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

Episodic Migraine Comorbidities: Avoiding Pitfalls and Taking Therapeutic Opportunities

Abstract

Migraine is a common neurologic disorder. This article will discuss a few factors that influence migraine (mostly episodic) and its treatment, such as sleep, obstructive sleep apnea (OSA), obesity, and affective disorders, as well as autoimmune diseases. Practitioners must be aware of these coexisting conditions (comorbidities) as they affect treatment. It is noted in literature that both the quantity (too much or too few hours) and the quality (OSA related) of sleep may worsen migraine frequency. An associated risk factor for OSA, obesity also increases migraine frequency in episodic migraine cases. A bidirectional relationship with migraine along with depression and anxiety is debated in the literature. Retrospective cohort studies are undecided and lack statistical significance, but prospective studies do show promising results on treatment of anxiety and depression as a means of improving migraine control. Finally, we address the topic of autoimmune diseases and migraine. While few studies exist at this time, there are cohort study groups looking into the association between rheumatoid arthritis, hypothyroidism, and antiphospholipid antibody. There is also evidence for the link between migraine and vascular diseases, including coronary and cerebral diseases. We suggest that these comorbid conditions be taken into account and individualized for each patient along with their pharmaceutical regimen. Physicians should seek a multifactorial treatment plan including diet, exercise, and healthy living to reduce migraine frequency.

http://bit.ly/2CgQhP9

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

The Diagnostic Performance of Ultrasonography and Computed Tomography in Differentiating Superficial from Deep Lobe Parotid Tumors

Abstract

Objectives

To validate and compare ultrasound (US) versus computed tomography (CT) criteria in the localization of superficial/deep lobe tumors of the parotid gland.

Design and Setting

This was a retrospective study of diagnostic tests performed from January 2008 to June 2017.

Participants

We included adult patients who were referred for a neck ultrasonography examination due to parotid tumors, and who subsequently underwent parotid surgery.

Main outcome measures

We assessed the location of parotid tumors, comparing the minimum fascia–tumor distance (MFTD) criterion on an US with eight CT criteria. We analyzed receiver operating characteristic (ROC) curves of the MFTD for malignant, benign, and all parotid tumors, and compared the accuracy, sensitivity, and specificity of the optimal MFTD with those of CT anatomical criteria.

Results

A total of 166 parotid tumors were included. The mean (SD) MFTD in superficial lobe tumors was significantly shorter than that of deep lobe tumors (1.2 [0.7] vs 2.8 [1.9] mm, effect size: 1.84; 95% CI, 1.27 to 2.41). The areas under the ROC curve were 0.63 for malignant tumors and 0.88 for benign tumors. The optimal MFTD cut point was 2.4 mm for the 154 benign parotid tumors and the accuracy, sensitivity, and specificity were 90%, 80% and 91%, respectively. For the 136 benign parotid tumors that underwent CT examination, three criteria had an accuracy of over 90% (FNline, tMasseter and Conn's arc), but the sensitivities were all below 50%.

Conclusions

MFTD is more feasible for benign tumors than for malignant tumors for the localization of parotid tumors. For benign parotid tumors, US is enough to guide operations.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TJI90s

Computerised tomography in the investigation of otalgia of unknown origin; our experience in 100 patients

Abstract

Otalgia is a common presenting symptom in the specialty of ENT. In its primary form it is caused by conditions and diseases affecting the outer, middle or inner ear structures, thus giving rise to pain and discomfort around the ear itself. However, in its secondary form (referred), pain can be remote from the source and thus provide greater diagnostic challenge due to the possibility of occult disease that is not well visualised.

This article is protected by copyright. All rights reserved.

http://bit.ly/2D5nSNF

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

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

Prognostic significance and population dynamics of peripheral monocytes in patients with oropharyngeal squamous cell carcinoma

Abstract

Background

Several inflammatory biomarkers are considered potential prognostic factors in various cancers. This study aimed to investigate the prognostic significance and population dynamics of pretreatment inflammatory biomarker levels in patients with oropharyngeal squamous cell carcinoma (OPSCC).

Methods

The influence of neutrophil counts, lymphocyte counts, monocyte counts, platelet counts, lymphocyte‐to‐monocyte ratio (LMR), neutrophil‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio on progression‐free survival (PFS), and overall survival (OS) was analyzed. We also analyzed the peripheral blood mononuclear cells collected from patients and healthy donors (HDs).

Results

Elevated monocyte count was an independent prognostic factor for PFS. Low LMR was an independent prognostic factor for OS. The proportion of intermediate monocytes was lower, and that of classical monocytes was higher in patients than in HDs. Furthermore, PD‐L1 expression on monocytes was higher in patients than in HDs.

Conclusions

We showed the prognostic significance and population dynamics of peripheral monocytes in patients with OPSCC.

http://bit.ly/2SWh4HH

Transnasal endoscopic surgery in selected nasal‐ethmoidal cancer with suspected brain invasion: Indications, technique, and outcomes

Abstract

Background

In nasal‐ethmoidal malignancies, brain involvement is associated with dismal prognosis.

Method

Patients undergoing endoscopic resection with transnasal craniectomy and subpial dissection (ERTC‐SD) for brain‐invading nasal‐ethmoidal cancer between 2008 and 2016 were included. Complications were analyzed in all patients, whereas oncological outcomes only in patients with pathological brain invasion. The prognostic impact of previous treatments, brain edema, and histology was assessed. Hospitalization ratio was calculated.

Results

Nineteen patients received ERTC‐SD and 11 had pathological‐proven brain invasion. Histologies were 6 olfactory neuroblastomas (ONB), 3 neuroendocrine carcinomas, and 2 intestinal‐type adenocarcinomas. Mean follow‐up was 21.9 months. Three‐year overall, local recurrence‐free, and distance recurrence‐free survivals were 65.5%, 81.8%, and 68.2%, respectively. Overall and distant recurrence‐free survivals were significantly better in patients with ONB (P = 0.032 and P = 0.013, respectively). Hospitalization ratio was 4.1%. Complication rate was 10.5%.

Conclusion

In selected nasal‐ethmoidal tumors with brain invasion, ERTC‐SD can provide good local control, satisfactory survival, and limited morbidity.

http://bit.ly/2ALcTap

Sequential therapy of neoadjuvant biochemotherapy with cetuximab, paclitaxel, and cisplatin followed by cetuximab‐based concurrent bioradiotherapy in high‐risk locally advanced oral squamous cell carcinoma: Final analysis of a phase 2 clinical trial

Abstract

Background

The prognosis of advanced oral squamous cell carcinoma is poor. We investigated the effect of cetuximab‐based sequential therapy as a primary treatment.

Methods

Forty‐seven treatment‐naive patients with advanced tumors originating from the oral cavity or oropharynx were enrolled. Neoadjuvant cetuximab, paclitaxel, and cisplatin were administered, followed by cetuximab‐based radiotherapy. Immunohistochemical staining was applied to study the tissues.

Results

The best overall response rate was 70.2%, including 4 patients with a complete response and 29 with a partial response. The median progression‐free and overall survival rates were 10.3 and 15.2 months, respectively. Patients with more than 50% tumor reduction with neoadjuvant therapy had better survival outcomes. Twenty‐two patients had severe adverse events with mostly dermatological complications. Of the 16 patients who received operations, 9 had increased PD‐L1 staining compared to pretreatment biopsy in the post hoc study.

Conclusion

The regimen was effective in selected patients. Increased PD‐L1 suggested altered tumor features.

http://bit.ly/2SPk08H

Locoregional failures and their relation to radiation fields following stereotactic body radiotherapy boost for oropharyngeal squamous cell carcinoma

Abstract

Background

To investigate the location of recurrences with respect to the radiation fields in oropharynx cancer after intensity‐modulated radiotherapy and stereotactic body radiotherapy (SBRT) boost.

Methods

Local and regional recurrences were delineated on diagnostic scans which were rigidly coregistered with treatment planning scans, then classified based on the location of the center of mass (COM) as well as volumetrically.

Results

In 195 patients, the 5‐year local and regional control were 90% and 93%, respectively. By COM, 76% of local recurrences were in‐field; 24% were out‐of‐field, significantly higher than 0%‐5% in the literature for conventional regimens (P < 0.01). Regional recurrences (19 in 12 patients) were largely within unirradiated neck levels (47%) and electively irradiated regions (42%).

Conclusions

The regimen with biological equivalent dose intensification provides excellent overall and in‐field local control. The highly conformal boost technique was, however, associated with increased out‐of‐field local failure.

http://bit.ly/2ALcS6l

Prognostic factors in patients with soft palate squamous cell carcinoma

Abstract

Background

To define the prognostic factors associated with outcome in patients with soft palate squamous cell carcinoma (SCC).

Methods

Previously untreated patients with soft palate and uvula SCC treated in our institution between 1997 and 2012 were collected. The prognostic value of clinical, hematological, and treatment characteristics was examined.

Results

We identified 156 patients, median age 58 years, with 71% drinkers, 91% smokers; 19% had synchronous cancer. Front‐line treatment was chemoradiotherapy in 58 (37%), radiotherapy alone in 60 (39%), surgery in 17 (11%), and induction chemotherapy in 21 patients (14%). The 5‐year actuarial overall survival (OS) and progression‐free survival (PFS) were 41% and 37%, respectively. In univariate analysis, T3‐T4 vs T1‐T2 stage, N2‐N3 vs N0‐N1 stage, and neutrophil count >7 g/L were associated with worse OS and PFS (P < .05).

Conclusion

In patients with soft palate SCC, inflammation biomarkers were associated with OS.

http://bit.ly/2SSnlnp

International validation of the revised European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ‐HN43: Phase IV

Abstract

Background

We validated the new European Organisation for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ‐HN43).

Methods

We enrolled 812 patients with head and neck cancer from 18 countries. Group 1 completed the questionnaire before therapy, and 3 and 6 months later. In group 2 (survivors), we determined test–retest reliability using intraclass correlation coefficients (ICC). Internal consistency was assessed using Cronbach's Alpha, the scale structure with confirmatory factor analysis, and discriminant validity with known‐group comparisons.

Results

Cronbach's alpha was >0.70 in 10 of the 12 multi‐item scales. All standardized factor loadings exceeded 0.40. The ICC was >0.70 in all but two scales. Differences in scale scores between known‐groups were >10 points in 17 of the 19 scales. Sensitivity to change was found to be sufficient in 18 scales.

Conclusions

Evidence supports the reliability and validity of the EORTC QLQ‐HN43 as a measure of quality of life.

http://bit.ly/2ALcODD

Visceral adipose tissue volume and CT‐attenuation as prognostic factors in patients with head and neck cancer

Abstract

Background

The aim of this study was to evaluate the relationship of the characteristics of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) to the disease progression‐free survival and distant failure‐free survival of head and neck squamous cell carcinoma (HNSCC).

Methods

We enrolled 152 HNSCC patients who underwent staging ¹⁸F‐fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT). Maximum FDG uptake (standardized uptake value [SUV]) and total lesion glycolysis (TLG) of the primary tumor and volume, CT‐attenuation (Hounsfield units [HU]), and FDG uptake of SAT and VAT were measured. Survival analysis using Cox proportional hazard modeling was performed to assess the relationship between the adipose tissue parameters of PET/CT and survival.

Results

Patients with low VAT volume and high VAT HU had significantly worse progression‐free survival and distant failure‐free survival than those with high VAT volume and low VAT HU. On multivariate analysis, the volume and HU of VAT were significantly correlated with disease progression‐free survival and distant failure‐free survival after adjusting for age, sex, body mass index, TNM stage, serum C‐reactive protein, maximum SUV, and TLG.

Conclusion

The volume and CT‐attenuation of VAT were significantly correlated with disease progression‐free survival and distant failure‐free survival in patients with HNSCC.

http://bit.ly/2SMhdND

Transoral laser microsurgery for glottic cancer in the elderly: Efficacy and safety

Abstract

Background

Data about the results of transoral laser microsurgery (TLM) in elderly patients are limited.

Methods

A retrospective study of 72 consecutive cases of glottic carcinoma (63 pT1 and 9 pT2 cases) in elderly patients (≥70 years old, mean 76 years) treated with TLM was made. A systematic review of the literature was performed.

Results

Six patients (8%) had postoperative complications, but no treatment‐related deaths were observed. Local recurrences occurred in 12 patients (16.5%): nine with pT1 (14%) and three with pT2 (33%) tumors. Five‐year disease‐specific survival (DSS), overall survival, and laryngectomy‐free survival were 95%, 68%, and 88%, respectively. The literature review indicated that TLM is safe and effective treatment for these patients, with few complications and good local control (>85%) and DSS (>90%) rates.

Conclusions

Our results and the information from the literature show that TLM for glottic cancer in elderly patients can lead to satisfactory treatment results.

http://bit.ly/2ALcLrr

Value of a smartphone‐compatible thermal imaging camera in the detection of peroneal artery perforators: Comparative study with computed tomography angiography

Abstract

Background

The aim of this study was to investigate the value of a smartphone‐compatible thermal imaging camera in the mapping of the peroneal artery perforators.

Methods

Twelve consecutive patients scheduled for fibular flap reconstruction were enrolled. The lower limbs were first studied using smartphone‐based dynamic infrared thermography (DIRT). During the rewarming, the hotspots were marked, small rubber markers were taped to the registered sites, and then the patients were sent for a CT scan. The diagnostic performance of smartphone‐based DIRT was evaluated by comparing the DIRT findings with CT angiography and intraoperative findings.

Results

DIRT detected 42 of the 57 dominant perforators in 24 limbs and resulted in a sensitivity of 73.7% and a positive predictive value of 65.6%.

Conclusions

The sensitivity and positive predictive value of the smartphone‐based DIRT are low. Currently, it should be used as an adjunctive tool together with the established imaging techniques.

http://bit.ly/2SMqaX3

Food‐related anaphylaxis fatalities: analysis of the Allergy Vigilance Network® database

http://bit.ly/2D6PYru

IgE‐specific immunoadsorption: New treatment option for severe refractory atopic dermatitis

http://bit.ly/2TLfUP4

AllergoOncology: microbiota in allergy and cancer ‐ an EAACI position paper

Abstract

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross‐talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome.

This article is protected by copyright. All rights reserved.

http://bit.ly/2D5BJn5

The functional biology of peanut allergens and possible links to their allergenicity

Abstract

Peanut is one of the most common food triggers of fatal anaphylaxis worldwide although peanut allergy affects only 1‐2% of the general population. Peanuts are the source of highly potent allergenic proteins. It is emerging that the allergenicity of certain proteins is linked to their biological function. Peanut is an unusual crop in that it flowers above ground but produces its seed‐containing pods underground. This so called geocarpic fruiting habit exposes pods and seeds during their development to soilborne pathogens and pests. Pest damage can also open routes of entry for opportunistic fungi such as Aspergillus. Although seed proteins have primary functions in nutrient reservoirs, lipid storage bodies, or the cytoskeleton, they have also evolved to act as part of the plant's defense system to enhance fitness and survival of the species. When interacting with pathogens or pests, these proteins modify and damage cells' membranes, interact with immune receptors and modulate signaling pathways. Moreover, following exposure, the immune system of predisposed individuals reacts to these proteins with the production of specific IgE. This review explores the evolutionary biology of peanut and its seed proteins and highlights possible links between the proteins' biological function and their allergenicity.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TKuA12

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

http://bit.ly/2D5fqxz

The evolving Editorial Board

http://bit.ly/2AG8Jk8

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

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

Blockade of YAP alleviates hepatic fibrosis through accelerating apoptosis and reversion of activated hepatic stellate cells

Publication date: March 2019

Source: Molecular Immunology, Volume 107

Author(s): Hai-xia Yu, Yao Yao, Fang-tian Bu, Yu Chen, Yu-ting Wu, Yang Yang, Xin Chen, Yan Zhu, Qin Wang, Xue-yin Pan, Xiao-ming Meng, Cheng Huang, Jun Li

Abstract

Yes-associated protein (YAP) is a significant downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a role in the progression and development of various liver diseases. In hepatic fibrosis development and reversion, the proliferation and apoptosis of activated hepatic stellate cells (HSCs) play a critical role. However, the contribution of YAP to hepatic fibrosis progression and reversion and the underlying mechanism have not been investigated. Here we investigated the expression and function of YAP in the proliferation and apoptosis of activated HSCs. We found that YAP expression was increased in liver fibrosis tissues from CCl₄-induced model mice and restored to normal level after stopping CCl₄ injection and 6 weeks of spontaneously recovery. YAP expression was elevated in HSC-T6 cells treated with TGF-β1 and recovered after MDI treatment. Silencing of YAP inhibited the activation and proliferation of HSC-T6 cells stimulated by TGF-β1. In addition, the apoptosis of activated HSC-T6 cells silenced for YAP was slightly enhanced. Furthermore, over-expression of YAP repressed the reversion of activated HSC-T6 cells mediated by MDI reversal. We found that HSC-T6 cells activated by TGF-β1 showed higher levels of nuclear YAP compared with MDI-treated cells, indicating that YAP was activated in HSC-T6 cells treated by TGF-β1. We also found that loss of YAP attenuated Wnt/β-catenin pathway activity in activated HSC-T6 cells. Treatment of VP, an inhibitor of the YAP-TEAD complex, reduced both activation and proliferation of HSC-T6 cells and increased apoptosis. Together these results indicated that reduced expression of YAP contributes to acquisition of the quiescent phenotype in HSCs. Our results suggest that YAP may be a useful target in HSCs activation and reversion.

http://bit.ly/2VNSaf9

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

Apnea Hypopnea Indices Categorized by REM/NREM Sleep and Sleep Positions in 100 Children with Adenotonsillectomy for Obstructive Sleep Apnea Disease

Publication date: Available online 12 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Asuka Nagao, Masahiro Komori, Taihei Kajiyama, Mutsumi Shimasaki, Daigo Hirakawa, Taisuke Kobayashi, Masamitsu Hyodo

Abstract

Objectives

In pediatric obstructive sleep apnea (OSA), the relationship between rapid eye movement sleep and upper airway collapse, and between sleep position and airway dimensions are well known. However, the interrelations between these factors and the obstructive apnea hypopnea index (O-AHI) have not been thoroughly investigated.

Methods

A retrospective study including 100 children who underwent adenotonsillectomy between March 2010 and July 2017. Total O-AHI was divided into four subcategories by sleep stage and position.

Results

Preoperatively 14 of 47 mild cases of OSA (1 < total O-AHI) and 17 of 18 moderate (5 < total O-AHI) had time showing severe apnea (10 < subcategorized O-AHI). Twenty-two of 24 severe cases (10 < total O-AHI) exhibited very severe apnea (30 < subcategorized O-AHI). All 11 very severe cases (30 < total O-AHI) experienced more than 50 apnea events per hour in at least one of the O-AHI subcategories. After surgery, 23 of 70 cases classified as completely resolved (total O-AHI < 1) still had mild apnea in the O-AHI subcategories, and six of 13 cases who continued to experience apnea events had moderate-to-severe apnea. Seventeen cases worsened in the O-AHI subcategories, and total O-AHI deteriorated in two cases of the 17. The amount of REM sleep and use of the supine position increased significantly postoperatively in the quartile groups with the lowest baseline values (p < 0.0001).

Conclusions

When an unexpected AHI value is encountered, the O-AHI subcategories may be informative regarding the indications for surgery and evaluating the efficacy thereof.

http://bit.ly/2SQKzdE

Bilateral Duplication of the Internal Auditory Canals and Bilateral Cochlear Implant Outcomes and Review

Publication date: Available online 12 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Murray R. Thompson, Catherine S. Birman

Abstract

Objectives

Bilateral duplication of the internal auditory canal (IAC) is rare and is associated with profound sensorineural hearing loss. The present study aims to review our experience with bilateral cochlear implantation (CI) in children with a duplication of the IAC and to review the literature.

Methods

The Sydney Cochlear Implant Centre database was searched for children with duplication of the internal auditory canal. Data was collected regarding clinical history, MRI and CT findings, auditory brainstem responses (ABR), tympanometry and otoacoustic emissions (OAE), visually reinforced orientation audiometry, auditory brainstem response, electrocochleography (ECochG), transtympanic electrical auditory brainstem response (ABR), aided cortical evoked potentials (CAEP) and intraoperative neural response telemetry (NRT) and CI evoked electrical auditory brainstem testing.

Results

two children with bilateral duplication of the IAC were identified who successfully underwent bilateral cochlear implantation. Audiological development was monitored for 2 and 3 years respectively, both children could spontaneously verbalise and displayed Categories of Auditory Performance (CAP) score of 5 and 6 respectively.

Conclusion

Children with duplication of the IAC, with accompanying cochlear nerve dysplasia (CND) can benefit from CI surgery, and verbal receptive and expressive language is possible.

http://bit.ly/2AJgA0c

CSF Leak After Endoscopic Skull Base Surgery in Children: A Single Institution Experience

Publication date: Available online 11 January 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Javan Nation, Alexander J. Schupper, Adam Deconde, Michael Levy

Abstract

Introduction

The endoscopic expanded endonasal approach (EEA) has been shown to be a safe and effective surgical technique in the resection of pediatric skull base lesions. Cerebrospinal fluid (CSF) leaks are among the most common complications of this approach. Here we review skull base resections using EEA in pediatric patients at our single institution, to identify potential risk factors for this surgical complication.

Methods

A retrospective chart review was conducted on pediatric patients at our single institution for patients 19 years-old and under, who underwent an EEA for resection of a skull base tumor.

Results

Thirty-nine pediatric patients (ages 1-19 years) with 8 different tumor pathologies underwent an EEA for resection of their skull base tumors. 21 patients experienced an intraoperative CSF leak, of which 10 (48%) were "high-flow" leaks and 11 (52%) were "low-flow" leaks. Nasoseptal flaps were only used to repair the intraoperative "high flow" leaks (n=10), and "low flow" and "no leaks" were repaired with allograft and fat. No patients experienced a post-operative CSF leak.

Conclusion

In our pediatric series, the skull base repair algorithm of using an NSF only in cases of "high flow" intraoperative leaks was effective, and no post-operative CSF leaks occurred. Not using an NSF in cases of "low-flow" or "no leak" cases allows for decreased anatomical disruption in the growing patient.

http://bit.ly/2SXDzvu

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

Morphological analysis of sigmoid sinus anatomy: clinical applications to neurotological surgery

The primary objective of this study was to use high-resolution micro-CT images to create accurate three-dimensional (3D) models of several intratemporal structures, and to compare several surgically important ...

http://bit.ly/2Hhwxke

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

http://bit.ly/2D5N5HC

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

Dynamic hip kinematics during recreational classical ballet and hula dance after total hip arthroplasty: two case reports

The in vivo assessment of the three-dimensional kinematics of the hip during dance activities in patients after total hip arthroplasty has not been previously reported. We evaluated the replaced hip kinematics du...

http://bit.ly/2QKt1hL

Concomitant hypersensitivity pneumonitis and occupational asthma caused by two different etiological agents.

Publication date: Available online 12 January 2019

Source: Annals of Allergy, Asthma & Immunology

Author(s): E. Solana, M.J. Cruz, C. Romero-Mesones, X. Muñoz

http://bit.ly/2FxoRb5

Another Look at Cyclosporine for Treating Antihistamine-Resistant Chronic Spontaneous Urticaria

Publication date: Available online 12 January 2019

Source: Annals of Allergy, Asthma & Immunology

Author(s): Miles Weinberger

http://bit.ly/2FmzLB8

Oral Challenge Outcomes in Children with Adverse Aminopenicillin Reactivity

Publication date: Available online 11 January 2019

Source: Annals of Allergy, Asthma & Immunology

Author(s): Alysa G. Ellis, Gordon Bloomberg

http://bit.ly/2FtQnGo

The Efficacy of 0.1% Tacrolimus Ophthalmic Suspension in the Treatment of Severe Atopic Keratoconjunctivitis

Publication date: Available online 11 January 2019

Source: Annals of Allergy, Asthma & Immunology

Author(s): Hiroyuki Yazu, Eisuke Shimizu, Naohiko Aketa, Murat Dogru, Naoko Okada, Kazumi Fukagawa, Hiroshi Fujishima

http://bit.ly/2FmaA1B

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.

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http://bit.ly/2D5kbaF

Acquired medial external auditory canal stenosis, anterior tympanomeatal angle blunting, and lateralized tympanic membrane: Nosology, diagnosis, and treatment

Publication date: Available online 11 January 2019

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): A. Karkas, G. Badidi, P. Odinet, P. Reynard, C. Martin

Abstract

Objectives

To analyze the etiologies, auditory consequences, diagnostic tools and therapeutic results of three often confused pathologies: acquired fibrous stenosis of the medial part of the external auditory canal (EAC), fibrous anterior tympanomeatal angle blunting, and lateralized tympanic membrane.

Material and methods

Retrospective study of 18 cases operated on over a 16-year period (14 patients: 7 female, 7 male; aged 11–64 years): 8 cases of medial EAC stenosis, 3 of blunting, and 7 of tympanic membrane lateralization.

Results

In all 3 pathologies, otoscopic and radiologic diagnosis was easily established, so that they could not be confused. All 3 induced > 33 dB conductive hearing loss. Medial EAC stenosis was secondary to chronic inflammation of the EAC, aggravated by surgery in 5 cases. Blunting was secondary to surgery altering the anterior tympanic annulus. Tympanic membrane lateralization was secondary to prior surgery without inflammatory process. Underlying EAC cholesteatoma was found in 3 cases of medial stenosis and in 1 case of blunting. Surgical results were disappointing in medial stenosis, with 62.5% recurrence and mean functional gain of 9 dB, and in blunting, with 66.7% recurrence and mean functional gain of 6 dB; auditory results were, however, good in these 2 pathologies when there was no recurrence of fibrosis. Results were significantly better in lateralized tympanic membrane, with 28.6% recurrence and mean functional gain of 16 dB.

Conclusion

The good results obtained in tympanic membrane lateralization seem to justify surgery in patients bothered by their hearing loss. The indication is more questionable in cases of medial fibrous stenosis and blunting, although significant auditory improvement is achieved in case of surgical success.

http://bit.ly/2FuW0nM

Anesthetic management for medialization laryngoplasty using concurrent infusions of dexmedetomidine, remifentanil, and propofol versus controls

Publication date: Available online 11 January 2019

Source: American Journal of Otolaryngology

Author(s): Kathryn S. Handlogten, Dale C. Ekbom, Megan C. Hamre, Toby N. Weingarten, Darrell R. Schroeder, Troy G. Seelhammer

Abstract

Purpose

Medialization laryngoplasty (ML) ± arytenoid adduction (AA) surgery poses a unique anesthetic challenge that requires periods of deep sedation and patient cooperation with phonation to assess voice function. The purpose of this study was to assess if the protocolized administration of dexmedetomidine, remifentanil, and propofol (DRP) is associated with reduced procedural duration and administration of other sedating medications.

Materials and methods

This was a retrospective 2:1 case matched study design; matched on age, sex, body mass index, AA, and surgical revision status. Data was obtained from the electronic medical record of a tertiary referral center. Cases underwent ML ± AA using DRP. Control subjects underwent surgery ML ± AA without DRP.

Results

58 DRP cases (43.1% AA) were matched with 116 control patients (44.8% AA). DRP was associated with decreases in fentanyl dose (50 [25, 100] vs. 100 [50, 150] mcg; p < 0.01), incidence and dose of midazolam (4 [6.9%] vs. 70 [60.3%]; p < 0.01; 1 [1, 1] vs. 2 [2, 2]; p < 0.02), operative duration (131 ± 33 vs. 160 ± 50 min; p < 0.01), and anesthetic duration (182 ± 35 vs. 219 ± 60.3 min; p < 0.01). When adjusted for timeline, it was observed that case duration was declining prior to DRP introduction; this trend persisted after DRP introduction. Hypopnea was more common with DRP (14 [24.1%] vs. 7 [6.0%]; p < 0.01).

Conclusions

DRP was associated with a substantial decrease in opioid and benzodiazepine administration. A reduction in procedural duration over time was also observed.

http://bit.ly/2Rp4jbT

C reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level

Abstract

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to nonsedating H1 antihistamines treatment. CRP gene encodes the C reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4‐week nonsedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non‐effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and β‐Hexosaminidase assay were conducted in HEK293T cells or RBL‐2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55(72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype was significantly associated with good response (OR=4.20, p=0.015), had lower serum CRP, IL‐6 and TNF‐α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (p<0.001). From the β‐Hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL‐2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.

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http://bit.ly/2FncIWI

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

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.

http://bit.ly/2Fsc2ys

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 

http://bit.ly/2VJ43mB

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 

http://bit.ly/2QLfhTW

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

http://bit.ly/2VM8ltl

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 

http://bit.ly/2VJ43mB

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 

http://bit.ly/2QLfhTW

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

http://bit.ly/2VM8ltl

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.

http://bit.ly/2H6liL1