Exacerbations in adults with asthma: A systematic review and external validation of prediction models

Publication date: Available online 15 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Rik JB. Loymans, Thomas PA. Debray, Persijn J. Honkoop, Evelien H. Termeer, Jiska B. Snoeck-Stroband, Tjard RJ. Schermer, Willem JJ. Assendelft, Merel Timp, Kian Fan Chung, Ana R. Sousa, Jaap K. Sont, Peter J. Sterk, Helen K. Reddel, Gerben ter Riet
BackgroundSeveral prediction models assessing future risk of exacerbations in adult patients with asthma have been published. Applicability of these models is uncertain because their predictive performance has often not been assessed beyond the population in which they were derived.ObjectiveThis study aimed to identify and critically appraise prediction models for asthma exacerbations and validate them in two clinically distinct populations.MethodsPubMed and EMBASE were searched to April 2017 for reports describing adult asthma populations in which multivariable models were constructed to predict exacerbations during any time frame. After critical appraisal, the models͛ predictive performances were assessed in a primary and a secondary care population for: author-defined exacerbations and for ATS/ERS-defined severe exacerbations.ResultsWe found 12 reports from which 24 prediction models were evaluated. Three predictors (previous healthcare-utilisation, symptoms, and spirometry values) were retained in most models. Assessment was hampered by sub-optimal methodology and reporting, and by differences in exacerbation outcomes. Discrimination (AUROC) of models for author-defined exacerbations was better in the primary care population (mean 0.71) than in the secondary care population (mean 0.60); and similar (0.65 and 0.62 respectively) for ATS/ERS defined severe exacerbations. Model calibration was generally poor, but consistent between the two populations.ConclusionThe preservation of three predictors in models derived from variable populations and the fairly consistent predictive properties of most models in two distinct validation populations suggest the feasibility of a generalizable model predicting severe exacerbations. Nevertheless, improvement of the models is warranted as predictive performances are below the desired level.

Association Between Obesity and Acute Severity Among Patients Hospitalized for Asthma Exacerbation

Publication date: Available online 14 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Sarah Kyuragi Luthe, Atsushi Hirayama, Tadahiro Goto, Mohammad Kamal Faridi, Carlos A. Camargo, Kohei Hasegawa
BackgroundAlthough studies have demonstrated relations between obesity and incident asthma, little is known about the association of obesity with acute severity in adults hospitalized for asthma exacerbation.ObjectivesTo investigate the association of obesity with acute severity of asthma exacerbation.MethodsThis is a retrospective cohort study using population-based data of 8 geographically diverse US states from 2010 through 2013. We included adults (age 18-54 years) hospitalized for asthma exacerbation. The outcome measures were markers of acute severity—use of mechanical ventilation (defined by noninvasive positive pressure ventilation and/or invasive mechanical ventilation) and hospital length of stay. To determine the association of obesity with each outcome, we fit multivariable models adjusting for patient-level confounders (eg, age, sex, race/ethnicity, primary insurance, quartiles for household income, residential status, and comorbidities) and potential patient clustering within hospitals.ResultsAmong the 72,086 patients hospitalized for asthma exacerbation, 24% were obese. Obesity was associated with a significantly higher risk of any mechanical ventilation use (8.3% vs 5.0%; adjusted odds ratio [OR], 1.77; 95% CI, 1.63-1.92; P < .001) driven by the higher risk of noninvasive positive pressure ventilation use (7.2% vs 3.4%; adjusted OR, 2.14; 95% CI, 1.96-2.35; P < .001). Likewise, obese patients were more likely to have a hospital length of stay of 3 or more days compared with nonobese patients (59.4% vs 46.5%; adjusted OR, 1.37; 95% CI, 1.32-1.43; P < .001). These findings were consistent with stratifications by age, sex, and race/ethnicity.ConclusionsIn this population-based study of adults hospitalized for asthma exacerbation, obesity was associated with higher acute severity.

In Vitro Diagnosis of Immediate Drug Hypersensitivity During Anesthesia: A Review of the Literature

Publication date: Available online 14 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Didier G. Ebo, Margaretha Faber, Jessy Elst, Athina L. Van Gasse, Chris H. Bridts, Christel Mertens, Luc S. De Clerck, Margo M. Hagendorens, Vito Sabato
Quantification of specific IgE (sIgE) antibodies constitutes an important measure to document anesthesia-related immediate hypersensitivity reactions (IHRs). However, only a few drug-specific assays are available and their predictive value is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from cellular tests such as basophil mediator release tests and basophil activation tests (BATs). To review the potential and limitations of quantification of sIgE, mediator release, and BAT in anesthesia-related IHRs, a literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE antibodies, leukotrienes, histamine, and tryptase; this was complemented by the authors' experience. The drugs and compounds that have predominantly been studied are neuromuscular blocking agents (NMBAs), β-lactams, latex, and chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to 92% and 92% to 100%, respectively. For sIgE β-lactams, sensitivity varies between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex, and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea components constitute reliable diagnostics. For drugs, the sensitivity of BAT varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator release tests seem to be abandoned and supplanted by BATs.

Anxiety, depression, and asthma control: Changes after standardized treatment

Publication date: Available online 15 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Joaquin Sastre, Astrid Crespo, Toni Fernandez-Sanchez, Manuel Rial, Vicente Plaza
BackgroundIt has been documented that anxiety and depression are prevalent in patients with asthma and are associated with greater frequency of exacerbations, increased use of health-care resources, and poor asthma control.ObjectivesOur study examined not only the association of asthma diagnosis with symptoms of depression/anxiety and asthma control at baseline, but also over a 6-month period of specialist supervision.MethodsWe enrolled 3,182 patients with moderate-severe asthma. All were evaluated with spirometry, ACT, and HADS (Hospital Anxiety and Depression Scale) at baseline and at 6 months. Treatments were decided by specialists according to published guidelines.ResultsAt baseline, 24.2% and 12% of patients were diagnosed with anxiety and depression, respectively, according to HADS. After 6 months, anxiety and depression improved, affecting 15.3% and 8.1% of patients, respectively (p<0.001); mean FEV1 and asthma control also improved (FEV1 from 81.6±20.9% to 86±20.8%; ACT from 15.8 ±4.7 to 19.4± 4.4; both p<0.001).Patients with anxiety and depression used significantly more health-care resources and had more exacerbations. A multivariate analysis showed that patients with anxiety, depression, and lower FEV1 (OR 0.20, 0.34, 0.62; p<.001, respectively) were independently associated with poor asthma control. A multiple linear regression analysis showed that anxiety had a nearly four-fold greater influence over asthma control than depression (0.326 / 0.85 = 4.075)ConclusionsUnder standardized asthma care and after a specific visit with the specialist, patients present significant improvement in these psychological disorders and exhibit better asthma control and functional parameters.

Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with Asymptomatic Prior Exposure: A Prospective Observational Study

Publication date: Available online 14 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Kyoung-Hee Sohn, Dong-Yoon Kang, Ju-Young Kim, Suh-Young Lee, Kyung-Hun Lee, Sae-Won Han, Hye-Ryun Kang
BackgroundOxaliplatin-related hypersensitivity reactions (HSRs), which can be life threatening, have introduced a dilemma regarding the use of chemotherapeutic agents. Because repeated exposure to oxaliplatin may increase the risk of sensitization, patients with a history of prior asymptomatic exposure require risk-stratified care.ObjectiveThis study aimed to elucidate the incidence and risk of oxaliplatin HSRs in patients with a history of asymptomatic prior exposure.MethodsWe performed a prospective observational study of patients who completed oxaliplatin-based chemotherapy between March 2013 and January 2015. Prior exposure to oxaliplatin, the oxaliplatin-free interval, reaction severity, eosinophil counts, and premedication were reviewed to assess the risk factors.ResultsA total of 793 patients were enrolled, among whom 148 (18.7%) experienced an HSR. The HSR incidence was 15.2% among oxaliplatin-naive patients but increased to 31.9% among those with a history of asymptomatic exposure and 75.0% among those with a history of oxaliplatin HSRs during the previous exposure, despite prophylaxis. The mean HSR onset cycle was earliest in the previous HSR group, followed by the previous asymptomatic exposure and nonexposure groups. The HSR severity also differed according to the previous exposure history and HSRs. In the multivariate analysis, prior exposure to oxaliplatin (odds ratio [OR], 3.78; 95% confidence interval [CI], 2.46-5.79) and a longer oxaliplatin-free interval (≥36 months; OR, 4.85; 95% CI, 1.60-14.37) were independent risk factors for HSRs.ConclusionsPrevious exposure to oxaliplatin is a risk factor for earlier HSR onset and more severe and frequent HSR episodes, even if prior therapy was well tolerated.

Protection against summer solar lentigo over-pigmentation with a SPF30 daily cream

Abstract

Background/purpose

The aim of this study was to measure lentigines' pigmentation over a long period of time and evaluate if summer over-pigmentation can be avoided by the use a SPF30 day skin cream.

Methods

Seventeen healthy female volunteers aged 50 and over and presenting lentigines participated in the study from spring to summer. Throughout the study, all subjects applied a SPF30 daily skin cream to only one hand. Color measurements of the target lesions were performed with a chromameter and with a color-calibrated camera. Target lesions were also imaged with in vivo reflectance confocal microscopy (RCM). A specific procedure for re-registering the images was developed to ensure that the same papillae were measured over time.

Results

Both color measurement methods, chromametry and color-calibrated camera, showed that lentigines treated over time with the SPF30 day skin cream were significantly lighter than the non-treated lentigines. The RCM images showed a decrease in the papillary contrast for the treated lentigines.

Conclusion

This study shows that this over-pigmentation can be avoided using a SPF30 day skin cream. Moreover, we have demonstrated that very fine re-registration of the RCM images is possible and ensures a more robust analysis.

Dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid in a patient with acquired reactive perforating collagenosis

Abstract

Bullous pemphigoid (BP) is a common autoimmune blistering disorder with unknown etiology. Recently, increasing numbers of BP cases which developed under the medication with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used antihyperglycemic drugs, have been reported in published works. Here, we report a case of DPP4i (teneligliptin)-associated BP that developed in a 70-year-old Japanese man. Interestingly, the patient had acquired reactive perforating collagenosis (ARPC), which is also known to be associated with the onset of BP. In the present case, clinical, histopathological and immunological findings suggested that DPP4i rather than ARPC was associated with the onset of BP.

Efficacy of low-dose 5-fluorouracil/cisplatin therapy for invasive extramammary Paget's disease

Abstract

Extramammary Paget's disease (EMPD) is one of the cutaneous adenocarcinomas. The effective chemotherapy for advanced EMPD has not been established. This study was designed to evaluate the efficacy of combination 5-fluorouracil (500 mg/body, 7 days/week) and cisplatin (5 mg/body 5 days/week) for invasive EMPD. Seventeen EMPD patients with multiple metastases who visited our dermatology clinic between October 2004 and May 2016 (mean age, 76.9 years; 10 men, seven women) were retrospectively analyzed. Eight EMPD patients underwent low-dose 5-fluorouracil/cisplatin therapy and nine patients chose best supportive care. The average number of treatment cycles was 12.3. All patients had a confirmed response, four (50%) showed a partial response, two (25%) stable disease and two progressive disease. The median times to progression-free and overall survival were 25.0 and 77.4 weeks, respectively. There was no severe (grade 3 and 4) adverse event. Although not significant, the survival of the patients treated with low-dose 5-fluorouracil/cisplatin therapy showed a trend toward improved survival as compared with best supportive care (P = 0.08, log–rank test). This regimen had low risk and relatively high disease control rate, suggesting that this regimen be recommended as one of the treatment options for advanced EMPD.

Successful treatment of chronic intractable pain with risperidone in a patient with acquired idiopathic generalized anhidrosis

Pyogenic granuloma-like Kaposi's sarcoma on the first toe

The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility

Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient,...

Garlic, green tea and turmeric extracts-mediated green synthesis of silver nanoparticles: Phytochemical, antioxidant and in vitro cytotoxicity studies

Publication date: Available online 14 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): D. Arumai Selvan, D. Mahendiran, R. Senthil Kumar, A. Kalilur Rahiman
Phyto-synthesis of silver nanoparticles (AgNPs) was achieved using aqueous garlic, green tea and turmeric extracts, and characterized by different spectroscopic techniques. Phytochemical analysis revealed the presence of rich amount of biochemicals in these extracts, which serve as reducing and capping agents for converting silver nitrate into AgNPs. FT IR spectroscopy confirmed the role of biomolecules in the bioreduction and efficient stabilization of AgNPs. UV–Vis DRS spectra showed a band around 450 nm characteristics of AgNPs. XRD patterns revealed the crystalline nature of the synthesized AgNPs with fcc structure. SEM and TEM analysis revealed the spherical shape of the synthesized AgNPs with an average particle size of 8 nm. EDX analysis confirmed the purity of the synthesized AgNPs with a strong signal at 3.2 keV. The antioxidant activity was assessed by ABTS, DPPH, p-NDA, H2O2 and DMSO scavenging assays, in which the AgNPs synthesized using green method showed remarkable activity with respect to the standard antioxidants ascorbic acid and rutin. In vitro cytotoxicity activity was tested on four cancer cell lines such as human breast adenocarcinoma (MCF-7), cervical (HeLa), epithelioma (Hep-2) and lung (A549) along with one normal human dermal fibroblasts (NHDF) cell line. The AgNPs synthesized using turmeric extract exhibits excellent antioxidant and cytotoxicity activity compared to that synthesized using other extracts.

Graphical abstract

Enhanced antimicrobial, anti-oxidant applications of green synthesized AgNPs- an acute chronic toxicity study of phenolic azo dyes & study of materials surface using X-ray photoelectron spectroscopy

Publication date: Available online 13 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Zia Ul Haq Khan, Amjad Khan, Young Mei Chen, Noor S. Shah, Arif Ullah Khan, Nawshad Muhammad, Kamran Tahir, Hidayat Ullah Shah, Zia Ullah Khan, Muhammad Shakeel, Muhammad Nadeem, Muhammad Imran, Pingyu Wan
The drug resistant bacteria and textile contaminations of water cause different sever health problem throughout the world. To overcome this issue, new environmental benign materials and methods are needed. Plant metabolites directed synthesis of nanoparticles is considered eco-friendly and easy in synthesis. Therefore, it was explicit for the synthesis of AgNPs. The prepared AgNPs were evaluated for antibacterial, antioxidant, photo-catalytic and electrochemical degradation properties as well as toxicity of degradation products on aquatic life. X-Ray Photoelectron Spectroscopy (XPS) has been used for analyzing the surface chemistry of prepared AgNPs. The particle size determines the interaction of nanoparticles with pathogens. Both Gram positive and negative bacteria (Escherichia coli and Staphylococcus areous) are used to determine the anti-microbial potency of the green synthesized AgNPs. The synthesized silver nanoparticles showed significant anti-bacterial applications against B. subtilus and S. aureus. The anti-oxidant applications of AgNPs also studied on comparison with vitamin C. The toxicity of the phenolic Azo dyes (PDA) has been studied against Fish, Daphnia and Green Algae. The electrode potential was studied in the electrochemical redox reaction of hydroxy phenol in aqueous media. Simple electrolyte was used to determine the current efficiency. For the stability of electrode multi cyclic voltammetry was also studied during redox reaction, which showed stability under the potential 0.4 to 0.2 V.

Graphical abstract

Eczema’s Big Break in Hollywood

The Night Of, an HBO miniseries released in 2016, made waves as a social commentary of racial prejudices plaguing the American criminal justice system. As a dermatology resident, I was equally struck by the amount of attention paid to John Turturro's character's (Jack Stone) eczema. Stone is an attorney desperate to show off his legal prowess in a big case, and he gets his chance after Nasir Khan (Riz Ahmed) is convicted of murdering a young girl he met earlier that night. A total of 15 minutes of the show over 8 episodes focus on Stone's eczema. Richard Price, a writer for the show, used eczema as "a metaphor for the frustrations of finding a solution and the entire judicial system." Patients affected by atopic dermatitis can relate to Stone's constant battle with the disease, and the scenes are accurate portrayals of the experience of many patients with eczema.

Cutaneous Diphtheria Mimicking Pyoderma Gangrenosum

This case report describes a patient with cutaneous diphtheria mimicking pyoderma gangrenosum.

Standardized Screening for Depression and Suicidal Ideation

This Viewpoint examines the role of the Patient Health Questionnaire-2 in dermatology concerning secondary psychiatric disorders that involve emotional disturbances and manifest in response to the psychologic stress caused by dermatologic conditions.

Diameter of Skin Lesions With and Without a Ruler

This analysis of survey results examines the accuracy with which medical students, internal medicine residents, and dermatology residents, fellows, and faculty can estimate the diameter of skin lesions in clinical photographs.

Practicing Safe Dermatology—Screening Out Liability

The article "Characteristics of Medical Liability Claims Against Dermatologists From 1991 Through 2015" by Kornmehl and colleagues is a welcome addition in our quest to understand how to reduce dermatology practice risk. The study confirms much of what we already knew or suspected but also provides some new interesting insights. It is reassuring to see that most malpractice cases against dermatologists are "abandoned, withdrawn or dismissed." Similarly, it is comforting to know that there has been a net reduction of 29.2% in paid claims for dermatologists. Is this secondary to improved patient care? The changing landscape of tort reform? Or both?

Colors Beyond the Visible

The process of painting restoration is in open view to all visitors at the Boston Museum of Fine Arts. Here, multiple techniques for analysis of painting damage caused by time and environmental conditions are openly displayed. One of those involves scanning under UV light. UV light, particularly at 360 nm, reveals what is on the surface of the painting, such as the quality of the top layer and any overlaid fungal growth. Furthermore, using a UV filter, the conservator is able to photograph what is underneath the paint, beyond what visible light can show. UV fluorescence photography is able to reveal the presence of natural resin varnishes and can also help in identifying any retouching and overpainting. Such studies are about contrasts and colors.

Trends in Medical Liability Claims Against Dermatologists

This study analyzes 24 years of data through 2015 from a nationally representative liability claims registry to compare the medical liability claims against dermatologists vs nondermatologists.

Herpes Zoster Rates in a Large Cohort of Patients With Systemically Treated Psoriasis

This cohort study examines estimated herpes zoster incidence rates among systemically treated patients with psoriasis in a community-based health care delivery setting.

Fluorouracil for Prevention of Keratinocyte Carcinoma

This randomized, double-blind, placebo-controlled trial examined the use of topical fluorouracil, 5%, to prevent keratinocyte carcinoma.

Newborn Treated With Drug That Triggered Maternal SJS During Pregnancy

This case report of a woman who developed Stevens-Johnson syndrome during pregnancy describes the treatment of her newborn with the culprit drug.

Tumor Classifications in 7th and 8th Editions of AJCC Cancer Staging Manual

This retrospective cohort study compares the tumor classifications for head and neck squamous cell carcinoma using the 7th vs 8th editions of the AJCC Cancer Staging Manual for head amd neck cutaneous csquamous cell carcinomas.

Error in Data in the Results Section

In the article titled "Management of Morgellons Disease With Low-Dose Trifluoperazine," an error occurred in the last paragraph of the Results section concerning the number of patients who achieved at least partial responses and baseline function with median dosages of the study treatment. The sentence now reads, "Among patients with median dosages of 2 mg/d, 10 (71%) achieved at least partial responses and 7 (50%) achieved baseline function…". The article was corrected online.

Hypercoagulable Conditions and Calciphylaxis in Renal Disease

This case-control study compares the hypercoagulability status of patients with calciphylaxis and renal disease with controls to identify conditions that are risk factors for developing calciphylaxis while controlling for chronic kidney disease.

Harvey, Irma, and Maria—The Dermatologic Risks of Hurricanes and Floods

Hurricane Harvey and Irma may be behind us, but many of the effects of the storms continue to unfold. Harvey dumped a record of 51 inches of rainfall over Texas and Louisiana in 6 days. Irma remained a category 5 hurricane for 3 days, making it the strongest Atlantic-basin hurricane recorded outside the Gulf of Mexico. More recently, Hurricane Maria hit the Dominican Republic and Puerto Rico.

Digital Photographic Assessment of Acne Vulgaris Using NORA Technology

This pilot validation study determines whether acne scoring through digital self-photographs is accurate and reliable compared with in-person examination findings in patients with acne vulgaris.

February 2018 Issue Highlights

Treatment for Livedoid Vasculopathy

This systematic review uses the MEDLINE and EMBASE databases to identify the available therapies for livedoid vasculopathy and their clinical outcomes.

Firefighter Skin Cancer and Sun Protection Practices

This survey study examines skin cancer history, skin cancer screening, and sun protection habits among active Florida firefighters.

Nongenital Molluscum Contagiosum in Persons Without Immune Deficiency

This Clinical Evidence Synopsis summarizes an updated Cochrane review that assessed effectiveness and safety of treatments for nongenital molluscum contagiosum in persons without immune deficiency.

Noninvasive Gene Expression Testing in Amelanotic Melanoma

This case report describes noninvasive gene expression testing in a patient with amelanotic melanoma.

Secukinumab Demonstrates High Sustained Efficacy and a Favorable Safety Profile in Patients with Moderate to Severe Psoriasis through 5 Years of Treatment (SCULPTURE Extension Study)

Abstract

Background

Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy and a favorable safety profile in the treatment of moderate to severe psoriasis and psoriatic arthritis.

Objective

To assess the efficacy and safety of secukinumab through 5 years of treatment in moderate to severe psoriasis.

Methods

In the core SCULPTURE study, Psoriasis Area and Severity Index (PASI) 75 responders at Week 12 continued receiving subcutaneous secukinumab until Year 1. Thereafter, patients entered the extension phase and continued treatment as per the core trial. Treatment was double-blinded until the end of Year 3 and open-label from Year 4. Here we focus on the 300 mg fixed-interval (every 4 weeks) treatment, the recommended per label dose. Efficacy data are primarily reported as observed but multiple imputation (MI) and last observation carried forward (LOCF) techniques were also undertaken as supportive analyses.

Results

At Year 1, 168 patients entered the extension study and at the end of Year 5, 126 patients completed 300mg (every 4 weeks) treatment. PASI 75/90/100 responses at Year 1 (88.9%, 68.5% and 43.8%, respectively) were sustained to Year 5 (88.5%, 66.4% and 41%). PASI responses were consistent regardless of the analysis undertaken (as observed, MI, or LOCF). The average improvement in mean PASI was approximately 90% through 5 years compared to core study baseline. DLQI (dermatology life quality index) 0/1 response also sustained through 5 years (72.7% at Year 1 and 65.5% at Year 5). The safety profile of secukinumab remained favorable, with no cumulative or unexpected safety concerns identified.

Conclusion

Secukinumab 300 mg treatment delivered high and sustained levels of skin clearance and improved quality of life through 5 years in patients with moderate to severe psoriasis. Favorable safety established in the secukinumab phase 2/3 program was maintained to 5 years.

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If it's red and scaly look for fungus: remember cutaneous protothecosis

Abstract

A 34-year-old woman presented with a 5-year old history of unilateral facial erythematous plaque and scattered papules. The lesions continue to spread slowly. She complains mild pruritus. No medical history including diabetes or immunosuppression were recorded. Physical examination showed large area of well-demarcated erythematous plaque on the right cheek(Fig.A) with infiltrating pinpointed-flesh papules at the margin with less scales(Fig.B).

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Two EDA Gene Mutations in Chinese Patients with Hypohidrotic Ectodermal Dysplasia

Abstract

Hypohidrotic (anhidrotic) ectodermal dysplasia (HED) is an inherited disorder and generally characterized by the diminution or absence of eccrine sweat glands, oligodontia, peg shaped teeth, and sparse hair.¹ X-linked Hypohidrotic (anhidrotic) ectodermal dysplasia (XLHED) is the most frequent inheritance patterns, though in some cases autosomal dominant and recessive inheritance patterns were also reported.^2,3 4 genes (EDA, EDAR, EDARADD and WNT10A) account for more than 90% of HED cases and the mutations in Ectodysplasin-A (EDA) gene are the most prevalent (58%).⁴

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Numbers on injectable treatments in the Netherlands in 2016

Abstract

Objective data on the number of cosmetic injectable treatments (Botulinum Toxin A and fillers) performed annually is lacking. These numbers would be helpfull in establishing the importance of this area in medicine from a medico-social perspective and to determine the incidence of side-effect. Numbers on the number of treatments or global volumes used provided by the American Society of Plastic Surgeons (ASPS) and the International Society of Aesthetic Plastic Surgery are erestricted to their members.^1,2

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The use of JAK inhibitors in the treatment of Progressive Systemic sclerosis

Abstract

Systemic sclerosis is a connective tissue disorder characterized by fibrosis. Patients may have restricted movement of the joints, Raynaud's phenomenon, self-amputation of the digits, dyspnea, and upper gastrointestinal symptoms. Excessive production of extracellular matrix (ECM) proteins such as type I collagen via transforming growth factor β (TGF β) are thought to be responsible for the fibrosis.¹

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Whole-exome sequencing for diagnosis of hereditary ichthyosis

Abstract

Background

Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care.

Objective

We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic work-up of inherited ichthyosis.

Methods

During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively.

Results

Genetic variants causative for the ichthyosis were identified in 27 out of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI).

Conclusion

WES appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice, and should be considered a first-tier genetic test in these patients.

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Is atopic dermatitis associated with obesity? A systematic review of observational studies

Abstract

Obesity has been associated with atopic dermatitis (AD), however the results have been conflicting. Our aim was to provide an update on current knowledge from observational studies addressing the possible association between obesity and AD.

Systematic literature review was performed by identifying studies addressing a possible link between AD and overweight/obesity from PubMed, Embase, and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale.

A total of 45 studies (comprising more than 90.000 individuals with AD) fulfilled the criteria and were included in the present review. The available studies revealed inconsistencies, but the majority indicated that obesity is associated with AD. Studies addressing obesity in infancy or early childhood (age < 2 years) and AD reported a positive association. From childhood into adulthood, there is a discrepancy in the observations, as the more recent prospective studies found a positive association, whereas this was not observed in older cross-sectional studies. The inconsistency might be explained by the difference in study design, the diagnostic criteria of AD, regional differences, and by the varied definitions of overweight and obesity used in the studies.

In Conclusion, overweight/obesity is associated with an increased risk of AD. Large prospective cohort studies are required to confirm the association between AD and obesity and the possibility that weight control in childhood may help to mitigate or reverse AD symptoms.

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The efficacy and safety of non-pharmacological therapies for the treatment of acne vulgaris: A systematic review and best-evidence synthesis

Abstract

Background

Acne vulgaris is a multifaceted skin disorder, affecting more than 85% of young individuals worldwide. Pharmacological therapy is not always desirable because of the development of antibiotic resistance or the potential risk of adverse effects. Non-pharmacological therapies can be viable alternatives for conventional therapies. However, sufficient evidence based support in the efficacy and safety of non-pharmacological therapies is lacking.

Objective

To assess the efficacy and safety of several non-pharmacological therapies in the treatment of acne vulgaris.

Methods

A systematic literature review, including a best-evidence synthesis was performed to identify literature. Three electronic databases were accessed and searched for studies published between January 2000 and May 2017.

Results

Thirty three eligible studies were included in our systematic review. Three main types of non-pharmacological therapies were identified: laser and light-based therapies, chemical peels and fractional microneedling radiofrequency. The majority of the included studies demonstrated a significant reduction on acne lesions. However, only 7 studies had a high methodologic quality. Based on these 7 trials, a best-evidence synthesis was conducted. Strong evidence was found for glycolic acid (10-40%). Moderate evidence was found for amino fruit acid (20-60%), IPL (400–700nm and 870 – 1200nm) and the diode laser (1450nm). Initially, conflicting evidence was found for pulsed dye laser (585-595nm). The most frequently reported side-effects for non-pharmacological therapies included erythema, tolerable pain, purpura, oedema and a few cases of hyperpigmentation, which were in most cases mild and transient.

Conclusion

Circumstantial evidence was found for non-pharmacological therapies in the treatment of acne vulgaris. However, the lack of high methodological quality among included studies prevented us to draw clear conclusions, regarding a stepwise approach. Nevertheless, our systematic review including a best-evidence synthesis did create order and structure in resulting outcomes in which a first step towards future research is generated.

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A prospective right–left comparative study to evaluate the efficacy and tolerability of combination of NB-UVB and topical bimatoprost 0.03% eye drops versus NB-UVB given alone in patients of vitiligo vulgaris

Abstract

The treatment of vitiligo has been a tough challenge for dermatologists. Phototherapy, apart from being first line monotherapy,¹ has also been used in combination with topical therapies like corticosteroids, khellin, phenylalanine, calcineurin inhibitors etc, with the aim of hastening and enhancing repigmentation and reducing side-effects.^2,3 Recent reports have highlighted darkening of iris, and eyelash and periocular hyperpigmentation induced by latanoprost (prostaglandin F2α analogue) used for treatment of glaucoma.⁴ Extrapolating these findings in treatment of vitiligo, we assessed the outcome of NB- UVB and topical bimatoprost 0.03% combination versus NB-UVB alone in a prospective right–left comparative study.

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Drug survival and post-drug survival of first-line immunosuppressive treatments for atopic dermatitis: comparison between methotrexate and cyclosporine

Abstract

Introduction

Cyclosporine and methotrexate are the two preferred first-line immunosuppressive treatments in atopic dermatitis. The aim of this study was to compare the treatment profiles of methotrexate and cyclosporine in daily practice as the first-line immunosuppressive treatment in atopic dermatitis, using two survival analyses, "drug survival" (time on the drug) and "post-drug survival" (time between two drugs).

Methods

Retrospective study including patients with moderate-to-severe atopic dermatitis treated with methotrexate or cyclosporine as the first-line immunosuppressive treatment. The reasons for discontinuation of treatment were collected: controlled disease, treatment failure, side event pregnancy and non-compliance. "Drug survival" and "post-drug survival" analyses were performed using the Kaplan Meier method and predictive factors were analyzed using uni- and multivariate Cox regression analyses.

Results

56 patients, among whom 25 patients treated with cyclosporine and 31 with methotrexate (median age: 34 ± 15 years) were included between 2007 and 2016. Reasons for discontinuation were not significantly different between "controlled disease" and other reasons (p=0.11). The median "drug survival" was significantly longer for methotrexate (23 months) than for cyclosporine (8 months) (p<0.0001). Six months from baseline, 93% of patients treated with methotrexate were still being treated vs 63% among patients treated with cyclosporine. The median of "post-drug survival" was significantly longer for methotrexate (12 months) than for cyclosporine (2 months). Only treatment with CYC was a predictive factor for decreased "drug survival" and "post-drug survival".

Conclusion

This is the first direct comparison between methotrexate and cyclosporine as first-line immunosuppressive treatments for moderate to severe atopic dermatitis in daily practice. We evidenced two different treatment profiles: the duration of methotrexate administration is longer than that of cyclosporine. "Post-drug survival" could be a new tool to assess the maintenance of effect of a drug after withdrawal in atopic dermatitis, and more broadly in chronic skin disease.

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Clinician surveys – time to make better use of this valuable resource for dermatologists

Abstract

Clinician surveys can be a useful resource to identify uncertainties in practice, determine expert or current opinion, define research priorities (as part of a priority setting partnership) and demonstrate feasibility of undertaking randomised clinical trials (RCT). Online survey programs such as SurveyMonkey^™ or Google surveys provide a simple step-by-step process to develop electronic surveys at little or no cost. These can be distributed using an email link to a nationwide audience via society membership groups.

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Primary cutaneous small/medium-sized pleomorphic T-cell lymphoproliferative disorder shows a common vascular pattern at dermoscopy

Abstract

Primary cutaneous small/medium-sized pleomorphic T-cell lymphoproliferative disorder (PCSM-TCLPD) is a rare and indolent primary cutaneous T-cell lymphoma variant [1], usually presenting as a solitary nodule or plaque in the head and neck [2] or rarely as multiple lesions in anatomic areas apart from head and neck [2]. Histology reveals the presence of a dense dermal infiltrate of CD4+, CD8-, small/medium pleomorphic cells [2] intermingled with reactive cells. Surgical or radiotherapic approach are the preferred option, while oral doxycycline has been suggested in cases with multiple lesions [2-3].

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A case of atypical eosinophilic pustular folliculitis that emerged following the administration of capecitabine

Abstract

A 66-year-old man presented with aggregated pruritic follicular papulopustules on the forearms and thighs (Figure A). Each papulopustule was 1 mm in size, and arose from the hair follicle area (Figure B). The patient had undergone laparoscopic colectomy one month prior, and had been given a course of chemotherapy with capecitabine at 4,200 mg per day orally for 14 days followed by a 7-day washout period.

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A cross-sectional analysis of the effects of increased resident autonomy on practice patterns and patient satisfaction

Abstract

The appropriate balance between autonomy and supervision in graduate medical education remains an understudied question within dermatology. A recent survey of residents in a large academic dermatology residency program revealed concerns over inadequate autonomy in outpatient clinics. Residents in this program rotate through general and specialty clinics as well as two continuity clinics, but the degree of autonomy remains attending dependent, with most clinics following an "apprenticeship model" where residents function as assistants to their attending.

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Ridge sowing of sunflower ( Helianthus annuus L.) in a minimum till system improves the productivity, oil quality, and profitability on a sandy loam soil under an arid climate

Abstract

Sunflower (Helianthus annuus L.) is a major oilseed crop grown for its edible oil across the globe including Pakistan. In Pakistan, the production of edible oil is less than the required quantity; the situation is being worsened with the increasing population. Thus, there is dire need to grow those sunflower genotypes which perform better under a given set of agronomic practices. In this 2-year study, we compared four sunflower genotypes, viz., Armoni, Kundi, Sinji, and S-278 for their yield potential, oil contents, fatty acid composition, and profitability under three sowing methods, viz., bed sowing, line sowing, and ridge sowing and two tillage system, viz., plow till and minimum till. Among the sunflower genotypes, the genotype Armoni produced the highest plant height, number of leaves, head diameter, 1000-achene weight, and achene yield; the oil contents and oleic acid were the highest in genotype Sinji. Among the sowing methods, the highest number of leaves per plant, head diameter, number of achenes per head, achene yield, and oil contents were recorded in ridge sowing. Among the tillage systems, the highest head diameter 16. 2 cm, 1000-achene weight (57.2 g), achene yield (1.8 t ha⁻¹), oil contents (35.2%), and oleic acid (15.2%) were recorded in minimum till sunflower. The highest net benefits and benefit to cost ratio were recorded in minimum till ridge sown Armoni genotype. In conclusion, the genotype Armoni should be grown on ridges to achieve the highest achene yield, oil contents, and net profitability.

Using network to enhance the insights on correlation and pollution assessment of co-occurring metals in marine sediments, the East China Sea

Abstract

In this study, sediment samples were collected from 24 sites in the East China Sea (ECS) to investigate the distribution characteristics, co-occurrence correlations, and ecological risks of metals. In surface sediments, metals presented a homologous banding distribution pattern decreasing seaward with distance. With network analysis, it indicated metals in this area might directly derive from the coastal river inputs. According to geo-accumulation indexes (I_geo), Cd was classified as moderate pollution at 58% sites, far above other metals. In addition, the potential ecological risk index (RI) was clustered with the ecological risk (ER) of Cd, which was regarded as considerable or high-risk level for most coastal stations. Thus Cd pollution in the ESC sediment should be paid more attention. In sum, the visualization of statistical analyses combined with geochemical approaches could reveal the potential sources of contaminants and ecological risks, thus facilitate the pollution evaluation in marine sediments.

Discrete Modules and Mesoscale Functional Circuits for Thermal Nociception within Primate S1 Cortex

This study addresses one long-standing question of whether functional separations are preserved for somatosensory modalities of touch, heat, and cold nociception within primate primary somatosensory (S1) cortex. This information is critical for understanding how the nature of pain is represented in the primate brain. Using a combination of submillimeter-resolution fMRI and microelectrode local field potential (LFP) and spike recordings, we identified spatially segregated cortical zones for processing touch and nociceptive heat and cold stimuli in somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys. The distances between zones were comparable (~3.4 mm) across stimulus modalities (heat, cold, and tactile), indicating the existence of uniform, modality-specific modules. Stimulus-evoked LFP maps validated the fMRI maps in areas 3b and 1. Isolation of heat and cold nociceptive neurons from the fMRI zones confirmed the validity of using fMRI to probe nociceptive regions and circuits. Resting-state fMRI analysis revealed distinct intrinsic functional circuits among functionally related zones. We discovered distinct modular structures and networks for thermal nociception within S1 cortex, a finding that has significant implications for studying chronic pain syndromes and guiding the selection of neuromodulation targets for chronic pain management.

SIGNIFICANCE STATEMENT Primate S1 subregions contain discrete heat and cold nociceptive modules. Modules with the same properties exhibit strong functional connection. Nociceptive fMRI response coincides with LFP and spike activities of nociceptive neurons. Functional separation of heat and cold pain is retained within primate S1 cortex.

A Shared Vision for Machine Learning in Neuroscience

With ever-increasing advancements in technology, neuroscientists are able to collect data in greater volumes and with finer resolution. The bottleneck in understanding how the brain works is consequently shifting away from the amount and type of data we can collect and toward what we actually do with the data. There has been a growing interest in leveraging this vast volume of data across levels of analysis, measurement techniques, and experimental paradigms to gain more insight into brain function. Such efforts are visible at an international scale, with the emergence of big data neuroscience initiatives, such as the BRAIN initiative (Bargmann et al., 2014), the Human Brain Project, the Human Connectome Project, and the National Institute of Mental Health's Research Domain Criteria initiative. With these large-scale projects, much thought has been given to data-sharing across groups (Poldrack and Gorgolewski, 2014; Sejnowski et al., 2014); however, even with such data-sharing initiatives, funding mechanisms, and infrastructure, there still exists the challenge of how to cohesively integrate all the data. At multiple stages and levels of neuroscience investigation, machine learning holds great promise as an addition to the arsenal of analysis tools for discovering how the brain works.

Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling at the Mouse Neuromuscular Junction

Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion that disruption of synaptic transmission is not sensed to trigger upregulation of QC. During studies of the effect of partial block of nAChRs on QC, we observed a small but reproducible increase in the decay kinetics of miniature synaptic currents. The change in kinetics was correlated with the increase in QC and raises the possibility that a change in postsynaptic nAChR conformation may be associated with the presynaptic increase in QC. We propose that, in addition to functioning in synaptic transmission, ionotropic muscle nicotonic nAChRs may serve as signaling molecules that participate in synaptic plasticity. Because nAChRs have been implicated in a number of disease states, the finding that nAChRs may be involved in triggering synaptic plasticity could have wide-reaching implications.

SIGNIFICANCE STATEMENT The signals that initiate synaptic plasticity of the nervous system are still incompletely understood. Using the mouse neuromuscular junction as a model synapse, we studied how block of neurotransmitter receptors is sensed to trigger synaptic plasticity. Our studies led to the surprising conclusion that neither changes in synaptic current nor spiking of the presynaptic or postsynaptic cell are sensed to initiate synaptic plasticity. Instead, postsynaptic nicotinic acetylcholine receptors (nAChRs), in addition to functioning in synaptic transmission, may serve as signaling molecules that trigger synaptic plasticity. Because nAChRs have been implicated in a number of disease states, the finding that they may mediate synaptic plasticity has broad implications.

Working with Schemas, Predicting with Schemas

Neural Mechanisms Underlying Cross-Modal Phonetic Encoding

Audiovisual (AV) integration is essential for speech comprehension, especially in adverse listening situations. Divergent, but not mutually exclusive, theories have been proposed to explain the neural mechanisms underlying AV integration. One theory advocates that this process occurs via interactions between the auditory and visual cortices, as opposed to fusion of AV percepts in a multisensory integrator. Building upon this idea, we proposed that AV integration in spoken language reflects visually induced weighting of phonetic representations at the auditory cortex. EEG was recorded while male and female human subjects watched and listened to videos of a speaker uttering consonant vowel (CV) syllables /ba/ and /fa/, presented in Auditory-only, AV congruent or incongruent contexts. Subjects reported whether they heard /ba/ or /fa/. We hypothesized that vision alters phonetic encoding by dynamically weighting which phonetic representation in the auditory cortex is strengthened or weakened. That is, when subjects are presented with visual /fa/ and acoustic /ba/ and hear /fa/ (illusion-fa), the visual input strengthens the weighting of the phone /f/ representation. When subjects are presented with visual /ba/ and acoustic /fa/ and hear /ba/ (illusion-ba), the visual input weakens the weighting of the phone /f/ representation. Indeed, we found an enlarged N1 auditory evoked potential when subjects perceived illusion-ba, and a reduced N1 when they perceived illusion-fa, mirroring the N1 behavior for /ba/ and /fa/ in Auditory-only settings. These effects were especially pronounced in individuals with more robust illusory perception. These findings provide evidence that visual speech modifies phonetic encoding at the auditory cortex.

SIGNIFICANCE STATEMENT The current study presents evidence that audiovisual integration in spoken language occurs when one modality (vision) acts on representations of a second modality (audition). Using the McGurk illusion, we show that visual context primes phonetic representations at the auditory cortex, altering the auditory percept, evidenced by changes in the N1 auditory evoked potential. This finding reinforces the theory that audiovisual integration occurs via visual networks influencing phonetic representations in the auditory cortex. We believe that this will lead to the generation of new hypotheses regarding cross-modal mapping, particularly whether it occurs via direct or indirect routes (e.g., via a multisensory mediator).

LRRK2 G2019S Induces Anxiety/Depression-like Behavior before the Onset of Motor Dysfunction with 5-HT1A Receptor Upregulation in Mice

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD). The neuropathology of LRRK2 mutation-related PD, including increased dopaminergic neurodegeneration and Lewy bodies, is indistinguishable from that of idiopathic PD. The subtle nonmotor phenotypes of LRRK2 mutation-related PD have not been fully evaluated. In the present study, we examined anxiety/depression-like behaviors and accompanying neurochemical changes in differently aged transgenic (Tg) mice expressing human mutant LRRK2 G2019S. Through multiple behavioral tests, including light–dark test, elevated plus maze, sucrose preference test, forced swimming test, and tail-suspension test, we found that anxiety/depression-like behavior appeared in middle-aged (43–52 weeks) Tg mice before the onset of PD-like motor dysfunction. These behavioral tests were performed using both male and female mice, and there were no sex-related differences in behavioral changes in the middle-aged Tg mice. Along with behavioral changes, serotonin levels also significantly declined in the hippocampus of Tg mice. Additionally, increases in the expression of the 5-HT_1A receptor (5-HT_1AR) grew more significant with aging and were detected in the hippocampus, amygdala, and dorsal raphe nucleus. In vitro study using the serotonergic RN46A and hippocampal HT22 cells showed that 5-HT_1AR upregulation was related to enhanced expression of LRRK2 G2019S and was attenuated by the LRRK2 inhibitor LRRK2-IN-1. Wild-type LRRK2 had no significant effect on 5-HT_1AR transcription. The present study provides the first in vivo and in vitro evidence demonstrating abnormal regulation of 5-HT_1AR along with the manifestation of anxiety/depression-like, nonmotor symptom in PD related to LRRK2.

SIGNIFICANCE STATEMENT Parkinson's disease (PD), the second most common neurodegenerative disorder, is clinically characterized by motor dysfunctions. In most cases, various nonmotor symptoms present several years before the onset of the classical motor features of PD and severely affect the quality of life of patients. Here, we demonstrate the causative role of leucine-rich repeat kinase 2 (LRRK2), a common PD-linked mutation, in the development of anxiety/depression-like behaviors. We found that age-dependent 5-HT_1A receptor upregulation in the hippocampus, amygdala, and dorsal raphe nucleus is accompanied by the expression of the LRRK2 mutant phenotype. Our findings demonstrating a potential mechanism for nonmotor psychiatric symptoms produced by LRRK2 mutation suggest that directly targeting the 5-HT_1A receptor can improve the therapeutic efficacy of drugs for PD-associated depression.

Signal Complexity of Human Intracranial EEG Tracks Successful Associative-Memory Formation across Individuals

Memory performance is highly variable among individuals. Most studies examining human memory, however, have largely focused on the neural correlates of successful memory formation within individuals, rather than the differences among them. As such, what gives rise to this variability is poorly understood. Here, we examined intracranial EEG (iEEG) recordings captured from 43 participants (23 male) implanted with subdural electrodes for seizure monitoring as they performed a paired-associates verbal memory task. We identified three separate but related signatures of neural activity that tracked differences in successful memory formation across individuals. High-performing individuals consistently exhibited less broadband power, flatter power spectral density slopes, and greater complexity in their iEEG signals. Furthermore, within individuals across three separate time scales ranging from seconds to days, successful recall was positively associated with these same metrics. Our data therefore suggest that memory ability across individuals can be indexed by increased neural signal complexity.

SIGNIFICANCE STATEMENT We show that participants whose intracranial EEG exhibits less low-frequency power, flatter power spectrums, and greater sample entropy overall are better able to memorize associations, and that the same metrics track fluctuations in memory performance across time within individuals. These metrics together signify greater neural signal complexity, which may index the brain's ability to flexibly engage with information and generate separable memory representations. Critically, the current set of results provides a unique window into the neural markers of individual differences in memory performance, which have hitherto been underexplored.

Diversity and Connectivity of Layer 5 Somatostatin-Expressing Interneurons in the Mouse Barrel Cortex

Inhibitory interneurons represent 10–15% of the neurons in the somatosensory cortex, and their activity powerfully shapes sensory processing. Three major groups of GABAergic interneurons have been defined according to developmental, molecular, morphological, electrophysiological, and synaptic features. Dendritic-targeting somatostatin-expressing interneurons (SST-INs) have been shown to display diverse morphological, electrophysiological, and molecular properties and activity patterns in vivo. However, the correlation between these properties and SST-IN subtype is unclear. In this study, we aimed to correlate the morphological diversity of layer 5 (L5) SST-INs with their electrophysiological and molecular diversity in mice of either sex. Our morphological analysis demonstrated the existence of three subtypes of L5 SST-INs with distinct electrophysiological properties: T-shaped Martinotti cells innervate L1, and are low-threshold spiking; fanning-out Martinotti cells innervate L2/3 and the lower half of L1, and show adapting firing patterns; non-Martinotti cells innervate L4, and show a quasi-fast spiking firing pattern. We estimated the proportion of each subtype in L5 and found that T-shaped Martinotti, fanning-out Martinotti, and Non-Martinotti cells represent ~10, ~50, and ~40% of L5 SST-INs, respectively. Last, we examined the connectivity between the three SST-IN subtypes and L5 pyramidal cells (PCs). We found that L5 T-shaped Martinotti cells inhibit the L1 apical tuft of nearby PCs; L5 fanning-out Martinotti cells also inhibit nearby PCs but they target the dendrite mainly in L2/3. On the other hand, non-Martinotti cells inhibit the dendrites of L4 neurons while avoiding L5 PCs. Our data suggest that morphologically distinct SST-INs gate different excitatory inputs in the barrel cortex.

SIGNIFICANCE STATEMENT Morphologically diverse layer 5 SST-INs show different patterns of activity in behaving animals. However, little is known about the abundance and connectivity of each morphological type and the correlation between morphological subtype and spiking properties. We demonstrate a correlation between the morphological and electrophysiological diversity of layer 5 SST-INs. Based on these findings we built a classifier to infer the abundance of each morphological subtype. Last, using paired recordings combined with morphological analysis, we investigated the connectivity of each morphological subtype. Our data suggest that, by targeting different cell types and cellular compartments, morphologically diverse SST-INs might gate different excitatory inputs in the mouse barrel cortex.

Sox2 Is Essential for Oligodendroglial Proliferation and Differentiation during Postnatal Brain Myelination and CNS Remyelination

In the CNS, myelination and remyelination depend on the successful progression and maturation of oligodendroglial lineage cells, including proliferation and differentiation of oligodendroglial progenitor cells (OPCs). Previous studies have reported that Sox2 transiently regulates oligodendrocyte (OL) differentiation in the embryonic and perinatal spinal cord and appears dispensable for myelination in the postnatal spinal cord. However, the role of Sox2 in OL development in the brain has yet to be defined. We now report that Sox2 is an essential positive regulator of developmental myelination in the postnatal murine brain of both sexes. Stage-specific paradigms of genetic disruption demonstrated that Sox2 regulated brain myelination by coordinating upstream OPC population supply and downstream OL differentiation. Transcriptomic analyses further supported a crucial role of Sox2 in brain developmental myelination. Consistently, oligodendroglial Sox2-deficient mice developed severe tremors and ataxia, typical phenotypes indicative of hypomyelination, and displayed severe impairment of motor function and prominent deficits of brain OL differentiation and myelination persisting into the later CNS developmental stages. We also found that Sox2 was required for efficient OPC proliferation and expansion and OL regeneration during remyelination in the adult brain and spinal cord. Together, our genetic evidence reveals an essential role of Sox2 in brain myelination and CNS remyelination, and suggests that manipulation of Sox2 and/or Sox2-mediated downstream pathways may be therapeutic in promoting CNS myelin repair.

SIGNIFICANCE STATEMENT Promoting myelin formation and repair has translational significance in treating myelin-related neurological disorders, such as periventricular leukomalacia and multiple sclerosis in which brain developmental myelin formation and myelin repair are severely affected, respectively. In this report, analyses of a series of genetic conditional knock-out systems targeting different oligodendrocyte stages reveal a previously unappreciated role of Sox2 in coordinating upstream proliferation and downstream differentiation of oligodendroglial lineage cells in the mouse brain during developmental myelination and CNS remyelination. Our study points to the potential of manipulating Sox2 and its downstream pathways to promote oligodendrocyte regeneration and CNS myelin repair.

Abdominal Vagal Afferents Modulate the Brain Transcriptome and Behaviors Relevant to Schizophrenia

Reduced activity of vagal efferents has long been implicated in schizophrenia and appears to be responsible for diminished parasympathetic activity and associated peripheral symptoms such as low heart rate variability and cardiovascular complications in affected individuals. In contrast, only little attention has been paid to the possibility that impaired afferent vagal signaling may be relevant for the disorder's pathophysiology as well. The present study explored this hypothesis using a model of subdiaphragmatic vagal deafferentation (SDA) in male rats. SDA represents the most complete and selective vagal deafferentation method existing to date as it leads to complete disconnection of all abdominal vagal afferents while sparing half of the abdominal vagal efferents. Using next-generation mRNA sequencing, we show that SDA leads to brain transcriptional changes in functional networks annotating with schizophrenia. We further demonstrate that SDA induces a hyperdopaminergic state, which manifests itself as increased sensitivity to acute amphetamine treatment and elevated accumbal levels of dopamine and its major metabolite, 3,4-dihydroxyphenylacetic acid. Our study also shows that SDA impairs sensorimotor gating and the attentional control of associative learning, which were assessed using the paradigms of prepulse inhibition and latent inhibition, respectively. These data provide converging evidence suggesting that the brain transcriptome, dopamine neurochemistry, and behavioral functions implicated in schizophrenia are subject to visceral modulation through abdominal vagal afferents. Our findings may encourage the further establishment and use of therapies for schizophrenia that are based on vagal interventions.

SIGNIFICANCE STATEMENT The present work provides a better understanding of how disrupted vagal afferent signaling can contribute to schizophrenia-related brain and behavioral abnormalities. More specifically, it shows that subdiaphragmatic vagal deafferentation (SDA) in rats leads to (1) brain transcriptional changes in functional networks related to schizophrenia, (2) increased sensitivity to dopamine-stimulating drugs and elevated dopamine levels in the nucleus accumbens, and (3) impairments in sensorimotor gating and the attentional control of associative learning. These findings may encourage the further establishment of novel therapies for schizophrenia that are based on vagal interventions.

This Week in The Journal

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain

Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo. However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event.

SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of their influence on the whole-brain networks. Here, we have longitudinally and noninvasively monitored the structural and functional network alterations in the mouse model of focal cerebral ischemia. Structural changes of fiber-density increases are stimulated in the endogenous tissue without further modulation by the stem cells, while functional networks are stabilized by the stem cells via a paracrine effect. These results will help decipher the underlying networks of brain plasticity in response to cerebral lesions and offer clues to unravelling the mystery of how stem cells mediate regeneration.

The Primary Role of Flow Processing in the Identification of Scene-Relative Object Movement

Retinal image motion could be due to the movement of the observer through space or an object relative to the scene. Optic flow, form, and change of position cues all provide information that could be used to separate out retinal motion due to object movement from retinal motion due to observer movement. In Experiment 1, we used a minimal display to examine the contribution of optic flow and form cues. Human participants indicated the direction of movement of a probe object presented against a background of radially moving pairs of dots. By independently controlling the orientation of each dot pair, we were able to put flow cues to self-movement direction (the point from which all the motion radiated) and form cues to self-movement direction (the point toward which all the dot pairs were oriented) in conflict. We found that only flow cues influenced perceived probe movement. In Experiment 2, we switched to a rich stereo display composed of 3D objects to examine the contribution of flow and position cues. We moved the scene objects to simulate a lateral translation and counter-rotation of gaze. By changing the polarity of the scene objects (from light to dark and vice versa) between frames, we placed flow cues to self-movement direction in opposition to change of position cues. We found that again flow cues dominated the perceived probe movement relative to the scene. Together, these experiments indicate the neural network that processes optic flow has a primary role in the identification of scene-relative object movement.

SIGNIFICANCE STATEMENT Motion of an object in the retinal image indicates relative movement between the observer and the object, but it does not indicate its cause: movement of an object in the scene; movement of the observer; or both. To isolate retinal motion due to movement of a scene object, the brain must parse out the retinal motion due to movement of the eye ("flow parsing"). Optic flow, form, and position cues all have potential roles in this process. We pitted the cues against each other and assessed their influence. We found that flow parsing relies on optic flow alone. These results indicate the primary role of the neural network that processes optic flow in the identification of scene-relative object movement.

BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells

The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, which are currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown. Here, we report that BMP5/7-deficient mice (Bmp5^–/–; Bmp7^–/–) lack mDA neurons due to reduced neurogenesis in the mDA progenitor domain. As molecular mechanisms accounting for these alterations in Bmp5^–/–; Bmp7^–/– mutants, we have identified expression changes of the BMP/SMAD target genes MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog). Conditionally inactivating SMAD1 in neural stem cells of mice in vivo (Smad1^Nes) hampered the differentiation of progenitor cells into mDA neurons by preventing cell cycle exit, especially of TH⁺SOX6⁺ (tyrosine hydroxylase, SRY-box 6) and TH⁺GIRK2⁺ (potassium voltage-gated channel subfamily-J member-6) substantia nigra neurons. BMP5/7 robustly increased the in vitro differentiation of human induced pluripotent stem cells and induced neural stem cells to mDA neurons by up to threefold. In conclusion, we have identified BMP/SMAD signaling as a novel critical pathway orchestrating essential steps of mammalian mDA neurogenesis in vivo that balances progenitor proliferation and differentiation. Moreover, we demonstrate the potential of BMPs to improve the generation of stem-cell-derived mDA neurons in vitro, highlighting the importance of sequential BMP/SMAD inhibition and activation in this process.

SIGNIFICANCE STATEMENT We identify bone morphogenetic protein (BMP)/SMAD signaling as a novel essential pathway regulating the development of mammalian midbrain dopaminergic (mDA) neurons in vivo and provide insights into the molecular mechanisms of this process. BMP5/7 regulate MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog) expression to direct mDA neurogenesis. Moreover, the BMP signaling component SMAD1 controls the differentiation of mDA progenitors, particularly to substantia nigra neurons, by directing their cell cycle exit. Importantly, BMP5/7 increase robustly the differentiation of human induced pluripotent and induced neural stem cells to mDA neurons. BMP/SMAD are routinely inhibited in initial stages of stem cell differentiation protocols currently being developed for Parkinson's disease cell replacement therapies. Therefore, our findings on opposing roles of the BMP/SMAD pathway during in vitro mDA neurogenesis might improve these procedures significantly.

KChIP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and Alleviates Inflammatory Hyperalgesia in Rats

Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a multifunctional protein belonging to the neuronal calcium sensor (NCS) family. Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG) neurons, suggesting the potential role of KChIP3 in peripheral sensory processing. Herein, we show that KChIP3 colocalizes with transient receptor potential ion channel V1 (TRPV1), a critical molecule involved in peripheral sensitization during inflammatory pain. Furthermore, the N-terminal 31-50 fragment of KChIP3 is capable of binding both the intracellular N and C termini of TRPV1, which substantially decreases the surface localization of TRPV1 and the subsequent Ca²⁺ influx through the channel. Importantly, intrathecal administration of the transmembrane peptide transactivator of transcription (TAT)-31-50 remarkably reduces Ca²⁺ influx via TRPV1 in DRG neurons and alleviates thermal hyperalgesia and gait alterations in a complete Freund's adjuvant-induced inflammatory pain model in male rats. Moreover, intraplantar injection of TAT-31-50 attenuated the capsaicin-evoked spontaneous pain behavior and thermal hyperalgesia, which further strengthened the regulatory role of TAT-31-50 on TRPV1 channel. In addition, TAT-31-50 could also alleviate inflammatory thermal hyperalgesia in kcnip3^–/– rats generated in our study, suggesting that the analgesic effect mediated by TAT-31-50 is independent of endogenous KChIP3. Our study reveals a novel peripheral mechanism for the analgesic function of KChIP3 and provides a potential analgesic agent, TAT-31-50, for the treatment of inflammatory pain.

SIGNIFICANCE STATEMENT Inflammatory pain arising from inflamed or injured tissues significantly compromises the quality of life in patients. This study aims to elucidate the role of peripheral potassium channel interacting protein 3 (KChIP3) in inflammatory pain. Direct interaction of the KChIP3 N-terminal 31-50 fragment with transient receptor potential ion channel V1 (TRPV1) was demonstrated. The KChIP3–TRPV1 interaction reduces the surface localization of TRPV1 and thus alleviates heat hyperalgesia and gait alterations induced by peripheral inflammation. Furthermore, the transmembrane transactivator of transcription (TAT)-31-50 peptide showed analgesic effects on inflammatory hyperalgesia independently of endogenous KChIP3. This work reveals a novel mechanism of peripheral KChIP3 in inflammatory hyperalgesia that is distinct from its classical role as a transcriptional repressor in pain modulation.

Diagnosis uPGrade—Advances in Pyoderma Gangrenosum

In this issue of JAMA Dermatology, 2 large, well-constructed studies remind dermatologists that even though pyoderma gangrenosum (PG) is a quintessential disease in medical dermatology, we still need data to better define the disease and reduce the risk of cognitive biases. We know the results of these biases well; even at referral centers and in clinical trials, alternative diagnoses can prevail 7% to 20% of the time. In these articles, one of the largest retrospective PG databases and a new tool for PG diagnosis validation are presented.

Age and Pyoderma Gangrenosum Presentation and Comorbidities

This cohort study evaluates the association of age with the clinical presentation and disease associations of pyoderma gangrenosum.

Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum

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Lenalidomide Treatment for Recurrent Erythema Multiforme

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Dermatologists Should Speak Out Against a Word Ban at CDC

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Gray-Brown Patches on the Face of a 62-Year-Old Woman

A 62-year-old woman with a history of rosacea and melasma presented with worsening gray-brown patches on the face; no oral or other cutaneous lesions were reported. What is your diagnosis?

Voice quality outcomes of idiopathic Parkinson disease medical treatment: a systematic review

Abstract

Introduction

To investigate voice quality (VQ) impairments in idiopathic Parkinson's disease (IPD) and to explore the impact of medical treatments and L-Dopa challenge testing on voice.

Methods

Relevant studies published between January 1980 and June 2017 describing VQ evaluations in IPD were retrieved using PubMed, Scopus, Biological Abstracts, BioMed Central, and Cochrane databases. Issues of clinical relevance, including IPD treatment efficiency and voice quality outcomes, were evaluated for each study. The grade of recommendation for each publication was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels.

Results

The database research yielded 106 relevant publications, of which 33 studies met the inclusion criteria, for a total of 964 IPD patients. Data were extracted by 3 independent physicians who identified 21, 11, and 1 trials with IIIb, IIb, and IIa evidence levels, respectively. The main VQ assessment tools used were acoustic testing (N=27), aerodynamic testing (N=10), subjective measurements (N=8), and videolaryngostroboscopy (N=3). The majority of trials (N=32/33) identified subjective or objective VQ improvements after medical treatment (N=10) or better VQ evaluations in healthy subjects compared to patients with IPD (N=22). Especially, our analysis supports that VQ overall improves during the L-Dopa challenge testing, making the VQ evaluation an additional tool for the IPD diagnosis. The methodology used to assess subjective and objective VQ substantially varied from one study to another. All of the included studies took into consideration the patient's clinical profile in the VQ analysis.

Conclusion

The majority of studies supported that VQ assessments remain useful as outcome measures of the effectiveness of medical treatment and could be helpful for the IPD diagnosis based on L-Dopa challenge testing. Further controlled studies using standardized and transparent methodology for measuring acoustic parameters are necessary to confirm the place of each tool in both IPD diagnosis and treatment evaluation.

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Moral realism and reliance on moral testimony

Abstract

Moral realism and some of its constitutive theses, e.g., cognitivism, face the following challenge. If they are true, then it seems that we should predict that deference to moral testimony is appropriate under the same conditions as deference to non-moral testimony. Yet, many philosophers intuit that deference to moral testimony is not appropriate, even in otherwise ordinary conditions. In this paper I show that the challenge is cogent only if the appropriateness in question is disambiguated in a particular way. To count against realism and its constitutive theses, moral deference must fail to be appropriate in specifically the way that the theses predict it is appropriate. I argue that this is not the case. In brief, I argue that realism and allied theses predict only that deference to moral testimony is epistemically appropriate, but that the intuitive data plausibly show only that it is not morally appropriate. If I am right, then there is reason to doubt the metaethical relevance of much of the skepticism regarding moral deference in recent literature.

Review of the methods for determination of reactive oxygen species and suggestion for their application in advanced oxidation induced by dielectric barrier discharges

Abstract

Advanced oxidation processes (AOPs) particularly non-thermal plasmas based on electrical discharges have been widely investigated for water and wastewater treatment. Dielectric barrier discharges (DBDs) generate large amounts of selective and non-selective reactive oxygen species (ROS) such as ozone, hydrogen peroxide, atomic oxygen, superoxide molecular anions and hydroxyl radicals, having been proved to be efficient for water decontamination among various forms of electrical discharge systems. The detection and quantification methods of these oxygen species in non-thermal plasmas have been reviewed. However, their application in dielectric barrier discharge has not been well studied. It is therefore imperative to summarise the various detection and quantification methods for oxygen-based species determination in AOPs, aqueous systems and non-thermal plasma processes. Thereafter, reviewed methods are suggested for the determination of ROS in DBD configurations to understand the consumption trend of these oxidants during treatment of water effluents and to evaluate the performance of the treatment reactor configuration towards the degradation of targeted pollutants.

Pheochromocytoma as a frequent false-positive in adrenal washout CT: A systematic review and meta-analysis

Abstract

Objective

To evaluate the proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT and the diagnostic performance of adrenal washout CT for differentiating adenoma from pheochromocytoma.

Methods

MEDLINE and EMBASE were searched to 28 March 2017. We included studies that used adrenal washout CT for characterisation of pheochromocytomas. Two independent reviewers assessed the methodological quality using Quality Assessment of Diagnostic Accuracy Studies-2. Proportions were pooled using an inverse variance method for calculating weights (random-effects). Sensitivity and specificity were pooled using hierarchical logistic regression modelling and plotted in a hierarchical summary receiver-operating-characteristics (HSROC) plot.

Results

Ten studies (114 pheochromocytomas) were included. The pooled proportion of pheochromocytomas meeting the criteria for adenomas was 35 % (95 % CI 20–51). For eight studies providing information on diagnostic performance, the pooled sensitivity and specificity for differentiating adenoma from pheochromocytoma were 0.97 (95 % CI 0.93–0.99) and 0.67 (95 % CI 0.44–0.84), respectively. The area under the HSROC curve was 0.97 (95 % CI 0.95–0.98).

Conclusions

There was a non-negligible proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT. Although overall diagnostic performance was excellent for differentiating adenoma from pheochromocytoma, specificity was relatively low.

Key Points

• Non-negligible proportion of pheochromocytomas can be mistaken for adenoma.

• Adrenal washout CT showed good sensitivity (97%) but relatively low specificity (67%).

• Findings other than washout percentage should be used when diagnosing pheochromocytomas

The Left Atrio-Vertebral Ratio: a new simple means for assessing left atrial enlargement on Computed Tomography

Abstract

Objective

The purpose of this study is to describe a new method to quickly estimate left atrial enlargement (LAE) on Computed Tomography.

Methods

Left atrial (LA) volume was assessed with a 3D-threshold Hounsfield unit detection technique, including left atrial appendage and excluding pulmonary venous confluence, in 201 patients with ECG-gated 128-slice dual-source CT and indexed to body surface area. LA and vertebral axial diameter and area were measured at the bottom level of the right inferior pulmonary vein ostium. Ratio of LA diameter and surface on vertebra (LAVD and LAVA) were compared to LA volume. In accordance with the literature, a cutoff value of 78 ml/m² was chosen for maximal normal LA volume.

Results

18% of LA was enlarged. The best cutoff values for LAE assessment were 2.5 for LAVD (AUC: 0.65; 95% CI: 0.58-0.73; sensitivity: 57%; specificity: 71%), and 3 for LAVA (AUC: 0.78; 95% CI: 0.72-0.84; sensitivity: 67%; specificity: 79%), with higher accuracy for LAVA (P=0.015). Inter-observer and intra-observer variability were either good or excellent for LAVD and LAVA (respective intraclass coefficients: 0.792 and 0.910; 0.912 and 0.937).

Conclusion

A left atrium area superior to three times the vertebral area indicates LAE with high specificity.

Key points

• Left atrial enlargement is a frequent condition associated with poor cardiac outcome.

• Left atrial enlargement is highly time-consuming to diagnose on CT.

• The left atrio-vertebral ratio quickly assesses left atrial enlargement.

• A left atrial area > three times vertebral area is highly specific.

The effects of mild germinal matrix-intraventricular haemorrhage on the developmental white matter microstructure of preterm neonates: a DTI study

Abstract

Objectives

To evaluate white matter (WM) microstructural changes in preterm neonates (PN) with mild germinal matrix-intraventricular haemorrhage (mGMH-IVH) (grades I and II) and no other associated MRI abnormalities, and correlate them with gestational age (GA) and neurodevelopmental outcome.

Methods

Tract-based spatial-statistics (TBSS) was performed on DTI of 103 patients studied at term-equivalent age, to compare diffusional parameters (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)) between mGMH-IVH neonates (24/103) and controls matched by GA at birth and sex. The relationship between DTI abnormalities, GA and neurodevelopmental outcome assessed with Griffiths' Developmental Scale-Revised:0-2 was explored using TBSS and Spearman-correlation analysis (p < .05).

Results

Affected neonates had lower FA, higher RD and MD of the corpus callosum, limbic pathways and cerebellar tracts. Extremely preterm neonates (GA < 29 weeks) presented more severe microstructural impairment (higher RD and MD) in periventricular regions. Neonates of GA ≥ 29 weeks had milder WM alterations (lower FA), also in subcortical WM. DTI abnormalities were associated with poorer locomotor, eye-hand coordination and performance outcomes at 24 months.

Conclusions

WM microstructural changes occur in PN with mGMH-IVH with a GA-dependent selective vulnerability of WM regions, and correlate with adverse neurodevelopmental outcome at 24 months.

Key Points

• DTI-TBSS analysis identifies WM microstructural changes in preterm neonates with mGMH-IVH.

• Extremely preterm neonates with mGMH-IVH presented more severe impairment of WM microstructure.

• Extremely preterm neonates with mGMH-IVH presented microstructural impairment of periventricular WM.

• mGMH-IVH affects subcortical WM in preterm neonates with gestational age ≥ 29 weeks.

• WM microstructural alterations are related to neurodevelopmental impairments at 24 months.

Microflow imaging: New Doppler technology to detect low-grade inflammation in patients with arthritis

Abstract

Aim

To assess the efficacy of microvascular imaging in detecting low-grade inflammation in arthritis compared with Power Doppler ultrasound (PDUS).

Method and materials

Patients presenting for ultrasound with arthralgia were assessed with grey-scale, PDUS and Superb Microvascular Imaging (SMI). Videoclips were stored for analysis at a later date. Three musculoskeletal radiologists scored grey-scale changes, signal on PDUS and/or SMI within these joints. If a signal was detected on both PDUS and SMI, the readers graded the conspicuity of vascular signal from the two Doppler techniques using a visual analogue scale.

Results

Eighty-three patients were recruited with 134 small joints assessed. Eighty-nine of these demonstrated vascular flow with both PD and SMI, whilst in five no flow was detected. In 40 joints, vascularity was detected with SMI but not with PDUS (p = 0.007). Out of the 89 joints with vascularity on both SMI and PDUS, 23 were rated as being equal; while SMI scored moderately or markedly better in 45 cases (p <0.001).

Conclusion

SMI is a new Doppler technique that increases conspicuity of Doppler vascularity in symptomatic joints when compared to PDUS. This allows detection of low grade inflammation not visualised with Power Doppler in patients with arthritis.

Key Points

• SMI detects vascularity with improved resolution and sensitivity compared to Power Doppler.

• SMI can detect low-grade inflammation not seen with Power Doppler.

• Earlier detection of active inflammation could have significant impact on treatment paradigms.

Carpal tunnel syndrome assessment with diffusion tensor imaging: Value of fractional anisotropy and apparent diffusion coefficient

Abstract

Objectives

To quantitatively assess carpal tunnel syndrome (CTS) with DTI by evaluating two approaches to determine cut-off values.

Methods

In forty patients with CTS diagnosis confirmed by nerve conduction studies (NCs) and 14 healthy subjects (mean age 58.54 and 57.8 years), cross-sectional area (CSA), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) at single and multiple levels with intraobserver agreement were evaluated.

Results

Maximum and mean CSA and FA showed significant differences between healthy subjects and patients (12.85 mm² vs. 28.18 mm², p < 0.001, and 0.613 vs. 0.524, p=0.007, respectively) (10.12 mm² vs. 19.9 mm², p<0.001 and 0.617 vs. 0.54, p=0.003, respectively), but not maximum and mean ADC (p > 0.05). For cut-off values, mean and maximum CSA showed the same sensitivity and specificity (93.3 %). However, mean FA showed better sensitivity than maximum FA (82.6 % vs. 73.9 %), but lower specificity (66.7 % vs. 80 %), and significant correlation for maximum CSA, 97 % (p < 0.01), with good correlation for maximum ADC and FA, 84.5 % (p < 0.01) and 62 % (p=0.056), respectively.

Conclusions

CSA and FA showed significant differences between healthy subjects and patients. Single measurement at maximum CSA is suitable for FA determination.

Key Points

• DTI showed that FA is stronger than ADC for CTS diagnosis.

• Single- and multiple-level approaches were compared to determine FA and ADC.

• Single-level evaluation at the thickest MN cross-sectional area is sufficient.

Thermal ablation of thyroid nodules: are radiofrequency ablation, microwave ablation and high intensity focused ultrasound equally safe and effective methods?

Abstract

Objectives

This study compares volume reduction of benign thyroid nodules three months after Radiofrequency Ablation (RFA), Microwave Ablation (MWA) or High Intensity Focused Ultrasound (HIFU) to evaluate which of these methods is the most effective and safe alternative to thyroidectomy or radioiodine therapy.

Material and Methods

Ninety-four patients (39 male, 55 female) with a total of 118 benign, symptomatic thyroid nodules were divided into three subgroups. HIFU was applied to 14 patients with small nodules. The other 80 patients were divided up into two groups of 40 patients each for RFA and MWA in the assumption that both methods are comparable effective. The pre-ablative and post-ablative volume was measured by ultrasound.

Results

RFA showed a significant volume reduction of nodules of 50 % (p<0.05), MWA of 44 % (p<0.05) and HIFU of 48 % (p<0.05) three months after ablation. None of the examined ablation techniques caused serious or permanent complications.

Conclusion

RFA, MWA and HIFU showed comparable results considering volume reduction. All methods are safe and effective treatments of benign thyroid nodules.

Key Points

• Thermal Ablation can be used to treat benign thyroid nodules

• Thermal Ablation can be an alternative to thyroidectomy or radioiodine therapy

• Radiofrequency Ablation, Microwave Ablation, High Intensity Focused Ultrasound are safe and effective

Safety analysis of holmium-166 microsphere scout dose imaging during radioembolisation work-up: A cohort study

Abstract

Objective

Radioembolisation is generally preceded by a scout dose of technetium-99m-macroaggregated albumin to estimate extrahepatic shunting of activity. Holmium-166 microspheres can be used as a scout dose (±250 MBq) and as a therapeutic dose. The general toxicity of a holmium-166 scout dose (¹⁶⁶Ho-SD) and safety concerns of an accidental extrahepatic deposition of ¹⁶⁶Ho-SD were investigated.

Methods

All patients who received a ¹⁶⁶Ho-SD in our institute were reviewed for general toxicity and extrahepatic depositions. The absorbed dose in extrahepatic tissue was calculated on SPECT/CT and correlated to clinical toxicities.

Results

In total, 82 patients were included. No relevant clinical toxicity occurred. Six patients had an extrahepatic deposition of ¹⁶⁶Ho-SD (median administered activity 270 MBq). The extrahepatic depositions (median activity 3.7 MBq) were located in the duodenum (3x), gastric fundus, falciform ligament and the lesser curvature of the stomach, and were deposited in a median volume of 15.3 ml, which resulted in an estimated median absorbed dose of 3.6 Gy (range 0.3–13.8 Gy). No adverse events related to the extrahepatic deposition of the ¹⁶⁶Ho-SD occurred after a median follow-up of 4 months (range 1–12 months).

Conclusion

These results support the safety of 250 MBq ¹⁶⁶Ho-SD in a clinical setting.

Key Points

• A holmium-166 scout dose is safe in a clinical setting.

• Holmium-166 scout dose is a safe alternative for ^99m Tc-MAA for radioembolisation work-up.

• Holmium-166 scout dose potentially has several benefits over ^99m Tc-MAA for radioembolisation work-up.

Rapid volumetric photoacoustic tomographic imaging with a Fabry-Perot ultrasound sensor depicts peripheral arteries and microvascular vasomotor responses to thermal stimuli

Abstract

Purpose

To determine if a new photoacoustic imaging (PAI) system successfully depicts (1) peripheral arteries and (2) microvascular circulatory changes in response to thermal stimuli.

Methods

Following ethical permission, 8 consenting subjects underwent PAI of the dorsalis pedis (DP) artery, and 13 completed PAI of the index fingertip. Finger images were obtained after immersion in warm (30-35 °C) or cold (10-15 °C) water to promote vasodilation or vasoconstriction. The PAI instrument used a Fabry-Perot interferometeric ultrasound sensor and a 30-Hz 750-nm pulsed excitation laser. Volumetric images were acquired through a 14 × 14 × 14-mm volume over 90 s. Images were evaluated subjectively and quantitatively to determine if PAI could depict cold-induced vasoconstriction. The full width at half maximum (FWHM) of resolvable vessels was measured.

Results

Fingertip vessels were visible in all participants, with mean FWHM of 125 μm. Two radiologists used PAI to correctly identify vasoconstricted fingertip capillary beds with 100% accuracy (95% CI 77.2-100.0%, p < 0.001). The number of voxels exhibiting vascular signal was significantly smaller after cold water immersion (cold: 5263 voxels; warm: 363,470 voxels, p < 0.001). The DP artery was visible in 7/8 participants (87.5%).

Conclusion

PAI achieves rapid, volumetric, high-resolution imaging of peripheral limb vessels and the microvasculature and is responsive to vasomotor changes induced by thermal stimuli.

Key points

• Fabry-Perot interferometer-based photoacoustic imaging (PAI) generates volumetric, high-resolution images of the peripheral vasculature.

• The system reliably detects thermally induced peripheral vasoconstriction (100% correct identification rate, p < 0.001).

• Vessels measuring less than 100 μm in diameter can be depicted in vivo.

Differences in myocardial strain between pectus excavatum patients and healthy subjects assessed by cardiac MRI: a pilot study

Abstract

Objectives

To evaluate differences in myocardial strain between pectus excavatum (PE) patients and healthy subjects (HS) assessed by cardiac MRI using the feature-tracking algorithm.

Methods

Cardiac MRI was performed in 14 PE patients and 14 HS (9:5 male to female in each group; age 11–30 years) using a 3T scanner. Post-examination analysis included manual biventricular contouring with volumetry and ejection fraction measurement by two independent radiologists. Dedicated software was used for automated strain assessment.

Results

In five of the PE patients, the right ventricular ejection fraction was slightly impaired (40–44 %). PE patients had a significantly higher left ventricular longitudinal strain (P=0.004), mid (P=0.035) and apical (P=0.001) circumferential strain as well as apical circumferential strain rate (P=0.001), mid right ventricular circumferential strain (P=0.008) and strain rate (P=0.035), and apical right ventricular circumferential strain (P=0.012) and strain rate (P=0.044) than HS. The right ventricular longitudinal strain and strain rate did not differ significantly between PE patients and HS.

Conclusions

Myocardial strain differs significantly between PE patients and HS. Higher myocardial strain in the mid and apical ventricles of PE patients indicates a compensation mechanism to enhance ventricular output against basal sternal compression.

Key Points

• The right ventricle is frequently affected by the pectus excavatum deformity.

• Cardiac MRI revealed differences in myocardial strain in pectus excavatum patients.

• Pectus excavatum patients exhibited higher strain in the mid/apical ventricles.

• A compensation mechanism to enhance ventricular output against sternal compression is possible.

Diffusion-weighted imaging in relation to morphology on dynamic contrast enhancement MRI: the diagnostic value of characterizing non-puerperal mastitis

Abstract

Objectives

To demonstrate the value of diffusion-weighted imaging (DWI) in the characterisation of mastitis lesions.

Methods

Sixty-one non-puerperal patients with pathologically confirmed single benign mastitis lesions underwent preoperative examinations with conventional MRI and axial DWI. Patients were categorised into three groups: (1) periductal mastitis (PDM), (2) granulomatous lobular mastitis (GLM), and (3) infectious abscess (IAB). Apparent diffusion coefficient (ADC) values of each lesion were recorded. A one-way ANOVA with logistic analysis was performed to compare ADC values and other parameters. Discriminative abilities of DWI modalities were compared using the area under the receiver operating characteristic curve (AUC). P < 0.05 was considered statistically significant.

Results

ADC values differed significantly among the three groups (P = 0.003) as well as between PDM and IAB and between PDM and GLM. The distribution of non-mass enhancement on dynamic contrast-enhanced (DCE) MRI differed significantly among the three groups (P = 0.03) but not between any two groups specifically. There were no differences in lesion location, patient age, T₂WI or DWI signal intensity, enhancement type, non-mass internal enhancement, or mass enhancement characteristics among the three groups.

Conclusions

ADC values and the distribution of non-mass enhancement are valuable in classifying mastitis subtypes.

Key points

• Mastitis subtypes exhibit different characteristics on DWI and DCE MRI.

• ADC values are helpful in isolating PDM from other mastitis lesions.

• Distribution of non-mass enhancement also has value in comparing mastitis subtypes.

Late iodine enhancement computed tomography with image subtraction for assessment of myocardial infarction

Abstract

Objective

To evaluate the feasibility of image subtraction in late iodine enhancement CT (LIE-CT) for assessment of myocardial infarction (MI).

Methods

A comprehensive cardiac CT protocol and late gadolinium enhancement MRI (LGE-MRI) was used to assess coronary artery disease in 27 patients. LIE-CT was performed after stress CT perfusion (CTP) and CT angiography. Subtraction LIE-CT was created by subtracting the mask volume of the left ventricle (LV) cavity from the original LIE-CT using CTP dataset. The %MI volume was quantified as the ratio of LIE to entire LV volume, and transmural extent (TME) of LIE was classified as 0%, 1–24%, 25–49%, 50–74% or 75–100%. These results were compared with LGE-MRI using the Spearman rank test, Bland-Altman method and chi-square test.

Results

One hundred twenty-five (29%) of 432 segments were positive on LGE-MRI. Correlation coefficients for original and subtraction LIE-CT to LGE-MRI were 0.79 and 0.85 for %MI volume. Concordances of the 5-point grading scale between original and subtraction LIE-CT with LGE-MRI were 75% and 84% for TME; concordance was significantly improved using the subtraction technique (p <0.05).

Conclusion

Subtraction LIE-CT allowed more accurate assessment of MI extent than the original LIE-CT.

Key Points

• Subtraction LIE-CT allows for accurate assessment of the extent of myocardial infarction.

• Subtraction LIE-CT shows a close correlation with LGE-MRI in %MI volume.

• Subtraction LIE-CT has significantly higher concordance with TME assessment than original LIE-CT.