAS scores were also lower on movement; 25.9 (± 16.8) vs. 40.5 (± 24.0), (P = 0.028) at 48 h. CONCLUSION We conclude that LIA conferred superior analgesia compared with intrathecal morphine 0.3 mg at 24 and 48 h following TKA. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01312415. Correspondence to John McNamara, MB, BCh, BAO, Cork University Hospital and University College Cork, Cork, Ireland E-mail: johnmcnamara9@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://bit.ly/2ylyqmW). © 2019 European Society of Anaesthesiology

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An Innovative Thread-looping Method for Facial Rejuvenation: Minimal Access Multiple Plane Suspension

Background: Management of facial rejuvenation has evolved over past decades. Facelift with barbed suture is a minimally invasive surgical technique for facial rejuvenation. This study examined the efficacy and associated complications of a new thread-looping procedure called minimal access multiple plane suspension. Methods: A total of 103 thread lifts were performed between 2014 and 2017. Patient satisfaction and adverse effects were evaluated. Results: In the majority of patients (88/103, 85.4%), the results obtained were considered satisfactory 3 months after the procedure. The incidence of complications was low. Only 5.8% of the patients had slight postoperation asymmetry that was easily corrected. Minor complications experienced by patients included palpable suture knots (12.6%), persistent facial swelling (7.88%), and facial dimpling (2.9%). The causes of procedure-related complications were reviewed and discussed. Conclusion: Reinforced by select anchoring points, "minimal access multiple plane suspension" suspends ptotic anatomic tissues, serving as an effective facial rejuvenation procedure with minimal downtime and satisfactory cosmetic results. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Received for publication August 4, 2018; accepted October 10, 2018. Presented at the Aesthetic Medicine World Congress Asia (AMWC Asia) & Taiwan Dermatology Aesthetic Conference (TDAC) 2018 in Taipei, Taiwan. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Yun-Ta Tsai, MD, Dr. Shine Clinic, 6F., No.3, Sec. 1, Zhongshan Rd., Banqiao Dist., New Taipei City 22063, Taiwan, E-mail: tuderek@gmail.com Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Remote sensing-based water quality assessment for urban rivers: a study in linyi development area

Abstract

Nowadays, urban rivers play an important role in city development and make great contributions to urban ecology. Most urban rivers are the drinking water sources and water quality is extremely critical. The current assessment method in national standard of China has multiple limitations; therefore, this paper introduces an advanced assessment, that is, Canadian Water Quality Index (CWQI). This method can help to provide comprehensive and objective water quality assessment for the urban rivers. Moreover, CWQI can prevent waste of the water resource, since current assessment is pessimistic and tent to underestimate water samples to a lower grade. Linyi development area is selected as study region and CWQI method is applied to assess two major urban rivers within the area. The water monitoring data from 2014 to 2017 is acquired in 24 parameters. Since the CWQI calculation is still based on traditional water quality measurement in parameters, there will be a huge cost when increasing research scale and accuracy. In this paper, remote sensing technique is employed to develop models of CWQI scores from satellite data. By utilizing 23 selected monitoring instances and matching satellite data, linear regression analysis shows that red band data has highest correlation with CWQI in both two urban rivers in the study region. In addition, two testing datasets with five instances for each river are used to validate the RS-based CWQI models and the results show that testing datasets can be fitted well. With the models, CWQI distribution diagrams are generated and assist both spatial and temporal analysis. Experimental results show that the proposed approach can indicate actual water quality pattern which is validated by field visit. The proposed approach in this paper has satisfying effectiveness and robustness.

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