Epidermólisis bullosa distrófica recesiva y embarazo

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): F. Boria, R. Maseda, M. Martín-Cameán, M. De la Calle, R. de Lucas
La epidermólisis bullosa distrófica es una enfermedad hereditaria rara debida a mutaciones del gen COL7A1. Su variante recesiva (EBDR) se caracteriza por una marcada disminución o ausencia completa de colágeno tipo VII (C7), que da lugar a una marcada fragilidad de la piel y las mucosas, desencadenando la formación de ampollas de forma espontánea o en respuesta a mínimos traumatismos. Son muy pocos los casos descritos en la literatura de esta enfermedad en embarazadas.Exponemos 2 casos de gestantes, ambas afectadas de EBDR, y su manejo en nuestra Unidad de Obstetricia de Alto Riesgo del Hospital Universitario La Paz. En ambos casos se realizó una cesárea a término, finalizando la gestación sin complicaciones mayores para la madre o el feto.A pesar de relacionarse con un mayor número de complicaciones maternas, la EBDR no representa una contraindicación para la gestación, y con un control adecuado, estas pacientes pueden ver su deseo genésico cumplido.Dystrophic epidermolysis bullosa is a rare inherited disease caused by mutations in the COL7A1 gene. Its recessive variant (recessive dystrophic epidermolysis bullosa) is characterized by the absence or considerably reduced expression of type VII collagen, which leads to marked fragility of the skin and mucous membranes and subsequent blister formation, whether spontaneously or following minimal injury. There have been very few reports of this disease in pregnant women.We present 2 cases of pregnant women with recessive dystrophic epidermolysis bullosa managed in our High-Risk Pregnancy Unit at Hospital Universitario La Paz, Madrid, Spain. Both patients underwent full-term cesarean delivery, with no further complications for mother or child.Although recessive dystrophic epidermolysis bullosa increases the risk of maternal complications, a patient is not advised against pregnancy. With adequate monitoring, these patients can fulfil their desire to become mothers.

Graphical abstract

¿Qué procedimientos diagnósticos deberíamos realizar ante una sospecha de reacción alérgica a un tatuaje? Propuesta basada en nuestra casuística

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): I. González-Villanueva, J.F. Silvestre Salvador
IntroducciónLos tatuajes se han convertido en una práctica muy popular en los países occidentales, sobre todo entre los más jóvenes. Las complicaciones asociadas a esta técnica incluyen procesos infecciosos, alérgicos, reacciones a cuerpo extraño e incluso procesos inflamatorios sistémicos.Pacientes y métodosSe ha realizado un estudio retrospectivo de todos los pacientes que acudieron a la consulta de Alergia cutánea por manifestar complicaciones en un tatuaje desde enero de 2002 a diciembre de 2016.ResultadosSe han incluido a 23 pacientes. De ellos, 9 presentaron complicaciones de forma precoz y en todos ellos la etiología fue infecciosa. De los 14 pacientes con reacciones tardías, 10 fueron diagnosticados de probable dermatitis de contacto alérgica a la tinta, sin embargo solo en 3 de los casos se pudo apuntar al alérgeno probablemente culpable y tan solo en uno de ellos se pudo demostrar. Se detectaron dos casos de sarcoidosis cutánea, uno de reacción granulomatosa a cuerpo extraño, y un caso de reacción neuropática en una paciente.ConclusionesLas complicaciones asociadas a los tatuajes son un motivo de consulta relativamente frecuente en las consultas de Dermatología. Proponemos un algoritmo diagnóstico basado en nuestra casuística, que ayude a orientar las distintas reacciones a tatuaje y con ello a iniciar las medidas terapéuticas oportunas.IntroductionTattooing has become a popular practice in western countries, particularly among younger populations. Tattoos, however, can cause complications, such as infections, allergic or foreign-body reactions, and even systemic inflammatory responses.Patients and methodsWe conducted a retrospective study of all patients seen for tattoo-related complications at our skin allergy unit between January 2002 and December 2016.ResultsWe studied 23 patients. Nine of these experienced early complications, all related to infection. The other 14 patients developed late reactions. Ten were diagnosed with probable allergic contact dermatitis to ink, but the suspect allergen was identified in just 3 cases and confirmed in just 1 of these. There were 2 cases of cutaneous sarcoidosis, 1 case of foreign body granuloma, and 1 case of neuropathy.ConclusionsComplications resulting from tattoos are relatively common dermatology complaints. Drawing from our experience, we propose a diagnostic algorithm designed to guide dermatologists in evaluating different reactions to tattoos and prescribing appropriate treatment.

Graphical abstract

Presentación atípica de infección por virus de herpes simple tipo ii (VHS II) refractaria a tratamiento con aciclovir en 2 pacientes hematológicos

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): D. Nieto Rodríguez, E. Sendagorta Cudós, J.M. Rueda Carnero, P. Herranz Pinto
Las infecciones por virus herpes presentan una frecuencia no desdeñable en pacientes hematológicos. El primer caso corresponde a una paciente con leucemia linfática crónica con un herpes genital extenso refractario a aciclovir, con respuesta parcial a foscarnet que hubo que suspender por efectos secundarios sistémicos. El segundo caso es el de una paciente con un linfoma de Hodgkin folicular que presentaba un herpes hipertrófico refractario a tratamiento con aciclovir, que respondió a cidofovir intralesional e imiquimod tópico. Los pacientes hematológicos, al igual que otros enfermos inmunodeprimidos, pueden presentar manifestaciones atípicas de infección por virus herpes, así como resistencia a los tratamientos que actúan por medio de la timidina quinasa viral. Esto hace necesario tener una alta sospecha clínica para poder alcanzar un diagnóstico precoz, y conocer los diferentes tratamientos alternativos disponibles.Herpesvirus infections are not uncommon in hematologic patients. Our first patient, diagnosed with chronic lymphatic leukemia, presented extensive genital herpes infection refractory to treatment with acyclovir and with a partial response to foscarnet, which had to be withdrawn due to systemic adverse effects. The second patient, diagnosed with follicular Hodgkin lymphoma, presented hypertrophic herpes infection refractory to treatment with acyclovir but that responded to intralesional cidofovir and topical imiquimod. As in other immunodepressed patients, herpesvirus infection in hematologic patients can present atypical manifestations, as well as resistance to treatments that act via the viral thymidine kinase. A high level of clinical suspicion is therefore needed to make an early diagnosis, together with extensive knowledge of the different treatments available.

Graphical abstract

Nódulo indurado en labio superior

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): A. Imbernón-Moya, E. Fernández-Cogolludo, M.Á. Gallego-Valdés

A Pink Tumor: Angiolymphoid Hyperplasia With Eosinophilia

Publication date: Available online 6 December 2017
Source:Actas Dermo-Sifiliográficas (English Edition)
Author(s): I. Pérez-López, A. Martínez-López, P. Aguayo-Carreras, M.J. Naranjo-Díaz

Gaps in Workplace Education For Prevention of Occupational Skin Disease

Abstract

Background

Occupational contact dermatitis (OCD) is a common occupational disease. Evidence suggests that education and training are effective prevention strategies. In spite of these known prevention strategies, workers continue to develop OCD. Little is reported regarding the actual training experience of workers.

Objective

To examine the training experience of workers with contact dermatitis to identify areas for improvement.

Methods

Participants were workers being assessed for contact dermatitis in an occupational health clinic. The anonymous survey collected demographics, workplace characteristics, and education and prevention practices.

Results

Approximately 80% reported general occupational health and safety training; however, only 49% reported skin-specific training (SST). For workers reporting SST, most received information regarding exposure avoidance, hand washing, and glove use. This content was reported as helpful by at least 50%. Workers who did not receive SST indicated the most important content would be warning signs of skin problems, how to avoid exposure and skin care while using gloves.

Conclusions

While the study was anonymous and used self-reported of training experience, the study suggests there are gaps in skin protection training. Addressing these gaps may lead to improved prevention and reduction in OCD.

Erupción variceliforme de Kaposi sobre quemaduras

Publication date: Available online 6 December 2017
Source:Piel
Author(s): María Noel Casas, Mariana Saez, Erika Lutz, Andrea Torres, Mariela Álvarez

The association between cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis

Abstract

Recent studies examining the association between atopic dermatitis (AD) and cardiovascular disease (CVD) and type 2 diabetes have shown inconsistent results. We compared the risk of CVD and diabetes between adult patients with and without AD by searching the Pubmed, Embase, and Web of Science databases. Data extraction was done by two independent reviewers. We found a total of 2,855 citations, of which 53 were considered relevant based on title and abstract. Sixteen publications were included in the qualitative analysis, of which 13 were also included in a quantitative meta-analysis of crude data. No association was observed between AD and unspecified, but suspected type 2, diabetes (pooled odds ratio [OR] 1.11; 95% confidence interval [CI] 0.87-1.42), hypertension (pooled OR 1.16; 95% CI 0.98-1.37), stroke (pooled OR 1.15; 95% CI 0.95-1.39) or myocardial infarction (pooled OR 1.14; 95% CI 0.83-1.56), but a positive association was observed with angina pectoris (OR 1.73; 95% CI 1.27-2.37). Meta-analysis on adjusted data gave similar results. While adults with AD in some populations have increased prevalence of cardiovascular risk factors, such as obesity and smoking, it is unlikely that AD represents an independent and clinically relevant risk factor for cardiometabolic disease.

This article is protected by copyright. All rights reserved.

Correction to John D. Norton “How to build an infinite lottery machine”

The economy of nature: the structure of evolution in Linnaeus, Darwin, and the modern synthesis

Abstract

We argue that the economy of nature constitutes an invocation of structure in the biological sciences, one largely missed by philosophers of biology despite the turn in recent years toward structural explanations throughout the philosophy of science. We trace a portion of the history of this concept, beginning with the theologically and economically grounded work of Linnaeus, moving through Darwin's adaptation of the economy of nature and its reconstitution in genetic terms during the first decades of the Modern Synthesis. What this historical case study reveals, we argue, is a window into the shifting landscape of the explanatory and ontic uses of structural concepts. In Linnaeus, the economy of nature has both ontic and explanatory import; in Darwin the ontic and explanatory aspects start to come apart (with the explanatory aspect being foregrounded); and finally, in the Modern Synthesis, the economy of nature is replaced by the conceptual toolkit of population genetics, the structural elements of which are nearly entirely explanatory. Having traced a historical trajectory of structural concepts that moves from an ontic formulation to an increasingly explanatory one, we conclude by outlining some insights for structural realism.

Revisiting Rosacea Criteria

Publication date: Available online 29 November 2017
Source:Dermatologic Clinics
Author(s): Mohammed D. Saleem

Teaser

Rosacea is one of the most common and misunderstood dermatologic conditions. Currently, rosacea criteria are based on expert opinion; the definition of rosacea is primarily a reflection of opinion that is prone to bias. It has been more than a decade since the initial criteria were created by the National Rosacea Society. Revisiting the criteria and incorporating evidence-based techniques used by rheumatology and psychiatry can improve the validity and reliability of rosacea criteria. Literature from other specialties is reviewed and a method proposed for developing valid criteria. Examples are provided to motivate and highlight the importance of implementing such techniques.

Rosacea Comorbidities

Publication date: Available online 29 November 2017
Source:Dermatologic Clinics
Author(s): Nora Vera, Nupur U. Patel, Lucia Seminario-Vidal

Teaser

Rosacea is a chronic inflammatory cutaneous disorder with an unclear pathogenesis. It has been associated with multiple comorbidities, including cardiovascular diseases, malignancies, depression, migraines, dementia, Parkinson disease, gastrointestinal disorders, and autoimmune conditions. The extent, clinical significance, and implications of these associations remain a topic of discussion. Further evaluation of these comorbidities may offer valuable insight for future screening practices and treatment recommendations.

Psychosocial Burden and Other Impacts of Rosacea on Patients’ Quality of Life

Publication date: Available online 29 November 2017
Source:Dermatologic Clinics
Author(s): Elias Oussedik, Marc Bourcier, Jerry Tan

Teaser

Rosacea is a common and chronic skin disorder with substantial impact on a patients' quality of life. Its varying phenotypic features and facial localization can adversely affect the mental health and socialization of those affected. Although there are no curative interventions, certain therapies have greater effect in improving patient quality of life. This article summarizes the associated psychosocial implications of rosacea. Several skin disease and rosacea-specific quality-of-life measures and their application in clinical care and research studies are also summarized. The recognition and management of the psychosocial impact of rosacea is critical to improving patient outcomes.

Validity and Reliability of a Rosacea Self-Assessment Tool

Publication date: Available online 28 November 2017
Source:Dermatologic Clinics
Author(s): Sara Moradi Tuchayi, Hossein Alinia, Lucy Lan, Olabola Awosika, Abigail Cline, Leah A. Cardwell, Dennis Hopkinson, Irma Richardson, Karen E. Huang, Steven R. Feldman

Teaser

The lack of validated rosacea assessment tools is a hurdle in assessing rosacea severity. This article discusses a valid and reliable rosacea severity self-assessment tool (RSAT) to measure rosacea severity. To determine test–retest validity, participants completed the self-assessment twice. A blinded physician graded the participant's disease severity with the Investigator Global Severity (IGS) score. Pearson correlations were used to assess the relationship between the self-assessment measure and the IGS. Test–retest RSAT measurements were correlated. The RSAT represents a valid and reliable tool. This tool may facilitate determination of rosacea severity in survey research studies.

Complexities of Rosacea

Publication date: Available online 16 November 2017
Source:Dermatologic Clinics
Author(s): Steven R. Feldman, Leah A. Cardwell, Sarah L. Taylor

Genotoxicity assessment of raw and treated water samples using Allium cepa assay: evidence from Perak River, Malaysia

Abstract

Allium cepa assay was carried out in this study to evaluate genotoxic effects of raw and treated water samples from Perak River in Perak state, Malaysia. Samples were collected from three surface water treatment plants along the river, namely WTPP, WTPS, and WTPK. Initially, triplicates of equal size Allium cepa (onions) bulbs, 25–30 mm in diameter and average weight of 20 g, were set up in distilled water for 24 h at 20 ± 2 °C and protected from direct sunlight, to let the roots to grow. After germination of roots (0.5–1.0 cm in length), bulbs were transferred to collected water samples each for a 96-h period of exposure. The root physical deformations were observed. Genotoxicity quantification was based on mitotic index and genotoxicity level. Statistical analysis using cross-correlation function for replicates from treated water showed that root length has inverse correlation with mitotic indices (r = − 0.969) and frequencies of cell aberrations (r = − 0.976) at lag 1. Mitotic indices and cell aberrations of replicates from raw water have shown positive correlation at lag 1 (r = 0.946). Genotoxicity levels obtained were 23.4 ± 1.98 (WTPP), 26.68 ± 0.34 (WTPS), and 30.4 ± 1.13 (WTPK) for treated water and 17.8 ± 0.18 (WTPP), 37.15 ± 0.17 (WTPS), and 47.2 ± 0.48 (WTPK) for raw water. The observed cell aberrations were adherence, chromosome delay, C-metaphase, chromosome loss, chromosome bridge, chromosome breaks, binucleated cell, mini cell, and lobulated nuclei. The morphogenetic deformations obtained were likely due to genotoxic substances presence in collected water samples. Thus, water treatment in Malaysia does not remove genotoxic compounds.

Impact of oral cadmium intoxication on levels of different essential trace elements and oxidative stress measures in mice: a response to dose

Abstract

The study evaluated the effect of oral intoxication of cadmium and the possible causes of oxidative stress and its preferential accumulation in different organs as well as sub-sequential effects in mice. Twenty-four Swiss albino male mice were divided into three groups viz., normal control group without cadmium chloride (CdCl₂), whereas a daily dose of 0.5 and 1.2 mg of CdCl₂ was orally administered for a period of a week to dose group 1 (DG-1) and dose group 2 (DG-2), respectively. A significant increase in the severity of cadmium toxicity was observed in animals as evidenced by aggravation in liver enzymes viz., serum alanine aminotransferase and aspartate transaminase, whereas lower levels of antioxidative stress markers in liver and kidney tissues of treated mice were observed as compared to normal control group. A significant depletion of calcium levels in liver tissues of DG-1 (217.36 ± 1.73 μg/g of wet tissues) and DG-2 (186.41 ± 1.56 μg/g of wet tissues) groups, along with Cd accumulation, was observed. To summarize, the current study would increase our understanding with respect to dose-dependent absorption of Cd and its toxicity led to mortality as well as adverse health effects in the body of mice.

Graphical abstract

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Bioengineered silver nanoparticles as potent anti-corrosive inhibitor for mild steel in cooling towers

Abstract

Silver nanoparticle-aided enhancement in the anti-corrosion potential and stability of plant extract as ecologically benign alternative for microbially induced corrosion treatment is demonstrated. Bioengineered silver nanoparticles (AgNPs) surface functionalized with plant extract material (proteinacious) was generated in vitro in a test tube by treating ionic AgNO₃ with the leaf extract of Azadirachta indica that acted as dual reducing as well as stabilizing agent. Purity and crystallinity of the AgNPs, along with physical and surface characterizations, were evaluated by performing transmission electron microscopy, Fourier transform infrared spectroscopy, energy dispersive x-ray spectra, single-area electron diffractions, zeta potential, and dynamic light scattering measurements. Anti-corrosion studies against mild steel (MS1010) by corrosion-inducive bacterium, Bacillus thuringiensis EN2 isolated from cooling towers, were evaluated by performing electrochemical impedance spectroscopy (EIS), weight loss analysis, and surface analysis by infrared spectroscopy. Our studies revealed that AgNPs profoundly inhibited the biofilm on MS1010 surface and reduced the corrosion rates with the CR of 0.5 mm/y and an inhibition efficiency of 77% when compared to plant extract alone with a CR of 2.2 mm/y and an inhibition efficiency of 52%. Further surface analysis by infrared spectra revealed that AgNPs formed a protective layer of self-assembled film on the surface of MS1010. Additionally, EIS and surface analysis revealed that the AgNPs have inhibited the bacterial biofilm and reduced the pit on MS1010. This is the first report disclosing the application of bioengineered AgNP formulations as potent anti-corrosive inhibitor upon forming a protective layer over mild steel in cooling water towers.

Graphical Abstract

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Identification of dihydrogambogic acid as a matrix metalloproteinase 1 inhibitor by high-throughput screening

From isolation to prosperity: Rediscovering the Carville Leprosarium

Publication date: Available online 1 December 2017
Source:Clinics in Dermatology
Author(s): Natalie J. Atkin
The stigma associated with leprosy, sometimes referred to as Hansen's Disease, has historically been linked with fear and discrimination, often leading to persecution and isolation in the form of quarantine. Consequently, harsh methods of "treatment" were often employed due to a global lack of knowledge regarding leprosy and its vector of transmission. In fact, leprosy was initially thought to be an inherited disorder, or even a punishment from G-d^2; however, within the last century, research on the malady has grown vastly, having been aided by the discovery of Mycobacterium leprae as the disease causing acid-fast bacillus in 1873.³ Throughout this time, several leprostatic agents, including sulfonamide-derived chemotherapeutic drugs, have also been introduced. Today, leprosy is a better-understood disease whose damage to the peripheral nervous system can be limited or reduced with the use of such drugs. The most optimal outcomes are observed in patients who are diagnosed early and treated with multidrug therapy (MDT) to counteract the possibility of drug resistance associated with monotherapy. Many significant contributions to today's understanding of leprosy are attributed to the diligence and dedication of researchers and clinicians at the National Leprosarium in Carville, Louisiana – an often forgotten and understated pioneer facility in the progress of dermatologic medicine.

Editorial Board

Publication date: November–December 2017
Source:Clinics in Dermatology, Volume 35, Issue 6

Table of Contents

Publication date: November–December 2017
Source:Clinics in Dermatology, Volume 35, Issue 6

Do cemeteries emit drugs? A case study from southern Germany

Abstract

The risk of earth burials for the environment and public health is a matter of controversial debate. The aim of the present study is to characterise the drainage of cemeteries with regard to the concentration of a number of pharmaceuticals and to the soil's hydrochemical properties, and to discuss these data in comparison with data obtained for surface waters located upstream of the cemeteries. Of the 12 drainage samples analysed using LC-ESI-MS/MS, seven contained carbamazepine (< 225 ng l⁻¹), five contained hydrochlorothiazide, one contained metoprolol (23 ng l⁻¹) and one contained traces of ibuprofen. The surface water samples contained a larger number of different drugs (8 of the 12 drugs under investigation) and higher concentrations (e.g. metropolol 2230 ng l⁻¹). The NO₃, NH₄, PO₄ and DOC concentrations and the electrical conductivity of the cemetery drainages were in several samples higher than those of the surface water samples. The NO₃ and NH₄ concentrations exceeded the legal contaminant limits of drinking water in only one case. The present study found that the release of drugs and nutrients from cemeteries, measured in surface water drug loads, presents a low environmental risk. However, the study is only a snapshot and long-term monitoring of cemetery drainages, including a broad range of pharmaceuticals and detailed hydrological investigations, will have to be carried out before more substantiated statements can be made.

Minimally invasive dorsal sympathicotomies for the treatment of hyperhidrosis: palmar microcirculatory assessment as an intraoperative-aid

Abstract

Background

Endoscopic transthoracic sympathicotomy has proven to be an effective and durable surgical treatment for severe primary hyperhidrosis. Anyhow, in some cases, especially in overweight patients, a thick overlying subpleural fat may obscure the sympathetic chain, precluding access to the ganglia and partial or total completion of the procedure. The aim of this study was to assess the value of palmar laser Doppler flowmetry (LDF) as an intraoperative-aid during minimally invasive dorsal sympathicotomies (T3) for the treatment of primary palmar hyperhidrosis.

Methods

The method was tested during 40 upper dorsal video-assisted minimally invasive sympathicotomies in 20 patients with bilateral palmar primary hyperhidrosis.

Results

The mean baseline LDF values were 36.05 pU (SD = 21.85 pU). The mean immediate postoperative LDF values were 75.94 pU (SD = 37.89 pU). A statistically significant difference was observed between preoperative and immediate (about 5 s after the sympathicotomies) postoperative values (p = 0.00000009).

Conclusions

According to our data, LDF allowed to obtain reliable and fast intraoperative evidence of a correct section of T3 ganglia. As such, we recommend LDF as a useful intraoperative tool when dealing with dorsal sympathicotomies for the treatment of palmar hyperhidrosis, both for the unexperienced surgeon and when the sympathetic chain is not clearly visualized.

Level of Evidence: Level IV, therapeutic study.

Ink-enhanced dermoscopy is a useful tool to differentiate acquired solitary plaque porokeratosis from other scaly lesions

Improving CT detection sensitivity for nodal metastases in oesophageal cancer with combination of smaller size and lymph node axial ratio

Abstract

Objectives

To investigate the value of CT with inclusion of smaller lymph node (LN) sizes and axial ratio to improve the sensitivity in diagnosis of regional lymph node metastases in oesophageal squamous cell carcinoma (OSCC).

Methods

The contrast-enhanced multidetector row spiral CT (MDCT) multiplanar reconstruction images of 204 patients with OSCC were retrospectively analysed. The long-axis and short-axis diameters of the regional LNs were measured and axial ratios were calculated (short-axis/long-axis diameters). Nodes were considered round if the axial ratio exceeded the optimal LN axial ratio, which was determined by receiver operating characteristic analysis.

Results

A positive predictive value (PPV) exceeding 50% is needed. This was achieved only with LNs larger than 9 mm in short-axis diameter, but nodes of this size were rare (sensitivity 37.3%, specificity 96.4%, accuracy 85.8%). If those round nodes (axial ratio exceeding 0.66 ) between 7 mm and 9 mm in size were considered metastases as well, it might improve the sensitivity to 67.2% with a PPV of 63.9% (specificity 91.6%, accuracy 87.2%).

Conclusion

Combination of a smaller size and axial ratio for LNs in MDCT as criteria improves the detection sensitivity for LN metastases in OSCC.

Key Points

• CT is widely used to assess metastatic lymph nodes.

• CT has low sensitivity in detecting metastases using conventional criteria.

• Diagnostic sensitivity of CT was improved by using lymph node axial ratio.

• New diagnostic criteria provide greater diagnostic confidence with PPVs exceeding 50%.

• New diagnostic criteria may help clinicians assess patients with oesophageal cancer.

High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation: Normal foetal brain development

Abstract

Purpose

To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains.

Methods

We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists.

Results

Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17–28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19–22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones.

Conclusion

PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19–22 weeks of gestation.

Key Points

• Post-mortem magnetic resonance imaging (PMMRI) of non-fixed head is feasible.

• PMMRI of unfixed in situ foetal brains preserves the natural tissue contrast.

• PMMRI provide a good depiction of the normal foetal brain development.

• PMMRI of unfixed in situ foetal brains preserves the skull integrity.

• PMMRI pattern of foetal brain development at early gestational age is described.

Revised PROPELLER for T2-weighted imaging of the prostate at 3 Tesla: impact on lesion detection and PI-RADS classification

Abstract

Purpose

To evaluate revised PROPELLER (RevPROP) for T2-weighted imaging (T2WI) of the prostate as a substitute for turbo spin echo (TSE).

Materials and methods

Three-Tesla MR images of 50 patients with 55 cancer-suspicious lesions were prospectively evaluated. Findings were correlated with histopathology after MRI-guided biopsy. T2 RevPROP, T2 TSE, diffusion-weighted imaging, dynamic contrast enhancement, and MR-spectroscopy were acquired. RevPROP was compared to TSE concerning PI-RADS scores, lesion size, lesion signal-intensity, lesion contrast, artefacts, and image quality.

Results

There were 41 carcinomas in 55 cancer-suspicious lesions. RevPROP detected 41 of 41 carcinomas (100%) and 54 of 55 lesions (98.2%). TSE detected 39 of 41 carcinomas (95.1%) and 51 of 55 lesions (92.7%). RevPROP showed fewer artefacts and higher image quality (each p < 0.001). No differences were observed between single and overall PI-RADS scores based on RevPROP or TSE (p = 0.106 and p = 0.107). Lesion size was not different (p = 0.105). T2-signal intensity of lesions was higher and T2-contrast of lesions was lower on RevPROP (each p < 0.001).

Conclusion

For prostate cancer detection RevPROP is superior to TSE with respect to motion robustness, image quality and detection rates of lesions. Therefore, RevPROP might be used as a substitute for T2WI.

Key points

• Revised PROPELLER can be used as a substitute for T2-weighted prostate imaging.

• Revised PROPELLER detected more carcinomas and more suspicious lesions than TSE.

• Revised PROPELLER showed fewer artefacts and better image quality compared to TSE.

• There were no significant differences in PI-RADS scores between revised PROPELLER and TSE.

• The lower T2-contrast of revised PROPELLER did not impair its diagnostic quality.

Noninvasive electrical conductivity measurement by MRI: a test of its validity and the electrical conductivity characteristics of glioma

Abstract

Objectives

This study noninvasively examined the electrical conductivity (σ) characteristics of diffuse gliomas using MRI and tested its validity.

Methods

MRI including a 3D steady-state free precession (3D SSFP) sequence was performed on 30 glioma patients. The σ maps were reconstructed from the phase images of the 3D SSFP sequence. The σ histogram metrics were extracted and compared among the contrast-enhanced (CET) and noncontrast-enhanced tumour components (NCET) and normal brain parenchyma (NP). Difference in tumour σ histogram metrics among tumour grades and correlation of σ metrics with tumour grades were tested. Validity of σ measurement using this technique was tested by correlating the mean tumour σ values measured using MRI with those measured ex vivo using a dielectric probe.

Results

Several σ histogram metrics of CET and NCET of diffuse gliomas were significantly higher than NP (Bonferroni-corrected p ≤ .045). The maximum σ of NCET showed a moderate positive correlation with tumour grade (r = .571, Bonferroni-corrected p = .018). The mean tumour σ measured using MRI showed a moderate positive correlation with the σ measured ex vivo (r = .518, p = .040).

Conclusions

Tissue σ can be evaluated using MRI, incorporation of which may better characterise diffuse gliomas.

Key Points

• This study tested the validity of noninvasive electrical conductivity measurements by MRI.

• This study also evaluated the electrical conductivity characteristics of diffuse glioma.

• Gliomas have higher electrical conductivity values than the normal brain parenchyma.

• Noninvasive electrical conductivity measurement can be helpful for better characterisation of glioma.

Ultrasound-guided percutaneous bone drilling for the treatment of lateral epicondylitis

Abstract

Objective

To determine the clinical efficacy of sonographically-guided percutaneous bone drilling of the lateral epicondyle (LE) for the treatment of patients with LE.

Methods

We included 24 patients with LE who reported pain in this study. All patients underwent sonographically-guided percutaneous bone drilling of the lateral epicondyle. Follow-up sonography and physical examinations were performed 1, 3 and 6 months after the procedure. The outcome measures included sonographic findings, visual analogue scale (VAS) score, maximum voluntary grip strength (MVGS) and patient-related tennis elbow evaluation (PRTEE) score.

Results

None of the patients had immediate complications during the procedure. The area of the extensor carpi radialis brevis (ECRB) tears decreased significantly at 1 month and declined gradually over the remaining 5 months of the study (p < 0.001). The mean pain VAS score was significantly lower at 6 months than preoperatively (respectively; p < 0.001). The mean MVGS increased significantly between pretreatment and 6 months post-treatment (p < 0.001), whereas the PRTEE score decreased significantly during the same period (p < 0.001).

Conclusion

Sonographically-guided percutaneous drilling is a quick and safe treatment option for LE that can be performed in an outpatient setting.

Key Points

• Percutaneous drilling of the lateral condyle is effective for the treatment of LE.

• The area of ECRB tears can be measured by US-guided saline injection.

• US-guided percutaneous drilling is a quick and safe treatment option for LE.

Software-based risk stratification of pulmonary adenocarcinomas manifesting as pure ground glass nodules on computed tomography

Abstract

Objectives

To assess the performance of the "Computer-Aided Nodule Assessment and Risk Yield" (CANARY) software in the differentiation and risk assessment of histological subtypes of lung adenocarcinomas manifesting as pure ground glass nodules on computed tomography (CT).

Methods

64 surgically resected and histologically proven adenocarcinomas manifesting as pure ground-glass nodules on CT were assessed using CANARY software, which classifies voxel-densities into three risk components (low, intermediate, and high risk). Differences in risk components between histological adenocarcinoma subtypes were analysed. To determine the optimal threshold reflecting the presence of an invasive focus, sensitivity, specificity, negative predictive value, and positive predictive value were calculated.

Results

28/64 (44%) were adenocarcinomas in situ (AIS); 26/64 (41%) were minimally invasive adenocarcinomas (MIA); and 10/64 (16%) were invasive ACs (IAC). The software showed significant differences in risk components between histological subtypes (P<0.001–0.003). A relative volume of 45% or less of low-risk components was associated with histological invasiveness (specificity 100%, positive predictive value 100%).

Conclusions

CANARY-based risk assessment of ACs manifesting as pure ground glass nodules on CT allows the differentiation of their histological subtypes. A threshold of 45% of low-risk components reflects invasiveness in these groups.

Key points

• CANARY-based risk assessment allows the differentiation of their histological subtypes.

• 45% or less of low-risk component reflects histological invasiveness.

• CANARY has potential role in suspected adenocarcinomas manifesting as pure ground-glass nodules.

The effect of iodine uptake on radiation dose absorbed by patient tissues in contrast enhanced CT imaging: Implications for CT dosimetry

Abstract

Objectives

To investigate the effect of iodine uptake on tissue/organ absorbed doses from CT exposure and its implications in CT dosimetry.

Methods

The contrast-induced CT number increase of several radiosensitive tissues was retrospectively determined in 120 CT examinations involving both non-enhanced and contrast-enhanced CT imaging. CT images of a phantom containing aqueous solutions of varying iodine concentration were obtained. Plots of the CT number increase against iodine concentration were produced. The clinically occurring iodine tissue uptake was quantified by attributing recorded CT number increase to a certain concentration of aqueous iodine solution. Clinically occurring iodine uptake was represented in mathematical anthropomorphic phantoms. Standard 120 kV CT exposures were simulated using Monte Carlo methods and resulting organ doses were derived for non-enhanced and iodine contrast-enhanced CT imaging.

Results

The mean iodine uptake range during contrast-enhanced CT imaging was found to be 0.02-0.46% w/w for the investigated tissues, while the maximum value recorded was 0.82% w/w. For the same CT exposure, iodinated tissues were found to receive higher radiation dose than non-iodinated tissues, with dose increase exceeding 100% for tissues with high iodine uptake.

Conclusions

Administration of iodinated contrast medium considerably increases radiation dose to tissues from CT exposure.

Key-points

• Radiation absorption ability of organs/tissues is considerably affected by iodine uptake

• Iodinated organ/tissues may absorb up to 100 % higher radiation dose

• Compared to non-enhanced, contrast-enhanced CT may deliver higher dose to patient tissues

• CT dosimetry of contrast-enhanced CT imaging should encounter tissue iodine uptake

Improving mTICI2b reperfusion to mTICI2c/3 reperfusions: A retrospective observational study assessing technical feasibility, safety and clinical efficacy

Abstract

Background

Recent studies suggested that modified Thrombolysis in Cerebral Infarction grade (mTICI) 3 reperfusions are associated with superior outcome to mTICI2b reperfusions, questioning if neurointerventionalists should generally strive to achieve mTICI3.

Methods

Retrospective analysis of successfully reperfused MCA occlusions (n=246) with available angiography runs between every manoeuvre was performed. Final reperfusion success and those between all single manoeuvres were evaluated applying the modified version of the TICI score (including TICI2c). Final TICI2c/3 reperfusions were dichotomized as 'direct' (reperfusion before final manoeuvre ≤mTICI2a) or 'secondary improved' (mTICI2b was achieved).

Results

Patients with mTICI2c reperfusion had similar outcome to patients with mTICI3 rather than mTICI2b reperfusions. Compared with mTICI2c/3-patients, mTICI2b-patients had lower rates of neurological improvement (33.3% vs. 61.2%, p<0.001) and good functional outcome (28.7% vs. 46.5%, p=0.008). In 28 patients, mTICI2b reperfusion was improved to mTICI2c/3 without complications. Outcome of patients with 'direct' or 'secondary improved' mTICI2c/3 did not differ (p>0.5).

Conclusion

Improving mTICI2b reperfusions to mTICI2c/3 reperfusions is sometimes technically feasible and safe, and associated with clinical benefit comparable to 'direct' mTICI2c/3 reperfusions. If confirmed, a more aggressive treatment approach in cases of already achieved mTICI2b may be justified, although proper patient selection is needed.

Key Points

• Patients with mTICI2c or 3 reperfusions have a comparable clinical course.

• mTICI2c/3 are associated with a larger therapeutic benefit than are mTICI2b reperfusions.

• Improving reperfusion from mTICI2b to mTICI2c/3 is sometimes feasible and reasonably safe.

• Outcome of patients with 'secondary improved' and 'direct' mTICI2c/3 is not different.

Bone marrow oedema predicts bone collapse in paediatric and adolescent leukaemia patients with corticosteroid-induced osteonecrosis

Abstract

Objectives

Corticosteroid treatment of paediatric leukaemia patients can lead to osteonecrosis (ON). We determined whether bone marrow oedema (BME) is an early sign of progressive ON and eventual bone collapse.

Methods

In a retrospective study, two radiologists reviewed MR imaging characteristics of 47 early stage epiphyseal ON in 15 paediatric and adolescent leukaemia patients. Associations between BME on initial imaging studies and subchondral fracture, disease progression and bone collapse were assessed by Cochran-Mantel-Haenszel tests. Differences in time to progression and bone collapse between lesions with and without oedema were assessed by log rank tests.

Results

Forty-seven occurrences of ON were located in weight bearing joints, with 77% occurring in the femur. Seventeen lesions progressed to collapse, two lesions worsened without collapse, and 28 remained stable or improved. BME was significantly associated with subchondral fracture (p = 0.0014), disease progression (p = 0.0015), and bone collapse (p < 0.001), with a sensitivity and specificity of 94% and 77%, respectively, for bone collapse. Time to progression for ON with oedema was 2.7 years (95% CI: 1.7-3.4); while the majority of no-oedema ON were stable (p = 0.0011).

Conclusions

BME is an early sign of progressive ON and eventual bone collapse in paediatric and adolescent leukaemia patients.

Key points

• Bone marrow oedema in corticosteroid-induced osteonecrosis predicts progression to bone collapse.

• Bone marrow oedema is associated with subchondral fractures in corticosteroid-induced osteonecrosis.

• Bone marrow oedema can be used to stratify patients to joint-preserving interventions.

• Absence of bone marrow oedema can justify a "wait and watch" approach.

Longitudinal study of sodium MRI of articular cartilage in patients with knee osteoarthritis: initial experience with 16-month follow-up

Abstract

Objectives

To evaluate the potential of sodium MRI to detect changes over time of apparent sodium concentration (ASC) in articular cartilage in patients with knee osteoarthritis (OA).

Methods

The cartilage of 12 patients with knee OA were scanned twice over a period of approximately 16 months with two sodium MRI sequences at 7 T: without fluid suppression (radial 3D) and with fluid suppression by adiabatic inversion recovery (IR). Changes between baseline and follow-up of mean and standard deviation of ASC (in mM), and their rate of change (in mM/day), were measured in the patellar, femorotibial medial and lateral cartilage regions for each subject. A matched-pair Wilcoxon signed rank test was used to assess significance of the changes.

Results

Changes in mean and in standard deviation of ASC, and in their respective rate of change over time, were only statistically different when data was acquired with the fluid-suppressed sequence. A significant decrease (p = 0.001) of approximately 70 mM in mean ASC was measured between the two IR scans.

Conclusion

Quantitative sodium MRI with fluid suppression by adiabatic IR at 7 T has the potential to detect a decrease of ASC over time in articular cartilage of patients with knee osteoarthritis.

Key Points

• Sodium MRI can detect apparent sodium concentration (ASC) in cartilage

• Longitudinal study: sodium MRI can detect changes in ASC over time

• Potential for follow-up studies of cartilage degradation in knee osteoarthritis

What are the differentiating clinical and MRI-features of enchondromas from low-grade chondrosarcomas?

Abstract

Objectives

To evaluate the role of clinical assessment, conventional and dynamic contrast-enhanced MRI in differentiating enchondromas from chondrosarcomas of long bone.

Methods

The following clinical and MRI findings were assessed: age, gender, pain, pain attributable to lesion, tumour location, tumour length, presence, depth of endosteal scalloping, bone marrow oedema, soft tissue oedema, cortical destruction, periosteal reaction, bone expansion, macroscopic fat, calcification, soft tissue mass, haemorrhage, dynamic contrast-enhanced MRI. Clinical and MRI findings were compared with histopathological grading.

Results

Sixty patients with central chondroid tumours were included (27 enchondromas, 10 cartilaginous lesions of unknown malignant potential, 15 grade 1 chondrosarcomas, 8 high-grade chondrosarcomas). Pain attributed to lesion, tumour length, endosteal scalloping > 2/3, cortical destruction, bone expansion and soft tissue mass were differentiating features between enchondromas and grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI could not differentiate enchondromas from grade 1 chondrosarcomas.

Conclusions

Previously reported imaging signs of chondrosarcomas are useful in the diagnosis of grade 1 lesions but have lower sensitivity than in higher grade lesions. Deep endosteal scalloping is the most sensitive imaging sign of grade 1 chondrosarcomas. Pain due to the lesion is an important clinical sign of grade 1 chondrosarcomas. Dynamic contrast-enhanced MRI is not useful in differentiating enchondromas from grade 1 chondrosarcomas.

Key Points

• Differentiation of enchondroma from low-grade chondrosarcoma is challenging for radiologists and pathologists.

• The utility of clinical assessment, conventional and dynamic contrast-enhanced MRI was uncertain.

• Clinical assessment and conventional MRI aid in differentiating enchondromas from low-grade chondrosarcoma.

• Dynamic contrast-enhanced MRI cannot differentiate enchondromas from grade 1 chondrosarcoma.

Development of a reliable simulation-based test for diagnostic abdominal ultrasound with a pass/fail standard usable for mastery learning

Abstract

Background

This study aimed to develop a test with validity evidence for abdominal diagnostic ultrasound with a pass/fail-standard to facilitate mastery learning.

Method

The simulator had 150 real-life patient abdominal scans of which 15 cases with 44 findings were selected, representing level 1 from The European Federation of Societies for Ultrasound in Medicine and Biology. Four groups of experience levels were constructed: Novices (medical students), trainees (first-year radiology residents), intermediates (third- to fourth-year radiology residents) and advanced (physicians with ultrasound fellowship). Participants were tested in a standardized setup and scored by two blinded reviewers prior to an item analysis.

Results

The item analysis excluded 14 diagnoses. Both internal consistency (Cronbach's alpha 0.96) and inter-rater reliability (0.99) were good and there were statistically significant differences (p < 0.001) between all four groups, except the intermediate and advanced groups (p = 1.0). There was a statistically significant correlation between experience and test scores (Pearson's r = 0.82, p < 0.001). The pass/fail-standard failed all novices (no false positives) and passed all advanced (no false negatives). All intermediate participants and six out of 14 trainees passed.

Conclusion

We developed a test for diagnostic abdominal ultrasound with solid validity evidence and a pass/fail-standard without any false-positive or false-negative scores.

Key Points

• Ultrasound training can benefit from competency-based education based on reliable tests.

• This simulation-based test can differentiate between competency levels of ultrasound examiners.

• This test is suitable for competency-based education, e.g. mastery learning.

• We provide a pass/fail standard without false-negative or false-positive scores.

Structured reports of videofluoroscopic swallowing studies have the potential to improve overall report quality compared to free text reports

Abstract

Purpose

To compare free text (FTR) and structured reports (SR) of videofluoroscopic swallowing studies (VFSS) and evaluate satisfaction of referring otolaryngologists and speech therapists.

Materials and methods

Both standard FTR and SR of 26 patients with VFSS were acquired. A dedicated template focusing on oropharyngeal phases was created for SR using online software with clickable decision-trees and concomitant generation of semantically structured reports. All reports were evaluated regarding overall quality and content, information extraction and clinical decision support (10-point Likert scale (0 = I completely disagree, 10 = I completely agree)).

Results

Two otorhinolaryngologists and two speech therapists evaluated FTR and SR. SR received better ratings than FTR in all items. SR were perceived to contain more details on the swallowing phases (median rating: 10 vs. 5; P < 0.001), penetration and aspiration (10 vs. 5; P < 0.001) and facilitated information extraction compared to FTR (10 vs. 4; P < 0.001). Overall quality was rated significantly higher in SR than FTR (P < 0.001).

Conclusion

SR of VFSS provide more detailed information and facilitate information extraction. SR better assist in clinical decision-making, might enhance the quality of the report and, thus, are recommended for the evaluation of VFSS.

Key Points

• Structured reports on videofluoroscopic exams of deglutition lead to improved report quality.

• Information extraction is facilitated when using structured reports based on decision trees.

• Template-based reports add more value to clinical decision-making than free text reports.

• Structured reports receive better ratings by speech therapists and otolaryngologists.

• Structured reports on videofluoroscopic exams may improve the comparability between exams.

CD95 Mediates Neurovascular Development

By Yoskaly Lazo-Fernandez, PhD

The cell surface receptor CD95 (also known as Fas or APO-1) is the best-characterized member of the tumor necrosis factor (TNF) receptor superfamily¹. Many receptors in this family, including CD95 are called Death Receptors because of their ability to induce apoptosis². In cells expressing CD95, apoptosis is triggered by the binding of this receptor's specific ligand, CD95L. This mechanism, which was originally discovered in the early nineties, allows CD95L-expressing T lymphocytes and natural killer cells to trigger apoptosis in their targets. For this reason, CD95 was initially considered as a mediator of cell death only³. However, some CD95 expressing cells are resistant to CD95L-mediated apoptosis indicating that the biological function of CD95 goes beyond cell death induction. In fact, in recent years, intensive research revealed that CD95 is an important mediator of non-apoptotic signals. As such, CD95 has been implicated in a variety of new biological processes including cancer cell invasion, neurite sprouting and cell proliferation. In general, these novel CD95 activities are mediated by activation of MAPK kinases like p38, JNK and ERK as well as transcription factors like NFkB^2–5.

ERK1/ERK2 was detected in perfusion fixed frozen sections of rat brain (cortex) using 15 µg/mL Rabbit Anti-Human/Mouse/Rat Phospho-ERK1/ERK2 (ERK1 T202/Y204, ERK2 T185/Y187) Antigen Affinity-purified Polyclonal Antibody (Catalog # AF1018) overnight at 4 °C. Tissue was stained with the Anti-Rabbit HRP-DAB Cell & Tissue Staining Kit (brown; Catalog # CTS005) and counterstained with hematoxylin (blue). View our protocol for Chromogenic IHC Staining of Frozen Tissue Sections.

Some of the newly reported, apoptosis-independent effects of CD95 activation are clearly relevant for the function of the nervous system. For example, CD95 has been shown to mediate neurite growth and branching in vitro⁶. Also, adult mice with impaired expression of CD95 exhibited neuronal atrophy and numerous neurological symptoms in their behavior⁷. However, it was unclear if the neurite growth effects would also be induced in vivo, and if the neurological consequences of CD95 gene deletion were directly related to CD95's activity rather than to autoimmune problems.

Recent work by the laboratory of Ana Martin-Villalba in Germany aimed at solving these questions. In their publication⁸, Si Chen et al. demonstrated that the activation of CD95 indeed regulates neuronal branching both in vitro and in vivo. These authors also uncovered cellular and molecular mechanisms involved in this response. An essential technique used in this project was the cell-specific modulation of the expression of CD95 and related proteins. The downregulation of CD95 in cortical neurons of the developing brain, both in the embryo and early after birth, lead to a marked reduction of dendrite total length (35%) and number of branching points (25%). Overexpression of CD95 in the same cells had the opposite effects.

Neuronal and vessel growth share common regulatory mechanisms, and since endothelial cells (EC) express CD95 while being resistant to apoptosis, the authors studied if CD95 is involved in vascular development in the brain. Their results indicated that CD95 stimulates developmental angiogenesis by promoting EC proliferation and branching. The source of the activation of CD95 was in a cell type derived from the immune system, the macrophages. In contrast to neurons or EC, CNS macrophages express high levels of CD95L in the developing brain. Specific deletion of CD95L in CNS macrophages lead to a similar reduction in dendrite or EC development plus neuronal morphological and functional impairment in vivo. Overall these results strongly suggest that CNS macrophages are important players in the regulation of neurovascular development through the non-apoptotic activation of CD95. This discovery provides a new potential strategy for the modulation of neuronal plasticity and angiogenesis in CNS developmental disorders.

Explore Neuroscience Research Area

Yoskaly Lazo Fernandez, PhD
Emory University, Department of Medicine/Renal Division
Dr. Lazo-Fernandez is interested in understanding the dietary factors that contribute to the development of hypertension and other chronic diseases.

References

1. Peter, Budd, Desbarats, Hedrick, Hueber, Newell, Owen, Pope, Tschopp, Wajant, Wallach, Wiltrout, Zörnig, Lynch. The CD95 Receptor: Apoptosis Revisited. Cell. 2007;129(3):447-450. doi:10.1016/j.cell.2007.04.031.
2. Guégan, Legembre. Nonapoptotic functions of Fas/CD95 in the immune response. The FEBS Journal. 2017. doi:10.1111/febs.14292.
   
3. Fouqué, Debure, Legembre. The CD95/CD95L signaling pathway: A role in carcinogenesis. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2014;1846(1):130-141. doi:10.1016/j.bbcan.2014.04.007.
   
4. Martin-Villalba, Llorens-Bobadilla, Wollny. CD95 in cancer: tool or target? Trends in Molecular Medicine. 2013;19(6):329-335. doi:10.1016/j.molmed.2013.03.002.
   
5. Sancho-Martinez, Martin-Villalba. Tyrosine phosphorylation and CD95: A FAScinating switch. Cell Cycle. 2009;8(6):838-842. doi:10.4161/cc.8.6.7906.
   
6. Zuliani, Kleber, Klussmann, Wenger, Kenzelmann, Schreglmann, Martinez, JAD R, Soriano, Vodrazka, Kuner, Groene, Herr, Krammer, Martin-Villalba. Control of neuronal branching by the death receptor CD95 (Fas/Apo-1). Cell Death and Differentiation. 2005;13(1):4401720. doi:10.1038/sj.cdd.4401720.
   
7. Šakić, Szechtman, Denburg, Gorny, Kolb, Whishaw. Progressive atrophy of pyramidal neuron dendrites in autoimmune MRL-lpr mice. Journal of Neuroimmunology. 1998;87(1-2):162-170. doi:10.1016/s0165-5728(98)00085-x.
   
8. Chen, Tisch, Kegel, Yerbes, Hermann, Hudalla, Zuliani, Gülcüler, Zwadlo, Engelhardt, CRD A, Martin-Villalba. CNS Macrophages Control Neurovascular Development via CD95L. Cell Reports. 2017;19(7):1378-1393. doi:10.1016/j.celrep.2017.04.056.

 

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It’s Right, It Fits, We Debated, We Decided, I Agree, It’s Ours, and It Works : The Gathering Confluence of Human Rights Legitimacy

Abstract

How should we understand human rights and why might we respect them? The current literature – both philosophical and historical – presents a barrage of conflicting accounts, including moral, functional, deliberative, legal, consensual, communitarian and pragmatic approaches. I argue that each approach captures a unique, common-sense – and, in principle, compatible – insight into why human rights warrant respect. Acknowledging this compatibility illuminates the myriad different avenues for legitimacy human rights enjoy, and provides a historical window into explaining how human rights rose to become the international community's ethical lingua franca. The depth and spread of convergence on human rights proved possible precisely because myriad people the world over found a wealth of disparate reasons for rallying under its banner. But even as human rights enjoy seven distinct sources of legitimacy, I argue that they are thereby opened for normative challenge on seven distinct fronts.

Medikamentöse Therapie des Nebennierenkarzinoms

Zusammenfassung

Hintergrund

Das Nebennierenkarzinom ist eine seltene Erkrankung mit ungünstiger Prognose und variablem Verlauf. Neben der möglichst vollständigen Resektion als wichtigste Therapie werden verschiedene medikamentöse Optionen eingesetzt.

Ziel

Neben den gängigen medikamentösen Therapieoptionen wird in diesem Artikel der aktuelle Stand zu zielgerichteten Therapieoptionen beleuchtet.

Material und Methoden

Selektive Literaturrecherche (PubMed) sowie Auswertung des eigenen Patientenkollektivs.

Ergebnisse und Diskussion

Unter den verschiedenen medikamentösen Therapieoptionen stellt Mitotan – trotz vieler Nebenwirkungen – weiterhin die Therapie der ersten Wahl sowohl im adjuvanten Setting als auch bei der fortgeschrittenen Erkrankung dar. Im weiteren Verlauf wird Mitotan bei Progress oder initial schon aggressiver Erkrankung um Chemotherapeutika (z. B. Kombination von Etoposid, Doxorubicin, Cisplatin) ergänzt. Die weitere Behandlung ist dann sehr vom individuellem Erkrankungsverlauf, der Höhe der ggf. vorliegenden Tumorlast und des Allgemeinzustands des Patienten abhängig.

Recent Advances in Intradural Spinal Tumors

Abstract

Intradural spinal tumors are rare tumors of the central nervous system. Due to the eloquence of the spinal cord and its tracts, compact architecture of the cord and nerves and the infiltrative nature of some of these tumors, surgical resection is difficult to achieve without causing neurological deficits. Likewise, chemotherapy and radiotherapy are utilized more cautiously in the treatment of intradural spinal tumors than their cranial counterparts. Targeted therapies aimed at the genetic alterations and molecular biology tailored to these tumors would be helpful, but are lacking.In this review, we review the major types of intradural spinal tumors, with an emphasis on genetic alterations, molecular biology and experimental therapies for these difficult to treat neoplasms.

De novo and secondary anaplastic meningiomas: a study of clinical and histomolecular prognostic factors

Abstract

Background

Following recent studies underlining the differences between de novo and secondary anaplastic meningiomas and the prognostic value of TERT promoter mutation, we decided to conduct a multicenter retrospective study to address these questions and determine specific prognostic factors in each of these two anaplastic meningioma subgroups.

Methods

Among the 68 meningioma cases initially selected, only 57 were confirmed as anaplastic meningiomas after centralized pathological review. TERT promoter mutation analysis was performed in all cases.

Results

Median overall survival was 2.6 years and 5-year survival rate was 10%. This study confirmed the better prognosis of de novo anaplastic meningiomas (28 tumors) compared to secondary anaplastic meningiomas (29 tumors) (p=0.02). In the "de novo" group, meningiomas diagnosed on histological anaplasia alone had a better prognosis than patients with a high number of mitoses with or without anaplasia (p=0.01). In the "secondary" group, tumors demonstrate very heterogeneous clinical courses leading to malignant transformation and time to first relapse as a low grade tumor was a strong predictor of overall survival (p=0.0007). TERT promoter mutation in anaplastic meningiomas was rare (14%) and did not influence overall survival, but was associated with a shorter recurrence-free survival in the secondary anaplastic meningioma subgroup (p=0.02). The absence of TERT promoter methylation, although rare (3/33 cases), may be associated with prolonged overall survival (p=0.02).

Conclusion

This study highlights the different prognoses of de novo and secondary anaplastic meningiomas with specific prognostic factors in each subgroup. The analysis of TERT mutation and methylation could provide additional prognostic insights.

Dual Process Theory: Systems, Types, Minds, Modes, Kinds or Metaphors? A Critical Review

Abstract

Dual process theory proposes clusters of features that form two dichotomous groups in cognition. One standing internal issue is defining what the reference of these two dichotomous groups could be in the mind or brain. Does dual process theory speak of two systems, types, minds, modes, kinds or just metaphors? A particular common answer is that differences in clusters of features are evidence of different underlying systems, often called system 1 and system 2. However, the suggestion to abandon the 'system' terminology is now common in the literature, but the consequences of doing so need to be addressed. This work reviews and critically discusses previous suggestions.

Nail-Extracting Behavior as an Unusual Manifestation of Adjustment Disorder, Confused with Onychotillomania

Abstract

Nails are the subject of various psychocutaneous disorders. This spectrum of disorders includes onychophagia, nail tic disorder, onychotillomania, and nail destruction associated with psychiatric disorders.[1] Although self-induced nail injuries, such as biting and rubbing, are common, there was an extraordinary case of self-inflicted, nail-extracting behaviors in an unusual presentation of adjustment disorder.

This article is protected by copyright. All rights reserved.

Metallothionein in Hermetia illucens (Linnaeus, 1758) larvae (Diptera: Stratiomyidae), a potential biomarker for organic waste system

Abstract

Black soldier fly, Hermetia illucens (Linnaeus, 1758), is an important economic fly as its larvae can be used for recycling organic waste, such as food waste and manure. H. illucens larvae (BSFL) could uptake Cd from substrates and accumulate it inside bodies, which need to be monitored during waste treatment. Metallothionein (MT) usually serve as biomarker because of its role in metal homeostasis, detoxification, and dose response of heavy metals. Therefore, a MT gene was cloned from H. illucens (HIMT) that encoded 40 amino acids with typical cysteine rich features, which had a high sequence identity with other insect MTs. The expression of HIMT and total MT protein was measured in BSFL fed by meals spiked with gradient dose of Cd (0, 5, 50, 500 mg/kg) for 24, 48, 72, and 96 h, respectively. Dose-associated response of HIMT and total MT were found and the possible correlative range of Cd was from 5 to 50 mg/kg. The expression of HIMT might be a potential biomarker for monitoring Cd contamination by H. illucens in terrestrial organic matters, which might further apply in waste transformation system.

Commercial silicate phosphate sequestration and desorption leads to a gradual decline of aquatic systems

Abstract

Laboratory desorption behaviour, function and elemental composition of commercially marketed silicate minerals used to sequester phosphorus pollution as well as Zeolite, Smectite, and Kaolinite were determined to see whether their use by environmental scientists and water managers in eutrophic waterways has the potential to contribute to longer-term environmental impacts. As expected, lower phosphorus concentrations were observed, following treatment. However, data relating to desorption, environmental fate and bioavailability of phospho-silicate complexes (especially those containing rare earth elements) appear to be underrepresented in product testing and trial publications. Analysis of desorption of phosphate (P) was > 5 μg[P]/L for all three non-commercial samples and 0 > μg[P]/L > 5 for all commercial silicates for a range of concentrations from 0 to 300 μg[P]/L. Based on a review of bioaccumulation data specific to the endangered Cherax tenuimanus (Hairy Marron) and other endemic species, this is significant considering anything > 20 μg[La]/L is potentially lethal to the hairy marron, other crustaceans and even other phyla. Where prokaryotic and eukaryotic effects are underreported, this represents a significant challenge. Especially where product protocols recommend continual reapplication, this is significant because both the forward and reverse reactions are equally important. The users of silicate minerals in water columns should accept the dynamic nature of the process and pay equal attention to both adsorption and desorption because desorption behaviour is an inherent trait. Even if broader desorption experimentation is difficult, expensive and time-consuming, it is a critical consideration nonetheless.

Response to “Phase IV head-to-head randomised controlled trial comparing ingenol mebutate 0.015% gel with diclofenac sodium 3% gel for the treatment of actinic keratosis on the face or scalp” – reply from authors

Abstract

We thank Drs Malvehy and Puig for their comments on the article; our responses follow. Drs Malvehy and Puig correctly note that the primary endpoint is complete clearance at the end of the first treatment course. Here, the rates are 34.5% for IngMeb and 23.5% for DS. It is not clear why Malvehy and Puig believe that a comparison at the same time point would be better.

This article is protected by copyright. All rights reserved.

Insight into litter decomposition driven by nutrient demands of symbiosis system through the hypha bridge of arbuscular mycorrhizal fungi

Abstract

Arbuscular mycorrhizal fungi (AMF) play an important role in litter decomposition. This study investigated how soil nutrient level affected the process. Results showed that AMF colonization had no significant effect on litter decomposition under normal soil nutrient conditions. However, litter decomposition was accelerated significantly under lower nutrient conditions. Soil microbial biomass in decomposition system was significantly increased. Especially, in moderate lower nutrient treatment (condition of half-normal soil nutrient), litters exhibited the highest decomposition rate, AMF hypha revealed the greatest density, and enzymes (especially nitrate reductase) showed the highest activities as well. Meanwhile, the immobilization of nitrogen (N) in the decomposing litter remarkably decreased. Our results suggested that the roles AMF played in ecosystem were largely affected by soil nutrient levels. At normal soil nutrient level, AMF exhibited limited effects in promoting decomposition. When soil nutrient level decreased, the promoting effect of AMF on litter decomposition began to appear, especially on N mobilization. However, under extremely low nutrient conditions, AMF showed less influence on decomposition and may even compete with decomposer microorganisms for nutrients.

Contiguous verrucous proliferations in syringocystadenoma papilliferum: a retrospective analysis with additional evaluation via mutation-specific BRAF V600E immunohistochemistry

Abstract

Syringocystadenoma papilliferum (SCAP) is a benign adnexal neoplasm with apocrine differentiation.^1,2 which may be derived from pluripotent cells.³ The lesion may develop within a pre-existing nevus sebaceus, but the majority of cases arise sporadically.³ Congenital lesions in a Blaschkoid distribution have also been reported, and these cases are thought to represent genetic mosaicism.^4,5,6 The tumor has a varied clinical appearance, but typically presents as a raised warty, hairless plaque or nodule.³

BRCA 1 and 2 mutation status: the elephant in the room during oncofertility counseling for young breast cancer patients.

Incorporating Blood-based Liquid Biopsy Information into Cancer Staging: Time for a TNMB System?

Abstract

Tissue biopsy is the standard diagnostic procedure for cancer. Biopsy may also provide material for genotyping, which can assist in the diagnosis and selection of targeted therapies but may fall short in cases of inadequate sampling, particularly from highly heterogeneous tumors. Traditional tissue biopsy suffers greater limitations in its prognostic capability over the course of disease, most obviously as an invasive procedure with potential complications, but also with respect to probable tumor clonal evolution and metastasis over time from initial biopsy evaluation. Recent work highlights circulating tumor DNA (ctDNA) present in the blood as a supplemental, or perhaps an alternative, source of DNA to identify the clinically-relevant cancer mutational landscape. Indeed, this non-invasive approach may facilitate repeated monitoring of disease progression and treatment response, serving as a means to guide targeted therapies based on detected actionable mutations in patients with advanced or metastatic solid tumors. Notably, ctDNA is heralding a revolution in the range of genomic profiling and molecular mechanisms to be utilized in the battle against cancer. This review will discuss the biology of ctDNA, current methods of detection and potential applications of this information in tumor diagnosis, treatment, and disease prognosis. Conventional classification of tumors to describe cancer stage follow the TNM notation system, heavily weighting local tumor extent (T), lymph node invasion (N), and detectable metastasis (M). With recent advancements in genomics and bioinformatics, it is conceivable that routine analysis of ctDNA from liquid biopsy (B) may make cancer diagnosis, treatment, and prognosis more accurate for individual patients. We put forward the futuristic concept of TNMB tumor classification, opening a new horizon for precision medicine with the hope of creating better outcomes for cancer patients.

Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma

Abstract

Background

A major limitation of circulating tumor DNA (ctDNA) for somatic mutation detection has been the low level of ctDNA found in a subset of cancer patients. We investigated whether using a combined isolation of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for EGFR mutation detection in NSCLC patients.

Patients and methods

Matched pretreatment tumor and plasma were collected from 84 patients enrolled in TIGER-X (NCT01526928), a Ph1/2 study of rociletinib in mutant EGFR NSCLC patients. The combined isolated exoRNA and cfDNA (exoNA) was analyzed for mutations using a targeted NGS panel (EXO1000), and compared to existing data from the same samples using analysis of ctDNA by BEAMing.

Results

For exoNA, the sensitivity was 98% for detection of activating EGFR mutations and 90% for EGFR T790M. The corresponding sensitivities for ctDNA by BEAMing were 82% for activating mutations and 84% for T790M. In a subgroup of patients with intrathoracic metastatic disease (M0/M1a; n = 21), the sensitivity increased from 26% to 74% for activating mutations (p = 0.003) and from 19% to 31% for T790M (p = 0.5) when using exoNA for detection.

Conclusions

Combining exoRNA and ctDNA increased the sensitivity for EGFR mutation detection in plasma, with the largest improvement seen in the subgroup of M0/M1a disease patients known to have low levels of ctDNA which poses challenges for ctDNA-only based mutation detection.

Clinical Trials

NCT01526928

Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3 . European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 90101 “CREATE”

Abstract

Background

Alveolar soft part sarcoma(ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3(TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the tyrosine kinase inhibitor(TKI) crizotinib in patients with advanced or metastatic ASPS.

Patients and methods

Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg twice daily. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The primary endpoint was the objective response rate(ORR) according to local investigator. Secondary endpoints included duration of response(DOR), disease control rate(DCR), progression-free survival(PFS), progression-free rate(PFR), overall survival(OS) and safety.

Results

Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and evaluable. Among 40 MET+ patients, 1 achieved a confirmed PR that lasted 215 days and 35 had stable disease(SD) as best response(ORR:2.5%, 95%CI:0.6-80.6%). Further efficacy endpoints in MET+ cases were DCR:90.0%(95%CI:76.3-97.2%), 1-year PFS rate: 37.5%(95%CI:22.9-52.1%) and 1-year OS rate:97.4%(95%CI:82.8-99.6%). Among 4 MET- patients, 1 achieved a PR that lasted 801 days and 3 had SD(ORR:25.0%,95%CI:0.6-80.6%) for a DCR of 100% (95%CI:39.8-100.0%). The 1 year PFS rate in MET- cases was 50%(95%CI:5.8-84.5%) and the 1-year OS rate was 75%(95%CI:12.8-96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea(34/48[70.8%]), vomiting (22/48[45.8%]), blurred vision(22/48[45.8%]), diarrhoea(20/48[41.7%]) and fatigue(19/48[39.6%]).

Conclusion

According to EORTC efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients.

Clinical trial number

EORTC 90101, NCT01524926

A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma

Abstract

Background

There is no standard first-line chemotherapy for recurrent/metastatic or unresectable locally advanced salivary gland carcinoma (SGC).

Patients and methods

We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities.

Results

Thirty-six eligible patients were enrolled. Thirty-three patients had recurrent/metastatic disease and three patients had locally advanced disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% (n = 15, 95% confidence interval [CI], 25.5% to 59.2%), the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8% to 87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3 to 12.3 months) and median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 (HER2) status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient.

Conclusion

This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive recurrent/metastatic or unresectable locally advanced SGC compared with conventional chemotherapy, which warrants further study.Clinical Trial Registration: UMIN-CTR (http://ift.tt/1QNm0c9), identification number: UMIN000005703.

PBPK/PD assessment for Parkinson’s disease risk posed by airborne pesticide paraquat exposure

Abstract

Exposure to several specific pesticides has led to an increase of Parkinson's disease (PD) risk. However, it is difficult to quantify the PD population risk related to certain pesticides in regions where environmental exposure data are scarce. Furthermore, the time trend of the prevalence and incidence of PD embedded in the background relationship between PD risk and pesticide exposures has not been well characterized. It has been convincingly identified that a key pesticide associated significantly with an increased risk trend of PD is paraquat (PQ). Here, we present a novel, probabilistic population-based exposure-response approach to quantify the contribution from PQ exposure to prevalence risk of PD. We found that the largest PQ exposure contributions occurred in its positive trend during 2004–2011, with the PQ contributing nearly 21 and 24%, respectively, to the PD prevalence rates among the age groups of 70–79 and ≥ 80 years in Taiwan. We also employed the present population risk model to predict the PQ-induced PD prevalence based on the projected rates of increase in PQ exposure associated with age-specific population. The predicted outcome can be used as an early warning signal for public health authorities. We suggest that a mechanistic understanding of the contribution of a specific pesticide exposure to PD risk trends is crucial to enhance our insights into the perspective on the impacts of environmental exposure on the neurodegenerative diseases.

Hidradenitis and smoking – reply from authors

Abstract

We thank Saleem et al., for providing commentary on a relevant aspect of statistical analysis and interpretation as it relates to our study, the primary objective for which was to assess the directionality and strength of relationship between tobacco smoking (TS) and hidradenitis suppurativa (HS).¹ To our knowledge, no previous population-based study has evaluated the effect of TS on actual incidence of disease. While we were able to establish that smokers had twice the adjusted likelihood of incident disease compared to non-smokers, we agree that relative measures of risk may overestimate the effect of an exposure, particularly when the outcome of interest is rare.

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Hydrochlorothiazide use and risk of non-melanoma skin cancer: A nationwide case-control study from Denmark

Publication date: Available online 4 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Sidsel Arnspang, David Gaist, Sigrun Alba Johannesdottir Schmidt, Lisbet Rosenkrantz Hölmich, Søren Friis, Anton Pottegård
BackgroundHydrochlorothiazide, one of the most frequently used diuretic and antihypertensive drugs in the United States and Western Europe, is photosensitizing and has previously been linked to lip cancer.ObjectiveTo examine the association between hydrochlorothiazide use and the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).MethodsFrom the Danish Cancer Registry, we identified patients (cases) with NMSC during 2004-2012. Controls were matched 1:20 by age and sex. Cumulative hydrochlorothiazide use (1995-2012) was assessed from the Danish Prescription Registry. Using conditional logistic regression, we calculated odds ratios (ORs) for BCC and SCC associated with hydrochlorothiazide use.ResultsHigh use of hydrochlorothiazide (≥50,000 mg) was associated with ORs of 1.29 (95% confidence interval [CI] 1.23-1.35) for BCC and 3.98 (95% CI 3.68-4.31) for SCC. We found clear dose-response relationships between hydrochlorothiazide use and both BCC and SCC; the highest cumulative dose category (≥200,000 mg HCTZ) had ORs of 1.54 (95% CI 1.38-1.71) and 7.38 (95% CI 6.32-8.60) for BCC and SCC, respectively. Use of other diuretics and antihypertensives was not associated with NMSC.LimitationsNo data on sun exposure was available.ConclusionsHydrochlorothiazide use is associated with a substantially increased risk of NMSC, especially SCC.

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Persian Gulf region: A Case and Review

Summary

Cerebral phaeohyphomycosis is frequently a fatal disease caused by truly neurotropic dematiaceous fungi. Although rare, this infection occurs especially among immunocompetent patients, and the clinical symptoms are often misdiagnosed as a cerebral tumor or bacterial brain abscess. The appropriate diagnosis and therapy of cerebral infections by melanized fungi are very challenging if they are caused by mysterious fungi with unknown ecological niche, natural habitat a host factors related to pathogenicity. We reported the second case of cerebral phaeohyphomycosis due to R. mackenziei in Iran and the first culture-confirmed case. In this report, the differential diagnosis and histopathological findings are discussed and a review of the literature is provided.

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Therapeutic and prognostic significance of PARP-1 in advanced mycosis fungoides and sezary syndrome

Abstract

While mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP-1, heat shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA-helicase (DDX17), and the α isoform of lamina-associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1 was overexpressed in patients with early stage of MF who developed later an aggressive disease. PARP-1 was evaluated as a new target for therapy, demonstrating the selective dose-dependent cytotoxic effect of PARP inhibitors on Sézary cells in comparison with non-malignant lymphocytes. In conclusion, we believe that PARP-1 may serve not only as a biomarker at initial biopsies for a disease that may become aggressive but also as a new therapeutic target of advanced MF and Sézary syndrome.

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Haze and health impacts in ASEAN countries: a systematic review

Abstract

Seasonal haze episodes and the associated inimical health impacts have become a regular crisis among the ASEAN countries. Even though many emerging experimental and epidemiological studies have documented the plausible health effects of the predominating toxic pollutants of haze, the consistency among the reported findings by these studies is poorly understood. By addressing such gap, this review aimed to critically highlight the evidence of physical and psychological health impacts of haze from the available literature in ASEAN countries. Systematic literature survey from six electronic databases across the environmental and medical disciplines was performed, and 20 peer-reviewed studies out of 384 retrieved articles were selected. The evidence pertaining to the health impacts of haze based on field survey, laboratory tests, modelling and time-series analysis were extracted for expert judgement. In specific, no generalization can be made on the reported physical symptoms as no specific symptoms recorded in all the reviewed studies except for throat discomfort. Consistent evidence was found for the increase in respiratory morbidity, especially for asthma, whilst the children and the elderly are deemed to be the vulnerable groups of the haze-induced respiratory ailments. A consensual conclusion on the association between the cardiovascular morbidity and haze is unfeasible as the available studies are scanty and geographically limited albeit of some reported increased cases. A number of modelling and simulation studies demonstrated elevating respiratory mortality rates due to seasonal haze exposures over the years. Besides, evidence on cancer risk is inconsistent where industrial and vehicular emissions are also expected to play more notable roles than mere haze exposure. There are insufficient regional studies to examine the association between the mental health and haze. Limited toxicological studies in ASEAN countries often impede a comprehensive understanding of the biological mechanism of haze-induced toxic pollutants on human physiology. Therefore, the lack of consistent evidence among the reported haze-induced health effects as highlighted in this review calls for more intensive longitudinal and toxicological studies with greater statistical power to disseminate more reliable and congruent findings to empower the institutional health planning among the ASEAN countries.

Synergistic phytoremediation of wastewater by two aquatic plants ( Typha angustifolia and Eichhornia crassipes ) and potential as biomass fuel

Abstract

The ability of a mixture of Typha angustifolia and Eichhornia crassipes to remove organics, nutrients, and heavy metals from wastewater from a Thailand fresh market was studied. Changes in physicochemical properties of the wastewater including pH, temperature, chemical oxygen demand, dissolved oxygen, biochemical oxygen demand (BOD), total P, TOC, conductivity, total Kjeldahl nitrogen, NO₃⁻-N, NH₃-N, and metal (Pb, Cd, and Zn) concentrations were monitored. In the aquatic plant (AP) treatment, 100% survival of both species was observed. Dry biomass production and growth rate of T. angustifolia were approximately 3.3× and 2.7× of those for E. crassipes, respectively. The extensive root system of the plants improved water quality as determined by a marked decrease in turbidity in the AP treatment after 7 days. BOD content served as a useful indicator of water quality; BOD declined by 91% over 21 days. Both T. angustifolia and E. crassipes accumulated similar quantities of metals in both roots and shoots. Accumulation of metals was as follows: Zn > Cd > Pb. A study of calorific value and biomass composition revealed that T. angustifolia and E. crassipes possessed similar carbon content (~ 35%), hydrogen content (~ 6%), and gross calorific value. E. crassipes contained up to 16.9% ash and 65.4% moisture. Both species are considered invasive in Thailand; however, they may nonetheless provide practical benefits: In addition to their combined abilities to treat wastewater, T. angustifolia holds potential as an alternative energy source due to its high biomass production.

The need for longer time horizons for cost-utility evaluation in bullous pemphigoid

Abstract

We read with interest the article from Mason et al offering a cost-effectiveness analysis comparing doxycycline and prednisolone as initial treatment for bullous pemphigoid (BP). ¹ As a prospective cost-utility analysis auxiliary to a multi-centre randomised controlled trial² with robust statistical modelling, the study is methodologically sound. The time horizon of the study was twelve months and the primary outcomes sought were short-term effectiveness and long-term safety.

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Response to “Phase IV head-to-head randomised controlled trial comparing ingenol mebutate 0.015% gel with diclofenac sodium 3% gel for the treatment of actinic keratosis on the face or scalp”

Abstract

We read with attention the recent paper by Stockfleth et al¹ on the efficacy and safety of Ingenol Mebutate 0.015% gel (IngMb) vs. diclofenac sodium 3% gel (DS) for the treatment of actinic keratosis (AK). Regarding this interesting study, we would like to address some comments to the authors.In this study, the primary endpoint was complete clearance of AKs (AKCLEAR100) at end of first treatment course (Week8, IngMeb; Week17, DS).

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The need for longer time horizons for cost-utility evaluation in bullous pemphigoid – reply from authors

Abstract

We thank Drs Liu and Sebaratnam for their commentary on our paper¹ and agree with their insights. The adverse event legacy or oral steroids may be a long one; their concerns support our proposed strategy of sparing oral steroids by starting on doxycycline. Of patients starting on doxycycline within the BLISTER trial, 57.8% subsequently received at least one prescription of prednisolone. Thus, the two strategies may converge over time, although possibly much less prednisolone is required to achieve remission at least in the first year.

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Hidradenitis and smoking

Abstract

Smoking is common in patients with hidradenitis suppurativa and may be a risk factor for the disease.¹ Garg et al reported in a large, population-based, retrospective cohort study that apparently new hidradenitis was seen in 0.20% (7,860/3,924,310) of smokers versus 0.11% (8,430/8,027,790) of non-smokers over a 3 year period.² They concluded that hidradenitis is twice as common among smokers, a finding that lay media have covered³, and suggest that populations at risk for hidradenitis be counselled for smoking cessation.²

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Associations between body mass index and severity of psoriasis.

Associations between body mass index and severity of psoriasis.

Clin Cosmet Investig Dermatol. 2017;10:493-498

Authors: Sobhan M, Farshchian M

Abstract
Objective: Compared with healthy people, overweight and obesity are more commonly found among those suffering from skin conditions such as psoriasis. The present study was an attempt to survey the relationship between obesity and intensity of psoriasis.
Patients and methods: A total of 42 patients with psoriasis who were referred to Farshchian Hospital, Hamadan, participated in this cross-sectional descriptive-analytical study. Patients were classified into mild, moderate and severe based on the intensity of the disease measured by Psoriasis Area and Severity Index (PASI). Body mass index (BMI), waist size, age, gender, smoking and drinking habits of the participants were measured and compared.
Results: A total of 15 (35.07%) patients had mild psoriasis, 9 (21.4%) patients had moderate psoriasis and 18 (42.9%) patients suffered from severe psoriasis. Mean BMI of mild psoriasis patients was 25.86±5.93 kg/m2, and this figure for the moderate and severe psoriasis patients was 30.85±3.77 kg/m2 and 26.96±5.68 kg/m2, respectively (P=0.096). Mean waist size of the mild psoriasis patients was 91.54±11.49 cm, and for moderate and severe patients, it was 99±8.39 cm and 92.17±10.73 cm, respectively (P=0.211).
Conclusion: The results of this study showed no significant difference between mean value of body mass index, waist size, age and gender in mild, moderate and severe groups of the psoriasis patients.

PMID: 29200884 [PubMed]

Children’s environmental chemical exposures in the USA, NHANES 2003–2012

Abstract

Children are vulnerable to environmental chemical exposures, but little is known about the extent of multiple chemical exposures among children. We analyzed biomonitoring data from five cycles (2003–2012) of the National Health and Nutrition Examination Survey (NHANES) to describe multiple chemical exposures in US children, examine levels of chemical concentrations present over time, and examine differences in chemical exposures by selected demographic groups. We analyzed data for 36 chemical analytes across five chemical classes in a sample of 4299 children aged 6–18. Classes included metals, pesticides, phthalates, phenols, and polycyclic aromatic hydrocarbons. We calculated the number and percent of chemicals detected and tested for secular trends over time in chemical concentrations. We compared log concentrations among groups defined by age, sex, race/ethnicity, and poverty using multiple linear regression models and report adjusted geometric means. Among a smaller subgroup of 733 children with data across chemical classes, we calculated the linear correlations within and between classes and conducted a principal component analysis. The percentage of children with detectable concentrations of an individual chemical ranged from 26 to 100%; the average was 93%, and 29 of 36 were detected in more than 90% of children. Concentrations of most tested chemicals were either unchanged or declined from earlier to more recent years. Many differences in concentrations were present by age, sex, poverty, and race/ethnicity categories. Within and between class correlations were all significant and positive, and the principal component analysis suggested a one factor solution, indicating that children exposed to higher levels of one chemical were exposed to higher levels of other chemicals. In conclusion, children in the USA are exposed to multiple simultaneous chemicals at uneven risk across socioeconomic and demographic groups. Further efforts to understand the effects of multiple exposures on child health and development are warranted.

Diagnostic value of 99m Tc-ethambutol scintigraphy in tuberculosis: compared to microbiological and histopathological tests

Abstract

Objective

Tuberculosis (TB) still remains the world's endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using ^99mTc. ^99mTc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of ^99mTc-ethambutol scintigraphy in detecting and localizing of TB.

Methods

Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370–555 MBq ^99mTc-ethambutol. ^99mTc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy.

Results

One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between ^99mTc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of ^99mTc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB 95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study.

Conclusion

^99mTc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra- and extra-pulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.

Design and Operation of the Transformed National Healthy Start Evaluation

Abstract

Purpose Improving pregnancy outcomes for women and children is one of the nation's top priorities. The Healthy Start (HS) program was created to address factors that contribute to high infant mortality rates (IMRs) and persistent disparities in IMRs. The program began in 1991 and was transformed in 2014 to apply lessons from emerging research, past evaluation findings, and expert recommendations. To understand the implementation and impact of the transformed program, there is a need for a robust and comprehensive evaluation. Description The national HS evaluation will include an implementation evaluation, which will describe program components that affect outcomes; a utilization evaluation, which will examine the characteristics of women and infants who did and did not utilize the program; and an outcome evaluation, which will assess the program's effectiveness with regard to producing expected outcomes among the target population. Data sources include the National HS Program Survey, a HS participant survey, and individual-level program data linked to vital records and the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. Assessment Descriptive analyses will be used to examine differences in risk profiles between participants and non-participants, as well as to calculate penetration rates for high-risk women in respective service areas. Multivariable analyses will be used to determine the impact of the program on key outcomes and will explore variation by dose, type of services received, and grantee characteristics. Conclusion Evaluation findings are expected to inform program decisions and direction, including identification of effective program components that can be spread and scaled.