Patient preference study for different characteristics of systemic psoriasis treatments (Protimisis)

Abstract

"The Protimisis" study was a multicenter, cross-sectional study investigating the relative importance and economic value that patients assign to different characteristics of systemic psoriasis treatments. Treatment preferences were investigated with the DCE methodology and patients had to decide over the most important aspects of different psoriasis treatments. A questionnaire regarding demographic data/medical history and the DLQI and EQ-5D-3L questionnaires were also completed.

A total of 310 patients were included. Out of those, 37.4% reported using oral medications for psoriasis as their most recent treatment, while the remaining patients reported treatment with injections once per week (14.8%), injections twice per week (7.4%), injections once every three months (29.4%) and intravenous injections every two months (8.4%) as their most recent treatment. Mean DLQI score was 6.6 (SD 6.5), and in the EQ-5D-3L index, 71.0% of patients reported having problems with anxiety or depression.

DCE analysis showed a clear preference for treatments with longer dosing intervals, rapid onset of action, lasting clinical response, low risk of SAEs and lower cost. The risk of SAEs was the most important treatment characteristic (54% of patients). Older patients showed less concern for safety matters than younger patients. The highest willingness-to-pay was recorded for treatments with longer dosing intervals and for safer treatment options.

Bacillus Calmette-Guerin, polysaccharide nucleic acid in the treatment of cutaneous and oral lichen planus

Abstract

The aim of this study was to evaluate the safety and efficacy of Bacillus Calmette-Guerin, polysaccharide nucleic acid (BCG-PSN) therapy in the treatment of oral and cutaneous LP. Twenty-four LP patients were included in this study and classified randomly into; Oral LP group (OLP), 11 patients and Cutaneous LP group (CLP), 13 patients. All patients received intradermal injections of BCG-PSN, twice weekly for three weeks. Patients with complete response were followed up for 3 months. The assessment in OLP was based on the reduction in the treated area, (Reticulation/Erythema/Ulceration) REU scoring system and numerical rating scale (NRS). CLP evaluated by the response to treatment as (complete, partial and no response) and visual analogue scale (VAS). There were highly significant differences in the diminution of lesion areas (p < .006), NRS scores (p < .001), REU score (p < .011), and VAS (p < .001) after treatment. The majority of patients achieved complete response after 3-week management. The BCG-PNS is safe and effective in the treatment of oral and cutaneous LP.

The concept of type 2 segmental mosaicism, expanding from dermatology to general medicine

Abstract

In autosomal dominant skin disorders, the well-known type 1 segmental mosaicism reflects heterozygosity for a postzygotic new mutation. By contrast, type 2 segmental mosaicism originates in a heterozygous embryo from an early postzygotic mutational event giving rise to loss of the corresponding wild-type allele, which results in a pronounced segmental involvement being superimposed on the ordinary, non-segmental phenotype. Today, this concept has been proven by molecular analysis in many cutaneous traits. The purpose of this review was to seek publications of cases suggesting an extracutaneous manifestation of type 2 segmental mosaicism. Case reports documenting a pronounced extracutaneous segmental involvement were collected from the literature available in PubMed and from personal communications to the author. Pertinent cases are compared to the description of cutaneous segmental mosaicism of type 1 or type 2 as reported in a given trait. In total, reports suggesting extracutaneous type 2 segmental mosaicism were found in 14 different autosomal dominant skin disorders. In this way, clinical evidence is accumulated that extracutaneous type 2 segmental mosaicism does likewise occur in many autosomal dominant skin disorders. So far, however, molecular proof of this particular form of mosaicism is lacking. The present review may stimulate readers to inform colleagues of other specialties on this new concept, in order to initiate further research in this particular field of knowledge that has important implications for diagnosis, treatment and genetic counseling.

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No BRAF V600E Mutation Identified in 28 Periocular Pyogenic Granuloma

Purpose: BRAF V600E mutations were recently identified in some pyogenic granulomas of skin, particularly lesions arising in patients with port wine stains. In this study, the authors analyzed BRAF gene status in 28 periocular pyogenic granulomas to determine its role in their pathogenesis. Methods: Retrospective review of ophthalmic pathology archives from 2007 to 2016 was used to identify pyogenic granulomas of the conjunctiva, eyelid, and orbit. Three eyelid nevi were also analyzed as positive controls. BRAF V600E status was assessed by pyrosequencing of DNA extracted from excess formalin-fixed, paraffin-embedded surgical material. Results: Microscopic examination of the periocular pyogenic granuloma specimens revealed proliferative vascular lesions, with radiating capillary channels surrounded by variable degrees of acute and chronic inflammation. Sequencing did not identify a BRAF V600E mutation in any of the 28 sporadic pyogenic granulomas, including 13 on the eyelid. In contrast, mutation analyses performed in parallel in melanocytic nevi of the eyelid identified BRAF V600E alterations in all 3 cases. Conclusions: The lack of BRAF V600E mutations in 28 sporadic pyogenic granulomas of the conjunctiva and eyelid suggests that such alterations are not a common driver in the pathogenesis of these periocular vascular lesions. Accepted for publication December 22, 2017. The study was funded in part by an unrestricted grant from Research to Prevent Blindness. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Charles G. Eberhart, M.D., Ph.D., 720 Rutland Ave, Ross Bldg 558, Baltimore, MD 21205. E-mail: ceberha@jhmi.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Photochemically Induced Crosslinking of Tarsal Collagen as a Treatment for Eyelid Laxity: Assessing Potentiality in Animal Tissue

Purpose: An experimental study to demonstrate in animal eyelids that the controlled exposure of excised tarsal plate to ultraviolet-A radiation can induce a rigidification effect due to photochemical crosslinking of the constitutive collagen. Methods: Excised strips of sheep tarsus were irradiated with ultraviolet-A rays (wavelength 365 nm) at low and high irradiances, in the presence of riboflavin as a photosensitizer, using radiation sources available for corneal collagen crosslinking procedure. The tensile strength and Young's modulus (stiffness) of irradiated and control samples were measured in a mechanical tester and analyzed statistically. Histologic examination of the specimens was carried out to evaluate the effect of radiation on the meibomian glands and collagen organization. Results: Mechanical evaluation showed that irradiation induced both stiffening and strengthening of the tarsal plate specimens, and this effect was enhanced at the higher levels of irradiance. The changes in mechanical properties can be attributed to a process of photochemically induced crosslinking of tarsal collagen. Histology revealed no changes in the meibomian glands or in the fibrous collagen system of the tarsus. Conclusions: These findings indicate that irradiation of tarsal collagen leading to tissue stiffening could be a safe procedure for treating lax eyelid conditions in human patients. Accepted for publication December 5, 2017. Supported by an unrestricted grant from the Queensland Eye Institute Foundation, South Brisbane, Queensland, Australia. The funders had no role in the concept, design, and conduct of the study; neither in the preparation, review, or approval of manuscript for publication. Australian Provisional Patent Application No. 2017900561 has been filed on February 21, 2017, and assigned to the Queensland Eye Institute Foundation, by the authors Tai M. Smith, Brendan G. Cronin, Shuko Suzuki, and Traian V. Chirila as inventors. Address correspondence and reprint requests to Traian V. Chirila, B.Eng., Ph.D., F.R.A.C.I., F.R.S.C., Queensland Eye Institute, 140 Melbourne Street, South Brisbane, QLD 4101, Australia. E-mail: traian.chirila@qei.org.au. © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome

A 4 year-old-boy was referred for distichiasis of the upper and lower lids of both eyes that had been present since at least 1 year of age. The patient's family history was notable for distichiasis and lymphedema affecting numerous family members. The patient was found to have a novel heterozygous variant (c.741_742insGG) in the FOXC2 gene. Mutations in the FOXC2 gene are associated with lymphedema-distichiasis syndrome. An important feature of lymphedema-distichiasis syndrome is that distichiasis is typically present prior to the onset of lymphedema. Accepted for publication November 5, 2017. Research to Prevent Blindness unrestricted departmental award (Vanderbilt University Medical Center, Department of Ophthalmology & Visual Sciences). The authors have no conflicts of interest to disclose. Address Correspondence and reprint requests to: Louise A. Mawn, M.D., F.A.C.S., Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232. E-mail: louise.a.mawn@vanderbilt.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Efficacy and safety of continuous every 2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase 3 trial (IXORA-P)

Abstract

Introduction

Ixekizumab is an interleukin-17A antagonist approved for treatment of moderate-to-severe plaque psoriasis with recommended 160-mg starting dose, then 80 mg every 2 weeks (Q2W) through Week 12, and every 4 weeks (Q4W) thereafter. This study evaluated continuous every 2-week dosing (Q2W) over 52 weeks.

Methods

In this Phase 3, multicentre, double-blinded, parallel-group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at Week 52 in patients with moderate-to-severe plaque psoriasis randomized at a 2:1:1 ratio to continuous Q2W (N=611), continuous Q4W (N=310), or dose adjustment per protocol (Q4W/Q2W, N=306), each with a 160-mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23.5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression.

Results

Co-primary endpoints were met at Week 52; Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85.9% and 79.0%, respectively (p=0.006), and static Patient Global Assessment 0/1 responses for Q2W and Q4W dose groups were 78.6% and 70.6%, respectively (p=0.005). Treatment-emergent and serious adverse events were comparable across dose groups.

Conclusions

Ixekizumab Q2W had higher efficacy at Week 52 compared to Q4W, with no increase in safety events.

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Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?

Abstract

Objective

Despite the heavy purulence observed in hidradenitis suppurativa (HS), kinetics of complement anaphylatoxins acting to prime chemotaxis of neutrophils has never been studied. Complement activation was explored in HS.

Methods

Circulating concentrations of complement factor C5a as well as of membrane attack complex C5b-9 were determined in the plasma of 54 treatment naïve patients and of 14 healthy controls as well as in the pus of seven patients. Results were correlated with Hurley stage and iHS4 score of severity. Peripheral blood mononuclear cells (PBMCs) were isolated form seven Hurley III stage patients and seven healthy volunteers and stimulated in the presence of 25% of plasma for the production of tumor necrosis factor-alpha (TNFα).

Results

Circulating C5a and C5b-9 were significantly greater in patient than in control plasma; however concentrations in pus were very low. Circulating C5a levels exceeding 28 ng/ml were associated with specificity greater than 90% with occurrence of HS. Circulating C5a and C5b-9 were greater among the more severe patients. PBMCs of patients produced great TNFα concentrations only when growth medium was enriched with patient plasma; this was reversed with the addition of the C5a blocker IFX-1.

Conclusions

Systemic complement activation occurs in HS and may be used as a surrogate biomarker of HS. C5a stimulates over-production of TNFα and may be a future therapeutic target.

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The Role of Sex, Gender, Health Factors, and Job Context in Workplace Accommodation Use Among Men and Women with Arthritis

Abstract

Background

With the aging of populations in many countries, workers are expected to remain employed longer but may struggle with the onset of common, chronic conditions like arthritis. To date, few studies have examined workplace policies and practices that could help accommodate individuals with arthritis, and fewer still have used a sex and gender-based approach to explore similarities and differences between women and men.

Objectives

This study compared the health and work contexts of workers aged ≥50 years to better understand similarities and differences between women and men in accommodation availability, need, use, and unmet needs.

Methods

A cross-sectional survey of men and women with osteoarthritis (OA), inflammatory arthritis (IA), or both OA and IA was administered online or by telephone and assessed demographics (e.g. age, education), health (e.g. pain, fatigue, workplace activity limitations), work context factors (e.g. job sector, full/part-time work, job control), and workplace accommodations (e.g. health benefits, flexible hours, special equipment/adaptations, modified duties). Sex and gender-based analyses examined similarities and differences between men and women and included descriptive statistics, multivariable multinomial analyses, and nested regression analyses.

Results

There was a 58.9% response rate and final sample of 463 participants (women, n = 266; men, n = 197; OA = 59.0%; IA/both IA and OA = 23.7%; unsure = 17.3%). Women and men were significantly different in a number of health (e.g. fatigue, health variability, workplace activity limitations) and work context factors (e.g. job sector, part-time work, job stress). However, in other respects, they were similar (e.g. pain, job involving physical demands, size of organization, shift work, union membership, job control). There were no differences between men and women in the availability or use of workplace accommodations. However, women reported significantly more accommodation needs and had greater unmet needs. Multivariable multinomial analyses found male/female as a binary variable did not explain differences in accommodation need, use, and unmet need. Nested analyses highlighted that differences in health variables explained male/female differences in accommodation need, while work context differences explained male/female differences in whether needs were met.

Conclusions

The findings highlight that women and men draw on a range of existing accommodation policies and practices to help manage their arthritis and that most have their accommodation needs met. Decomposing the context within which men and women with arthritis work suggests that women may face health and work context challenges that differ from men and that are related to greater accommodation needs and unmet need. This highlights potential vulnerabilities in the work of women that need to be addressed.

A TRIGLYCERIDE-RICH LIPOPROTEIN ENVIRONMENT EXACERBATES RENAL INJURY IN THE ACCELERATED NEPHROTOXIC NEPHRITIS MODEL

Summary

Hyperlipidemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalised metabolic derangements. Under both situations, the lipid profile is characterised by accumulation of triglyceride-rich lipoproteins (TGRLs). This lipid profile is increasingly recognised as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper-TGRL state was generated in C57BL/6 mice using the poloxamer-407 (P-407) and immune complex-mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper-TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68⁺ macrophages. The hypersensitive response to ANTN was not seen in low density lipoprotein receptor knock-out mice fed with high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P-407. These data indicate that a hyper-TGRL state might be more detrimental to the kidneys than low density lipoprotein driven hypercholesterolemia during immune complex-mediated nephritis. We speculate that the hyper-TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects. This article is protected by copyright. All rights reserved.

Impact of long-term fertilization practices on the soil aggregation and humic substances under double-cropped rice fields

Abstract

Soil organic matter (SOM) content and soil aggregation are essential components of soil structure, which plays an important role in soil quality and fertility. Also, the SOM content, aggregation, and humus substances in paddy field were affected by application of fertilization practices. However, there is still limited information about the effects of long-term different fertilization practices on soil aggregation and carbon content in the humic acid (C-HAF), fulvic acid (C-FAF), and humin (C-HUM) fractions under double-cropping rice (Oryza sativa L.) system in Southern China paddy fields. Therefore, the effects of long-term fertilizer application on soil aggregation and C-HUM, C-HAF, and C-FAF contents in 0–5-, 5–10-, and 10–20-cm soil depth under double-cropped rice fields in Southern China were investigated. The experiment located at NingXiang County in Hunan Province, China begins in 1986 and the experiment includes five treatments: without fertilizer input (CK), mineral fertilizer alone (MF), rice straw residues and mineral fertilizer (RF), 30% organic matter and 70% mineral fertilizer (LOM), and 60% organic matter and 40% mineral fertilizer (HOM). The results showed that the soil total organic carbon content in paddy soils with RF, LOM, and HOM treatments was significant higher (P < 0.05) than that of the CK treatment at early and late rice maturity stages. The different sizes of soil aggregates with different fertilization treatments were decreased as HOM > LOM > RF > MF > CK. The HOM treatment had the highest percentage of soil aggregates in each size class and the CK treatment had the lowest percentage of soil aggregates in each size class in 0–5-, 5–10-, and 10–20-cm soil depth at early and late rice maturity stages. The soil C-HAF, C-FAF, and C-HUM contents were increased by long-term combined application of manure with mineral fertilizer practices. Meanwhile, the results indicated that the soil C-HAF, C-FAF, and C-HUM contents with RF, LOM, and HOM treatments were significantly higher (P < 0.05) than that of the CK treatment at early and late rice maturity stages. As a result, the soil total organic carbon content, each size class of soil aggregates, and soil C-HAF, C-FAF, and C-HUM contents were increased by long-term combined application of manure with mineral fertilizer in double-cropped rice fields.

Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population

Abstract

Although immune checkpoint inhibitors (ICI) significantly improve the survival of advanced melanoma, more than half of the patients received no benefit. To predict outcomes, efforts to associate baseline peripheral blood biomarkers were started in patients given treatment with ipilimumab. Among the most critical markers is an increased neutrophil-to-lymphocyte ratio (NLR), which negatively correlates with outcome. Although several baseline factors have been reported to correlate with outcome in patients treated with nivolumab/pembrolizumab (eosinophil count, lymphocyte count, lactate dehydrogenase [LDH], and c-reactive protein [CRP]), a positive link between NLR and outcome has yet to be shown.

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Wide skin markings pattern - melanoma descriptor or patient-related factor?

Abstract

We are intrigued by the findings reported in the letter titled "Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs"(1). Bassoli et al investigated the association of the "wider skin marking pattern" with cutaneous melanoma. They state that this feature corresponds to "…linear intercepting furrows, lighter than the lesion's overall pigmentation and wider compared to the surrounding skin. The authors conclude that "recognition of wider skin markings may…prompt the clinician to obtain a biopsy specimen." We respectfully ask the authors to clarify several aspects of their study methodology.

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Application of in vivo reflectance confocal microscopy (RCM) and ex vivo fluorescence confocal microscopy (FCM) in most common subtypes of Basal Cell Carcinoma and correlation with histopathology

Abstract

Basal cell carcinoma (BCC) accounts for 80% of non-melanoma skin cancer. The identification of the histological subtype is crucial for the correct management of the tumor. In vivo reflectance confocal microscopy (RCM) is a novel technique that has demonstrated high sensitivity and specificity in the in vivo diagnosis of BCC. In an effort to determine reliable criteria for preoperative diagnosis of BCC subtypes, Longo et al. and Peppelman et al., described RCM criteria present in different BCC subtypes.

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Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C

Abstract

Background

Hyaluronan is a large, linear glycosaminoglycan present throughout the narrow extracellular space of the vital epidermis. Increased hyaluronan metabolism takes place in epidermal hypertrophy, wound healing and cancer. Hyaluronan is produced by hyaluronan synthases (HAS1-3) and catabolized by hyaluronidases (HYAL1 and -2), reactive oxygen species (ROS), and the KIAA1199 protein.

Objectives

To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C.

Methods

Hyaluronan synthesis and expression of the hyaluronan-related genes were analyzed during epidermal maturation from a simple epithelium to a fully differentiated epidermis in organotypic cultures of rat epidermal keratinocytes (REK) using qRT-PCR, immunostainings, and western blotting, in the presence and absence of vitamin C.

Results

With epidermal stratification, both the production and the degradation of hyaluronan were enhanced, resulting in an increase of hyaluronan fragments of various sizes. While the mRNA levels of Has3 and KIAA1199 remained stable during the maturation, Has1, Has2, and Hyal2 showed a transient upregulation during stratification, Hyal1 remained permanently increased, and the hyaluronan receptor Cd44 decreased. At maturation, Vitamin C downregulated Has2, Hyal2 and Cd44, while it increased high molecular mass hyaluronan in the epidermis, and reduced small fragments in the medium, suggesting stabilization of epidermal hyaluronan.

Conclusions

Epidermal stratification and maturation is associated with enhanced hyaluronan turnover, and release of large amounts of hyaluronan fragments. The high turnover is suppressed by vitamin C, which is suggested to enhance normal epidermal differentiation in part through its effect on hyaluronan.

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Levocarnitine for vismodegib-associated muscle spasms: a pilot randomized, double-blind, placebo-controlled, investigator initiated trial

Abstract

Smoothened inhibitors (SIs) are a new, targeted therapy for the treatment of advanced basal cell carcinoma (BCC), but their usage is significantly limited by the most common side effect, muscle spasms. Muscle spasms affect up to 80% of users, and are the most common reason for drug discontinuation despite tumor response. Currently, no placebo-controlled trials exist to guide the management of vismodegib-related muscle spasms. The medical literature suggests that the naturally occurring substance, levocarnitine (LC), can improve contractile function of muscle and reduce markers of exercise-induced stress. Hence, we explored the effect of oral LC on vismodegib-related muscle spasms via a double-blind, randomized, placebo-controlled, two-period crossover design.

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Factors associated with delayed referral for infantile hemangioma necessitating propranolol

Abstract

Background

Oral propranolol is the gold-standard to treat infantile hemangiomas. There is better efficacy and a lower risk of sequelae if therapy is started before the end of the growth phase, but most children are referred too late. Herein, we report the first study to investigate the delay and its associated factors when referring infants with infantile hemangiomas that need propranolol therapy.

Objectives

The primary objective was to determine the delay in referral (time between age at referral [first phone contact] and the optimal age for referral (fixed at 75 days). The second objective was to determine the impact of weighted factors associated with delayed referral assessed by logistic regression performed on two subgroups (referral <75 vs. >75 days).

Methods

Monocentric, retrospective, observational study included infants with infantile hemangiomas treated with oral propranolol between August 2014 and May 2017.

Results

82 children (83% females) were included. Before referral, 81 (99%) children had seen another physician (a pediatrician in 67% of cases). Median age at referral was 99 [2-478] days and 63% phoned after 75 days. Median age at the first visit was 111 days [2-515] and median age when propranolol was started was 128 days [32-541]. After adjustment, in multivariate analyses, location on the lips (OR (CI_95%): 4.21[1.19–14.89]) and superficial hemangioma (OR (CI_95%): 4.19 [1.55–11.34]) emerged as the most significant factors to influence referral before 75 days.

Conclusions

This study adds to our understanding regarding delayed referral and has identified targets for future information campaigns.

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Comparison of fungal fluorescent staining and ITS rDNA PCR-based sequencing with conventional methods for the diagnosis of onychomycosis

Abstract

Background

The current gold standard for diagnosing onychomycosis is direct microscopic examination and culturing. Fungal culture is a time-consuming procedure, while direct microscopy of potassium hydroxide (KOH) mounts suffers from low sensitivity. More rapid and sensitive methods for the diagnosis of onychomycosis are in high demand.

Objective

To establish an effective method for the diagnosis of onchomycosis by assessing the efficacies of fungal fluorescent staining and internal transcribed spacer (ITS) ribosomal DNA (rDNA) polymerase chain reaction (PCR)-based sequencing.

Methods

A total of 204 clinical specimens from patients with suspected onychomycosis were analysed. The gold standard for a true positive sample was positive by KOH, culturing, or both methods. All specimens were also tested by fungal fluorescent staining and its rDNA PCR-based sequencing. We compared the detection, sensitivity, and specificity for these two methods with conventional methods.

Results

In total, 126 (62%) and 102 (50%) were detected by fluorescent staining and PCR-based sequencing, respectively. According to the conventional diagnostic standard, the sensitivity of fluorescent staining and PCR-based sequencing was 97% and 78%, respectively, and specificities of 89% and 90%, respectively. Use of fluorescence enhanced the sensitivity of direct examination by 12% compared with KOH. PCR-based sequencing increased the sensitivity by 6% compared with culturing.

Conclusions

Fluorescence microscopy has a higher sensitivity for the detection of fungi in nail specimens compared with KOH and can be used as a rapid screening tool. PCR-based sequencing was faster and more sensitive compared with culture and when used in conjunction with fluorescence microscopy resulted in higher efficiency.

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Molecular genetic analyses of human endogenous retroviral elements belonging to the HERV-P and -R family in Primary Cutaneous T-Cell Lymphomas

Abstract

Mycosis fungoides (MF) is characterized by longstanding, scaly patch lesions preferentially involving the buttocks and body areas infrequently exposed to sunlight and by a slow evolution over years from patches to plaques and eventually tumors or erythroderma. Lymph node and visceral involvement, as well as large cell transformation, frequently occur in the late stages of the disease [1]. Sézary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma (CTCL) with leukemic involvement, an aggressive clinical behavior and poor prognosis [2].

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Studying the effect of systemic and biological drugs on intima-media thickness in patients suffering from moderate and severe psoriasis

Abstract

Background

Psoriasis has been related to a large number of cardiovascular risk factors such as hypertension, diabetes mellitus and arteriosclerosis. The increased carotid intima-media thickness (IMT) could be considered to be a marker of generalized arteriosclerosis.

Objective

To assess the effect of systemic and biological drugs on psoriatic patients′ carotid IMT.

Methods

A prospective study was performed. We studied 53 patients with moderate and severe psoriasis from our psoriasis dermatological unit, analyzing lipid and glucose metabolism and performing a carotid IMT sonography before introduction of systemic and biological drugs. After that, we performed an 8-month closely analytic and sonographic follow-up.

Results

The IMT of the psoriatic patients treated with biological drugs tended to decrease, although this occurrence was not statistically significant (p=0.086). The subgroup analysis revealed that patients treated with Methotrexate (p=0,045) and Anti Il-12/23 (p=0,010) presented a decrease of their IMT levels. This analysis also showed a decrease in glycaemia and insulin levels in patients treated with TNF-alpha Inhibitors and Ustekinumab.

Conclusions

Our study suggest that the carotid-IMT may benefits from treatment with biological drugs, particularly Anti IL-12/23, and methotrexate in patients suffering from moderate and severe psoriasis. However, larger longitudinal studies should be performed in order to fully confirm these results.

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Use of Medical Photography Among Dermatologists: A Nationwide Online Survey Study

Abstract

Background

Medical photography enhances patient care, medical education, and research. Despite medical photography's widespread use, little is known about how dermatologists choose to implement photography in routine clinical practice, and how they approach issues of image storage, image security, and patient consent.

Objective

To characterize dermatologists' medical photography habits and opinions.

Methods

A 32-item anonymous, multiple-choice SurveyMonkey questionnaire about medical photography practices was emailed to program directors of the 117 United States (US) dermatology residency programs between May and August 2015, with a request to forward to faculty and affiliated dermatologists. Only board-certified dermatologists practicing in the US were eligible. The Institutional Review Board exempted our study from full review.

Results

Our survey included 153 board-certified dermatologists, primarily representing the northeast (43.1%) and identifying as academic dermatologists (75.5%). Medical photography is prevalent: 61.8% report everyday use and 21.7% photograph every patient. Those reporting rare use (3.3%) were, on average, 20 years older. Dermatologists most commonly use photography to mark biopsy sites (87.5%), track disease (82.9%), and for education/teaching (72.4%). Nearly half (46%) use smartphone cameras. Emailing and texting photographs with patients or colleagues are common (69.1%). Most dermatologists (75.7%) always request patient consent for photographs. Only 23.7% adhere to a photography protocol and 73.9% desire more training opportunities.

Conclusion

Dermatologists value medical photography. While patterns of image acquisition, storage, and consent are noted, a variety of methods and preferences exist. Clearer photography guidelines and increased educational resources are likely to improve image quality, exchangeability, and confidentiality.

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Identification and Validation of Appropriate Reference Genes for qRT-PCR Analysis in Corynebacterium glutamicum

Abstract

Real-time quantitative PCR (qRT-PCR) is a fast and efficient technology for detecting gene expression levels in the study of the Corynebacterium glutamicum protein expression system, but it requires normalization to ensure the reliability of the results obtained. We selected 13 genes from the commonly used housekeeping genes and from transcriptome data as candidate reference genes. The Ct values of the 13 genes were obtained by qRT-PCR at different fermentation stages and under three stress conditions (temperature, acid, and salt). The expression stability of the reference genes was evaluated by geNorm and NormFinder software. For the study of different growth stages, the most appropriate reference genes are Ncgl2772 and leua, which encode acetyl-CoA carboxylase beta subunit and 2-isopropylmalate synthase, separately. For the study of different stress factors, the optimal minimum number of reference genes is 3, with Ncgl2772, gyrb encoding DNA gyrase B and siga encoding RNA polymerase sigma factor A as the most suitable combination. Additionally, clpx and clpc, encoding ClpX and ClpC protease subunits, were used to validate the candidate reference genes. The identification of new reference genes makes qRT-PCR more convenient, and using these genes for normalization can improve the accuracy and reliability of the measurements of target gene expression levels obtained by qRT-PCR for C. glutamicum.

Age-related differences in the functional properties of lips compared with skin

Abstract

Background/aims

Lips can easily become dry and rough and their biggest problems are drying and chapping. The cause of those problems is considered to be that the stratum corneum (SC) moisture is small and its barrier function is low. However, those problems decrease in subjects as they approach 40 years of age, after which problems due to their shape and color increase. The purpose of this study was to investigate relationships between SC properties of the lips during aging and to clarify the cause(s) of lip problems.

Methods

One hundred and 38 Japanese female subjects with normal skin ranging in age from 16 to 78 years were enrolled in the study. The capacitance and transepidermal water loss (TEWL) values, viscoelasticity, and color of their lips were measured and compared with their cheeks.

Results

The capacitance values for the lip and the cheek increased and TEWL values for both areas decreased with age. TEWL values for the lip decreased until ~30 years of age and this is considered to be related to the problem of drying. Although the maximum amplitude U_f of the lip increased with age, the U_r/U_f had no correlation with age. As for color, the L* and a* values decreased with age.

Conclusion

Age-related changes with regard to SC functions, viscoelasticity and color of the lips have been clarified for the first time, and it is clear that these changes are related to problems of the lips. Compared with the cheeks, differences with the lips are more apparent.

Non-invasive evaluation of human mucosal structures by multiphoton laser scanning tomography in vitro

Abstract

Background

Mucous membranes may be affected by various diseases and the diagnostic accessibility is limited. Multiphoton laser tomography (MPT) is a useful tool for in vivo evaluation of superficial skin structures and might also be useful for the imaging of mucosa.

Objectives

In order to investigate the suitability of MPT for the evaluation of mucous membranes, tissue samples of different donors and anatomical localizations have been imaged.

Methods

Human mucosa samples from the urinary bladder, palatine tonsil and ocular conjunctiva were investigated by MPT and subsequently compared with conventional histology.

Results

Horizontal images of the epithelium and the underlying connective tissue were obtained using the autofluorescence and second harmonics generation signals by MPT. The stratification of multilayered epithelium was consistently reproduced. Also inflammatory changes like lymphocytic infiltrates and widened intercellular spaces were imaged in some cases.

Conclusion

Mucous tissue samples were obtained and MPT imaging was successfully performed. In the direct comparison with histology of the same tissue samples, the characteristic morphology of the epithelia was found. Further studies are necessary in order to compare images of healthy and diseased mucosal epithelium and the use of MPT for its evaluation in vivo.

Plasma exeresis for active acne vulgaris: Clinical and in vivo microscopic documentation of treatment efficacy by means of reflectance confocal microscopy

Herpes zoster at the vaccination site in immunized healthy children

Abstract

In this case series, we report seven immunized healthy children without underlying immunodeficiency who presented with herpes zoster that correlated with varicella-zoster vaccination site. The morphology of the lesions included erythematous papules, pseudovesicles, and plaques, with associated pain in two and pruritus in three patients; systemic symptoms ranged from none to low-grade fevers, upper respiratory symptoms, and joint pain. These cases highlight the clinical, diagnostic, and therapeutic implications of herpes zoster in vaccinated children.

Metastatic melanoma with dedifferentiation and extensive rhabdomyosarcomatous heterologous component

Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52 year-old woman was diagnosed with invasive melanoma (Breslow depth 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with two morphologies: an epithelioid morphology expressing S100 and MART-1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin. This metastasis was found to have BRAF V600E mutation. In 2015, a thoracic epidural mass biopsy showed atypical spindle cells with focal HMB-45 but essentially no S100 expression. Numerous rhabdomyoblasts, some with striations that were strongly positive for desmin and myogenin, were present. In 2016, a right nephrectomy was performed for metastasis to the kidney, and showed sheets of spindle cells and rhabdomyoblasts expressing desmin and myogenin but not S100. Only focal areas demonstrated expression of HMB-45 and SOX-10, supporting the melanocytic origin of the tumor. The numerous rhabdomyoblasts and the loss of S100 expression in the metastatic lesions in this case could have easily led to misdiagnosis if the clinical history was not known.

Tools, techniques, and technologies for pollution prevention, control, and resource recovery

Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study

OnabotulinumtoxinA is approved for the prevention of headache in those with chronic migraine (CM); however, more clinical data on the risk-benefit profile for treatment beyond one year is desirable.

Tropical Dermatology, 2nd ed

The effect of dietary selenium addition on the concentrations of heavy metals in the tissues of fallow deer ( Dama dama L.) in Croatia

Abstract

The aim of this research was to determine the concentrations of cadmium, lead, mercury, and arsenic and the essential elements iron and selenium in the tissues (muscle, kidney, liver, spleen, and fat) of fallow deer (Dama dama L.) without and with supplemental selenium addition. Another aim was to determine the effect of selenium addition on the indicators of oxidative stress, namely, the levels of superoxide dismutase, glutathione peroxidase, glutathione, and vitamin E. The research was carried out with 40 fallow deer during two research periods. Supplemental feed without selenium addition was provided during the first research period, and supplemental feed with added selenium (3 mg/kg) was provided for 60 days during the second research period. The concentration of selenium in tissues was higher in the second research period than in the first research period (in kidney tissue, 0.957 vs. 0.688 mg/kg, P < 0.05). The dietary addition of selenium decreased (P < 0.05) the concentrations of some heavy metals (lead in the spleen = 0.06 vs. 0.27 mg/kg and in the fatty tissue = 0.17 vs. 0.69 mg/kg; arsenic in the muscle tissue = 0.005 vs. 0.014 mg/kg, liver = 0.003 vs. 0.009 mg/kg, spleen = 0.004 vs. 0.013 mg/kg, and fat = 0.008 vs. 0.016 mg/kg). The activity of glutathione peroxidase was significantly higher (P < 0.05) in the second research period than in the first research period (1375.36 vs. 933.23 U/L).

In situ investigation of heavy metals at trace concentrations in greenhouse soils via portable X-ray fluorescence spectroscopy

Abstract

Soil pollution by heavy metals (HMs) has rapidly become a major threat to vegetable security. Nearly all cultivated soils are at risk of metal accumulation, and greenhouse soils are among the most heavily impacted soils. In this study, a rapid assessment of HMs at trace concentrations was conducted via portable X-ray fluorescence (PXRF) spectroscopy in Shouguang, China. Measurements were made via PXRF under in situ, ex situ and sieved conditions and by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. The performance of each PXRF measure relative to the ICP-MS method was assessed by linear regression. Redundancy analysis was performed to quantify the proportion of explained variability between the PXRF and ICP-MS data. Evaluation of the possible sources of HMs and their potential risks was then conducted by multivariate analysis. The results showed that the PXRF data were closely correlated with ICP-MS quantification for Cu, Mn and Zn, whereas no significant correlations were found for As, Ni and Pb. The uncertainties of PXRF measurement derived from soil heterogeneity accounted for 20.02% of total variability and those from moisture and particle size accounted for 20.15%. The geo-accumulation index (I_geo) indicated that the greenhouse soils were potentially contaminated by Cu and Zn (I_geo > 0), which can be attributed to anthropogenic activities. Overall, PXRF spectroscopy is promising as a rapid and nondestructive in situ technique for assessing the potential risks of HMs at trace concentrations in greenhouse soils.

Geochemistry of rare earth elements within waste rocks from the Montviel carbonatite deposit, Québec, Canada

Abstract

Several rare earth element (REE) mine projects around the world are currently at the feasibility stage. Unfortunately, few studies have evaluated the contamination potential of REE and their effects on the environment. In this project, the waste rocks from the carbonatites within the Montviel proterozoic alkaline intrusion (near Lebel-sur-Quévillon, Quebec, Canada) are assessed in this research. The mineralization is mainly constituted by light REE (LREE) fluorocarbonates (qaqarssukite-Ce, kukharenkoite-Ce), LREE carbonates (burbankite, Sr-Ba-Ca-REE, barytocalcite, strontianite, Ba-REE-carbonates), and phosphates (apatite, monazite). The gangue minerals are biotites, chlorite, albite, ankerite, siderite, and calcite. The SEM-EDS analyses show that (i) the majority of REE are associated with the fine fraction (< 106 μm), (ii) REE are mainly associated with carbonates, (iii) all analyzed minerals preferably contain LREE (La, Ce, Pr, Nd, Sm, Eu), (iv) the sum of LREE in each analyzed mineral varies between ~ 3 and 10 wt%, (v) the heavy REE (HREE) identified are Gd and Yb at < 0.4 wt%, and (vi) three groups of carbonate minerals were observed containing variable concentrations of Ca, Na, and F. Furthermore, the mineralogical composition of REE-bearing minerals, REE mobility, and REE speciation was investigated. The leachability and geochemical behavior of these REE-bearing mine wastes were tested using normalized kinetic testing (humidity cells). Leachate results displayed higher LREE concentrations, with decreasing shale-normalized patterns. Thermodynamical equilibrium calculations suggest that the precipitation of secondary REE minerals may control the REE mobility.

Cutaneous meningeal heterotopia on the thigh

Abstract

Cutaneous aggregates of meningeal cells have been variously designated as cutaneous meningioma, meningeal heterotopia, and ectopic meningeal rest, with most cases occurring on the head and neck.^1,2 We present an unusual dermal collection of meningeal, adipose, and smooth muscle tissue arising on the thigh of an adult.

Melanoma Mimicking Rosai-Dorfman Disease

Abstract

Despite advances in treatment and increased public awareness, the incidence of melanoma has dramatically increased over the last 50 years ^1,2. Primary and secondary prevention is critical for decreasing the incidence and improving outcomes in melanoma³. A proper clinical and histopathological diagnosis is necessary for definitive management.

Effect of dewatering and composting on helminth eggs removal from lagooning sludge under semi-arid climate

Abstract

In this work, we assessed the drying and composting effectiveness of helminth eggs removal from sewage sludge of a lagoon wastewater treatment plant located in Chichaoua city. The composting was run after mixing sludge with green waste in different proportions: M1 (½ sludge + ½ green waste), M2 ( \( \raisebox{1ex}{\(2\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) sludge + \( \raisebox{1ex}{\(1\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) green waste), and M3 ( \( \raisebox{1ex}{\(1\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) sludge + \( \raisebox{1ex}{\(2\)}\!\left/ \!\raisebox{-1ex}{\(3\)}\right. \) green waste) for 105 days. The analysis of the dewatered sewage sludge showed a load of 8–24 helminth eggs/g of fresh matter identified as Ascaris spp. eggs (5–19 eggs/g) followed by Toxocara spp. (0.2 to 2.4 eggs/g); Hookworm spp. and Capillaria spp. (0.4–1 egg/g); Trichuris spp., Taenia spp., and Shistosoma spp. (< 1 egg/g) in the untreated sludge. After 105 days of treatment by composting, we noted a total reduction of helminth eggs in the order of 97.5, 97.83, and 98.37% for mixtures M1, M2, and M3, respectively. The Ascaris spp. eggs were reduced by 98% for M1 and M3 treatments and by 97% for M₂ Treatment. Toxocara spp., Hookworm spp., Trichuris spp., Capillaria spp., and Shistosoma spp. eggs were totally eliminated (100% decrease) and the Taenia spp. was absent from the first stage of composting. These results confirm the effectiveness of both dehydrating and composting processes on the removal of helminth eggs.

Agminated Spitz naevi or metastatic spitzoid melanoma?

Oral retinoids and depression: reply from the authors

We strongly agree with both teams that our review has limitations including the paucity of the information of some reported cases and the limitations inherent to the Naranjo score. Nevertheless, the Naranjo score was developed to achieve consensus in estimating the probability that a drug has caused an adverse event. It is the only tool that can be used to homogenize the reading of very heterogeneous notifications.

This article is protected by copyright. All rights reserved.

Pre-treatment magnetic resonance-based texture features as potential imaging biomarkers for predicting event free survival in anal cancer treated by chemoradiotherapy

Abstract

Aim

To assess regular MRI findings and tumour texture features on pre-CRT imaging as potential predictive factors of event-free survival (disease progression or death) after chemoradiotherapy (CRT) for anal squamous cell carcinoma (ASCC) without metastasis.

Materials and methods

We retrospectively included 28 patients treated by CRT for pathologically proven ASCC with a pre-CRT MRI. Texture analysis was carried out with axial T2W images by delineating a 3D region of interest around the entire tumour volume. First-order analysis by quantification of the histogram was carried out. Second-order statistical texture features were derived from the calculation of the grey-level co-occurrence matrix using a distance of 1 (d1), 2 (d2) and 5 (d5) pixels. Prognostic factors were assessed by Cox regression and performance of the model by the Harrell C-index.

Results

Eight tumour progressions led to six tumour-specific deaths. After adjusting for age, gender and tumour grade, skewness (HR = 0.131, 95% CI = 0-0.447, p = 0.005) and cluster shade_d1 (HR = 0.601, 95% CI = 0-0.861, p = 0.027) were associated with event occurrence. The corresponding Harrell C-indices were 0.846, 95% CI = 0.697-0.993, and 0.851, 95% CI = 0.708-0.994.

Conclusion

ASCC MR texture analysis provides prognostic factors of event occurrence and requires additional studies to assess its potential in an "individual dose" strategy for ASCC chemoradiation therapy.

Key Points

• MR texture features help to identify tumours with high progression risk.

• Texture feature maps help to identify intra-tumoral heterogeneity.

• Texture features are a better prognostic factor than regular MR findings.

Genotype prediction of ATRX mutation in lower-grade gliomas using an MRI radiomics signature

Abstract

Objectives

To predict ATRX mutation status in patients with lower-grade gliomas using radiomic analysis.

Methods

Cancer Genome Atlas (TCGA) patients with lower-grade gliomas were randomly allocated into training (n = 63) and validation (n = 32) sets. An independent external-validation set (n = 91) was built based on the Chinese Genome Atlas (CGGA) database. After feature extraction, an ATRX-related signature was constructed. Subsequently, the radiomic signature was combined with a support vector machine to predict ATRX mutation status in training, validation and external-validation sets. Predictive performance was assessed by receiver operating characteristic curve analysis. Correlations between the selected features were also evaluated.

Results

Nine radiomic features were screened as an ATRX-associated radiomic signature of lower-grade gliomas based on the LASSO regression model. All nine radiomic features were texture-associated (e.g. sum average and variance). The predictive efficiencies measured by the area under the curve were 94.0 %, 92.5 % and 72.5 % in the training, validation and external-validation sets, respectively. The overall correlations between the nine radiomic features were low in both TCGA and CGGA databases.

Conclusions

Using radiomic analysis, we achieved efficient prediction of ATRX genotype in lower-grade gliomas, and our model was effective in two independent databases.

Key Points

• ATRX in lower-grade gliomas could be predicted using radiomic analysis.

• The LASSO regression algorithm and SVM performed well in radiomic analysis.

• Nine radiomic features were screened as an ATRX-predictive radiomic signature.

• The machine-learning model for ATRX-prediction was validated by an independent database.

Shear-wave elastography can evaluate annulus fibrosus alteration in adolescent scoliosis

Abstract

Objectives

In vitro studies showed that annulus fibrosus lose its integrity in idiopathic scoliosis. Shear-wave ultrasound elastography can be used for non-invasive measurement of shear-wave speed (SWS) in vivo in the annulus fibrosus, a parameter related to its mechanical properties. The main aim was to assess SWS in lumbar annulus fibrosus of scoliotic adolescents and compare it to healthy subjects.

Methods

SWS was measured in 180 lumbar IVDs (L3L4, L4L5, L5S1) of 30 healthy adolescents (13 ± 1.9 years old) and 30 adolescent idiopathic scoliosis patients (13 ± 2 years old, Cobb angle: 28.8° ± 10.4°). SWS was compared between the scoliosis and healthy control groups.

Results

In healthy subjects, average SWS (all disc levels pooled) was 3.0 ± 0.3 m/s, whereas in scoliotic patients it was significantly higher at 3.5 ± 0.3 m/s (p = 0.0004; Mann-Whitney test). Differences were also significant at all disc levels. No difference was observed between males and females. No correlation was found with age, weight and height.

Conclusion

Non-invasive shear-wave ultrasound is a novel method of assessment to quantitative alteration of annulus fibrosus. These preliminary results are promising for considering shear-wave elastography as a biomechanical marker for assessment of idiopathic scoliosis.

Key Points

• Adolescent idiopathic scoliosis may have an altered lumbar annulus fibrosus.

• Shear-wave elastography can quantify lumbar annulus fibrosus mechanical properties.

• Shear-wave speed was higher in scoliotic annulus than in healthy subjects.

• Elastography showed potential as a biomechanical marker for characterizing disc alteration.

High-pitch low-voltage CT coronary artery calcium scoring with tin filtration: accuracy and radiation dose reduction

Abstract

Objectives

To investigate diagnostic accuracy and radiation dose of high-pitch CT coronary artery calcium scoring (CACS) with tin filtration (Sn100kVp) versus standard 120kVp high-pitch acquisition.

Methods

78 patients (58% male, 61.5±9.1 years) were prospectively enrolled. Subjects underwent clinical 120kVp high-pitch CACS using third-generation dual-source CT followed by additional high-pitch Sn100kVp acquisition. Agatston scores, calcium volume scores, Agatston score categories, percentile-based risk categorization and radiation metrics were compared.

Results

61/78 patients showed coronary calcifications. Median Agatston scores were 34.9 [0.7–197.1] and 41.7 [0.7–207.2] and calcium volume scores were 34.1 [0.7–218.0] for Sn100kVp and 35.7 [1.1–221.0] for 120kVp acquisitions, respectively (both p<0.0001). Bland-Altman analysis revealed underestimated Agatston scores and calcium volume scores with Sn100kVp versus 120kVp acquisitions (mean difference: 16.4 and 11.5). However, Agatston score categories and percentile-based risk categories showed excellent agreement (ĸ=0.98 and ĸ=0.99). Image noise was 25.8±4.4HU and 16.6±2.9HU in Sn100kVp and 120kVp scans, respectively (p<0.0001). Dose-length-product was 9.9±4.8mGy*cm and 40.9±14.4mGy*cm with Sn100kVp and 120kVp scans, respectively (p<0.0001). This resulted in significant effective radiation dose reduction (0.13±0.07mSv vs. 0.57±0.2mSv, p<0.0001) for Sn100kVp acquisitions.

Conclusion

CACS using high-pitch low-voltage tin-filtered acquisitions demonstrates excellent agreement in Agatston score and percentile-based cardiac risk categorization with standard 120kVp high-pitch acquisitions. Furthermore, radiation dose was significantly reduced by 78% while maintaining accurate risk prediction.

Key points

• Coronary artery calcium scoring with tin filtration reduces radiation dose by 78%.

• There is excellent correlation between high-pitch Sn100kVp and standard 120kVp acquisitions.

• Excellent agreement regarding Agatston score categories and percentile-based risk categorization was achieved.

• No cardiac risk reclassifications were observed using Sn100kVp coronary artery calcium scoring.

Liver fibrosis: stretched exponential model outperforms mono-exponential and bi-exponential models of diffusion-weighted MRI

Abstract

Objectives

To compare the ability of diffusion-weighted imaging (DWI) parameters acquired from three different models for the diagnosis of hepatic fibrosis (HF).

Methods

Ninety-five patients underwent DWI using nine b values at 3 T magnetic resonance. The hepatic apparent diffusion coefficient (ADC) from a mono-exponential model, the true diffusion coefficient (D_t ), pseudo-diffusion coefficient (D_p ) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched exponential model were compared with the pathological HF stage. For the stretched exponential model, parameters were also obtained using a dataset of six b values (DDC^#, α^#). The diagnostic performances of the parameters for HF staging were evaluated with Obuchowski measures and receiver operating characteristics (ROC) analysis. The measurement variability of DWI parameters was evaluated using the coefficient of variation (CoV).

Results

Diagnostic accuracy for HF staging was highest for DDC^# (Obuchowski measures, 0.770 ± 0.03), and it was significantly higher than that of ADC (0.597 ± 0.05, p < 0.001), D_t (0.575 ± 0.05, p < 0.001) and f (0.669 ± 0.04, p = 0.035). The parameters from stretched exponential DWI and D_p showed higher areas under the ROC curve (AUCs) for determining significant fibrosis (≥F2) and cirrhosis (F = 4) than other parameters. However, D_p showed significantly higher measurement variability (CoV, 74.6%) than DDC^# (16.1%, p < 0.001) and α^# (15.1%, p < 0.001).

Conclusions

Stretched exponential DWI is a promising method for HF staging with good diagnostic performance and fewer b-value acquisitions, allowing shorter acquisition time.

Key Points

• Stretched exponential DWI provides a precise and accurate model for HF staging.

• Stretched exponential DWI parameters are more reliable than D _p from bi-exponential DWI model

• Acquisition of six b values is sufficient to obtain accurate DDC and α

Are pancreatic IPMN volumes measured on MRI images more reproducible than diameters? An assessment in a large single-institution cohort

Abstract

Objectives

To assess reproducibility of volume and diameter measurement of intraductal papillary mucinous neoplasms (IPMNs) on MRI images.

Methods

Three readers measured the diameters and volumes of 164 IPMNs on axial T2-weighted images and coronal thin-slice navigator heavily T2-weighted images using manual and semiautomatic techniques. Interobserver reproducibility and variability were assessed.

Results

Interobserver intraclass correlation coefficients (ICCs) for the largest diameter measured using manual and semiautomatic techniques were 0.979 and 0.909 in the axial plane, and 0.969 and 0.961 in the coronal plane, respectively. Interobserver ICCs for the volume measurements were 0.973 and 0.970 in axial and coronal planes, respectively. The highest intraobserver reproducibility was noted for coronal manual measurements (ICC 0.981) followed by axial manual measurements (ICC 0.969). For the diameter measurements, Bland-Altman analysis revealed the lowest interobserver variability for manual axial measurements with an average range of 95% limits of agreement (LOA) of 0.68 cm. Axial and coronal volume measurements showed similar 95% LOA ranges (8.9 cm³ and 9.4 cm³, respectively).

Conclusions

Volume and diameter measurements on axial and coronal images show good interobserver and intraobserver reproducibility. The single largest diameter measured manually on axial images showed the highest reproducibility and lowest variability. The 95% LOA may help define reproducible size changes in these lesions using measurements from different readers.

Key Points

• MRI measurements by different radiologists can be used for IPMN follow-up.

• Both diameter and volume measurements demonstrate excellent interobserver and intraobserver reproducibility.

• Manual axial measurements show the highest interobserver reproducibility in determining size.

• Axial and coronal volume measurements show similar limits of agreement.

• Manual axial measurements show the lowest variability in agreement range.

Dual-energy CT: a phantom comparison of different platforms for abdominal imaging

Abstract

Objectives

Evaluation of imaging performance across dual-energy CT (DECT) platforms, including dual-layer CT (DLCT), rapid-kVp-switching CT (KVSCT) and dual-source CT (DSCT).

Methods

A semi-anthropomorphic abdomen phantom was imaged on these DECT systems. Scans were repeated three times for CTDIvol levels of 10 mGy, 20 mGy, 30 mGy and different fat-simulating extension rings. Over the available range of virtual-monoenergetic images (VMI), noise as well as quantitative accuracy of hounsfield units (HU) and iodine concentrations were evaluated.

Results

For all VMI levels, HU values could be determined with high accuracy compared to theoretical values. For KVSCT and DSCT, a noise increase was observed towards lower VMI levels. A patient-size dependent increase in the uncertainty of quantitative iodine concentrations is observed for all platforms. For a medium patient size the iodine concentration root-mean-square deviation at 20 mGy is 0.17 mg/ml (DLCT), 0.30 mg/ml (KVSCT) and 0.77mg/ml (DSCT).

Conclusion

Noticeable performance differences are observed between investigated DECT systems. Iodine concentrations and VMI HUs are accurately determined across all DECT systems. KVSCT and DLCT deliver slightly more accurate iodine concentration values than DSCT for investigated scenarios. In DLCT, low-noise and high-image contrast at low VMI levels may help to increase diagnostic information in abdominal CT.

Key Points

• Current dual-energy CT platforms provide accurate, reliable quantitative information.

• Dual-energy CT cross-platform evaluation revealed noticeable performance differences between different systems.

• Dual-layer CT offers constant noise levels over the complete energy range.

Imaging prediction of nonalcoholic steatohepatitis using computed tomography texture analysis

Abstract

Objectives

To determine if texture analysis of non-contrast-enhanced CT (NECT) images is able to predict nonalcoholic steatohepatitis (NASH).

Methods

NECT images from 88 patients who underwent a liver biopsy for the diagnosis of suspected NASH were assessed and texture feature parameters were obtained without and with filtration. The patient population was divided into a predictive learning dataset and a validation dataset, and further divided into groups according to the prediction of liver fibrosis as assessed by hyaluronic acid levels. The reference standard was the histological result of a liver biopsy. A predictive model for NASH was developed using parameters derived from the learning dataset that demonstrated areas under the receiver operating characteristic curve (AUC) of >0.65. The resulting model was then applied to the validation dataset.

Results

In patients without suspected fibrosis, the texture parameter mean without filter and skewness with a 2-mm filter were selected for the NASH prediction model. The AUC of the predictive model for the validation dataset was 0.94 and the accuracy was 94%. In patients with suspicion of fibrosis, the mean without filtration and kurtosis with a 4-mm filter were selected for the NASH prediction model. The AUC for the validation dataset was 0.60 and the accuracy was 42%.

Conclusions

In patients without suspicion of fibrosis, NECT texture analysis effectively predicted NASH.

Key Points

• In patients without suspicion of fibrosis, NECT texture analysis effectively predicted NASH.

• The mean without filtration and skewness with a 2-mm filter were modest predictors of NASH in patients without suspicion of liver fibrosis.

• Hepatic fibrosis masks the characteristic texture features of NASH.

Endovascular interventional modalities for haemorrhage control in abnormal placental implantation deliveries: a systematic review and meta-analysis

Abstract

Objectives

To examine the evidence regarding the effectiveness and safety of endovascular interventional modalities for haemorrhage control in abnormal placentation deliveries.

Methods

MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to July 2017. Blood loss volume was regarded as the primary endpoint. Other important results are described. Random and fixed effects models were used for the meta-analysis.

Results

Of 385 studies identified, 69 (1,811 patients, mean age 32.9 years, range 23–39 years) were included. Mean gestational age at delivery was 35.1 weeks (range 27–38 weeks). Of 1,395 patients who underwent endovascular intervention, 587 (42%) had placenta accreta, 254 (18%) placenta increta and 313 (22%) placenta percreta. Prophylactic balloon occlusion of the internal iliac arteries (PBOIIA) was performed in 470 patients (33.6%), of the abdominal aorta (PBOAA) in 460 patients (33%), of the uterine artery (PBOUA) in 181 patients (13%), and of the common iliac arteries (PBOCIA) in 21 patients (1.5%). Primary embolization of the UA was performed in 246 patients (18%), of the pelvic collateral arteries in 12 patients (0.9%), and of the anterior division of the IIA in 5 patients (0.3%). Follow-up ranged from 0.5 to 42 months. Endovascular intervention was associated with less blood loss than no endovascular intervention (p < 0.001) with the lowest blood loss volume in patients who underwent PBOAA (p < 0.001). PBOAA was associated with a lower rate of hysterectomy (p = 0.030). Endovascular intervention did not result in increases in operative time or hospital stay.

Conclusions

Endovascular intervention is effective in controlling haemorrhage in abnormal placentation deliveries. PBOAA was associated with a lower rate of hysterectomy and less blood loss than other modalities.

Key points

• Endovascular intervention in abnormal placentation deliveries is effective in reducing blood loss.

• Endovascular intervention did not result in longer operative time or hospital stay.

• Prophylactic balloon occlusion of the abdominal aorta is superior to other modalities.

Intravoxel incoherent motion magnetic resonance imaging for differentiating metastatic and non-metastatic lymph nodes in pancreatic ductal adenocarcinoma

Abstract

Objectives

To evaluate the diagnostic potential of intravoxel incoherent motion (IVIM) DWI for differentiating metastatic and non-metastatic lymph node stations (LNS) in pancreatic ductal adenocarcinoma (PDAC).

Methods

59 LNS histologically diagnosed following surgical resection from 15 patients were included. IVIM DWI with 12 b values was added to the standard MRI protocol. Evaluation of parameters was performed pre-operatively and included the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f). Diagnostic performance of ADC, D, D* and f for differentiating between metastatic and non-metastatic LNS was evaluated using ROC analysis.

Results

Metastatic LNS had significantly lower D, D*, f and ADC values than the non-metastatic LNS (p< 0.01). The best diagnostic performance was found in D, with an area under the ROC curve of 0.979, while the area under the ROC curve values of D*, f and ADC were 0.867, 0.855 and 0.940, respectively. The optimal cut-off values for distinguishing metastatic and non-metastatic lymph nodes were D = 1.180 × 10⁻³ mm²/s; D* = 14.750 × 10⁻³ mm²/s, f = 20.65 %, and ADC = 1.390 × 10⁻³ mm²/s.

Conclusion

IVIM DWI is useful for differentiating between metastatic and non-metastatic LNS in PDAC.

Key Points

• IVIM DWI is feasible for diagnosing LN metastasis in PDAC.

• Metastatic LNS has lower D, D*, f, ADC values than non-metastatic LNS.

• D-value from IVIM model has best diagnostic performance, followed by ADC value.

• D* has the lowest AUC value.

Monilethrix: A case report imaged by trichoscopy, reflectance confocal microscopy and histopathology

Statistical Controversies in Clinical Research: Limitations of open-label studies assessing antiangiogenic therapies with regard to evaluation of vascular adverse drug events. A meta-analysis

Abstract

Background

Previous meta-analyses have shown paradoxical increased risk of bleeding and thrombotic events in patients receiving antiangiogenics (AA) that may be simply explained by the studies design included. By a meta-epidemiological approach, we aim to investigate the impact of double-blind (DB) and open-label study designs on the risks of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated with AA.

Materials and Methods

We searched Medline, Cochrane, ClinicalTrials.gov databases, and proceedings of major oncology congresses for clinical trials published from January 2003 to January 2016. Randomized clinical trials that assigned patients with solid cancers to AA or control groups were eligible for inclusion. Combined odds ratios (OR) for the risks of bleeding events, VTE and ATE were calculated for open and DB trials. Estimation bias of the treatment effect was determined by the ratio of odds ratio (ROR), by dividing the OR values obtained in open-label trials by those obtained in DB trials.

Results

The literature-based meta-analysis included 166 trials (72,024 patients). For bleeding events, comparison of AA versus control yielded an overall OR of 2.41 (95% CI 2.12-2.73; P <0.001), but this risk was overestimated by 1.68 (95% CI 1.33-2.13) in open-label studies. Concerning VTE, the OR was 1.19 (95% CI 1.04-1.35; P =0.012) overall with AA, but this effect disappears when considering only DB trials (OR 0.99, 95% CI, 0.83-1.17). The corresponding ROR showed a significant overestimation of 1.53 (95% CI 1.19-1.96) in open-label trials. For ATE, an OR of 1.59 (95% CI 1.30-1.94; P <0.001) was observed, associated with a significant overestimation of 1.65 (95% CI 1.13-2.43) in open-label trials.

Conclusions

Open-label studies overestimated the risk of vascular adverse events with AA by at least 50%. Meta-analyses assessing adverse drug events should therefore be restricted to DB randomized trials.

EXPRESSION III: Patient´s Expectations and Preferences regarding Physician–Patient Relationship and Clinical Management. Results of the International NOGGO/ENGOT-ov4-GCIG study in 1,830 Ovarian Cancer Patients from European countries.

Abstract

Backround

The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician-patient relationship and treatment

Patients and methods

A questionnaire was developed based on the experiences of the national German survey Expression II, and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version.

Results

From December 2009 to October 2012, a total of 1,830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The 3 most important aspects, identified by patients to improve the treatment for ovarian cancer included: "the therapy should not induce alopecia" (42%), "there must be more done to counter fatigue" (34.5%), and "the therapy should be more effective" (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included.

Conclusion

This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

Developing Androgen Receptor Targeting for Salivary Gland Cancers

Phase 1-2 trial designs: how early should efficacy guide the dose recommendation process?

Nivolumab versus docetaxel in previously treated advanced non-small cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract

Background

Long-term data with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti–programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and non-squamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.

Patients and methods

Patients were randomized 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m² every 3 weeks) until progression or discontinuation. The primary endpoint of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.

Results

After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% (95% confidence interval [CI], 14–21%) versus 8% (95% CI, 6–11%) in the pooled population with squamous or non-squamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).

Conclusions

After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.

Clinical trial registration

CheckMate 017: NCT01642004; CheckMate 057: NCT01673867

CHK1 Inhibition in Soft-Tissue Sarcomas: Biological and Clinical Implications

Abstract

Background

Inhibition of ChK1 appears as a promising strategy for selectively potentiate the efficacy of chemotherapeutic agents in G1 checkpoint-defective tumor cells such as those that lack functional p53 protein. The p53 pathway is commonly dysregulated in soft-tissue sarcomas (STS) through mutations affecting TP53 or MDM2 amplification. GDC-0575 is a selective ATP-competitive inhibitor of CHK1.

Methods

We have performed a systematic screening of a panel of 10 STS cell lines by combining the treatment of GDC-0575 with chemotherapy. Cell proliferation, cell death and cell cycle analysis were evaluated with high throughput assay. In vivo experiments were performed by using TP53-mutated and TP53 wild-type patient-derived xenograft models of STS. Clinical activity of GDC-0575 combined with chemotherapy in patients with TP53-mutated and TP53 wild-type STS was also assessed.

Results

We found that GDC-0575 abrogated DNA damage-induced S and G2–M checkpoints, exacerbated DNA double-strand breaks and induced apoptosis in STS cells. Moreover, we observed a synergistic or additive effect of GDC-0575 together with gemcitabine in vitro and in vivo in TP53-proficient but not TP53-deficient sarcoma models. In a phase 1 study of GDC-0575 in combination with gemcitabine, two patients with metastatic TP53-mutated STS had an exceptional, long-lasting response despite administration of a very low dose of gemcitabine whereas one patient with wild-type TP53 STS had no clinical benefit. Genetic profiling of samples from a patient displaying secondary resistance after 1 year showed loss of one preexisting loss-of-function mutation in the helical domain of DNA2.

Conclusion

We provide the first pre-clinical and clinical evidence that potentiation of chemotherapy activity with a CHK1 inhibitor is a promising strategy in TP53-deficient STS and deserves further investigation in the phase 2 setting.

Molecular detection and genotypic characterization of enteric adenoviruses in a hospital wastewater

Abstract

Hospital wastewater (HWW) represents a major source of the diffusion of many antibiotics and some toxic pathogenic microorganisms in the aquatic environment. Sanitation services play a critical role in controlling transmission of numerous waterborne pathogens, especially enteric human adenoviruses (HAdVs) that can cause acute gastroenteritis. This study intended to evaluate the human adenoviruses (HAdVs) detection rates, to determine the genotype of these viruses and to assess the efficiency of HAdVs removal in hospital pilot wastewater treatment plant (PWWTP) in Tunis City, Tunisia. Therefore, hospital wastewater samples (n = 102) were collected during the study year from the two biological wastewater treatment techniques: natural oxidizing ponds and the rotating biological disks or biodisks. Nested polymerase chain reaction (Nested PCR) was used to evaluate the HAdVs detection rates. The genotype of HAdVs positive samples was achieved by the sequencing of the PCR products. HAdVs were detected in 64% (65/102) of positive wastewater samples. A substantial increase in the frequencies of HAdVs was observed at the exit of the two wastewater treatment techniques studied. The typing of HAdVs species F showed the occurrence of only HAdVs type 41. This data acquired for the first time in Tunisia showed high persistence and survival of HAdVs in the two biological wastewater treatment techniques experienced, and mainly highlighted the poor virological quality of the treated wastewater intended for recycling, agriculture reuse, and discharges into the natural receiving environments. Consequently, tertiary wastewater treatment appeared necessary in this case to decrease the load of enteric viruses flowing in the water environment.

Lichen sclerosus on the face

Subcutaneous methotrexate in patients with moderate to severe psoriasis: a critical appraisal

Summary

Aim

Warren et al¹ set out to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe chronic plaque psoriasis.

Setting and design

This is a prospective, double-blind, randomised (3:1), placebo-controlled study, conducted across 16 centres in Germany, France, the Netherlands, and the UK.

Study exposure

Methotrexate-naïve adults with a diagnosis of moderate to severe chronic plaque psoriasis for at least 6 months before baseline were randomly assigned to receive weekly subcutaneous injections of either methotrexate at a starting dose of 17.5 mg, or placebo for 16 weeks (first phase).Dose escalation to 22.5 mg/week was implemented after 8 weeks if patients did not achieve PASI 50. Treatment was combined with folic acid 5 mg/week. The first phase of the study was followed by an open-label period from 16-52 weeks (second phase), in which both groups received weekly methotrexate injections. At week 24, dose escalation to 22.5 mg/week was possible in patients not achieving PASI 50.

Outcomes

Psoriasis severity was measured using the PASI (Psoriasis Area and Severity Index). The authors also used two other psoriasis severity measures and two quality of life measures, looked at safety indices and performed a sub-study analysing paired skin biopsies at baseline and week 16 (histopathology, immunohistochemistry and expression of interleukin (IL)17A, interferon-γ and tumour necrosis factor-α).

Primary outcome measures

The primary outcome was the proportion of patients reaching PASI 75 at week 16.

Results

120 patients were included in this trial, most of whom were middle-aged white men with longstanding psoriasis and a mean BMI of 30.1 kg/m². PASI 75 was achieved in 41% of patients receiving methotrexate vs. 10% of patients receiving placebo (RR 3.93, 95% CI 1.31–11.81; p=0.0026) at week 16. Subcutaneous methotrexate was generally well tolerated, with no serious adverse events related to this treatment over the 52-week study.

Conclusions

Warren et al conclude that the 52-week risk-benefit profile of subcutaneous methotrexate is favourable in patients with psoriasis.

This article is protected by copyright. All rights reserved.

Oral retinoids and depression

Abstract

We are concerned about the content and possible misinterpretation of a research letter by Le Moigne et al. published on 19 June 2017 in the British Journal of Dermatology online.[1]

We share the concern expressed by the authors about possible psychiatric effects of oral retinoids. However, case reports rank low in the hierarchy of evidence, as a result of their inherent limitations, including publication bias and a lack of control groups.

This article is protected by copyright. All rights reserved.

A new mobile learning module using smartphone wallpapers in identification of medical fungi for medical students and residents

Abstract

Introduction

Medical students and residents will encounter many cutaneous fungal infections in medical practice. However, the training for identification of medical fungi has been insufficient due to limited lecture-based courses. The objective of this study was to evaluate the impact of using smartphone-based wallpapers in learning the microscopic morphology and colony characteristics of medical fungi for medical students and residents.

Methods

A smartphone-based wallpaper learning module using a wallpaper-changing software application (app) was introduced in this 3-week training course. Twenty-six participants were enrolled and divided into two groups: nondermatology trainees, including medical students and postgraduate year one (PGY-1) doctors who have not yet specialized, and dermatology trainees (dermatology residents). All of the participants completed a 3-week training course, and the effectiveness of the module was evaluated by pre- and post-course multiple-choice examinations.

Results

Both nondermatology and dermatology trainees scored significantly higher in post-course examinations than pre-course examinations (P < 0.001). The dermatology trainees performed better than nondermatology trainees in the pre-course examinations (P < 0.001). In the post-course examinations, no significant difference in scores was noted between dermatology and nondermatology trainees (P = 0.573).

Discussion

The smartphone-based wallpaper learning module was effective in helping medical students and residents learn and memorize morphologic characteristics of fungi. In comparison to conventional lecture-based learning, this new mobile module was more readily accessible and convenient for learners to engage in learning.

Disseminated actinomycetoma due to Nocardia wallacei

Abstract

Background

Actinomycetoma caused by Nocardia usually responds well to antibiotics. Emerging species of Nocardia, such as N. wallacei, can be a therapeutic challenge.

Aims

Confirm the therapeutic effectivity of linezolid in multidrug resistant Nocardia Wallacei actinomycetoma.

Materials and Methods

We evaluated the medical management of an 18-year-old man with multidrug resistant actinomycetoma of the left leg caused by N. transvalensis complex treated 17 years ago with linezolid 1200 mg a day. This bacteria was recently reclassified as Nocardia Wallacei by specific molecular biology technique.

Results

The infection was cured after 3 months of treatment; the patient remained asymptomatic for the past 17 years. No adverse effects were found.

Discussion

Frequently, strains of N. transvalensis complex have aminoglycoside resistance; in this case, we highlight the effectiveness of linezolid for the successful medical management of multidrug resistant actinomycetoma.

Conclusion

Linezolid can be an alternative for the treatment of multidrug resistant Nocardia Wallacei.

Treatment response to omalizumab in patients with refractory chronic spontaneous urticaria

Abstract

Background

Previous clinical trials have demonstrated the efficacy and safety of the anti-IgE monoclonal antibody omalizumab in chronic spontaneous urticaria (CSU) not responding to antihistamine treatment. The primary aim of our study was to describe the response patterns of patients with refractory CSU treated with omalizumab in a real-world clinical setting.

Methods

A retrospective analysis of medical records of 20 patients with refractory CSU was performed. Demographic, clinical, and laboratory features were retrieved and analyzed in correlation with treatment data.

Results

Mean age of our patient population was 54.5 years, while the majority were females (15/20 cases, 75%). Mean disease duration prior to omalizumab administration was 21.8 months. All patients had a history of chronic urticaria, refractory to high antihistamine and corticosteroid treatment, and responded favorably to omalizumab after administration of 1–5 doses of omalizumab; complete response was observed in 17/20 patients (85%) and well-controlled disease in the remaining 3/20 patients (15%). In a subset of cases (6/20, 30%), best response to omalizumab was achieved after interval administration of a 9-day course of methylprednisolone (total dose of 188 mg). Late response to omalizumab (after three-month treatment) was significantly correlated (P = 0.026) with shorter disease duration before initiation of omalizumab.

Conclusion

In the present series, omalizumab, either alone or in combination with a short-term course of corticosteroids, was highly effective in resolution of refractory CSU. Furthermore, disease duration prior to omalizumab had a significant effect on timing of response.

Occupational allergic contact dermatitis caused by antibiotics in healthcare workers – relationship with non-immediate drug eruptions

Summary

Background

Occupational allergic contact dermatitis (ACD) in healthcare workers (HCWs) is common, but systemic antibiotics are rarely reported as the cause.

Objectives

Characterize occupational ACD by handling systemic antibiotics.

Method

A retrospective analysis was performed of ACD caused by systemic antibiotics among HCWs patch tested between 2010 and 2016 with a series of systemic antibiotics.

Results

We studied 4 female nurses aged 28–47 years who developed ACD while working in surgical departments. They had eczema of the hands, and forearms or face, and 1 patient, who previously had exanthema caused by flucloxacillin, also developed a generalized rash following airborne exposure to systemic antibiotics. Patch tests showed positive reactions to ampicillin and cefazolin in 1 patient, to cefotaxime and ceftriaxone in 2 patients, and to several penicillins in another patient. Three patients also reacted to rubber allergens, fragrances, and/or preservatives. All patients admitted having direct and sporadic exposure to systemic antibiotic solutions. Avoidance resulted in a significant improvement of ACD, but 1 patient had to change job.

Conclusions

Occupational ACD caused by β-lactam antibiotics, particularly cephalosporins, is significant in HCWs. Cross-reactions between β-lactams are similar to those described in non-immediate drug eruptions. A relationship between systemic delayed drug hypersensitivity and ACD, as observed in 1 case, suggests that patients should avoid future use of the antibiotic to which they are sensitized.

Textile contact dermatitis caused by octylisothiazolinone in compression stockings

Toying with the Toolbox: How Metaphysics Can Still Make a Contribution

Abstract

Current analytic metaphysics has been claimed to be, at best, out of touch with modern physics, at worst, actually in conflict with the latter (Callender, in: French, Saatsi (eds) The continuum companion to the philosophy of science, Continuum, London, 2011; Ladyman and Ross Every thing must go: metaphysics naturalized, Oxford University Press, Oxford, 2007). While agreeing with some of these claims, it has been suggested that metaphysics may still be of service by providing a kind of 'toolbox' of devices that philosophers of science can access in order to help provide an interpretation of theories in fundamental physics (French and McKenzie in Eur J Anal Philos 8:42–59, 2012; see also French and McKenzie, in: Bigaj, Wuthrich (eds) Metaphysics in contemporary physics, Rodopi, Amsterdam, 2015). In this context it has been argued that 'standard' forms of dispositionalism simply cannot be sustained in the context of modern physics but that certain 'non-standard' views may provide the resources to help explicate the sense in which physics may be regarded as 'modally informed'. Here that suggestion will be further extended in order to consider the implications both with regard to the overall relevance of metaphysics given advances in science and for the prospects of a naturalised metaphysics more generally. In particular, this paper will focus on three concerns: (1) that the particular tools identified are not, in fact, 'scientifically disinterested' and thus that the distinction between 'naturalised' and 'non-naturalised' metaphysics is at best vague or poorly drawn; (2) that the usefulness of such tools depends on their being shaped to fit the relevant physics and thus the latter 'guts' metaphysics; (3) that if metaphysics does prove to be useful in this sense then we have no reason to scorn non-naturalised metaphysics to begin with.

Social Science as a Guide to Social Metaphysics?

Abstract

If we are sympathetic to the project of naturalising metaphysics, how should we approach the metaphysics of the social world? What role can the social sciences play in metaphysical investigation? In the light of these questions, this paper examines three possible approaches to social metaphysics: inference to the best explanation from current social science, conceptual analysis, and Haslanger-inspired ameliorative projects.

Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced cutaneous melanoma

Abstract

The combination of dabrafenib and trametinib demonstrated encouraging antitumor activity and tolerability, at initial analysis, in Japanese patients with BRAF V600 mutant advanced melanoma warranting further investigation. This study evaluated the safety and tolerability, pharmacokinetics (PK) and preliminary efficacy of dabrafenib 150 mg b.i.d. plus trametinib 2 mg q.d. in Japanese patients with BRAF V600E/K mutant solid tumors (phase 1) and melanoma (phase 2). Phase 1 was primarily intended to assess safety and tolerability as assessed by adverse events (AE), and the primary end-point in phase 2 was to assess confirmed overall response rate (ORR). The secondary end-points in phase 1 included PK, confirmed/unconfirmed ORR and duration of response (DOR). The secondary end-points in phase 2 were PK, unconfirmed ORR, DOR, safety and tolerability. A total of 12 cutaneous melanoma patients were enrolled in the study (six in phase 1 and six in phase 2) and received the combination therapy of dabrafenib and trametinib. Common AE (≥50.0%) included pyrexia (75%), increased aspartate aminotransferase (67%), peripheral edema (50%) and nasopharyngitis (50%). The investigator-assessed ORR was reported in five patients (83%) in phase 1 and was also reported in five patients (83%; 95% confidence interval, 35.9–99.6; P < 0.0001) in phase 2. Plasma concentrations of both dabrafenib and trametinib seemed to a reach steady state by week 3. Overall, efficacy and PK properties for the dabrafenib plus trametinib combination in Japanese patients were comparable with those seen in global studies.

Efficacy of oral cholecalciferol on rhododendrol-induced vitiligo: A blinded randomized clinical trial

Abstract

Rhododendrol (RD), 4-(4-hydroxyphenyl)-2-butanol, inhibits melanin synthesis and has been used for skin-whitening cosmetic products. RD has been very effective in lightening skin pigmentation, but some persons have developed so-called RD vitiligo, in which vitiligo starts on the face, neck and hands where topical RD has been applied and even extended over skin areas where RD has not been applied. RD vitiligo lesions in some patients have lasted for years and have been resistant to conventional vitiligo treatments. We examined the effects of cholecalciferol on RD vitiligo in a blinded randomized clinical trial. Forty-eight female RD vitiligo patients were recruited for the trial and were randomized into two groups: the vitamin D (VD)-intervention group that received daily 5000 IU cholecalciferol for 5 months and the control group. Three blinded investigators scored vitiligo improvement by comparing photographic images of baseline and at 5-month observation. Serum 25(OH)D3 of RD vitiligo patients was not significantly different from age-matched healthy volunteers. Twenty-two in the VD-intervention group and 23 in the control group completed the 5-month observation. Serum 25(OH)D3 levels were significantly increased after the 5-month VD intervention, while the control group did not change. The improvement scores were significantly higher in the VD-intervention group than the control group. The improvement scores were positively correlated with the serum 25(OH)D3 levels after the 5-month intervention period but not before the treatment. This blinded randomized clinical trial showed favor in administrating 5000 IU cholecalciferol daily to RD vitiligo patients.

Case of atopic dermatitis concurrent with idiopathic thrombocytopenic purpura, whose serum thymus and activation-regulated chemokine level remained undetectable

Abstract

We report a 9-year-old Japanese female patient with atopic dermatitis associated with idiopathic thrombocytopenic purpura. She demonstrated high serum immunoglobulin (Ig)E and IgE specific to several environmental allergens, but extremely low serum thymus and activation-regulated chemokine (TARC) levels regardless of the disease progression. This case suggests platelets as the main source of serum TARC.

A novel image processing workflow for the in vivo quantification of skin microvasculature using dynamic optical coherence tomography

Abstract

Background

Currently, imaging technologies that can accurately assess or provide surrogate markers of the human cutaneous microvessel network are limited. Dynamic optical coherence tomography (D-OCT) allows the detection of blood flow in vivo and visualization of the skin microvasculature. However, image processing is necessary to correct images, filter artifacts, and exclude irrelevant signals. The objective of this study was to develop a novel image processing workflow to enhance the technical capabilities of D-OCT.

Materials and methods

Single-center, vehicle-controlled study including healthy volunteers aged 18-50 years. A capsaicin solution was applied topically on the subject's forearm to induce local inflammation. Measurements of capsaicin-induced increase in dermal blood flow, within the region of interest, were performed by laser Doppler imaging (LDI) (reference method) and D-OCT.

Results

Sixteen subjects were enrolled. A good correlation was shown between D-OCT and LDI, using the image processing workflow. Therefore, D-OCT offers an easy-to-use alternative to LDI, with good repeatability, new robust morphological features (dermal-epidermal junction localization), and quantification of the distribution of vessel size and changes in this distribution induced by capsaicin. The visualization of the vessel network was improved through bloc filtering and artifact removal. Moreover, the assessment of vessel size distribution allows a fine analysis of the vascular patterns.

Conclusion

The newly developed image processing workflow enhances the technical capabilities of D-OCT for the accurate detection and characterization of microcirculation in the skin. A direct clinical application of this image processing workflow is the quantification of the effect of topical treatment on skin vascularization.

Editor's Choice

Editorial board

Horizontal and vertical sections of scalp biopsy specimens from dermatomyositis patients with scalp involvement

Scalp involvement in dermatomyositis manifests as a pruritic eruption with erythema and scaling associated with nonscarring alopecia. We characterized the histologic features of scalp dermatomyositis using horizontal and vertical sections. Characteristic findings of scalp dermatomyositis include preserved follicular architecture, hair counts consistent with chronic telogen effluvium, telangiectasia and mucin.

Skin in the Game: Existing and Upcoming Physician Payment Models in Dermatology

Efficacy and Safety of Topical Oxymetazoline Cream 1.0% for Treatment of Persistent Facial Erythema Associated With Rosacea: Findings From the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Most rosacea treatments targeting inflammatory lesions do not improve persistent facial erythema.Topical oxymetazoline hydrochloride cream 1.0% effectively reduced erythema versus vehicle in patients with moderate to severe persistent facial erythema of rosacea, with favorable tolerability.Topical oxymetazoline represents a new treatment option for patients with persistent erythema of rosacea.

Consultative Teledermatology in the Emergency Department and Inpatient Wards: A Survey of Potential Referring Providers.