ADJUVANT PRETREATMENT WITH ALUM PROTECTS NEONATAL MICE IN SEPSIS THROUGH MYELOID CELL ACTIVATION

ABSTRACT

The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Especially in the premature neonate where outcomes from sepsis are so dismal, pretreatment strategies to prevent sepsis have received inadequate consideration. Aluminum-based adjuvants (alum) are currently used in many pediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pre-treatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum pretreatment improves survival to polymicrobial sepsis in both wild-type, and in T- and B- cell-deficient neonatal mice, but not in caspase-1/11 null mice. Moreover, alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases bacterial colonization in the peritoneum. Bone marrow-derived neutrophils from alum-pretreated neonates produce more extracellular traps (NETs), and exhibit increased expression of neutrophil elastase (NE) after in vitro stimulation with phorbol esters. In addition, alum pretreatment increases bone marrow and splenic hematopoietic stem cell expansion following sepsis. Pretreatment of neonatal mice with an alum-based adjuvant can stimulate multiple innate immune cell functions, and improve survival. These novel findings suggest a therapeutic pathway for the use of existing alum-based adjuvants for preventing sepsis in premature infants. This article is protected by copyright. All rights reserved.

The application of titanium dioxide, zinc oxide, fullerene, and graphene nanoparticles in photodynamic therapy

Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of therapeutics. In the field of photodynamic therapy (PDT), this targeting advantage of NPs could help ensure dru...

The migrant crisis comes to Minnesota: a dermatologist's perspective

Microbial contamination of open-but-unused portions of wound dressings stored in home settings

Abstract

The purpose of this study was to investigate incidence rates and levels of microbial contamination in open-but-unused portions of wound dressings stored in home settings. Portions of wound dressings were collected at up to four home visits for 104 clients undertaking wound management within their home. A control sample and stored sample was collected on each home visit and sent for pathology testing to identify levels of microbial contamination. The stored open-but-unused wound dressings were managed according to a written protocol. Of the tested samples (n = 776), 6% of control samples and 7% of test samples had microbial contamination. From regression analysis, the stored samples were more likely to have microbial contamination than control samples, but results were not statistically significant. In comparing occasions of storage and handling across four home visits, after adjusting for sample group and dressing type, none of the home visit occasion regressions were statistically significant. In conclusion, storage of open-but-unused portions of wound dressings kept in home settings does not appear to increase the rate of microbial contamination compared to newly opened wound dressings.

Distribution of Elastic Fibers in the Lacrimal Sac and Nasolacrimal Duct of Japanese Cadavers.

Purpose: To investigate the distribution of elastic fibers in lacrimal sac and nasolacrimal duct of Japanese cadavers. Methods: We examined 8 lacrimal sacs and nasolacrimal ducts of 7 Japanese cadavers (4 right sides, 4 left sides; 3 mal es, 4 females; average age of 89 years at death) that were preserved with 10% buffered formalin. The harvested specimens were transversely sectioned. All specimens were stained with Elastica van Gieson. Micrographs were taken, and then converted to white and black images, and the elastic fiber density of 4 locations (middle and upper levels of lacrimal sac, and middle and lower levels of nasolacrimal duct) was compared. Results: Elastic fibers showed greater distribution in the lamina propria, compared with the submucosal tissue, at all locations (p

Spontaneous Rupture of Lacrimal Gland Pleomorphic Adenoma: Pivotal Role in Masquerading Orbital Cellulitis.

The authors aim to report a 68-year-old patient presenting with acute swelling and redness of orbital area diagnosed initially as orbital cellulitis. Surgical excision was decided based on clinical and imaging findings with the diagnosis of pleomorphic adenoma of the lacrimal gland. Lacrimal gland pleomorphic adenoma usually presents with painless gradual swelling of upper eyelid. In an exceptionally rare circumstance, this case showed acute orbital inflammation, and imaging findings of orbital inflammation mostly focused around the cystic space of the lacrimal gland tumor. Histologic evaluation confirmed a ruptured cystic space of pleomorphic adenoma with foreign body-type inflammatory reaction. The authors propose spontaneous rupture of cystic space in the lacrimal gland pleomorphic adenoma as underlying mechanism for acute presentation of this tumor. Imaging and clinical characteristics and also prognostic implication of this phenomenon are discussed. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Acute Localized Exanthematous Pustulosis (ALEP): Review of Literature with Report of Case Caused by Amoxicillin-Clavulanic Acid

Abstract

Acute localized exanthematous pustulosis (ALEP) is a localized form of acute generalized exanthematous pustulosis, characterized by acute onset of multiple nonfollicular, pinhead-sized, sterile pustules following drug administration. Antibiotics, especially β-lactams and macrolides, have been implicated in the majority of cases, although eruption after nonsteroidal antiinflammatory drugs and many other medications has also been reported. Skin reaction arises quickly within a few hours, resolving rapidly within a few days without treatment, and it is usually accompanied by fever and neutrophilic leukocytosis. We report herein all cases of ALEP described in literature, adding the case of a 35-year-old woman admitted to our hospital with outbreak of erythematous pustules on her face, neck, and chest after amoxicillin–clavulanic acid treatment.

Multiparametric Imaging Improves Confidence in the Diagnosis of Multinodular and Vacuolating Neuronal Tumor of the Cerebrum [LETTERS]

Reply: [LETTERS]

Selective Poststent Balloon Angioplasty for Carotid Stenting [LETTERS]

Redefining the Pulvinar Sign in Fabry Disease [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity.

MATERIALS AND METHODS:

We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls.

RESULTS:

The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables.

CONCLUSIONS:

The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease.

Erratum [ERRATA]

Reply: [LETTERS]

Anterior Circulation Acute Ischemic Stroke Associated with Atherosclerotic Lesions of the Cervical ICA: A Nosologic Entity Apart [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Mechanical thrombectomy for patients with acute ischemic stroke with tandem occlusions has been shown to present varying reperfusion successes and clinical outcomes. However, the heterogeneity of tandem occlusion etiology has been strongly neglected in previous studies. We retrospectively investigated patients with acute ischemic stroke atherothrombotic tandem occlusion.

MATERIALS AND METHODS:

All consecutive patients with acute ischemic stroke with atherothrombotic tandem occlusions treated with mechanical thrombectomy in our center between September 2009 and April 2015 were analyzed. They were compared with patients with acute ischemic stroke with dissection-related tandem occlusion and isolated intracranial occlusion treated during the same period. Comparative univariate and multivariate analyses were conducted, including demographic data, safety, and rates of successful recanalization and good clinical outcome.

RESULTS:

Despite comparable baseline severity of neurologic deficits and infarct core extension, patients with atherothrombotic tandem occlusions were older (P < .001), were more frequently smokers (P < .001), and had globally more cardiovascular risk factors (P < .001) than the other 2 groups of patients. The patients with atherothrombotic tandem occlusions had significantly longer procedural times (P < .001), lower recanalization rates (P = .004), and higher global burden of procedural complications (P < .001). In this group, procedural complications (OR = 0.15, P = .02) and the TICI 2b/3 reperfusion scores (OR = 17.76, P = .002) were independently predictive factors of favorable clinical outcome.

CONCLUSIONS:

Our study suggests that atherothrombotic tandem occlusions represent a peculiar and different nosologic entity compared with dissection-related tandem occlusions. This challenging cause of acute ischemic stroke should be differentiated from other etiologies in patient management in future prospective studies.

Imaging Appearances and Pathologic Characteristics of Spinal Epidural Meningioma [SPINE]

BACKGROUND AND PURPOSE:

Spinal epidural meningioma is an uncommon tumor. This study aimed to analyze the imaging and pathologic characteristics of this rare tumor.

MATERIALS AND METHODS:

Fourteen confirmed cases of epidural meningioma were retrospectively reviewed, and imaging characteristics and pathologic findings were analyzed to identify the typical features.

RESULTS:

The mean age of the patients (4 men, 10 women) was 44.9 years. Twelve tumors were in the cervical spinal canal, and 2, in the thoracic spinal canal. There were 9 en plaque meningiomas, 4 dumbbell-shaped meningiomas, and 1 fusiform/ovoid meningioma. The epidural meningiomas extended over 2–5 spinal segments (mean, 3.2 spinal segments). A soft epidural mass was seen in 12/14 (86%) patients. Dural calcification was seen in 8/14 (57%) tumors. Tumor caused intervertebral foramen enlargement in 10/14 (71%) patients and adhered to the nerve roots in 11/14 (79%) patients. Intradural invasion was seen in 8/14 (57%) patients. The dural tail sign was present in 13/14 (93%) tumors on contrast-enhanced T1WI. Regarding pathologic type, 10 of 14 (71%) were psammomatous, 2 of 14 (14%) were meningothelial, 1 of 14 (7%) was angiomatous, and 1 of 14 (7%) was transitional. During follow-up (mean follow-up, 73.4 months; range, 4–192 months), 7 patients had recurrence. Recurrences were between 4 and 192 months after the operation.

CONCLUSIONS:

Epidural meningioma has 3 different growth patterns. Dural thickening, calcification, invasion, and epidural mass formation are characteristic features of epidural meningioma. Regular follow-up imaging is required to detect recurrence.

Health Care Economics: A Study Guide for Neuroradiology Fellows, Part 2 [REVIEW ARTICLE]

SUMMARY:

In this second article, we continue the review of current health care economics as it relates to radiologists, specifically framed by topics defined by the Accreditation Council for Graduate Medical Education in the evaluation of neuroradiology fellows. The discussion in this article is focused on topics pertaining to levels 4 and 5, which are the more advanced levels of competency defined by the Accreditation Council for Graduate Medical Education Neuroradiology Milestones on Health Care Economics and System Based Practice.

Two-Center Experience in the Endovascular Treatment of Ruptured and Unruptured Intracranial Aneurysms Using the WEB Device: A Retrospective Analysis [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The safety and efficacy of the Woven EndoBridge (WEB) device for the treatment of cerebral aneurysms has been investigated in several studies. Our objective was to report the experience of 2 neurovascular centers with the WEB device in the treatment of broad-based intracranial aneurysms, including the technical feasibility and safety as well as short- and midterm angiographic and clinical follow-up-results.

MATERIALS AND METHODS:

We performed a retrospective analysis of all ruptured and unruptured aneurysms treated with a WEB device (WEB Single-Layer and Single-Layer Sphere) between August 2014 and February 2017. Primary outcome measures included the feasibility of implantation and the angiographic outcome. Secondary outcome measures included the clinical outcome at discharge and procedural complications.

RESULTS:

One hundred two aneurysms in 101 patients, including 37 (36.3%) ruptured aneurysms, were treated with the WEB device. Implantation was successful in 98 (96.1%) aneurysms. Additional devices (stents/coils) were necessary in 15.3% (15/98) of aneurysms. Procedural complications occurred in 4.9% (5/102). Of these, 4 were thromboembolic events and 1 was an intraprocedural rupture. Angiographic follow-up at 3 and 12 months was available for 79.6% (78/98) and 50.0% (49/98) of all aneurysms to date, respectively, showing a sufficient aneurysm occlusion in 80.7% (63/78) at 3 months and 77.6% (38/49) at 12 months. Delayed aneurysm ruptures have not been observed during the follow-up period to date.

CONCLUSIONS:

The WEB device offers a safe and effective treatment option for broad-based intracranial aneurysms without the need for dual antiplatelet therapy.

Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer

Abstract

Background

Incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies.

Patients and methods

All data are from 2009 to 2014, including 13 089 people ages 20–69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer.

Results

Oncogenic oral HPV DNA is detected in 3.5% of all adults age 20–69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will 'ever' develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had 'elevated risk' (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2–4 partners or did not smoke and had ≥5 partners) had 'medium risk' (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was 'low' among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%).

Conclusions

Screening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.

Hidradenitis suppurativa and diabetes mellitus: A systematic review and meta-analysis

The relationship between hidradenitis suppurativa and diabetes mellitus is not well understood.

The superiorly based bilobed flap for nasal reconstruction

The laterally based bilobed flap is commonly used for the reconstruction of small- to medium-sized defects of the distal portion of the nose; However, when this flap is used to repair defects that are larger, more cephalic, or more lateral on the nose, there is a risk for lower nasal distortion. Reorienting the base superiorly preserves the advantages of the traditional design while minimizing this risk.

Effective removal of ammonia nitrogen from waste seawater using crystal seed enhanced struvite precipitation technology with response surface methodology for process optimization

Abstract

Traditional biological treatment was not effective for removing nitrogen from saline wastewater due to the inhibition of high salinity on biomass activity. In this context, a method of removing ammonia nitrogen from waste seawater was proposed by struvite precipitation which was enhanced by seeding technique. The abundant magnesium contained in waste seawater was used as the key component of struvite crystallization without additional magnesium. The effects of pH and P:N molar ratio on ammonia nitrogen removal efficiency were studied. The results showed that optimum pH value was in range of 8.5–10 and the P:N molar ratio should be controlled within 2:1–3:1. XRD and SEM-EDS analyses of the precipitates proved that Ca²⁺ and excess Mg²⁺ contained in waste seawater inhibited the struvite crystallization by competing PO₄³⁻ to form by-products. Then, seeding technique for enhancing the struvite crystallization was investigated, and the results indicated that using preformed struvite as crystal seed significantly improved the ammonia nitrogen removal efficiency, especially when initial ammonia nitrogen concentration was relatively low. Moreover, response surface optimization experiment following a Box-Behnken design was conducted. A response surface model was established, based on which optimum process conditions were determined and interactions between various factors were clarified. At last, economic evaluation demonstrated this proposed method was economic feasible.

Hair mercury and risk assessment for consumption of contaminated seafood in residents from the coast of the Persian Gulf, Iran

Abstract

The health risks of mercury exposure due to the high consumption of aquatic were assessed for fishermen and non-fishermen families living on the Bandar Abbas, Bushehr, and Mahshahr cities located in the coast of Persian Gulf (Iran). The mean hair mercury concentration of people in Bandar Abbas, Bushehr, and Mahshahr cities was obtained 1.56 ± 0.17, 1.97 ± 0.22, and 5.12 ± 0.3 μg g⁻¹, respectively. Hair mercury concentration in 8.8% of people exceeded the no observed adverse effects level (NOAEL) of 10 μg g⁻¹ declared by the World Health Organization (WHO). The fish and shrimps consumption, place of living, and fisher and non-fisherman family were variables that significantly effected on mercury levels in the hair. The effect of other factors (age, sex, and number of dental amalgam fillings) on hair mercury was not significant. The mean concentrations of mercury in three fish species in Mahshahr exceeded the recommended maximum standard level (0.5 μg g⁻¹) set by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA). The estimated weekly intake (EWI) for mercury in some fish species in Bandar Abbas, Bushehr, and Mahshahr was higher than the provisional tolerable weekly intake (1.6 μg kg⁻¹ bw) set by European Food Safety Authority (EFSA) for some groups. The significant positive correlation between daily mercury intake and hair mercury concentration of people (r = 0.64, P < 0.001) reasserts that the hair mercury concentration could be explained by fish consumption. HQ > 1 was obtained for women in child bearing age in fishermen families in Bandar Abbas and Bushehr cities, children in fishermen families in Bushehr, and for all groups of population except adult in non-fishermen families in Mahshahr. So, the limited consumption of some fish species for these groups of people is recommended. The maximum of allowable fish consumption rate was 0.70 meals/month for Pseudorhombus arsius from Mahshahr fish for women of child bearing age. Also, it is necessary to create and monitor and enforce environmental standards, preventing the entry of pollutants released into the marine aquatic environment without proper early treatment.

Rare-earth elements in human colostrum milk

Abstract

Rare-earth elements (REEs) are used in a growing number of applications, and their release to environment has increased over the decades. Knowledge of REEs in human milk and factors that could possibly influence their concentration is scarce. This study evaluated the concentrations of 16 REEs (Ce, Eu, Er, Gd, La, Nd, Pr, Sc, Sm, Dy, Ho, Lu, Tb, Tm, Y, and Yb) in human colostrum milk collected from Polish women (n = 100) with the ICP-OES technique. The concentrations (mean ± SD) of Pr (41.9 ± 13.2 μg L⁻¹), Nd (11.0 ± 4.0 μg L⁻¹), La (7.1 ± 5.2 μg L⁻¹), and Er (2.2 ± 0.8 μg L⁻¹) were found above detection limits. The total mean ± SD concentration of detected REEs was 60.9 ± 17.8 μg L⁻¹. Current smokers displayed significantly increased Nd concentrations compared to women who had never smoked. No other associations between REEs in colostrum milk and age, diet in pregnancy (food supplement use and frequency of fish, meat, and vegetable consumption) or place of living (urban/rural) were found. This study adds to general understanding of the occurrence and turnover of REEs in women and human fluids.

Artificial 137 Cs and natural 40 K in mushrooms from the subalpine region of the Minya Konka summit and Yunnan Province in China

Abstract

A study on ¹³⁷Cs pollution and activity concentrations of ⁴⁰K in mushrooms of the genera Cortinarius, Leccinum, Russula, Tricholoma, Tylopilus, and Xerocomus from two neighboring regions in southwest China in 2010–2013 revealed different patterns of pollution with ¹³⁷Cs, which seemed to be highly dependent on climate conditions. Tricholoma matsutake was collected in Yunnan before and after the Fukushima Dai-ichi nuclear accident and showed similar contamination with ¹³⁷Cs. Mushrooms from the elevation of 2800–3480 m above sea level on the east slope of Minya Konka and forest topsoil showed higher contamination with ¹³⁷Cs than mushrooms from the highlands of Yunnan. In detail, the activity concentration of ¹³⁷Cs in caps of mushrooms from Minya Konka were in the range 62 ± 6–280 ± 150 Bq kg⁻¹ dry biomass and from Yunnan at < 4.4–83 ± 3 Bq kg⁻¹ dry biomass. The climate in the region of the Minya Konka is much colder than in Yunnan, which seems to favor deposition of ¹³⁷Cs at higher altitudes from global atmospheric circulation. The activity concentration of ⁴⁰K in mushrooms and soils highly exceeded that of ¹³⁷Cs. The assessed annual effective doses for ¹³⁷Cs in 1 kg of consumed mushrooms of the genera Leccinum and Xerocomus in Yunnan were low, i.e., in the range < 0.0043–0.049 ± 0.004 μSv, while those for ⁴⁰K were 0.26 ± 0.02–0.81 ± 0.09 μSv.

Incorrectly Reported Request for Reply

In the Letter to the Editor titled "Types of Shade Vary in Protection Just Like Sunscreens," published online on June 21, 2017, and commenting on the Original Investigation titled "Sun Protection by Beach Umbrella vs Sunscreen With a High Sun Protection Factor: A Randomized Clinical Trial" by Ou-Yang et al, it was incorrectly reported that Dr Ou-Yang, corresponding author of the Original Investigation, had been shown a copy of the letter and offered an opportunity to reply. Dr Ou-Yang had not seen the letter at that time nor received the request for reply. The Letter to the Editor has been corrected online.

The Linear Nail Streak

This case report describes 2 persons with external thumbnail characteristics indicative of linear nail streak.

Repurposing Medications

My dad grew up on a chicken farm. One winter in my youth, while at an extended family gathering in his little farm town in mid-Missouri, I was complaining to him about my severe chapped lips. "Well, farmers around here would tell you to put chicken [manure] on chapped lips. That's a sure cure." Looking around the circle of conversation, I saw several relatives, farmers, and locals affirming this statement. For the next dozen years I was perplexed by the recommendation and silent about any further lip concerns.

October 2017 Issue Highlights

Pathophysiology and Treatment Considerations for Erosive Pustular Dermatosis

In this issue of JAMA Dermatology, Mervak et al describe the rare condition of erosive pustular dermatosis (EPD) that presented in a series of patients after undergoing fully ablative carbon dioxide laser resurfacing or deep chemical peel. Several weeks to months after the procedure, the patients exhibited facial nonhealing erythematous plaques with overlying pustules, erosions, and yellow crust. Results of histologic and microbial work-up were nondiagnostic, which was consistent with EPD. Each patient experienced an arduous and lengthy healing regimen, as is expected with this difficult diagnosis. The authors conclude that tincture of time and reassurance in addition to antibiotics, anti-inflammatories, and immunomodulators are warranted in the treatment of EPD. In the wake of increasing demand for elective surgical treatments, this case series highlights an important and fortunately rare adverse effect of ablative procedures. This phenomenon begs the questions, Are these cases underreported? What is the pathophysiology of EPD? What other options exist for treatment?

Types of Shade Vary In Protection Just Like Sunscreens

To the Editor In their randomized clinical trial in a recent issue of JAMA Dermatology, Ou-Yang et al concluded that shade from a beach umbrella provides less effective sun protection than high-SPF sunscreen. We urge care in interpretation of this study. The results cannot be generalized to conclude that shade is an ineffective means of sun protection.

Uniform Nomenclature to Describe Clinical Features of Pigmented Lesions

This Editorial describes how uniform terminology to describe features of malignancy facilitates communication among physicians, trainees, and disciplines.

Dysmorphophobia and the Wolf Man

Body dysmorphic disorder (BDD) is characterized by an impairing preoccupation with a perceived defect in appearance that is not observable or appears very slight to others. Although BDD was only recently formally recognized, dysmorphophobia has a long history in psychiatry, dating back to the 19th century. Dysmorphia is a Greek word meaning ugliness, specifically of the face, and first appeared in the Histories of Herodotus referring to the myth of the ugliest girl in Sparta. Although being commonly used for nearly a century, the term dysmorphophobia is actually a misnomer because BDD is not a truly phobic condition. Not just a reflection of modern-day preoccupation with beauty and appearance, BDD is a chronic and often severe psychiatric illness that lies along a spectrum, ranging from mild to life-threatening symptoms.

Radiotherapy for Extremity and Trunk Merkel Cell Carcinoma After Resection

This cohort study analyzes the National Cancer Database records of patients with Merkel cell carcinoma treated with curative radiation therapy to evaluate the overall survival of 4 different radiation dose regimens.

Topical Sinecatechins, 10%, for Superficial Basal Cell Carcinoma

This randomized clinical trial compares topical sinecatechins ointment, 10%, vs placebo in the treatment of superficial basal cell carcinoma.

Noninvasive Test for NASH and Hepatic Fibrosis in Patients With Psoriasis

This cohort study evaluates if a noninvasive test for nonalcoholic steatohepatitis and hepatic fibrosis can be used in patients with psoriasis to aid in determining eligibility for methotrexate therapy, monitor for development of methotrexate-induced hepatotoxic effects, and monitor for worsening of hepatic fibrosis scores during methotrexate therapy.

Postirradiation Lichen Sclerosus et Atrophicus

This case report describes a patient who developed postirradiation lichen sclerosus et atrophicus.

Association of Vitamin D Receptor Polymorphisms With Nonmelanoma Skin Cancer Risk

This case-control study analyzes the contributions of known risk factors and polymorphisms to the development of nonmelanoma skin cancer.

Error in Affiliation

In the article by Albers et al titled "Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone," published online August 2, 2017, there was an error in the affiliations. Dr Arbiser is also at the Atlanta Veterans Administration Medical Center, Decatur, Georgia. The error has been corrected online.

Factors Associated With a Mole-Prone Phenotype in Late Adolescence

This cohort study from the Study of Nevi in Children examines host, behavioral, and dermoscopic factors in early adolescence that are associated with a mole-prone phenotype in late adolescence.

Moon Dust

We will soon commemorate the 50th anniversary of the Apollo moon missions that culminated in the first lunar landing on July 20, 1969. Many of us still recall Neil Armstrong's stirring words as he emerged from the lunar module: "That's one small step for [a] man, one giant leap for mankind."

Genotypical Phenotypic Features of BAP1 Cancer Syndrome

This study of 10 patients identified through clinical screening and 205 patients identified through literature review describes 8 new families with germline mutations in BAP1 and provides a comprehensive review of reported cases.

Descriptions of Cutaneous Lupus Erythematosus in the 19th Century

The varied cutaneous presentations of lupus erythematosus (LE) continue to make its diagnosis challenging even for experienced diagnosticians. In accordance with its many manifestations, cutaneous LE has been known by several different names throughout history. During the mid-19th century, dermatologists at the prominent Paris and Vienna schools of dermatology began synthesizing the diverse cutaneous features of LE into a uniform diagnosis.

Naltrexone Treatment of Familial Benign Pemphigus (Hailey-Hailey Disease)

This case series evaluates whether low-dose naltrexone is efficacious and safe in the treatment of recalcitrant familial benign pemphigus (Hailey-Hailey disease).

Background and Room Illumination in Color Identification of Skin Lesions

This study examines the variability in color identification and perception of skin lesions in the context of background color and room illumination.

Forthcoming Meetings

EGFRvIII vaccine in glioblastoma—InACT-IVe or not ReACTive enough?

Variant III of the epidermal growth factor receptor (EGFRvIII) fulfills many criteria of a suitable target for a glioblastoma vaccine. Unlike many tumor-associated self antigens currently targeted in vaccine trials, it is specifically expressed by tumor cells but not in healthy tissue, thus representing a so-called neoantigen. The in-frame deletion of the extracellular domain in EGFRvIII results in the fusion of exons 1 and 8 and thus generates a peptide sequence encompassing the fusion point, which is foreign to the immune system. EGFRvIII is the most common gain-of-function mutation in glioblastoma shown to contribute to the malignant phenotype by complex cytokine network alterations.¹ Preclinical studies have shown immunogenicity and efficacy in several tumor models.² In the clinical development the vaccine (rindopepimut) has early on been tested in patients with newly diagnosed glioblastoma to ensure low tumor burden and a sufficient time window to achieve a meaningful immune response. The single-arm ACTIVATE, ACT II, and ACT III trials in patients with newly diagnosed, resected, EGFRvIII+ glioblastoma demonstrated a median survival of 20–22 months, comparing favorably to historical matched controls.³

Highlights from the Literature

Meeting Update—World Federation of Neuro-Oncology Societies (WFNOS) Meeting 2017

ID(H)entifying checkpoint inhibitor candidates among diffuse glioma

See the article by Berghoff et al on pages 1460–1468.

Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma

Abstract

Background

Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with cancer; however, little is known about PA or prognostic communication in MG. Moreover, research has yet to evaluate the impact of cognitive impairment on PA and preferred forms of communication.

Methods

Fifty MG patients and 32 paired caregivers were evaluated in this exploratory study with a semi-structured PA assessment aimed to measure their awareness of MG incurability and LE. Full PA was defined as awareness of MG incurability and accurate estimate of LE. The assessment included a survey about preferences for prognostic communication (items from the Prognosis and Treatment Perceptions Questionnaire), neurocognitive assessment (Hopkins Verbal Learning Test–Revised, Trail Making Test Parts A and B, and the Controlled Oral Word Association Test), and measurements of mood (Hospital Anxiety and Depression Scale) and quality of life (Functional Assessment of Cancer Therapy–Brain [FACT-Br]).

Results

Twenty (40%) patients and 22 (69%) caregivers had full PA. Thirty (60%) patients and 23 (72%) caregivers reported that prognostic information was extremely or very important, and 21 (42%) patients and 16 (50%) caregivers desired more prognostic information. Patients with memory impairment more frequently believed that prognostic information was important (P = 0.04, P = 0.03) and desired more information (P = 0.05, P = 0.003) as compared with those without impairment.

Conclusions

Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.

Caddyshack therapeutics: overcoming glioblastoma adaptation

See the article by McNeill et al on pages 1469–1480.

Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma

Abstract

Background

Sonidegib (LDE225) is a potent, selective hedgehog (Hh) inhibitor of Smoothened. This study explored the safety and pharmacokinetics of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response.

Methods

Pediatric patients aged ≥1 to <18 years were included according to a Bayesian design starting at 372 mg/m² of continuous once daily oral sonidegib. Tumor samples were analyzed for Hh pathway activation using a validated 5-gene Hh signature assay. In phase II, pediatric patients were treated at the recommended phase II dose (RP2D) while adults received 800 mg daily.

Results

Sixteen adult (16 MB) and 60 pediatric (39 MB, 21 other) patients with an age range of 2–17 years were enrolled. The RP2D of sonidegib in pediatric patients was established at 680 mg/m² once daily. The phase II study was closed prematurely.The 5-gene Hh signature assay showed that the 4 complete responders (2 pediatric and 2 adult) and 1 partial responder (adult) all had Hh-activated tumors, while 5 patients with activated Hh had either stable disease (n = 3) or progressive disease (n = 2). No patient with an Hh-negative signature (n = 50) responded. The safety profile for pediatric patients was generally consistent with the one established for adult patients; however, growth plate changes were observed in prepubertal pediatric patients.

Conclusions

Sonidegib was well tolerated and the RP2D in pediatric patients was 680 mg/m² once daily. Five of the 10 MB patients with activated Hh pathway demonstrated complete or partial responses.

Phase II trial of dacomitinib, a pan–human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification

Abstract

Background

We conducted a multicenter, 2-stage, open-label, phase II trial to assess the efficacy and safety of dacomitinib in adult patients with recurrent glioblastoma (GB) and epidermal growth factor receptor gene (EGFR) amplification with or without variant III (EGFRvIII) deletion.

Methods

Patients with first recurrence were enrolled in 2 cohorts. Cohort A included patients with EGFR gene amplification without EGFRvIII mutation. Cohort B included patients with EGFR gene amplification and EGFRvIII mutation. Dacomitinib was administered (45 mg/day) until disease progression/unacceptable adverse events (AEs). Primary endpoint was progression-free survival (PFS; RANO criteria) at 6 months (PFS6).

Results

Thirty patients in Cohort A and 19 in Cohort B were enrolled. Median age was 59 years (range 39–81), 65.3% were male, and Eastern Cooperative Oncology Group Performance Status 0/1/2 were 10.2%/65.3%/24.5%, respectively. PFS6 was 10.6% (Cohort A: 13.3%; Cohort B: 5.9%) with a median PFS of 2.7 months (Cohort A: 2.7 mo; Cohort B: 2.6 mo). Four patients were progression free at 6 months and 3 patients were so at 12 months. Median overall survival was 7.4 months (Cohort A: 7.8 mo; Cohort B: 6.7 mo). The best overall response included 1 complete response and 2 partial responses (4.1%). Stable disease was observed in 12 patients (24.5%: eight in Cohort A and four in Cohort B). Diarrhea and rash were the most common AEs; 20 (40.8%) patients experienced grade 3–4 drug-related AEs.

Conclusions

Dacomitinib has a limited single-agent activity in recurrent GB with EGFR amplification. The detailed molecular characterization of the 4 patients with response in this trial can be useful to select patients who could benefit from dacomitinib.

Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study

Abstract

Background

Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program.

Methods

We identified 1302166 patients with diagnoses of nonhematologic malignancies originating outside of the CNS between 2010 and 2013 and described the incidence proportion and survival of patients with brain metastases.

Results

We identified 26430 patients with brain metastases at diagnosis of cancer. Patients with small cell and non–small cell lung cancer displayed the highest rates of identified brain metastases at diagnosis; among patients presenting with metastatic disease, patients with melanoma (28.2%), lung adenocarcinoma (26.8%), non–small cell lung cancer not otherwise specified/other lung cancer (25.6%), small cell lung cancer (23.5%), squamous cell carcinoma of the lung (15.9%), bronchioloalveolar carcinoma (15.5%), and renal cancer (10.8%) had an incidence proportion of identified brain metastases of >10%. Patients with brain metastases secondary to prostate cancer, bronchioloalveolar carcinoma, and breast cancer displayed the longest median survival (12.0, 10.0, and 10.0 months, respectively).

Conclusions

In this study we provide generalizable estimates of the incidence and prognosis for patients with brain metastases at diagnosis of a systemic malignancy. These data may allow for appropriate utilization of brain-directed imaging as screening for subpopulations with cancer and have implications for clinical trial design and counseling of patients regarding prognosis.

The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

Abstract

"Tumor-associated macrophages" (TAMs) form a significant cell population in malignant tumors and contribute to tumor growth, metastasis, and neovascularization. Gliomas are characterized by extensive neo-angiogenesis, and knowledge of the role of TAMs in neovascularization is important for future anti-angiogenic therapies. The phenotypes and functions of TAMs are heterogeneous and more complex than a classification into M1 and M2 inflammation response types would suggest. In this review, we provide an update on the current knowledge of the ontogeny of TAMs, focusing on diffuse gliomas. The role of TAMs in the regulation of the different processes in tumor angiogenesis is highlighted and the most recently discovered mechanisms by which TAMs mediate resistance against current antivascular therapies are mentioned. Novel compounds tested in clinical trials are discussed and brought in relation to different TAM-related angiogenesis pathways. In addition, potential therapeutic targets used to intervene in TAM-regulated tumor angiogenesis are summarized.

Correlation of immune phenotype with IDH mutation in diffuse glioma

Abstract

Background

Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors.

Methods

Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II–IV from The Cancer Genome Atlas (TCGA) database.

Results

TIL and PD-L1 expression were observed in approximately half of WHO grade II/III gliomas. IDH-wt status was associated with significantly higher TIL infiltration and PD-L1 expression among all (grades II–IV) cases (n = 174, P < 0.001) and within the cohort of glioblastomas (n = 131, P < 0.001). In low-grade glioma (LGG) and glioblastoma cohorts of TCGA, significantly higher PD-L1 gene expression levels were evident in IDH-wt compared with IDH-mut samples (LGG: N = 516; P = 1.933e-11, GBM: N = 161; P < 0.009). Lower PD-L1 gene expression was associated with increased promoter methylation (Spearman correlation coefficient −0.36; P < 0.01) in the LGG cohort of TCGA. IDH-mut gliomas had higher PD-L1 gene promoter methylation levels than IDH-wt gliomas (P < 0.01).

Conclusions

The immunological tumor microenvironment of diffuse gliomas differs in association with IDH mutation status. IDH-wt gliomas display a more prominent TIL infiltration and higher PD-L1 expression than IDH-mut cases. Mechanistically this may be at least in part due to differential PD-L1 gene promoter methylation levels. Our findings may be relevant for immune modulatory treatment strategies in glioma patients.

Prognostic significance of preoperative neutrophilia on recurrence-free survival in meningioma

Abstract

Background

Meningioma is the most common primary intracranial tumor and recurrence is one of the important challenges in patient management. Prognostic factors for tumor recurrences in these patients especially before surgical resection are not fully characterized. Several studies have indicated an association between changes in hematologic laboratory parameters with patient outcomes in solid malignancies. We aimed to assess the association between hematologic parameters and tumor recurrence in patients with meningioma.

Methods

Preoperative complete blood count (CBC) data were analyzed in patients with newly diagnosed meningioma (n = 222). Clinical data, including history of corticosteroid therapy, tumor characteristics, and follow-up, were obtained. Recurrence-free survival (RFS) was evaluated using Cox proportional hazards models and log-rank tests.

Results

Using preoperative CBC data from patients prior to any steroid therapy, 51 (23%) patients had neutrophilia. In univariate analysis, neutrophilia was significantly associated with meningioma recurrence (hazard ratio [HR] 2.73; P < 0.01). Neither leukocytosis nor lymphocytosis was associated with RFS. In multivariate analysis, after adjusting for tumor grade, tumor size, and extent of resection, neutrophilia remained an independent prognostic factor for RFS (HR 2.23, P = 0.01). Forty-six (21%) patients had low hemoglobin levels indicative of anemia, and the presence of anemia showed a trend toward high risk for recurrence (HR 1.83; P = 0.06).

Conclusions

The presence of neutrophilia was associated with higher rate of tumor recurrence in patients with meningioma. Validation of these results and the biologic role of neutrophilic inflammatory/immune reaction in meningioma requires further investigation.

Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer

Abstract

Background

Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases.

Methods

Using human-derived TNBC cell lines, synthetic lethal small interfering RNA kinase screens were evaluated with brain-penetrant inhibitors against MEK1/2 (selumetinib, AZD6244) or phosphatidylinositol-3 kinase (PI3K; buparlisib, BKM120). Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination. Tumors were analyzed by western blot and multiplexed kinase inhibitor beads/mass spectrometry to assess treatment effects.

Results

Screens identified MEK+PI3K and MEK+PDGFR inhibitors as tractable, rational combinations. Dual treatment of selumetinib with buparlisib or pazopanib was synergistic in TNBC cells in vitro. Both combinations improved survival in intracranial SUM149 and MDA-MB-231Br, but not MDA-MB-468 or MDA-MB-436. Treatments decreased mitogen-activated protein kinase (MAPK) and PI3K (Akt) signaling in sensitive (SUM149 and 231Br) but not resistant models (MDA-MB-468). Exploratory analysis of kinome reprogramming in SUM149 intracranial tumors after MEK ± PI3K inhibition demonstrates extensive kinome changes with treatment, especially in MAPK pathway members.

Conclusions

Results demonstrate that rational combinations of the clinically available inhibitors selumetinib with buparlisib or pazopanib may prove to be promising therapeutic strategies for the treatment of some TNBC brain metastases. Additionally, effective combination treatments cause widespread alterations in kinase pathways, including targetable potential resistance drivers.

BAP1 mutations in high-grade meningioma: implications for patient care

Abstract

We have recently shown that the breast cancer (BRCA)1-associated protein-1 tumor suppressor gene (BAP1) is inactivated in a subset of clinically aggressive meningiomas that display rhabdoid histomorphology. Immunohistochemistry for BAP1 protein provides a rapid and inexpensive method for screening suspected cases. Notably, some patients with BAP1-mutant meningiomas have germline BAP1 mutations and BAP1 tumor predisposition syndrome (TPDS). It appears that nearly all patients with germline BAP1 mutations develop malignancies by age 55, most frequently uveal melanoma, cutaneous melanoma, pleural or peritoneal malignant mesothelioma, or renal cell carcinoma, although other cancers have also been associated with BAP1 TPDS. Therefore, when confronted with a patient with a potentially high-grade rhabdoid meningioma, it is important that neuropathologists assess the BAP1 status of the tumor and that the patient's family history of cancer is carefully ascertained. In the appropriate clinical setting, genetic counseling and germline BAP1 DNA sequencing should be performed. A cancer surveillance program for individuals who carry germline BAP1 mutations may help identify tumors such as uveal melanoma, cutaneous melanoma, and renal cell carcinoma at early and treatable stages. Because BAP1-mutant meningiomas are rare tumors, multi-institutional efforts will be needed to evaluate therapeutic strategies and to further define the clinicopathologic features of these tumors.

Global incidence of malignant brain and other central nervous system tumors by histology, 2003–2007

Abstract

Background

Previous reports have shown that overall incidence of malignant brain and other central nervous system (CNS) tumors varied significantly by country. The aim of this study was to estimate histology-specific incidence rates by global region and assess incidence variation by histology and age.

Methods

Using data from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer's (IARC) Cancer Incidence in Five Continents X (including over 300 cancer registries), we calculated the age-adjusted incidence rates (AAIR) per 100000 person-years and 95% CIs for brain and other CNS tumors overall and by age groups and histology.

Results

There were significant differences in incidence by region. Overall incidence of malignant brain tumors per 100000 person-years in the US was 5.74 (95% CI = 5.71–5.78). Incidence was lowest in Southeast Asia (AAIR = 2.55, 95% CI = 2.44–2.66), India (AAIR = 2.85, 95% CI = 2.78–2.93), and East Asia (AAIR = 3.07, 95% CI = 3.02–3.12). Incidence was highest in Northern Europe (AAIR = 6.59, 95% CI = 6.52–6.66) and Canada (AAIR = 6.53, 95% CI = 6.41–6.66). Astrocytic tumors showed the broadest variation in incidence regionally across the globe.

Conclusion

Brain and other CNS tumors are a significant source of cancer-related morbidity and mortality worldwide. Regional differences in incidence may provide clues toward genetic or environmental causes as well as a foundation for broadening knowledge of their epidemiology. Gaining a comprehensive understanding of the epidemiology of malignant brain tumors globally is critical to researchers, public health officials, disease interest groups, and clinicians and contributes to collaborative efforts in future research.

Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients

Abstract

Background

RNAs within extracellular vesicles (EVs) have potential as diagnostic biomarkers for patients with cancer and are identified in a variety of biofluids. Glioblastomas (GBMs) release EVs containing RNA into cerebrospinal fluid (CSF). Here we describe a multi-institutional study of RNA extracted from CSF-derived EVs of GBM patients to detect the presence of tumor-associated amplifications and mutations in epidermal growth factor receptor (EGFR).

Methods

CSF and matching tumor tissue were obtained from patients undergoing resection of GBMs. We determined wild-type (wt)EGFR DNA copy number amplification, as well as wtEGFR and EGFR variant (v)III RNA expression in tumor samples. We also characterized wtEGFR and EGFRvIII RNA expression in CSF-derived EVs.

Results

EGFRvIII-positive tumors had significantly greater wtEGFR DNA amplification (P = 0.02) and RNA expression (P = 0.03), and EGFRvIII-positive CSF-derived EVs had significantly more wtEGFR RNA expression (P = 0.004). EGFRvIII was detected in CSF-derived EVs for 14 of the 23 EGFRvIII tissue-positive GBM patients. Conversely, only one of the 48 EGFRvIII tissue-negative patients had the EGFRvIII mutation detected in their CSF-derived EVs. These results yield a sensitivity of 61% and a specificity of 98% for the utility of CSF-derived EVs to detect an EGFRvIII-positive GBM.

Conclusion

Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs.

Combination therapy with potent PI3K and MAPK inhibitors overcomes adaptive kinome resistance to single agents in preclinical models of glioblastoma

Abstract

Background

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Prognosis remains poor despite multimodal therapy. Developing alternative treatments is essential. Drugs targeting kinases within the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) effectors of receptor tyrosine kinase (RTK) signaling represent promising candidates.

Methods

We previously developed a non-germline genetically engineered mouse model of GBM in which PI3K and MAPK are activated via Pten deletion and Kras^G12D in immortalized astrocytes. Using this model, we examined the influence of drug potency on target inhibition, alternate pathway activation, efficacy, and synergism of single agent and combination therapy with inhibitors of these 2 pathways. Efficacy was then examined in GBM patient-derived xenografts (PDX) in vitro and in vivo.

Results

PI3K and mitogen-activated protein kinase kinase (MEK) inhibitor potency was directly associated with target inhibition, alternate RTK effector activation, and efficacy in mutant murine astrocytes in vitro. The kinomes of GBM PDX and tumor samples were heterogeneous, with a subset of the latter harboring MAPK hyperactivation. Dual PI3K/MEK inhibitor treatment overcame alternate effector activation, was synergistic in vitro, and was more effective than single agent therapy in subcutaneous murine allografts. However, efficacy in orthotopic allografts was minimal. This was likely due to dose-limiting toxicity and incomplete target inhibition.

Conclusion

Drug potency influences PI3K/MEK inhibitor–induced target inhibition, adaptive kinome reprogramming, efficacy, and synergy. Our findings suggest that combination therapies with highly potent, brain-penetrant kinase inhibitors will be required to improve patient outcomes.

From code to speaker meaning

Abstract

This paper has two aims. One is to defend an incrementalist view of the evolution of language, not from those who think that syntax could not evolve incrementally, but from those who defend a fundamental distinction between Gricean communication or ostensive inferential communication (Scott-Phillips, Sperber, Tomasello, originally based on Grice) and code-based communication. The paper argues against this dichotomy, and sketches ways in which a code-based system could evolve into Gricean communication. The second is to assess the merits of the Sender–Receiver Framework, originally formulated by David Lewis, and much elaborated and set into an evolutionary context by Brian Skyrms and colleagues, as a framework for thinking about the evolution of language. Despite the great strengths of that framework, and despite the great value of a framework that is both general and formally tractable, I argue that there are critical features of language that it fails to capture .

Patient-specific devices and population-level evidence: evaluating therapeutic interventions with inherent variation

Abstract

Designing and manufacturing medical devices for specific patients is becoming increasingly feasible with developments in 3D printing and 3D imaging software. This raises the question of how patient-specific devices can be evaluated, since our 'gold standard' method for evaluation, the randomised controlled trial (RCT), requires that an intervention is standardised across a number of individuals in an experimental group. I distinguish several senses of patient-specific device, and focus the discussion on understanding the problem of variations between instances of an intervention for RCT evaluation. I argue that, despite initial appearances, it is theoretically possible to use RCTs to evaluate some patient-specific medical devices. However, the argument reveals significant difficulties for ensuring the validity of such trials, with implications for how we should think about methods of evidence gathering and regulatory approaches for these technologies.

Flavonoids inhibit chronically-exposed arsenic-induced proliferation and malignant transformation of HaCaT cells

Abstract

Background

Apart from exposure to UV-radiation, studies show relationship between skin cancer and chronic ingestion of arsenic through drinking water. Chemopreventive strategies could help in reducing the toxic effects of arsenic and arsenic-induced skin cancer.

Methods

Cytotoxicity of arsenic on human skin keratinocytes HaCaT cells was evaluated using MTT and trypan blue assays. Arsenic-induced malignant transformant HaCaT cells were selected through soft agar colony assay. Cell cycle progression was analyzed through FACS. The expressions of genes modulated by arsenic were studied through RT-PCR.

Results

The lower concentrations (0.1-0.5 μM) of arsenic were non-toxic and transformed HaCaT cells on chronic exposure, and also enhanced the cell proliferation. Silibinin and fisetin reduced the arsenic-induced cell proliferation and malignant transformation. A slight increase in G2-M phase cell population was also observed. The anti-proliferation effects of flavonoids on HaCaT transformants were further enhanced when combined with gamma radiation. Chronic and acute exposure of arsenic modulated the expression of transformation associated genes including Bcl-2A1, IGFL-1, Rab31 and TNC in HaCaT cells.

Conclusions

Chronic exposure of lower arsenic concentrations caused malignant transformation of skin keratinocytes and that effect was attenuated by flavonoids silibinin and fisetin. Thus chemoprevention could reduce arsenic-caused detrimental effects on skin cells.

This article is protected by copyright. All rights reserved.

Pulsed light reduces the toxicity of the algal toxin okadaic acid to freshwater crustacean Daphnia pulex

Abstract

This constitutes the first study to report on the reduction in toxicity of the dinoflagellate algal toxin okadaic acid after novel pulsed light (PL) treatments where ecotoxicological assessment was performed using a miniaturised format of the conventional in vivo freshwater crustacean Daphnia sp. acute toxicity test. Bivalves accumulate this toxin, which can then enter the human food chain causing deleterious health effects such as diarrhetic shellfish poisoning. This miniaturised toxicological bioassay used substantially less sample volume and chemical reagents. Findings revealed a 24-h EC₅₀ of 25.87 μg/L for PL-treated okadaic acid at a UV dose of 12.98 μJ/cm² compared to a 24-h EC₅₀ of 1.68 μg/L for the untreated okadaic acid control, suggesting a 15-fold reduction in toxicity to Daphnia pulex. The bioassay was validated in this study and correlated well with the "classic" ISO format (r = 0.98) using the traditional reference chemical potassium dichromate (K₂Cr₂O₇). Reduction by up to 65% in PL-treated okadaic acid concentration was confirmed by LC-MS/MS analysis. Findings from this study have positive ecological, societal and enterprise implications, such as the development of PL technology for the prevention or reduce algal contamination of fisheries and aquaculture industries.

Botanical Complementary and Alternative Medicine for Pruritus: a Systematic Review

Abstract

Purpose of Review

Complementary and alternative medicine (CAM) is widely used by patients who suffer from chronic pruritus, but there is little data on the efficacy or antipruritic mechanism of these interventions. This review assesses the current understanding of the clinical efficacy and purported mechanisms of CAM therapy for pruritic skin disease, and serves as a basis for further investigation into the pharmacological basis of plant-based CAM for pruritus and patient motivations in the adoption of these types of therapies.

Recent Findings

To assess the current state of the literature, we queried multiple databases for reports of botanical CAM therapies for pruritic skin conditions. Numerous in vitro and animal studies show positive results, but antipruritic effects in human trials are varied. Many of these topical and systemic therapies have demonstrated measurable impact on inflammatory pathways, including some that are known to be crucial in transmission of itch signaling.

Summary

CAM is a frequently utilized but somewhat poorly understood intervention for chronic pruritus, though our understanding of the impact of these therapies on pruritus has improved in recent years. Further studies into the mechanism and efficacy of CAM-based therapies for chronic pruritus, and patient attitudes towards these practices, are warranted.

Enzymatic activity induction of GST-family isoenzymes from pesticide mixture used in floriculture

Abstract

Glutathione S-transferases (GSTs) comprise a number of genes that codify for a group of isoenzymes that participate in phase II xenobiotic detoxification by means of conjugation with glutathione, producing hydrosoluble compounds. It has been demonstrated that some pesticides are substrates for GST isoenzymes. Floriculture is one of the main economic activities in the municipalities of Villa Guerrero and Atlacomulco; pesticides, applied as mixtures, are intensively used in this activity. In this study, total GST enzymatic activity and glutathione S-transferases theta 1 (GSTT1) enzymatic activity were calculated for a group of floriculture workers exposed to pesticides and for an unexposed group. The former comprised 169 floriculture workers, while the latter, 96 students. The value of the median GST enzymatic activity in the exposed group was 0.560 and 0.169 μmol/min/mL in the unexposed individuals. GSTT1 activity was 1.234 μmol/min/mL in the exposed group and 0.221 μmol/min/mL in the unexposed group. Mann-Whitney U test showed a significant difference between these groups, for both total GST and GSTT1, p < 0.001. Our results show that exposure to pesticides increases the activities of total GST and GSTT1 enzymes.

Metabolic Strategies of Melanoma Cells: Mechanisms, Interactions with the Tumor Microenvironment, and Therapeutic Implications

Abstract

Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There is also data to support that the metabolic phenotypes of melanoma cells depend upon contributions from both intrinsic oncogenic pathways and extrinsic factors in the tumor microenvironment. This review summarizes current understanding of the metabolic processes that promote cutaneous melanoma tumorigenesis and progression, the regulation of cancer cell metabolism by the tumor microenvironment, and the impact of metabolic pathways on targeted and immune therapies.

This article is protected by copyright. All rights reserved.

Melanoma sponge on pigmentation gene to reduce tumour-suppressive microRNAs

Abstract

MicroRNAs (miRs) were originally described as non-coding RNA molecules that mediate the inhibition of translation of their target genes by binding to distinctive, now called canonical, MicroRNA Response Elements (MREs). After binding to MREs, which are usually located near the 3'UTR of their target mRNA, a complex protein machinery (RNA-induced silencing complex, RISC) mediates mRNA decay and/or the inhibition of translation initiation (Mione and Bosserhoff, 2015). However, the diversity of microRNA regulation and function has greatly expanded over the last several years, and more non-canonical functions of miRs are emerging.

In the study by Gilot et al. (covered in this N&V), the group reveals a novel and exciting mechanism of how mRNAs appear as potent miR sponges that sequester tumour-suppressive miRs, thereby lessening the function of these miRs. Here, they convincingly present how the sequestration of tumour-suppressive miR-16 can de-repress its target genes and promote melanoma progression.

This article is protected by copyright. All rights reserved.

Assessing Cosmetic Rhinoplasty Outcomes

Developing effective methods to evaluate surgical outcomes is more important than ever. Peers, patients, and payers increasingly judge the quality of surgical procedures based on measurable outcomes. The government, health care review websites, and others are actively seeking benchmarks to compare our individual surgical results with those of other surgeons across the country and around the world. It is in our best interest to identify equitable methods of measuring our outcomes, and cosmetic surgery outcomes are among the most difficult to measure. Rating cosmetic results in rhinoplasty—with wide variability in what is considered ideal or is even possible for a given patient—is particularly challenging. Prior studies have examined patients' and surgeons' perceptions following rhinoplasty. However, both patients and surgeons have inherent biases that interfere with objective analyses of rhinoplasty outcomes. Unbiased casual observers are better suited to independently rate improvement following cosmetic rhinoplasty.

Rhinoplasty and Social Perceptions of Attractiveness and Health

This survey study measures naive observers' perceptions of attractiveness, success, and overall health of patients who have undergone rhinoplasty.

Current Trends in Management of Submental Liposis

This pooled analysis of phase 3 trials evaluates the efficacy of deoxycholic acid injection compared with submental liposuction among patients with submental liposis.

Nasolabial Incision Technique for Facial Paralysis Management

This case series compares the preoperative and postoperative facial function of patients who underwent a nasolabial fold creation procedure using the minimal nasolabial incision technique.

Virtual Surgery for the Nasal Airway

This cross-sectional study examines survey data from surgeons to determine whether virtual surgery planning via computational fluid dynamics for nasal airway obstruction procedures affects surgeon decision making.

Industry Payments Among Dermatology Clinical Practice Guidelines Authors

This study uses data extraction from the Open Payments database to evaluate the monetary values and types of payments received by physician authors of dermatology guidelines and the accuracy of conflict of interest disclosure statements.

Barber Recognition of Pseudofolliculitis Barbae and Acne Keloidalis Nuchae

This cross-sectional study analysis assesses barber knowledge and recommendations regarding various dermatologic conditions common among clients who use predominantly African American barbershops.

Industry Influence in Dermatology Clinical Practice Guideline Development

In his farewell address to the nation, in 1961, President Dwight D. Eisenhower warned about the rising influence of the military establishment and the arms industry. "The potential for the disastrous rise of misplaced power exists," the President said, referring to the military-industrial complex, "and will persist."

Long-term Change in the Risk of Skin Cancer After Organ Transplantation

This population-based nationwide cohort study evaluates the long-term change in the risk of skin cancer after organ transplantation in Norway.

A Strange Digital Tumor

A man in his 60s presented with severe fatigue, and his medical history was notable for primary hyperparathyroidism 6 years prior to presentation, for which the patient refused therapeutic management; examination revealed a large tumor on the distal part of the right fourth finger. What is your diagnosis?

Dermal Hyperneury and Multiple Sclerotic Fibromas in MEN 2A Syndrome

This case report describes dermatologic similarities among family members with the familial medullary thyroid carcinoma variant of multiple endocrine neoplasia type 2A syndrome and cutaneous manifestations of multiple endocrine neoplasia type 2B and PTEN hamartoma-tumor syndromes.

Diagnostic Accuracy of Virtual Pathology vs Traditional Microscopy

This study compares diagnostic accuracy using whole-slide images with diagnostic accuracy using traditional microscopy for cutaneous diseases.

Telangiectasias on the Lower Extremity

A woman in her 80s presented with a 1-year history of blanchable, salmon-colored, monomorphic macules and fine telangiectasias localized to her right lower leg. What is your diagnosis?

The Most Beautiful People

This study used People magazine to compare standards of beauty in 1990 with present-day standards.

Margin Mapping of Lentigo Maligna and Lentigo Maligna Melanoma With HRCM-RV

This study evaluates whether handheld reflectance confocal microscopy with radial video mosaicing improves diagnostic accuracy in patients with lentigo maligna and lentigo maligna melanoma.

Pustular Eruption After Treatment With Complementary and Alternative Medicine

This case report describes a patient with metastatic non–small cell lung carcinoma who experienced acnelike lesions after treatment with an herbal tonic.

The Epidemic of Guns

The shooting in Las Vegas, Nevada, that left 59 people dead, 10 times that number wounded, and thousands of people with the psychological distress from being present at the scene during and after the massacre has once again raised the issue of what we as a nation can and should do about guns. The solution lies in not just focusing on Las Vegas and the hundreds of other mass shootings that have occurred in the United States in the last 14 months, but rather to underscore that on average almost 100 people die each day in the United States from gun violence. The 36 252 deaths from firearms in the United States in 2015 exceeded the number of deaths from motor vehicle traffic crashes that year (36 161). That same year, the US Centers for Disease Control and Prevention reported that 5 people died from terrorism. Since 1968, more individuals in the United States have died from gun violence than in battle during all the wars the country has fought since its inception.

Association of Delays in Surgery for Melanoma With Insurance Type

This cohort study investigates whether patients with Medicaid are more likely than patients with Medicare or private insurance to experience delays in surgery for melanoma.

HPV-Induced Atypical Pigmented High-grade Dysplasia of the Scrotum

This case report describes a patient with HPV-induced atypical pigmented high-grade dysplasia of the scrotum.

Delay and Disparity in Time to Surgical Treatment for Melanoma

The relationship between patient health insurance status, health care use, and outcomes has been explored in great depth and detail over decades for myriad diseases in the United States. Likewise, health services research has become increasingly relevant within the specialty of dermatology, especially as the emergence of "big data" and advanced analytics continue to transform overall health care delivery.

Treatment of Psychiatric Disorders and Skin-Restricted Lupus Remission

This observational cohort study investigates the association between treatment of psychiatric disorders and skin-restricted lupus remission in a patient cohort over 2.5 years.

Brentuximab Vedotin for Patients With Refractory Lymphomatoid Papulosis

This phase 2 trial of 12 patients assesses the efficacy and safety of brentuximab vedotin for lymphomatoid papulosis.

Severity strata for five patient-reported outcomes in adults with atopic dermatitis

Abstract

Background

Multiple patient-reported outcomes have been used to assess the burden of atopic dermatitis (AD). Some are disease specific, e.g. the Patient Oriented Eczema Measure (POEM). While others pertain to itch, e.g. Numerical Rating Scale (NRS)-itch, ItchyQoL and 5-D itch, or dermatologic disease in general, e.g. Dermatology Life Quality Index (DLQI). Development of severity strata is essential for proper interpretability of these assessments. We sought to confirm previously developed strata for POEM, DLQI and raw ItchyQoL, and develop strata for the NRS-itch, mean ItchyQOL and 5-D itch scale for use in adults with AD.

Methods

Self-administered questionnaires were completed by 210 adults with AD in a dermatology practice setting. Strata were selected using an anchoring approach based on patient-reported disease severity.

Results

We confirmed the existing strata for POEM (mild=0-7, moderate=8-16, severe=17-28) (kappa=0.440), DLQI (mild=0-5, moderate=6-10, severe=11-30) (kappa=0.398) and NRS-itch (mild=0-3, moderate=4-6, severe=7-10) (kappa=0.499). However, the preferred band for raw ItchyQoL was mild=22-58, moderate=59-74 and severe=75-110 (kappa=0.379) and mean ItchyQOL was mild=1-2.9, moderate=3.0-3.9, severe=4.0-5.0 (kappa=0.374). The preferred band for 5-D itch scale was mild=0-11, moderate=12-17 and severe=18-25 (kappa=0.331).

Conclusions

Existing strata for POEM and DLQI perform well in adult AD. Previously reported strata for VAS-itch performed best for NRS-itch. We identified banding for the raw ItchyQoL for our AD population that varies slightly from the banding published for a more heterogeneous population. Finally, we proposed strata for mean ItchyQOL and 5-D itch scale in adult AD.

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Insulin-Like Growth Factor-II mRNA-Binding Protein 3 as a Novel Prognostic Biomarker for Acral Lentiginous Melanoma

Acral lentiginous melanoma (ALM) is a distinctive histopathological subtype of melanoma that typically occurs on the palms, soles, and nail beds. Because of their anatomical locations, ALMs are typically diagnosed at late stages, resulting in a poor prognosis.¹ Insulin-like growth factor-2 mRNA-binding protein 3 (IMP-3) plays significant roles in cell proliferation, migration, and adhesion by enhancing IGF-2 protein expression in malignant tumours.² We evaluated the associations between IMP-3 expression and clinicopathological features, including the western blot profile, Ki-67 index, BRAF mutation, and long-term survival, among patients with ALM.

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Seasonality of hair loss: a time series analysis of Google Trends data 2004 to 2016

Hair loss is a frequently encountered dermatologic complaint that often generates psychological distress. Prior studies have demonstrated a seasonal pattern to hair loss. Maximal proportions of telogen hair have been found to occur in the summer, whereas lowest rates of telogen hairs occur in the winter. Additionally, a recent study demonstrated that maximal hair shedding occurs in August and September, and that the percentage of hairs in the anagen phase peaks at the beginning of spring.

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Efficient antibacterial nanosponges based on ZnO nanoparticles and doxycycline

Publication date: Available online 18 October 2017
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Diego F. Suárez, Ana P.F. Monteiro, Daniele C. Ferreira, Frederico D. Brandão, Klaus Krambrock, Luzia V. Modolo, Maria E. Cortés, Rubén D. Sinisterra
Bacterial soft rot is responsible for the loss of about 25% of worldwide production in vegetables and fruits. Efforts have been made to develop an effective nanosponge with the capacity to load and release antibacterial drugs to protect plants. Based on the potential of the ZnO nanoparticles (ZnO–NPs) to achieve this goal, this study synthesized NP via the sol-gel and hydrothermal methods by controlling native defects, such as oxygen vacancies, using thermal treatments and reduced atmospheres. To characterize the ZnO NPs, X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), optical spectroscopy, electron paramagnetic resonance (EPR), Zeta Potential measurements and surface area with the Brunauer–Emmett–Teller (BET) method were used. The photophysical and photochemical properties via spin trapping method aligned with EPR using UVA light showed a greater formation of electron-hole pairs and hydroxyl radicals for the reduced ZnO NPs when compared with the oxidized ones. Additionally, we found that reduced ZnO-NPs have high effectively against Escherichia coli, Erwinia carotovora and Pantoea sp. bacteria using the photocatalytic effect in the UV range. Moreover, ZnO-NPs loaded with DOX release profile enables the release of DOX within 46days, where 25% was released during the first 10h followed by a second delivery phase with an interesting short-term efficacy (<1day) against E. carotovora and Pantoea sp. Bacteria. For the first time, it was demonstrated that ZnO-NPs and ZnO-NPs loaded with DOX have efficient UV photocatalytic activities against bacterial soft rot infections.

CD10 and the nail

Response of the Endothelium to the Epicutaneous Application of Leukotriene B4

Background: Vascular changes, both endothelial and functional, are crucial events in inflammatory responses. Objectives: To investigate the dynamics of endothelial cell (EC) and functional changes during acute inflammation in an in vivo model of the skin using leukotriene B₄. Methods: EC proliferation, vascular network size, vessel diameter (VD), and hypoxia-inducible factor (HIF)-1α were studied by immunohistochemical CD31/Ki67 double staining and single staining of HIF-1α. Cutaneous perfusion (CP) was assessed using the Twente Optical Perfusion Camera. Results: The initial phase illustrated an increase in VD, Ki67+ EC, and HIF-1α expression and late-phase vascular expansion. The HIF-1α and Ki67+ EC expression was limited. CP and VD were augmented after 24 h. Conclusion: The early phase of inflammation is characterized by EC proliferation and HIF-1α expression. Vascular expansion continues over time. CP and VD are seen in both phases of inflammation. Angiogenesis, vascular network formation, and perfusion are time-dependent processes which are mutually related during inflammation.
Skin Pharmacol Physiol 2017;30:306-314

Morphometric and morphologic parameters of the heart in healthy Alouatta guariba clamitans (Cabrera, 1940)

Abstract

Background

This study aimed at assessing the heart function of one neotropical primate (Alouatta guariba clamitans) kept in captivity using radiography, electrocardiogram (ECG) and Doppler echocardiography.

Methods

Ten adult healthy howler monkeys (A. g. clamitans) were evaluated under general anaesthesia. Vertebral Heart Scores (VHS) were obtained from radiographic studies. Ejection fraction, shortening fraction of left ventricle, left atrial/aortic root ratio, ascending aortic diameter, peak velocity of pulmonary, mitral, tricuspid and aortic blood flow and other values were measured by Doppler echocardiography. Heart rate, mean electrical axis of QRS complex, P, Q, R, S, T amplitude, P, PR interval, QRS, QT interval duration and ST segment unbalancing were measured by ECG.

Results and conclusions

Exam techniques were akin the ones used in humans. Doppler echocardiographic, radiographic, electrocardiographic and clinical parameters for howler monkey were described and correlated. The results have shown profiles of cardiovascular function and structure of A. g. clamitans.

Necrobiotic xanthogranuloma treated with lenalidomide

Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.

Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.

Clin Cosmet Investig Dermatol. 2017;10:403-411

Authors: Tan SP, Brown SB, Griffiths CE, Weller RB, Gibbs NK

Abstract
Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P<0.01, respectively). Data from the clinical study indicated that once daily oral l-histidine significantly reduced (P<0.003) AD disease severity by 34% (physician assessment using the SCORingAD tool) and 39% (patient self-assessment using the Patient Oriented Eczema Measure tool) after 4 weeks of treatment. No improvement was noted with the placebo (P>0.32). The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids and combined with its safety profile suggests that it may be a safe, nonsteroidal approach suitable for long-term use in skin conditions that are associated with filaggrin deficits such as AD.

PMID: 29042806 [PubMed]

Efficacy of the combined use of a mild foaming cleanser and moisturizer for the care of infant skin.

Efficacy of the combined use of a mild foaming cleanser and moisturizer for the care of infant skin.

Clin Cosmet Investig Dermatol. 2017;10:393-401

Authors: Okamoto N, Umehara K, Sonoda J, Hotta M, Mizushima H, Takagi Y, Matsuo K, Baba N

Abstract
OBJECTIVE: Despite the application of skin care treatments, many infants have skin problems such as dryness and erythema. We proposed a new combination skin care for infants which consisted of a foaming cleanser with lower surfactant activity and moisturizers that contained pseudo-ceramide.
SUBJECTS AND METHODS: A total of 50 infants (age: 3-24 months) with insignificant levels of dry skin were enrolled in this usage trial. The parents washed the infants with the test cleanser while bathing and then applied the moisturizer (lotion or cream) containing pseudo-ceramide. Prior to and following the 4-week usage period, visual evaluation of the skin condition was conducted by a dermatologist, in addition to instrumental analysis.
RESULTS: Erythema and papule, accompanied by dryness, were commonly observed at week 0. However, by week 4, these symptoms significantly improved; the condition of none of the subjects deteriorated. The number of infants with lower cutaneous barrier function and higher skin pH decreased. The parents of the infants recognized improvements in the skin symptoms and were appreciative of the test materials.
CONCLUSION: The combined usage of the foaming cleanser with lower surfactant activity and a moisturizer containing pseudo-ceramide may be effective in maintaining healthy infant skin and ameliorating the skin symptoms.

PMID: 29042805 [PubMed]

Clinical and dermoscopic characteristics of a patient with cutaneous and mucosal manifestations of Peruvian wart

Second primary cutaneous T-cell lymphoma in patients with non-Hodgkin lymphoma: a chicken-or-the-egg issue

Pigmentary mosaicism with trisomy 7

Epidemiological survey of patients with psoriasis in Matsumoto city, Nagano Prefecture, Japan

Abstract

A local epidemiological survey of psoriasis was conducted from 19 February to 30 June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and psoriatic erythroderma (0.3%). The topical therapeutic agents included corticosteroids (84.0%), vitamin D₃ analogs (61.5%), and a combination of calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant phototherapy in which narrow band ultraviolet B therapy accounted for the majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the recent evolution of psoriasis treatment, the use of biologics has been increasing. This study demonstrates the changes of treatment trends of psoriasis in a non-metropolitan regional area.

Dermographism in a patient with fever

Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma: long-term remission after brentuximab vedotin

Evaluation of narrow band ultraviolet B phototherapy in the treatment of chronic actinic dermatitis in Chinese patients

Abstract

Few studies have been conducted in chronic actinic dermatitis (CAD) treated with narrowband ultraviolet B (NB UVB) phototherapy, especially in Asian patients. We aim to evaluate the efficacy and safety of NB UVB phototherapy in Chinese patients with CAD. 19 CAD patients of Fitzpatrick skin phototype IV received NB UVB phototherapy in spring and treatments were given 3 times weekly with incremental dose and maintenance therapy was given twice weekly for 3–4 weeks. The mean initial, endpoint, and cumulative dose of NB UVB was 0.08, 0.33, and 6.0 J/cm², respectively. Patients totally received 27 times of treatments in average. 87.5% of previously ultraviolet B（UVB） sensitive patients and 75% of previously ultraviolet A（UVA） sensitive patients had normal or improved MED after phototherapy. The percentage of patients returned to normal UVB phototesting was higher than that of patients returned to normal UVA phototesting (68.8% vs. 37.5%). The mean 1-week DLQI and the need for using immunosuppressive agents and antihistamines were significantly reduced after treatment (p < .01 or p < .05). In conclusion, prophylactic NB UVB phototherapy is effective and safe in treatment of CAD in Chinese patients with Fitzpatrick skin phototype IV.