Association between the clinical and histopathological classifications of actinic keratosis and the efficacy of topical imiquimod treatment

Abstract

We investigated the association between the clinical and histopathological classifications of actinic keratosis (AK) and the efficacy of topical imiquimod treatment. Forty patients (55 lesions) with AK were treated with topical 5% imiquimod and the efficacy of imiquimod for AK was evaluated based on the clinical/histopathological changes. The complete remission (CR) rates in patients with the different clinical classifications of AK were 85.4% (erythematous type) and 46.2% (hyperkeratotic type). The CR rates in the different histopathological classifications of AK were 80% (hypertrophic type), 81.8% (atrophic type) and 42.9% (bowenoid type). The results revealed that determining the clinical and histopathological type of AK was important for selecting a therapeutic method. The topical imiquimod treatment could be expected to be more effective for AK clinically classified as the erythematous type, or histopathologically classified as the atrophic or hypertrophic type. However, it would be expected to be less effective for the treatment of AK clinically classified as the hyperkeratotic type or histopathologically classified as the bowenoid type. Our observations suggest that we can predict the efficacy of topical imiquimod therapy in AK by determining its clinical and histopathological type.

Purpura fulminans in congenital protein C deficiency successfully treated with fresh frozen plasma and thrombomodulin

Case of subungual tumoral melanosis: The detection of melanoma cells and dermoscopic features

Successful treatment with rituximab in a Japanese patient with systemic sclerosis-associated interstitial lung disease resistant to oral steroid and cyclophosphamide

Diagnostic criteria, severity classification and guideline of lichen sclerosus et atrophicus

Abstract

We established diagnostic criteria and severity classification of lichen sclerosus et atrophicus, because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there is no clinical guideline for lichen sclerosus et atrophicus in Japan, so we proposed its clinical guideline. The clinical guidelines were formulated by clinical questions and recommendations on the basis of evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guidelines easy to use and reliable including the newest evidence, and to present guidance for various clinical problems in treatment of lichen sclerosus et atrophicus.

The Investigated Question and Study Design in Cross-sectional Studies Response to “Chronic Urticaria and the Metabolic Syndrome: a Cross-sectional Community-based Study of 11,261 Patients” Authors Reply

We read with interest the letter by Soria et al. We have been studying Chronic Urticaria (CU) for several years. During this time, we have evaluated the disease and associated conditions from several aspects. The study presented by Soria et al. compared the severity of CU between a small group of obese CU patients and another small group of non-obese CU patients, all recruited in inpatient clinics of a hospital setting.

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Two novel mutations in the TSC2 gene causing severe phenotype in nervous system and skin in a patient with tuberous sclerosis complex

Tuberous sclerosis complex (TSC1, OMIM 191100 and TSC2 OMIM 613254) is an autosomal dominant neurocutaneous disorder that affects multiple organs, associated with the development of wide spread hamartomatous lesions including brain, eyes, lungs, heart, liver, kidneys and skin. Mutations in the tumor suppressor genes, TSC1 at 9q34 and TSC2 at 16p13.3, which encode the proteins hamartin and tuberin respectively, detected in approximately 85-90% of the cases. The majority of cases occur sporadically, with a family history found in only 30% of patients.

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Immolation dans notre centre de traitement des brûlés de 2011 à 2016

Publication date: Available online 18 December 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): S. Chatelain, K. Serror, M. Chaouat, M. Mimoun, D. Boccara
L'immolation par le feu est dans certains pays tels que l'Iran ou la Tunisie une pratique couramment employée afin de mettre fin à ses jours. Des études ont été réalisées sur ce sujet dans de nombreux pays développés et en voie de développement, permettant de faire ressortir des sujets à risque selon les pays. Cependant nous n'avons pas à ce jour de données récentes sur la population d'immolés par le feu en France. Nous avons réalisé une étude épidémiologique rétrospective sur les immolations entre 2011 et 2016 au centre de traitement des brûlés de l'hôpital Saint-Louis à Paris, en nous appuyant sur les facteurs favorisants retrouvés dans la littérature. Nous avons étudié la prévalence, et les caractéristiques des patients entrant en hospitalisation pour ce motif. Entre 2011 et 2016, 1098 patients ont été hospitalisés dans notre service. Cinquante patients ont été admis pour cause d'immolation, soit 5 % de la population hospitalisée. L'âge moyen à l'entrée était de quarante-six ans, majoritairement des hommes (62 %). La surface cutanée totale brûlée moyenne était de 34,5 %, et la durée moyenne de séjour de cinquante-trois jours. Neuf décès sont survenus dans cette population (18 %), chez des patients des deux sexes, brûlés à 62,5 % en moyenne et d'un âge similaire à celui de notre cohorte. Il s'agissait d'un passage à l'acte suicidaire pour quarante-neuf patients, avec seulement un cas d'immolation criminelle. Des antécédents psychiatriques ont été retrouvés chez trente-cinq patients (70 %). Vingt et un d'entre eux avaient déjà tenté de se suicider précédemment (42 %). Neuf patients étaient alcooliques chroniques et quatre toxicomanes. Les motifs fréquents de passage à l'acte étaient une rupture sentimentale, un décès ou des problèmes financiers. Les produits utilisés étaient le white spirit, l'alcool à brûler et l'essence. La prévalence des immolations dans notre étude est très faible par rapport à celle retrouvée dans les pays en voie de développement. La majorité de notre cohorte est composée de patients ayant des antécédents de troubles de l'humeur. Les antécédents de tentative de suicide sont également un facteur de risque majeur de passage à l'acte suicidaire par immolation. Des mesures de prévention devraient être mises en place pour prévenir ce risque.The prevalence of immolation by fire in France is uncertain. We carried out a retrospective epidemiological study on immolations between 2011 and 2016 at the burn treatment centre at the hôpital Saint-Louis in Paris. We studied the prevalence and characteristics of patients entering hospital for this reason. Between 2011 and 2016, a total of 1098 patients were hospitalized in the centre, of which 50 were admitted for immolation, i.e. five percent of the hospitalized population. The average age at entry was 46 years, and they were mostly men (62%). All but one was a suicide attempt. The average total burn area was 34.5%, and the average length of stay in the centre was 53 days. The products used for the immolation were mostly white spirit, alcohol or gasoline. Nine (18%) out of the 50 patients died, burned at 62.5% on average. A psychiatric history was reported in 35 patients and 21 had previously attempted suicide; nine patients were chronic alcoholics and four were drug addicts. The most frequently reported reasons for the suicide attempt were sentimental breakdown, death of a relative or financial problem. The prevalence of immolation in our study is very low compared to that found in developing countries. The majority of our cohort is composed of patients with a history of psychiatric disorders. The history of attempted suicide is also a major risk factor for committing suicidal acts by immolation. Prevention measures should be implemented to reduce this risk.

Hyperkalzämie

Zusammenfassung

Die Hyperkalzämie stellt ein häufiges klinisches Problem dar. Normalerweise ist die Kalziumkonzentration im Blutserum streng reguliert. Eine Hyperkalzämie tritt auf, wenn das Gleichgewicht zwischen intestinaler Kalziumaufnahme, renaler Kalziumexkretion und ossärem Kalziumstoffwechsel gestört ist. Der erste Schritt in der Evaluation der Hyperkalzämie besteht darin, diese durch eine wiederholte Messung zu bestätigen. Zusätzlich sollten Albumin und Eiweiß bestimmt werden, um ein korrigiertes Kalzium zu berechnen. Der nächste diagnostische Schritt ist die Messung des Serumparathormons, um zwischen einer nebenschilddrüsenbedingten und einer nicht nebenschilddrüsenbedingten Form zu unterscheiden. Bei den nebenschilddrüsenbedingten Hyperkalzämien stellt der primäre Hyperparathyreoidismus (PHPT) die mit Abstand häufigste Form dar. Ein symptomatischer PHPT sollte, wenn möglich, operativ saniert werden. Ein niedriger Wert (<20 pg/ml) für das intakte Parathormon (PTH) spricht hingegen für das Vorliegen einer nicht nebenschilddrüsenbedingten Hyperkalzämie. In einem solchen Fall empfiehlt sich die Bestimmung von Parathormon-related Protein (PTHrP) sowie der Vitamin-D-Metaboliten. In der überwiegenden Mehrzahl der Fälle mit dieser Konstellation liegt eine tumorbedingte Hyperkalzämie vor. 80–90 % aller Hyperkalzämien sind durch einen PHPT oder eine Tumorhyperkalzämie bedingt, während viele andere Ursachen entsprechend selten sind. Ist keine Operation beim PHPT gewünscht oder handelt es sich um eine Tumorhyperkalzämie, stehen medikamentöse Therapieformen zur Verfügung.

YouTube as a source of information on skin bleaching: a content analysis

Summary

Background

Skin bleaching is a common, yet potentially harmful body modification practice.

Aim

To describe the characteristics of the most widely viewed YouTube™ videos related to skin bleaching.

Methods

The search term 'skin bleaching' was used to identify the 100 most popular English-language YouTube videos relating to the topic. Both descriptive and specific information were noted.

Results

Among the 100 manually coded skin-bleaching YouTube videos in English, there were 21 consumer-created videos, 45 internet-based news videos, 30 television news videos and 4 professional videos. Excluding the 4 professional videos, we limited our content categorization and regression analysis to 96 videos. Approximately 93% (89/96) of the most widely viewed videos mentioned changing how you look and 74% (71/96) focused on bleaching the whole body. Of the 96 videos, 63 (66%) of videos showed/mentioned a transformation. Only about 14% (13/96) mentioned that skin bleaching is unsafe. The likelihood of a video selling a skin bleaching product was 17 times higher in internet videos compared with consumer videos (OR = 17.00, 95% CI 4.58–63.09, P < 0.001). Consumer-generated videos were about seven times more likely to mention making bleaching products at home compared with internet-based news videos (OR = 6.86, 95% CI 1.77–26.59, P < 0.01).

Conclusions

The most viewed YouTube video on skin bleaching was uploaded by an internet source. Videos made by television sources mentioned more information about skin bleaching being unsafe, while consumer-generated videos focused more on making skin-bleaching products at home.

Tinea capitis mimicking dissecting cellulitis in three children

Abstract

Tinea capitis mimicking dissecting cellulitis is a rare presentation, and there is a paucity of information regarding this presentation in the literature. Three children 10-14 years of age who presented with an unusual clinical manifestation of tinea capitis that clinically resembled dissecting cellulitis are reported. The patients were treated with systemic antifungals for 3-4 months. Treatment success was measured according to repeat fungal cultures and clinical assessment of hair regrowth at follow-up visits. All three patients had resolution of infection, with negative repeat fungal cultures and complete hair regrowth without scarring. These cases highlight a rare inflammatory subtype of tinea capitis that can be easily misdiagnosed and therefore improperly treated, prolonging the duration of infection.

Impacts of global changes on the biogeochemistry and environmental effects of dissolved organic matter at the land-ocean interface: a review

Abstract

Dissolved organic matter (DOM) is an important component in the biogeochemistry and ecosystem function of aquatic environments at the highly populated land-ocean interface. The mobilization and transformation of DOM at this critical interface are increasingly affected by a series of notable global changes such as the increasing storm events, intense human activities, and accelerating glacier loss. This review provides an overview of the changes in the quantity and quality of DOM under the influences of multiple global changes. The profound implications of changing DOM for aquatic ecosystem and human society are further discussed, and future research needs are suggested for filling current knowledge gaps. The fluvial export of DOM is strongly intensified during storm events, which is accompanied with notable changes in the chemical composition and reactivity of DOM. Land use not only changes the mobilization of natural DOM source pools within watersheds but also adds DOM of distinct chemical composition and reactivity from anthropogenic sources. Glacier loss brings highly biolabile DOM to downstream water bodies. The changing DOM leads to significant changes in heterotrophic activity, CO₂ out gassing, nutrient and pollutant biogeochemistry, and disinfection by-product formation. Further studies on the source, transformations, and downstream effects of storm DOM, temporal variations of DOM and its interactions with other pollutants in human-modified watersheds, photo-degradability of glacier DOM, and potential priming effects, are essential for better understanding the responses and feedbacks of DOM at the land-ocean interface under the impacts of global changes.

Persistent plasticizers and bisphenol in the cheese of Tunisian markets induced biochemical and histopathological alterations in male BALB/c mice

Abstract

Clinical evidences, experimental models, and epidemiology of many studies suggest that phthalate-based plasticizers, aliphatic ester, and bisphenol A (BPA) have major risks for humans by targeting different organs and body systems. The current study has been designed firstly to analyze three categories of cheese with and without their exposure to the sun and packed in packages with an inner surface plastic-covered film in order to identify the dibutyl phthalate (DBP); benzyl butyl phthalate (BBP); bis(2-ethylhexyl) phthalate (DEHP); diisodecyl phthalate (DiDP); diisononyl phthalate (DiNP); and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) by GC-MS/MS, except for the bisphenol A, which is by UPLC-MS/MS, and secondly to assess the toxicity of the identified chemical molecules and cheese samples on the liver and kidney of mice. Our results showed that the cheese contains high quantities of DBP and DEHP with the concentrations up to 0.46 and 2.339 mg/kg, respectively. Other types of cheese, such as rolled and triangular cheeses, contain little quantities of the all substances at concentrations below the standard limits. In vivo, the obtained data clearly demonstrated that the acute administration of DBP, DEHP, and the tested cheese significantly induced liver and kidney injuries in mice manifested by a rise in plasma alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, lactate dehydrogenase, urea, creatinine, and uric acid when compared with control animals. In addition, the histopathological study confirmed the perturbation of biochemical parameters and showed that the hepatic and renal structures were altered. Indeed, the hepatotoxic and nephrotoxic effects are more pronounced when cheese was exposed to the sun.

Experimental research on the electromagnetic radiation (EMR) characteristics of cracked rock

Abstract

Coal rock would emit the electromagnetic radiation (EMR) while deformation and fracture, and there exists structural body in the coal rock because of mining and geological structure. In this paper, we conducted an experimental test the EMR characteristics of cracked rock under loading. Results show that crack appears firstly in the prefabricated crack tip then grows stably parallel to the maximum principal stress, and the coal rock buckling failure is caused by the wing crack tension. Besides, the compressive strength significantly decreases because of the precrack, and the compressive strength increases with the crack angle. Intact rock EMR increases with the loading, and the cracked rock EMR shows stage and fluctuant characteristics. The bigger the angle, the more obvious the stage and fluctuant characteristics, that is EMR becomes richer. While the cracked angle is little, EMR is mainly caused by the electric charge rapid separates because of friction sliding. While the cracked angle is big, there is another significant contribution to EMR, which is caused by the electric dipole transient of crack expansion. Through this, we can know more clear about the crack extends route and the corresponding influence on the EMR characteristic and mechanism, which has important theoretical and practical significance to monitor the coal rock dynamical disasters.

Diversification and microscopic structure of tissues in endemic and endangered species of Dawkinsia tambraparniei from the river Tamiraparani, Tamil Nadu, India

Abstract

We investigated the study on the endemic and endangered species of Dawkinsia tambraparniei were confined only the areas of the river Tamiraparani. These species are under threats due to the menace of anthropogenic stress. To recognize the crisis behind the particular species, it was analyzed histologically and molecularly from the five pollutant levels of river Tamiraparani. Histologically, the microscopic examinations were also carried out from the crucial organs such as the brain, gill, heart, kidney, and liver, which confirm the spiky survivability of the endemic fish. Assessment of fish organ damages was observed highly in Kokkirakulam and Vannarapettai. Probably with conserved molecular sequences, the species can be identified out from the encountered surveillance of the particular taxa leading to the evolutionary circumstances. The phylogenetic analysis of Dawkinsia tambraparniei populations showed that Cheranmadevi and Vallandau sites populations were closely distributed. Even though the species have similarity sequences of each population were shown that the closely related with same genus but other sub-species. The observed results emphasize the conventional measures to conserve the endemic species and more effectual planning to the proximity of endurances in inhabited zone.

Analogies and differences among bacterial and viral disinfection by the photo-Fenton process at neutral pH: a mini review

Abstract

Over the last years, the photo-Fenton process has been established as an effective, green alternative to chemical disinfection of waters and wastewaters. Microorganisms' inactivation is the latest success story in the application of this process at near-neutral pH, albeit without clearly elucidated inactivation mechanisms. In this review, the main pathways of the combined photo-Fenton process against the most frequent pathogen models (Escherichia coli for bacteria and MS2 bacteriophage for viruses) are analyzed. Firstly, the action of solar light is described and the specific inactivation mechanisms in bacteria (internal photo-Fenton) and viruses (genome damage) are presented. The contribution of the external pathways due to the potential presence of organic matter in generating reactive oxygen species (ROS) and their effects on microorganism inactivation are discussed. Afterwards, the effects of the gradual addition of Fe and H₂O₂ are assessed and the differences among bacterial and viral inactivation are highlighted. As a final step, the simultaneous addition of both reagents induces the photo-Fenton in the bulk, focusing on the differences induced by the homogeneous or heterogeneous fraction of the process and the variation among the two respective targets. This work exploits the accumulated evidence on the mechanisms of bacterial inactivation and the scarce ones towards viral targets, aiming to bridge this knowledge gap and make possible the further application of the photo-Fenton process in the field of water/wastewater treatment.

Low temperature effects on nitrification and nitrifier community structure in V-ASP for decentralized wastewater treatment and its improvement by bio-augmentation

Abstract

The vegetation-activated sludge process (V-ASP) has been proved to be an environment-friendly decentralized wastewater treatment system with extra esthetic function and less footprint. However, the effects of low temperature on the treatment performance of V-ASP and related improvement methods are rarely investigated, up to now. In this work, the effect of low temperature on nitrification in V-ASP was comprehensively investigated from overall nitrification performance, substrate utilization kinetics, functional enzymatic activities, and microbial community structure shift by comparison with conventional ASP. Bio-augmentation methods in terms of single-time nitrifier-enriched biomass dosage were employed to improve nitrification efficiency in bench- and full-scale systems. The experiment results demonstrated that the NH₄⁺–N removal efficiency in V-ASP system decreased when the operational temperature decreased from 30 to 15 °C, and the decreasing extent was rather smaller compared to ASP, as well as ammonium and nitrite oxidation rates and enzymatic activities, which indicated the V-ASP system possesses high resistance to low temperature. With direct dosage of 1.6 mg nitrifier/gSS sludge, the nitrification efficiency in V-ASP was enhanced dramatically from below 50% to above 90%, implying that bio-augmentation was effective for V-ASP whose enzymatic activities and microbial communities were both also improved. The feasibility and effectiveness of bio-augmentation was further confirmed in a full-scale V-ASP system after a long-term experiment which is instructive for the practical application.

The effect of electron competition on chromate reduction using methane as electron donor

Abstract

We studied the effect of electron competition on chromate (Cr(VI)) reduction in a methane (CH₄)-based membrane biofilm reactor (MBfR), since the reduction rate was usually limited by electron supply. A low surface loading of SO₄²⁻ promoted Cr(VI) reduction. The Cr(VI) removal percentage increased from 60 to 70% when the SO₄²⁻ loading increased from 0 to 4.7 mg SO₄²⁻/m²-d. After the SO₄²⁻ loading decreased back to zero, the Cr(VI) removal further increased to 90%, suggesting that some sulfate-reducing bacteria (SRB) stayed in the reactor to reduce Cr(VI). However, a high surface loading of SO₄²⁻ (26.6 mg SO₄²⁻/m²-d) significantly slowed down the Cr(VI) reduction to 40% removal, which was probably due to competition between Cr(VI) and SO₄²⁻ reduction. Similarly, when 0.5 mg/L of Se(VI) was introduced into the MBfR, Cr(VI) removal percentage slightly decreased to 60% and then increased to 80% when input Se(VI) was removed again. The microbial community strongly depended on the loadings of Cr(VI) and SO₄²⁻. In the sulfate effect experiment, three genera were dominant. Based on the correlation between the abundances of the three genera and the loadings of Cr(VI) and SO₄²⁻, we conclude that Methylocystis, a type II methanotroph, reduced both Cr(VI) and sulfate, Meiothermus only reduced Cr(VI), and Ferruginibacter only reduced SO₄²⁻.

The effects of dissolved organic matter and feeding on bioconcentration and oxidative stress of ethylhexyl dimethyl p -aminobenzoate (OD-PABA) to crucian carp ( Carassius auratus )

Abstract

Bioconcentration of UV filters in organisms is an important indicator for the assessment of environmental hazards. However, bioconcentration testing rarely accounts for the influence of natural aquatic environmental factors. In order to better assess the ecological risk of organic UV filters (OUV-Fs) in an actual water environment, this study determined the influences of dissolved organic matter (DOM) (0, 1, 10, and 20 mg/L) and feeding (0, 0.5, 1, and 2% body weight/d) on bioconcentration of ethylhexyl dimethyl p-aminobenzoate (OD-PABA) in various tissues of crucian carp (Carassius auratus). Moreover, oxidative stress in the fish liver caused by the OD-PABA was also investigated by measuring activities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST), and levels of glutathione (GSH) and malondialdehyde (MDA). The bioconcentration of OD-PABA in the fish tissues was significantly decreased with the presence of DOM indicating a reduction of OD-PABA bioavailability caused by DOM. The bioconcentration factors (BCFs) decreased by 28.00~50.93% in the muscle, 72.67~96.74% in the gill, 37.84~87.72% in the liver, and 10.32~79.38% in the kidney at different DOM concentrations compared to those of the non-DOM treatments. Significant changes in SOD, CAT, GST, GSH, and MDA levels were found in the DOM- and OD-PABA-alone treatments. However, there were no significant differences in the SOD, CAT, GST, and MDA levels found when co-exposure to OD-PABA and DOM. Feeding led to lower OD-PABA concentrations in the fish tissues, and the concentrations were decreased with increasing feeding ratios. BCFs in various tissues reduced by 39.75~72.52% in the muscle, 56.86~79.73% in the gill, 66.41~87.50% in the liver, and 75.88~89.10% in the kidney, respectively. In the unfed treatments, the levels of SOD and MDA were significantly higher than those of the fed ones while GST and GSH levels were remarkably inhibited indicating the enhanced effect of starvation to oxidative stress. There was no markedly alternation of the biomarker levels observed between different fed treatments. In conclusion, our study indicated that both DOM and feeding reduced bioconcentration of OD-PABA and alleviated oxidative stress to some extent in the crucian carp.

A familial case of nail patella syndrome with a heterozygous in-frame indel mutation in the LIM domain of LMX1B

Nail patella syndrome (NPS; MIM161200) involves the classical clinical tetrad of nail aplasia/hypoplasia, patellar aplasia/hypoplasia, elbow arthrodysplasia, and iliac horns [1,2]. Other body systems, such as the kidneys and eyes, are also involved [3]. NPS is an autosomal dominant disorder caused by heterozygous loss-of-function mutations in LIM homeobox transcription factor 1 beta (LMX1B) [4]. LMX1B is a member of the LIM-homeobox transcription factors and is comprised of one DNA-binding homeodomain and two protein-binding LIM domains, LIM-A and LIM-B domains [3].

EGFR transactivation is involved in TNF-α-induced expression of thymic stromal lymphopoietin in human keratinocyte cell line

Thymic stromal lymphopoietin (TSLP), a paralog of Interleukin (IL)-7, is involved in inflammatory skin disorders, such as atopic dermatitis and psoriasis. TSLP activates dendritic cells to produce Th2 chemokines and is highly expressed in the epithelium in the skin of patients with atopic dermatitis [1]. TSLP receptor deficiency attenuates IL-4, IL-13, and IgE production in ovalbumin-sensitized mice [2]. Thus, TSLP is considered as the master cytokines of allergy [3]. In addition, Elisabetta et al.

Histone modifiers: Dynamic regulators of the cutaneous transcriptome

By regulating the accessibility of the genome, epigenetic regulators such as histone proteins and the chromatin-modifying enzymes that act upon them control gene expression. Proper regulation of this "histone code" allows for the precise control of transcriptional networks that are essential for establishing and maintaining cell fate and identity, disruption of which may drive carcinogenesis. How these dynamic epigenetic regulators contribute to both skin homeostasis and disease is only beginning to be understood.

In Memorium - Professor Robin AJ Eady, MB BS Lond(1967) MRCP(1970) FRCP(1982) FMedSci(2002) MBE(2014) DSc. (b.29 November 1940 d.2 August 2017)

Perception of ABC (Asymmetry, Borders and Color) Parameters in the Screening for Melanoma. Model Exercise with Experienced Dermatologists

Scroll Reconstruction: Fine Tuning of the Interface Between Middle and Lower Thirds in Rhinoplasty

Abstract

Background

The junction between upper and lower lateral cartilages, known as "the scroll area," is an important determinant of the spatial relationship between the middle and lower nasal thirds.

Objectives

We offer a graduated and reproducible surgical technique of scroll area management, that takes into consideration anatomic, functional and aesthetic relationships.

Methods

This study was a retrospective review of the recorded intraoperative information to investigate the frequency of the use of scroll reconstruction techniques and perioperative parameters that relate to unintended component alterations in the scroll area. 364 consecutive primary open approach rhinoplasty cases performed by the first author (O.B.) between July 2011 and September 2015 were included in the study.

Results

Of the 364 cases who underwent primary open approach rhinoplasty, 329 received some form of scroll reconstruction. Scroll reconstruction was performed in all deviated cases, and 88% of straight noses. The most common technique for scroll reconstruction was overlapping repair (88.3%). As expected, both alar rim and alar crease asymmetries were very frequent in the deviated nose group, 89.4% and 75% respectively. Alar rim and alar crease asymmetries were frequent enough in the straight nose group to deserve special attention, 14.2% and 10.4% respectively.

Conclusions

With careful attention to anatomic details of the scroll area, nasal tip refinements can be performed with predictable safety and accuracy. Our approach is a graduated, reproducible, and individualized way of scroll area management that aims to create the ideal cartilage configuration while preventing unintended component alterations.

Commentary on: Biceps Augmentation Using Solid Silicone Implants

The author presents the largest series of biceps augmentation of 21 males over a five-year period.¹ The augmentation was via a solid silicone implant placed either submuscularly or subfascially in the upper arm. The mean age was 42.6 years. The majority of patients wanted an increase in size of the biceps for purely aesthetic reasons (16), however five patients received augmentation for contour restoration of a ruptured biceps muscle. The majority (15), received a submuscular implant whilst 8 received a subfascial implant. Complications were high (48%) with a reoperation rate of 23.8%. There was a higher rate of implant malposition in the subfascial group. Being a new area of interest and endeavor, it is encouraging that the author is honest about the problems with this procedure.

Biceps Augmentation Using Solid Silicone Implants

Abstract

Background

Biceps augmentation using solid silicone implants has been increasingly requested in recent years despite a paucity of literature evaluating the safety and efficacy of this procedure.

Objectives

The purpose of this study was to provide information about complications, surgical planning, and aesthetic outcomes of biceps augmentation.

Methods

A retrospective chart review was conducted for patients undergoing solid silicone biceps augmentation in the author's practice from April 2011 through May 2016. Collected data were analyzed to assess the indications for surgery, quantity of complications, and need for surgical revision, and to evaluate aesthetic outcome.

Results

Twenty-one male patients were included in the study. The mean age was 42.6 years and the mean follow up was 7.1 months. Indications for surgery include a desire to increase biceps size (n = 16), and correction of biceps deformity after biceps tendon rupture (n = 5). Eight patients underwent subfascial implant placement and 13 submuscular implant placement. Complications occurred in 10 patients (48%) including asymmetry (n = 4), seroma (n = 3), surgical site infection (SSI) (n = 1), cellulitis (n = 1), and hematoma (n = 1). The overall reoperation rate was 23.8%. Implant malposition occurred in 3 of the 8 (38%) of subfascial implant placement patients. Complications requiring revision surgery were higher for subfascial implants 37.5% vs 15.4% for submuscular.

Conclusions

Biceps augmentation with a solid silicone implant can increase upper arm volume and correct asymmetry and deformity resulting from muscle injury. Submuscular biceps implant placement is recommended over subfascial insertion to avoid implant malposition.

Level of Evidence: 4

Commentary on: Liposuction-Augmentation Mammaplasty

The authors' describe a novel technique of combining liposuction with breast augmentation to achieve lifting of the nipple-areola complex (NAC) and/or volume equalization prior to implant-based breast augmentation with same sized silicone implants.¹ They compared their results with two other techniques, mastopexy-augmentation mammoplasty (MAM) and reduction-augmentation mammoplasty (RAM). The authors' series on liposuction-augmentation mammaplasty (LAM) consisted of 125 patients (198 breasts).

Oral Contraceptive Management in Aesthetic Surgery: A Survey of Current Practice Trends

Abstract

Background

Oral contraceptive pills (OCPs) are currently used by approximately 16% of all women aged 15 to 44 in the United States and have been used by 80% of all sexually active women at some point in their lives. However, no guidelines exist for discontinuation of OCP therapy before or after elective cosmetic surgery.

Objectives

The aim of this study is to establish current practice trends regarding perioperative OCP management in aesthetic surgery.

Methods

An eight-item online survey was distributed to members of the American Society of Plastic Surgeons (ASPS). Survey results were analyzed to determine if surgeons' practice setting, years of experience, annual cosmetic volume, or types of cosmetic procedures performed affected their perioperative management of OCPs.

Results

A total of 220 questionnaires were collected (11.9% response rate). Only 31.8% of surgeons reported any discontinuation of OCPs pre- or postoperatively. Among physicians, 7.3% reported only preoperative discontinuation, 24.5% reported OCP discontinuation both pre- and postoperatively, and 0.0% of physicians reported discontinuation of OCPs only postoperatively. There was no statistically significant difference between the percentage of surgeons in academic practice who discontinue OCPs perioperatively (P = 0.335). There was no statistical significance towards overall years in practice (P = 0.152). There were no significant differences between the three groups in the number of cosmetic procedures performed annually or percentage breakdown of procedures performed.

Conclusions

Despite OCP therapy being a known risk factor for venous thromboembolic events, a majority of surgeons performing cosmetic surgery do not routinely recommend perioperative cessation.

Single-phase cerium oxide nanospheres: An efficient photocatalyst for the abatement of rhodamine B dye

Abstract

Single-phase mesoporous CeO₂ nanospheres were synthesized by template-free hydrothermal approach by the synthesis of CeCO₃OH precursor combined with the calcination at 350 °C for 3.0 h. Precursor and calcined products were characterized by XRD, TGA, FESEM, EDX, TEM, N₂ adsorption–desorption and pore size distribution analysis, UV-vis diffuse reflectance (UV-vis DRS), and photoluminescence (PL) analysis. The morphologies of CeO₂ nanospheres were controlled via the optimization of urea concentration during the synthesis. Calcined CeO₂ exhibited excellent photocatalytic activity of rhodamine B (RhB) dye degradation under UV-visible irradiation and mild acidic condition. Scavenger test analysis was used to confirm that the hydroxyl radicals, superoxide radicals, and photogenerated holes are the active photoinduced species of RhB degradation. A comparative study of PL intensity, dye adsorption, and zeta potential measurement revealed the efficient dye adsorption over different CeO₂ photocatalysts. The RhB degradation rate constant has been found to raise linearly with increase of the surface properties. Repeatability test analysis proved the higher catalytic stability of CeO₂ nanospheres without any noticeable loss of activity. Mass spectroscopy and ion chromatography analyses were used to detect the intermediate by-product formation. Finally, based on the results of intermediate detection, possible degradation pathways were also proposed including radical reactions, ring opening, and de-nitrification.

Photobiomodulation in the Metabolism of LPS-exposed Epithelial Cells and Gingival Fibroblasts

Abstract

This study assessed the effects of photobiomodulation (PBM) to cells previously exposed to lipopolysaccharides (LPS). Human gingival fibroblasts (HGF) and epithelial cells (HaCaT) were seeded in wells of 24-well plates containing complete culture medium (DMEM). After 24h, the DMEM was replaced by serum-free DMEM, and cells were exposed to LPS of Escherichia coli (E. coli) (10 μg/mL) for 24, 48, and 72h. The cells were subjected to specific parameters of phototherapy (PT) (LASERTable—InGaAsP—780 ± 3nm, 25mW, 3J/cm²). Cell proliferation (alamarBlue^®), viability (Trypan Blue), and synthesis of CCL2 (ELISA) were evaluated. Data were statistically analyzed by the Kruskal-Wallis and Mann-Whitney test (α = 5%). Proliferation and viability of both cell lines decreased after LPS treatment at 48 and 72h. Enhanced synthesis of CCL2 by gingival fibroblasts occurred at 24h, while epithelial cells increased synthesis of this chemokine at 48 and 72h. PBM enhanced cell proliferation and viability in a time-dependent manner for both cell lines exposed or not to LPS, while synthesis of CCL2 by cells exposed to PT decreased over time. PBM caused biomodulatory effects on gingival fibroblasts and epithelial cells previously treated with LPS. These effects may decrease tissue inflammatory response and accelerate wound healing of oral mucosal tissue.

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Theoretical Insight into the Emission Properties of the Luciferin and Oxyluciferin of Latia

Abstract

Latia neritoides is a small limpet-like snail that produces a bright green bioluminescence (BL) via a unique light-emitting system. The process, mechanism and even light emitter of its light emission remain unknown, although this BL has been known for decades. Unlike the other BL systems, neither the luciferin (Luc) nor the oxyluciferin (OxyLuc) of Latia is fluorescent according to the previous experiments. In order to help to identify its bioluminophore, we studied the geometrical and electronic structures and absorption and fluorescence spectra of Latia Luc and its six analogues as well as its OxyLuc in the gas phase and in water. The calculated results provide clear evidence of the lack of fluorescence in the Luc and OxyLuc of Latia. For the analogues of Latia Luc, the electron-withdrawing or electron-donating ability of the substituted group affects the fluorescence. The results shed new light on the BL mechanism and will likely aid the understanding of Latia BL.

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Establishment of Photo-aging In Vitro by Repetitive UVA Irradiation: Induction of Characteristic Markers of Senescence and its Prevention by PAPLAL with Potent Catalase Activity

Abstract

To understand a role of UVA radiation in photo-aging of the skin, we established a model of photo-aging cells using cultured human dermal fibroblasts. Repeated low dose UVA radiation for 10 consecutive days induced senescence in fibroblasts, characterized with 1) increased level of senescence-associated β-galactosidase, 2) flattened large cell shape, 3) accumulation of reactive oxygen species, 4) yellowish coloration and 5) expression of p16. These were also observed in chronologically aged fibroblasts (doubling times >20), whereas none of these were detected in young cells (doubling times <10). Collectively, we propose that fibroblasts exposed to repetitive UVA radiation may be a good model of aged cells to study the mechanism of aging and photo-aging and further to search for novel agents preventing cellular senescence. In addition, H₂O₂ was produced in the culture medium by a single low dose of UVA irradiation. Further, PAPLAL, a nanoparticle of platinum and palladium having potent catalase-like activity, significantly delayed the onset of H₂O₂-induced cell senescence. The present study strongly indicates that repetitive short term UVA irradiation induces aging of cells possibly via H₂O₂ and may be suppressed by potent anti-H₂O₂ agents.

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Enhanced Photocatalytic Activity of Vacuum activated TiO2 Induced by Oxygen Vacancies

Abstract

TiO₂ (Degussa P25) photocatalysts harboring an abundant oxygen vacancies (vacuum P25) were manufactured using a simple and economic vacuum deoxidation process. Control experiments showed that temperature and time of vacuum deoxidation had a significant effect on vacuum P25 photocatalytic activity. After 240 min of visible light illumination, the optimal vacuum P25 photocatalysts (vacuum deoxidation treated at 330°C for 3h) reaches as high as 94% and 88% of photodegradation efficiency for Rhodamine B (RhB) and tetracycline respectively, which are around 4.5 and 4.9 times as that of pristine P25. The XPS, PL and EPR analyses indicated that the oxygen vacancies were produced in the vacuum P25 during the vacuum deoxidation process. The oxygen vacancies states can produce vacancy energy level located below the conduction band minimum, which resulting in the band gap narrowing, thus extending the photoresponse wavelength range of vacuum P25. The positron annihilation analysis indicated that the concentrations ratio of bulk and surface oxygen vacancies could be adjusted by changing the vacuum deoxidation temperature and time. Decreasing the ratio of bulk and surface oxygen vacancies was shown to improve photo-generated electron-hole pairs separation efficiency, which leads to an obvious enhancement of the visible photocatalytic activities of vacuum P25.

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Biogenic Hierarchical MIL-125/TiO2@SiO2 Derived from Rice Husk and Enhanced Photocatalytic Properties for Dye Degradation

Abstract

The hierarchical porous heterostructured MIL-125/TiO₂@SiO₂ composites are successfully obtained by biogenic-templated method using rice husk both as biomorphic. The products are characterized by X-ray diffraction, N₂-adsorption-desorption analysis, scanning electron microscopy and Fourier transform infrared spectroscopy. The results reveal that MIL-125/TiO₂@SiO₂ possesses a hierarchical porous structure in scale from micrometer to nanometer with high Brunauer-Emmett-Teller (BET) surface area (385.7 - 902.7 m²/g). The photocatalytic mechanism was discussed in detail. Meanwhile, the activity of MIL-125/TiO₂@SiO₂ for the photocatalytic degradation of rhodamine B in aqueous medium is significantly higher than that of P25. The current work provides some concept and methods in the development of MOF-based photocatalysts.

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Insight Into Malachite Green Degradation, Mechanism, and Pathways by Morphology Tuned α-NiMoO4 Photocatalyst

Abstract

The microwave hydrothermal process was used for the synthesis of various morphologies of α-NiMoO₄ by simply adjusting the pH during experimental conditions. The effect of morphology/size on the photocatalytic performances for degradation of malachite green (MG) has been investigated under UV-Vis/visible light irradiation. Nanorod morphology has strong tendency to degrade (88.18%) the MG as compared to spherical quantum-sized (57.65%) and layered square microsheet (37.98%) under UV-Vis irradiation in 180 min. The active species trapping experiment revealed that active species (OH^•, O₂^•̶, and h⁺) play a crucial role for MG degradation. The high BET surface area, greater amount of oxygen defect, and efficient separation of electron-hole pair are responsible for MG degradation. About seventeen types of organic fragments of MG were confirmed by high resolution-quadruple time of flight electrospray ionization mass spectroscopy (HR-QTOF ESI/MS) technique on the basis of retention time and molecular masses. Degradation mechanism and pathways were proposed that follow the demethylation, nitration, decarboxylation, hydrolysis, decarboxylation, and oxidation reaction. The reduction of total organic carbon revealed the mineralization of MG during photocatalytic degradation process. Therefore, this paper represents the investigation of MG degradation by various morphology of α-NiMoO₄ and detailed degradation mechanism and pathways.

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Vascular ultrasound in pediatrics: utility and application of location and measurement of jugular and femoral vessels

Abstract

Objective

To measure the depth (D _p) and diameter (D _m) of the internal jugular vein (IJV), femoral vein (FV), and femoral artery (FA) in pediatric patients to evaluate the clinical implications.

Methods

This study included 125 pediatric patients. All of them underwent bilateral ultrasound study of vessels and were classified into three groups based on anthropometric and demographic parameters.

Results

Measured mean D _p values were: 0.72 (0.34) cm for the FA, 0.79 (0.35) cm for the FV, and 0.77 (0.24) cm for the IJV. Mean antero-posterior D _m values were: 0.37 (0.17) cm for the FA, 0.42 (0.22) cm for the FV, and 0.59 (0.23) cm for the IJV. D _p and D _m increased with age (A), weight (W), height (H), and body surface area (BSA). In the lower ranges of these variables, D _p was similar for all three studied vessels (0.6–0.7 cm). In the higher ranges, femoral vessel D _p values (1.1–1.2 cm) were larger than jugular ones (0.9 cm). Additionally, in these low ranges, IJV D _m values were larger than femoral ones (0.45–0.50 vs. 0.25 cm). In the higher ranges, diameter values were similar (0.6–0.7 cm).

Conclusions

In pediatric patients, major vessels can be located and their depth and diameter measured by vascular ultrasound. In younger patients, jugular and femoral vessels had similar depth values; in older ones, they had similar diameters. Ultrasound measurements in pediatric patients could facilitate the choice of the vessel to be cannulated, the catheter diameter, and the length of the needle to be used. Vascular canalization of IJV may be recommended as the first choice because of its low depth and large diameter.

Bladder cancer in an inguinal vesical hernia

Abstract

A 60-year-old male patient presented with intermittent right-sided scrotal swelling for the last 4 months. On ultrasonography, a fluid-filled cavity extending through the right inguinal canal into the scrotum was noted with inferior displacement of the right testis. Multiple papillary hyperechoic lesions with internal vascularity on Doppler ultrasound were protruding into the fluid-filled cavity. Computed tomography showed herniation of the bladder through the right inguinal canal into the scrotum with mural components in the herniated segment. Hernioplasty followed by transurethral tumor resection showed urothelial carcinoma with invasion into the muscular layer. Vesical herniation through the inguinal canal is uncommon. Additionally, the presence of bladder carcinoma within a herniated portion of the bladder is exceedingly rare.

Oraler Lichen planus

Zusammenfassung

Der orale Lichen planus ist eine nichtinfektiöse chronische Entzündungsform der Mundschleimhaut, die zusammen mit einer klassischen kutanen Manifestation oder an anderen Schleimhäuten wie der Konjunktiva oder im Genitalbereich auftreten kann. Die Ursache dieser Erkrankung ist nach wie vor ungeklärt, während die klinisch und histopathologisch sehr ähnliche orale lichenoide Reaktion durch dentale Werkstoffe oder Medikamente ausgelöst werden kann. Dieser Beitrag gibt eine Übersicht über die wichtigsten Erkenntnisse und therapeutischen Konzepte in Bezug auf diese beiden Erkrankungsformen und versucht somit dem klinisch aktiven Kollegen eine Hilfestellung in Diagnostik und Therapie zu geben.

Synthesis of AgCl/Ag3PO4 Composite Photocatalysts and Study on Photodegradation Activity Based on a Continuous Reactor

Abstract

Novel AgCl/Ag₃PO₄ photocatalysts were synthesized by a simple precipitation method, in which AgCl was coated onto Ag₃PO₄ particles, as uncovered by X-ray diffractometry, transmission electron microscopy, and ultraviolet–visible spectrometry. Different from previous research on photocatalytic degradation, we studied the performance of methyl orange photodegradation on a small continuous flow reactor. The highest degradation activity of 97% was achieved by the 2 wt.% AgCl/Ag₃PO₄ after 8 min of visible light irradiation, while pure Ag₃PO₄ degraded only 71% methyl orange under same conditions. The degradation rate constant of the 2 wt.% AgCl/Ag₃PO₄ was 1.36 times higher than that of pure Ag₃PO₄. The AgCl/Ag₃PO₄ maintained high photocatalytic activity after five cycles, without any significant decrease.

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Distinct features of C/N balance regulation in Prochlorococcus sp. strain MIT9313

Abstract

The abundance and significant contribution to global primary production of the marine cyanobacterium Prochlorococcus have made it one of the main models in marine ecology. Several conditions known to cause strong effects on the regulation of N-related enzymes in other cyanobacteria lacked such effect in Prochlorococcus. Prochlorococcus sp. strain MIT9313 is one of the most early-branching strains among the members of this genus. In order to further understand the C/N control system in this cyanobacterium, we studied the effect of the absence of three key elements in the ocean, namely N, P and Fe, as well as the effect of inhibitors of the N assimilation or photosynthesis on the N metabolism of this strain. Furthermore, we focused our work in the effect of ageing, as the age of cultures has clear effects on the regulation of some enzymes in Prochlorococcus. To reach this goal, expression of the main three regulators involved in N assimilation in cyanobacteria, namely ntcA, glnB and pipX, as well as that of icd (encoding for isocitrate dehydrogenase) were analysed. Our results show that the control of the main proteins involved in the C/N balance in strain MIT9313 differs from other model Prochlorococcus strains.

Cohesive Polydensified Matrix® hyaluronic acid volumizer injected for cheek augmentation has additional positive effect on nasolabial folds

Increased senescent CD8+ T cells in the peripheral blood mononuclear cells of Behçet’s disease patients

Abstract

Behçet's disease (BD) is a chronic inflammatory disease characterized by recurrent mucocutaneous, ocular, and skin lesions. Immunosenescence is associated with increased susceptibility to infection and chronic low grade inflammation. This study aimed to investigate the differences in the frequencies of immunosenescent cells in the peripheral blood mononuclear cells (PBMCs) of patients with BD. PBMCs were isolated from age-matched patients with active BD (n = 19), inactive BD (n = 20), disease controls (DCs, n = 15) and healthy controls (HCs, n = 15). The frequencies of senescent CD4+ T cells (CD3+ CD4+ CD27− CD28− cells), CD8+ T cells (CD3+ CD8+ CD27− CD28− cells) and B cells (CD19+ CD27− IgD− cells) were analyzed using flow cytometry. Senescence-associated β galactosidase activity was also measured in CD8+ T cells using flow cytometry with 5-dodecanoylaminofluorescein di-β-d-galactopyranoside. Frequencies of senescent CD4+ and CD19+ cells were not significantly different between the groups. The frequency of senescent CD8+ T cells was significantly higher in active BD than in DCs and HCs. C-reactive protein and erythrocyte sedimentation rate levels, which indicate disease activity, did not correlate with increased frequencies of immunosenescent cells. Steroid treatment, specific organ involvement, and HLA-B51 status did not have a significant influence on the frequencies of immunosenescent cells. Frequencies of senescence-associated β galactosidase+ CD8+ T cells were significantly higher in active BD and inactive BD compared to DCs and HCs. There was an increased frequency of senescent CD8+ T cells in the PBMCs of patients with BD.

Acknowledgement to reviewers

Lower Face Rejuvenation with Injections: Botox, Juvederm, and Kybella for Marionette Lines and Jowls

Summary: A 55-year-old woman requesting noninvasive rejuvenation of the lower face received multimodal injections in a single office visit to rejuvenate the jowls. The patient experienced no adverse events other than self-limiting bruising at the hyaluronic acid injection site and minimal edema. The outcomes were evaluated as follows: (1) by the patient using the self-rated Face-Q assessment and (2) by 5 plastic surgeons (none of whom were the author of this study) based on the WAS scale and before and after photographs to evaluate the corners of the mouth and the marionette lines. This case study report suggests that the combined use of neuromodulator, hyaluronic acid dermal filler, and synthetic deoxycholic acid can rejuvenate the lower face as a minimally invasive alternative to surgery to the satisfaction of the patient and 6 plastic surgeons (including the author).

Feasibility of Bone Perfusion Evaluation in Cadavers Using Indocyanine Green Fluorescence Angiography

Summary: Bone perfusion evaluation methods in cadaver studies have yet to be established. The aim of this report was to introduce and validate the feasibility of indocyanine green (ICG) fluorescence angiography for evaluation of bone perfusion in the femoral medial condyle in cadavers. In 4 fresh nonembalmed cadavers (2 female), the descending genicular artery was dissected and carefully cannulated bilaterally. A 10 mL solution containing 5 mL ICG solution and 5 mL methylene blue solution was injected into the descending genicular artery. After the injection, the medial femoral condyle was cut with an oscillating saw. A photograph was taken of the cut ends of the bone. The cut ends of the bones were observed using a near-infrared camera. Images corresponding to the previously taken photographs of the cut ends were captured for comparative analysis. After injection of methylene blue and ICG, the blue dye could be seen in the periosteum in all specimens, but not inside the cortex or the cancellous region of the bone. When observed with ICG fluorescence angiography, however, the cancellous region was highlighted through small perforators penetrating the periosteum. Perfusion inside the medial femoral condyle in cadavers was confirmed using ICG fluorescence angiography. Our method can be especially beneficial in confirming the bone perfusion of a new bone flap based on a particular artery, both in cadavers as well as in patients, because ICG can be injected into specific arteries.

Nāgārjuna and the Philosophy of Language

Abstract

The purpose of this paper is to examine some of the key points of Nāgārjuna's discussion of problems relating to the philosophy of language. We will focus on two works from Nāgārjuna's yukti-corpus that address these matters most explicitly, the Vigrahavyāvartanī (VV) and the Vaidalyaprakaraṇa (VP). The discussion will concentrate on four topics: Nāgārjuna's views on semantics, the problem of empty names, the relation between language and momentariness, and the implications of Madhyamaka views on parts and wholes for the existence of language.

Crossover is not associated with faster trial accrual

Interim monitoring for non-inferiority trials: minimizing patient exposure to inferior therapies

Abstract

Background

The goal of a non-inferiority randomized trial is to demonstrate that an experimental treatment is not unacceptably worse than a standard treatment. The experimental treatment is known to have less toxicity or other quality-of-life benefits as compared to the standard treatment, so that a small decrement in efficacy would be acceptable. Interim monitoring of randomized trials is used to stop trials early if the conclusions of the trial become definitive early. In the context of a non-inferiority trial, of special interest is stopping a trial early when the experimental treatment is inferior to the standard treatment.

Methods

Methods for performing interim monitoring of non-inferiority trials are reviewed for their ability to minimize patient exposure to inferior experimental treatments. Examples of trials from the literature are discussed along with a computer simulation of a simple non-inferiority monitoring rule.

Results

Interim monitoring for non-inferiority trials is shown to substantially reduce the exposure of patients to inferior therapies when, in fact, the experimental treatment is inferior to the standard treatment. Interim monitoring rules typically used in superiority trials may be sub-optimal for non-inferiority trials, and may unnecessarily expose patients to inferior therapies. Examples of trials with inferior experimental arms and trials with sub-optimal monitoring rules are given.

Conclusions

Appropriate interim monitoring of non-inferiority trials can reduce the exposure of patients to inferior therapies when the experimental treatment is inferior to the standard treatment.

Androgen Deprivation Therapy and Risk of Rheumatoid Arthritis in Patients with Localized Prostate Cancer

Abstract

Background

Androgens are generally immunosuppressive, and men with untreated hypogonadism are at increased risk for autoimmune conditions. To date, there has been no evidence linking androgen deprivation therapy (ADT) to autoimmune diseases, including rheumatoid arthritis (RA). We investigated the association between ADT and RA in patients with prostate cancer.

Patients and methods

We identified 105,303 men age 66 years or older who were diagnosed with stage I-III prostate cancer from 1992 through 2006 using the Surveillance, Epidemiology, and End Results-Medicare linked database, excluding patients with a history of RA. χ² test was used to compare 5-year Kaplan-Meier rates of RA diagnoses. Competing risk Cox regression using inverse probability of treatment weighting was utilized to examine the association between pharmacologic ADT and diagnosis of RA.

Results

The 43% of patients (N=44,785) who received ADT experienced a higher 5-year rate of RA diagnoses compared to men who did not (5.4% versus 4.4%, P<0.001). Receipt of any ADT was associated with a 23% increased risk of being diagnosed with RA (hazard ratio 1.23, 95% confidence interval 1.09-1.40, P=0.001). The risk of being diagnosed with RA increased with a longer duration of ADT, from 19% with 1-6 months and 29% with 7-12 months to 33% with ≥13 months (P_trend<0.001).

Conclusions

Consistent with the immunosuppressive properties of androgens, we demonstrated for the first time that ADT was associated with an elevated risk of being diagnosed with RA in this large cohort of elderly men with prostate cancer. The risk was higher with a longer duration of ADT. Linking ADT to an increased risk of being diagnosed with an autoimmune condition adds to mounting evidence of the adverse effects of ADT that should prompt physicians to thoughtfully weigh its risks and benefits.

A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with a MYC regulated SNP rs6983267

Abstract

Background

MYC is a well-established cancer driver gene regulating the expression of numerous genes, indicating that polymorphisms in MYC response elements could affect tumorigenesis through altering MYC regulation. We performed integrative multistage study to evaluate the effects of variants in MYC response elements and colorectal cancer (CRC) risk.

Patients and methods

We systematically integrated ChIP-Seq, DNase-Seq and transcription factor motif data to screen variants with potential ability to affect the MYC binding affinity. Then we conducted a two-stage case-control study, totally consisting of 4,830 CRC cases and 4,759 controls in Chinese population to identify risk polymorphisms and interactions. The effects of risk variants were confirmed by functional assays in CRC LoVo, SW480 and HCT15 cells.

Results

We identified a novel polymorphism rs11777210 in KBTBD11 significantly associated with CRC susceptibility (P = 2.43 × 10⁻¹²). Notably, we observed a significant interaction between rs11777210 and MYC nearby rs6983267 (P_-multi = 0.003, P_-add = 0.005), subjects carrying rs6983267 GG and rs11777210 CC genotypes showing higher susceptibility to CRC (2.83-fold) than those carrying rs6983267 TT and rs11777210 TT genotypes. We further demonstrated that rs6983267 T>G increased MYC expression, and MYC bound to and negatively regulated KBTBD11 expression when the rs11777210 C risk allele was present. KBTBD11 was downregulated in tumor tissues, and KBTBD11 knockdown promoted cell proliferation and inhibited cell apoptosis.

Conclusion

The rs11777210 is a potential predictive biomarker of CRC susceptibility, and KBTBD11 functions as a putative tumor suppressor in tumorigenesis. Our study highlighted the high CRC risk of people carrying rs6983267 G and rs11777210 C alleles, and provided possible biological mechanism of the interaction.

Phase I-II clinical trial design: A state-of-the-art paradigm for dose finding

Abstract

Background

Conventional phase I algorithms for finding a phase-2 recommended dose (P2RD) based on toxicity alone is problematic because the maximum tolerated dose (MTD) is not necessarily the optimal dose with the most desirable risk-benefit trade-off. Moreover, the increasingly common practice of treating an expansion cohort at a chosen MTD has undesirable consequences that may not be obvious.

Patients and methods

We introduce the phase I-II paradigm and the EffTox design, which utilizes both efficacy and toxicity to choose optimal doses for successive patient cohorts and find the optimal P2RD. We conduct computer simulation study to compare the performance of the EffTox design with the traditional 3 + 3 design and the continuous reassessment method.

Results

By accounting for the risk-benefit trade-off, the EffTox phase I-II design overcomes the limitations of conventional toxicity-based phase I designs. Numerical simulations show that the EffTox design has higher probabilities of identifying the optimal dose and treats more patients at the optimal dose.

Conclusions

Phase I-II designs, such as the EffTox design, provide a coherent and efficient approach to finding the optimal P2RD by explicitly accounting for risk-benefit trade-offs underlying medical decisions.

Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters - patient centered endpoints in trials of maintenance therapy

Abstract

Background

Health related quality of life (HRQOL) was a secondary endpoint in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient centered endpoints.

Patients and Methods

HRQOL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified endpoints included mean differences in HRQOL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQOL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ.

Results

There were statistically significant differences between PZ and P in QLQ-C30 global health status (GHC) (5.5 points; 95%CI, 0.7 to 10.4, P=0.024) from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95%CI, -0.033 to 0.069, P=0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI, 3.6 to 12.5, P = 0.001). QAPFS was 386 days (95%CI, 366 to 404 days) with PZ vs 359 days (95%CI, 338 to 379 days) with placebo (P=0.052). PD was associated with a decline in HRQOL (P<0.0001). Median time to second-line chemotherapy was 19.7 months with PZ and 15.0 months with P (HR 0.72, 95%CI 0.69 to 0.86, P=0.0001).

Conclusions

There were small to no significant mean score differences in global HRQOL and EQ5D-3L between PZ and placebo respectively despite the increased toxicity of PZ. Exploratory endpoints including QAPFS, impact of specific symptoms on HRQOL during treatment and at PD help place the PFS gain with PZ in context and interpret the results. Additional patient centered endpoints should be considered in trials of maintenance therapy in EOC beyond mean differences in HRQOL scores alone, to support the benefit to patients of prolongation of PFS.

Clinical Trials Registration Number

NCT00866697

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC

Ann Oncol 2017; 00: 1–8 (doi:10.1093/annonc/mdx305)

Low Rates of Tree Nut Allergy in Peanut-Allergic Patients

Publication date: Available online 16 December 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Kara B. McNamara, Brian C. Schroer

Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma

Publication date: Available online 16 December 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Necdet B. Gunsoy, Sarah M. Cockle, Steven W. Yancey, Oliver N. Keene, Eric S. Bradford, Frank C. Albers, Ian D. Pavord
BackgroundMepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. The early identification of patients likely to receive long-term benefit from treatment could ensure effective resource allocation.ObjectiveTo assess potential continuation rules for mepolizumab in addition to initiation criteria defined as 2 or more exacerbations in the previous year and blood eosinophil counts of 150 cells/μL or more at initiation or 300 cells/μL or more in the previous year.MethodsThis post hoc analysis included data from 2 randomized, double-blind, placebo-controlled studies (NCT01000506 and NCT01691521) of mepolizumab in patients with severe eosinophilic asthma (N = 1,192). Rules based on blood eosinophils, physician-rated response to treatment, FEV1, Asthma Control Questionnaire (ACQ-5) score, and exacerbation reduction were assessed at week 16. To assess these rules, 2 key metrics accounting for the effects observed in the placebo arm were developed.ResultsPatients not meeting continuation rules based on physician-rated response, FEV1, and the ACQ-5 score still derived long-term benefit from mepolizumab. Nearly all patients failing to reduce blood eosinophils had counts of 150 cells/μL or less at baseline. For exacerbations, assessment after 16 weeks was potentially premature for predicting future exacerbations.ConclusionThere was no evidence of a reliable physician-rated response, ACQ-5 score, or lung function–based continuation rule. The added value of changes in blood eosinophils at week 16 over baseline was marginal. Initiation criteria for mepolizumab treatment provide the best method for assessing patient benefit from mepolizumab treatment, and treatment continuation should be reviewed on the basis of a predefined reduction in long-term exacerbation frequency and/or oral corticosteroid dose.

The Allergist's Role in Anaphylaxis and Food Allergy Management in the School and Childcare Setting

Publication date: Available online 16 December 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Julie Wang, Theresa Bingemann, Anne F. Russell, Michael C. Young, Scott H. Sicherer
Anaphylaxis and food allergy management in childcare facilities and schools are growing challenges. An increasing number of children experience severe allergic reactions on school grounds as evidenced by reports of epinephrine use. Data also suggest that the prevalence of food allergy may be increasing, with a large percentage of school-aged children at risk for anaphylaxis. Moreover, anaphylaxis may occur for the first time in a previously undiagnosed child at school or childcare setting, suggesting that general preparedness is essential. Management includes strategies for minimizing the risk of reactions and allergen exposures as well as readiness to recognize and treat allergic reactions of any severity. The primary objective of this report is to offer health care providers an overview of relevant evidence, resources, and expert opinion to assist with developing interprofessional collaborative counsel on school food allergy management and anaphylaxis preparedness with families, schools, and childcare settings. We present the current evidence base, suggest resources, and highlight areas of current controversy that warrant further study.

Anaphylactic Reactions After Discontinuation of Hymenoptera Venom Immunotherapy: A Clonal Mast Cell Disorder Should Be Suspected

Publication date: Available online 16 December 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Patrizia Bonadonna, Roberta Zanotti, Mauro Pagani, Massimiliano Bonifacio, Luigi Scaffidi, Elisa Olivieri, Maurizio Franchini, Federico Reccardini, Maria Teresa Costantino, Chiara Roncallo, Marina Mauro, Elisa Boni, Fabio Lodi Rizzini, Maria Beatrice Bilò, Anna Rosaria Marcarelli, Giovanni Passalacqua
BackgroundUp to 75% of patients with severe anaphylactic reactions after Hymenoptera sting are at risk of further severe reactions if re-stung. Venom immunotherapy (VIT) is highly effective in protecting individuals with ascertained Hymenoptera venom allergy (HVA) and previous severe reactions. After a 3- to 5-year VIT course, most patients remain protected after VIT discontinuation. Otherwise, a lifelong treatment should be considered in high-risk patients (eg, in mastocytosis). Several case reports evidenced that patients with mastocytosis and HVA, although protected during VIT, can re-experience severe and sometimes fatal reactions after VIT discontinuation.ObjectiveTo evaluate whether patients who lost protection after VIT discontinuation may suffer from clonal mast cell disorders.MethodsThe survey describes the characteristics of patients who received a full course of VIT for previous severe reactions and who experienced another severe reaction at re-sting after VIT discontinuation. Those with a Red Española de Mastocitosis score of 2 or more or a serum basal tryptase level of more than 25 ng/mL underwent a hematological workup (bone marrow biopsy, KIT mutation, expression of aberrant CD25) and/or skin biopsy.ResultsNineteen patients (mean age, 56.3 years; 89.5% males) were evaluated. All of them had received at least 4 years of VIT and were protected. After VIT discontinuation they were re-stung and developed, in all but 1 case, severe anaphylactic reactions (12 with loss of consciousness, in the absence of urticaria/angioedema). Eighteen patients (94.7%) had a clonal mast cell disorder, 8 of them with normal tryptase.ConclusionsLooking at this selected population, we suggest that mastocytosis should be considered in patients developing severe reactions at re-sting after VIT discontinuation and, as a speculation, patients with mastocytosis and HVA should be VIT-treated lifelong.