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Δευτέρα 22 Οκτωβρίου 2018

Ambient Fine Aerosol Concentrations in Multiple Metrics in Taconite Mining Operations

Abstract
Studies in environmental epidemiology and of occupational cohorts have implicated the effects of fine particulates with increased risk of cardiovascular diseases. Motivated by this evidence, we conducted an ambient air monitoring campaign to characterize fine aerosol concentrations around various taconite ore processes in six taconite mines in northeastern Minnesota. The ore processes were first categorized into 16 broad work areas/buildings. We then took air samples at 91 fixed locations using an array of direct-reading instruments to obtain measurements of mass (PM2.5 or particles with aerodynamic diameter <2.5 µm, and respirable particulate matter or RPM), alveolar-deposited surface area (ADSA), and particle number (PN) concentrations. At each location, a respirable gravimetric pump (which was used for calibration purposes) and the instruments measured the ambient dust level for 4 h producing ~240 1-min averaging real-time measurements. To analyze these data, we fit a Bayesian hierarchical model with an autoregressive order 1 correlation structure to estimate pooled concentrations for the 16 work areas/buildings while accounting for temporal correlation. PM2.5 and RPM average ambient concentrations were highly correlated to each other (Pearson's correlation = 0.98), followed by ADSA and PN correlation (R = 0.77). Office and control room areas were found to have the lowest concentrations in all four metrics when compared to other groups. Distinguishing between concentration levels among the remaining groups was more difficult due to the high uncertainty associated with the geometric mean estimates. The geometric standard deviation within location (GSDWL) generally ranged from 1 to 3 for all exposure metrics, except for a few locations that may have had changes in the work activities that generated the observed peaks and variability during the sampling duration. The geometric standard deviation between locations estimates were generally higher than GSDWL, which may indicate larger variability in the processes/activities between locations within each broad work area/building. Future work may look into whether it is feasible to use area measurements for epidemiological investigation and use personal measurements (if available) to validate such approach.

Recruitment of Activated Neutrophils Correlates with Disease Severity in Adult Crohn's Disease

Clinical &Experimental Immunology, Volume 0, Issue ja, -Not available-.


Microplastics Are Turning Up Everywhere, Even In Human Excrement

Microplastics are not just showing up on beaches like this one in the Canary Islands. They are showing up in human waste.

A very small study shows that microplastics are in human waste in many parts of the world. While it's not entirely clear what that means for our health, it might be a sign that we need to pull back.

(Image credit: Desiree Martin/AFP/Getty Images)

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Vertical Medial Thigh Contouring

Excess thigh laxity is a problem for many patients following significant weight loss. Thigh laxity has both vertical and horizontal components that require correction to optimize the aesthetic appearance of the thigh. The vertical vector is best corrected first with a lower body lift or extended abdominoplasty. The remaining loose skin in the medial thigh can then be removed using a horizontal vector resulting in a vertical incision. Residual vertical skin excess is also removed parallel to the groin crease. This article describes the author's surgical approach and management of medial thigh deformity in the significant weight loss patient.

Common Complications and Management After Massive Weight Loss Patient Safety in Plastic Surgery

This article discusses strategies to prevent and manage the most common complications seen in body contouring surgery. General approaches to avoidance and treatment of these complications are addressed, including wound dehiscence, delayed wound healing, seroma, hematoma, infections of the surgical or remote sites, lymphedema, suture extrusion, and fat necrosis. Procedure-specific complications and pearls to avoiding complications in these cases are presented. Difficult problems, such as management of the disappointed patient, also are discussed.

Safety in Body Contouring to Avoid Complications

Body contouring after weight loss is becoming more prevalent. An appropriate systematic approach that starts from the first consultation needs to focus on residual comorbidities and weight of the patient. A thorough discussion about potential outcomes manages expectations. Preoperative optimization with smoking, herbal cessation, and nutritional assessment is mandatory. Planned staged approach minimizes lengthy procedures associated with increased postoperative morbidity. In the operating room, appropriate ambient temperature, positioning of the patient, and continuous discussion between surgeon and anesthesiologist prevent further complications. Careful transition to postoperative care with early ambulation and use of compressive garments add to an approach to minimize postoperative complications.

Arm Contouring in the Massive-Weight-Loss Patient

Brachioplasty is an increasingly popular procedure performed for improved arm contour in the massive-weight-loss population. There are challenging deformities presented in this population, such as redundant skin, posterior arm lipodystrophy, and loosening of fascial layers of the upper arm and chest wall that must be addressed to achieve successful contour of the arms. Common complications can be minimized with meticulous technique and knowledge of surgical anatomy. Additionally, brachioplasty can be combined with liposuction of the posterior arm as a safe and effective method for arm contouring without a higher risk of complications.

Buttock Lifting

There are some precise rules to succeed with a buttock lift. The article begins with a reminder about the ideal buttock shape. It explains the different quality of skin that is essential to be aware of at the back part of the body. Afterward it gives the tightening rule and the author's application in buttock lift. The markings and the cutting principles are described in detail. At the end, the article describes the problems of volume at the buttocks and about the author's new flap that is useful to avoid violin deformation. The article finishes with some examples of surgeries.

Bra-Line Back Lift

Upper back deformity caused by aging or fluctuations in weight are cosmetically and functionally unappealing to patients. Natural upper torso adherence zones create tether points that lead to horizontal and vertical laxity. Bra-line back lift is a versatile technique that can be used in any individual showing signs of redundant skin and adiposity. A 3-layered space-obliterating suture closure method prevents seroma and eliminates need for drain. Predictable outcomes correcting laxity from neck to lower back can be achieved. Gentle learning curve yields consistent and predictable results. Patient acceptance of the procedure, its results, and satisfactory morbidity rates have been universal.

In Response to “Descriptive Survival Study of Nail Melanoma Patients Treated With Functional Surgery vs Distal Amputation”



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The Prognostic Value of Inositol Polyphosphate 5-Phosphatase in Cutaneous Squamous Cell Carcinoma

Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in cancer development and progression. We found that low INPP5A expression is associated with aggressive tumors and poor outcomes. INPP5A is a novel tumor marker that may help in the management of cutaneous squamous cell carcinoma.

VEGF-A inhibition as a potential therapeutic approach in Merkel cell carcinoma



Genetic Abnormalities in Large to Giant Congenital Nevi: Beyond NRAS mutations

Large and giant congenital melanocytic nevi (CMN) are rare melanocytic lesions mostly caused by post-zygotic NRAS alteration. Molecular characterization is usually focused on NRAS and BRAF genes in a unique biopsy of the CMN. However, large/giant CMN may exhibit phenotypic differences among distinct areas, and patients differ in features such as presence of multiple CMN or Spilus-like lesions. Herein, we have characterized a series of 21 large/giant CMN including Spilus-type nevus patients (9/21 cases, 42.8%).

EU Panel Backs Drug for Rare Hereditary Angioedema

Lanadelumab would be the first monoclonal antibody for preventing recurrent attacks of HAE in patients ages 12 years and older.
International Approvals

Growth Hormone Deficiency and Nonalcoholic Fatty Liver Disease with Insights from Humans and Animals: Pediatric Implications

Metabolic Syndrome and Related Disorders, Ahead of Print.


Plasma Growth Arrest-Specific 6 Protein and Genetic Variations in the GAS6 Gene in Patients with Metabolic Syndrome

Metabolic Syndrome and Related Disorders, Ahead of Print.


Multimodal image registration for liver radioembolization planning and patient assessment

Abstract

Purpose

Multimodal imaging plays a key role in patient assessment and treatment planning in liver radioembolization. It will reach its full potential for convenient use in combination with deformable image registration methods. A registration framework is proposed for multimodal liver image registration of multi-phase CT, contrast-enhanced late-phase T1, T2, and DWI MRI sequences.

Methods

A chain of four pair-wise image registrations based on a variational registration framework using normalized gradient fields as distance measure and curvature regularization is introduced. A total of 103 cases of 35 patients was evaluated based on anatomical landmarks and deformation characteristics.

Results

Good anatomical correspondence and physical plausibility of the deformation fields were attained. The global mean landmark errors vary from 3.20 to 5.36 mm, strongly influenced by low resolved images in z-direction. Moderate volume changes are indicated by mean minimum and maximum Jacobian determinants of 0.44 up to 1.88. No deformation foldings were detected. The mean average divergence of the deformation fields range from 0.08 to 0.16 and the mean harmonic energies vary from 0.08 to 0.58.

Conclusion

The proposed registration solutions enable the combined use of information from multimodal imaging and provide an excellent basis for patient assessment and primary planning for liver radioembolization.



Benefits of a membership in a psoriasis patient organisation: a quasi-experimental longitudinal study

Abstract

Background and Objectives

Patient organisations play an important role in supporting patients with chronic diseases and allow information transfer beyond professional care structures. Until now, only few studies have investigated the benefits of a dermatological patient organisation. In this study, potential benefits of joining the German Psoriasis Association (Deutscher Psoriasis Bund e. V., DPB) were surveyed.

Methods

The quasi-experimental longitudinal design included four groups of individuals suffering from psoriasis: those (1) with DPB membership of 5 years, (2) with voluntary new membership, (3) with randomly awarded membership, and (4) without membership. Participants were interviewed two times in 12 months, about quality of life, depression, participation in patient education classes, health status, and treatment benefits.

Results

295 individuals participated (mean age 54 years; 50.3% females). At the outset of the study, participants with voluntary new membership rated their health status worse and showed higher depression scores than those with awarded membership. The proportion of participants who joined patient education classes only increased in the group of long-term members. Health status worsened in the group of non-members, and it improved in the group of those with awarded and voluntary new membership. Treatment benefit only increased in the voluntary new members group.

Conclusions

DPB membership seems to be associated with some relief from psoriasis-related strains, particularly in the group of those who joined voluntarily. This could be due to the fact that individuals who become members out of their own volition are more likely to seek information and, therefore, benefit from their active engagement.



Integrating Clinical and Epidemiological Data on Allergic Diseases Across Birth Cohorts: a MeDALL Harmonization Study

Abstract
International collaborations among birth cohorts to better understand asthma and allergies have increased in the last years. However, differences in definitions and methods preclude direct pooling of original individual participant data. We harmonized data from 14 birth cohorts, with three to 20 follow-ups, from nine European countries, as part of the Mechanisms of the Development of Asthma and Allergies (MeDALL) project. The harmonization process followed six steps: organization of the harmonization panel; identification of variables relevant to MeDALL objectives (candidate variables); proposal of a definition for each candidate variable (reference definition); assessment of the compatibility of each cohort variable to its reference definition (inferential equivalence) and classifications of this inferential equivalence as complete, partial, or impossible; workshop to agree on the reference definitions and classifications of inferential equivalence; and data preparation and delivery through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definition was classified as complete, partial and impossible for 70%, 15% and 15% of the variables, respectively. A harmonized database was delivered. In birth cohorts of asthma and allergies, the harmonization of data for pooled analyses is feasible and may achieve high inferential comparability. The MeDALL harmonization approach can be used in other collaborative projects.

The Development and Validation of a Clinical Prediction Rule to Predict Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing Homes

Abstract
The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among nursing home residents is high. Healthcare workers (HCWs) often serve as a vector in the transmission of MRSA. The ability to identify residents who are likely to transmit MRSA to HCWs' hands and clothing during clinical care is important so that infection control measures, such as Contact Precautions, can be employed. We developed a clinical prediction rule with demographics and clinical characteristics as predictors of MRSA transmission to HCWs' gowns collected from residents of community nursing homes in Maryland and Michigan between 2012-2014. We externally validated this model in a cohort of Veterans Affairs nursing home residents from 7 states between 2012-2016. The prediction model, which included sex, race, resident dependency on HCWs for care, the presence of any device, diabetes, and chronic skin breakdown, showed good performance (c-statistic=0.70, sensitivity=76%, specificity=49%) in the development set. The decision curve analysis indicates this model has greater clinical utility than using a nares surveillance culture for MRSA colonization, which is current clinical practice for placing hospital inpatients on Contact Precautions. The prediction rule demonstrated less utility in the validation cohort, suggesting a separate rule should be developed for residents of Veterans Affairs nursing homes.

Issue Information

Experimental Dermatology, Volume 27, Issue 11, Page 1192-1192, November 2018.


Clinical Snippets

Experimental Dermatology, Volume 27, Issue 11, Page i-i, November 2018.


Application of the HTA Core Model for complex evaluation of the effectiveness and quality of Radium-223 treatment in patients with metastatic castration resistant prostate cancer

Health technology assessment (HTA) is currently one of the major challenges in assessing medical innovations and healthcare systems. In Europe, the European Network for Health Technology Assessment (EUnetHTA) ...

Antipsychotic Drugs Don't Ease ICU Delirium Or Dementia

A major study published Monday finds that widely prescribed antipsychotic drugs like haloperidol are no more effective than a placebo for treating delirium.

Though widely prescribed in hospital intensive care units to treat hallucinations and other signs of delirium, Haldol and similar drugs are no better than a placebo for such patients, a study finds.

(Image credit: Nehru Sulejmanovski/Getty Images)

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Specialisation and the Incommensurability Among Scientific Specialties

Abstract

In his mature writings, Kuhn describes the process of specialisation as driven by a form of incommensurability, defined as a conceptual/linguistic barrier which promotes and guarantees the insularity of specialties. In this paper, we reject the idea that the incommensurability among scientific specialties is a linguistic barrier. We argue that the problem with Kuhn's characterisation of the incommensurability among specialties is that he presupposes a rather abstract theory of semantic incommensurability, which he then tries to apply to his description of the process of specialisation. By contrast, this paper follows a different strategy: after criticising Kuhn's view, it takes a further look at how new scientific specialties emerge. As a result, a different way of understanding incommensurability among specialties will be proposed.



Leptomeningeal tumor response to combined MAPK/ERK inhibition in V600E mutated gliomas despite undetectable CSF drug levels

dabrafenibtrametinibBRAFleptomeningeal disseminationglioma

Editorial on “Interpretation of time-to-event outcomes in randomized trials: an online randomized experiment” by I. R. Weir et al.



Techniques for generating attenuation map using cardiac SPECT emission data only: a systematic review

Abstract

To reliably interpret and perform quantitative analysis, attenuation correction for cardiac single-photon emission computed tomography (SPECT) is fundamental. Thus, knowledge of the patient-specific attenuation map for accurate correction is required in SPECT quantitative imaging. The aim of this systematic review is to present general principles of attenuation correction and provide a structured summary of the approaches that have been proposed for generating the attenuation map for cardiac SPECT. We identified relevant articles published in English pertaining to the attenuation map (AM) determination using SPECT emission data only by searching PubMed, EMBASE, Scopus, and Web of Science databases. Moreover, other articles were hand searched. The protocol of this systematic review was registered in PROSPERO and the code given is CRD42017060512. Transmissionless techniques of determining attenuation map including calculated methods, statistical modeling for simultaneous estimation of attenuation and emission, consistency conditions criteria, using scattered data and other methods were reviewed. Methods for performing attenuation map for cardiac SPECT are developing and the progresses made are promising. However, much work is needed to assess the efficacy of the correction schemes in the clinical routine.



Beyond Annulus Size: Imaging for TAVR Planning

Abstract

Purpose of Review

The aim of this article is to review the role of imaging in pre-procedural assessment prior to transcatheter aortic valve replacement (TAVR)—with a focus on relevant anatomic findings apart from the size of the aortic annulus.

Recent Findings

Pre-procedure imaging prior to TAVR heavily emphasizes assessment of the aortic annulus for appropriate valve sizing, with computed tomography angiography (CTA) emerging as the test of choice due to its ability to assess not only the aortic annulus but also the thoracoabdominal aorta and peripheral vasculature. Some patients with underlying kidney disease may be at increased risk of renal dysfunction following contrast-enhanced CTA; however, alternate imaging techniques can be performed to mitigate this risk such as magnetic resonance imaging.

Summary

Familiarity with underlying anatomic variability and pathology relevant to TAVR implantation in addition to annulus size, as well as imaging approaches in patients with renal dysfunction, will allow radiologists to better contribute to multidisciplinary discussion for potential TAVR candidates.



Against predicativism about names

Abstract

According to predicativism about names, names which occur in argument positions have the same type of semantic contents as predicates. In this paper, I shall argue that these bare singular names do not have the same type of semantic contents as predicates. I will present three objections to predicativism—the modal, the epistemic, and the translation objections—and show that they succeed even against the more sophisticated versions of predicativism defended by Fara and Bach.



Endothelium-dependent and -independent functions in migraineurs



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Simulation study on X-ray phase contrast imaging with dual-phase gratings

Abstract

Purpose

Two phase gratings in an X-ray grating interferometers can solve several technical challenges for clinical use of X-ray phase contrast. In this work, we adapt and evaluate this setup design to clinical X-ray sources and detectors in a simulation study.

Methods

For a given set of gratings, we optimize the remaining parameter space of a dual-phase grating setup using a numerical wave front simulation. The simulation results are validated with experimentally obtained visibility measurements on a setup with a microfocus tube and a clinical X-ray detector. We then confirm by simulation that the Lau condition for the \(G_0\) grating also holds for two phase gratings. Furthermore, we use a \(G_0\) grating with a fixed period to search for periods of matching phase grating configurations.

Results

Simulated and experimental visibilities agree very well. We show that the Lau condition for a dual-phase grating setup requires the interference patterns of the first phase grating to constructively overlay at the second phase grating. Furthermore, a total of three setup variants for given \(G_{0}\) periods were designed with the simulation, resulting in visibilities between 4.5 and 9.1%.

Conclusion

Dual-phase gratings can be used and optimized for a medical X-ray source and detector. The obtained visibilities are somewhat lower than for other Talbot–Lau interferometers and are a tradeoff between setup length and spatial resolution (or additional phase stepping, respectively). However, these disadvantage appears minor compared to the overall better photon statistics, and the fact that dual-phase grating setups can be expected to scale to higher X-ray energies.



Biophysical properties of striae rubra and striae alba in human skin: Comparison with normal skin

Skin Research and Technology, EarlyView.


The role of in vivo reflectance confocal microscopy in assessing the stability of vitiligo vulgaris prior to cellular grafting

Skin Research and Technology, EarlyView.


Micro‐relief analysis with skin capacitive imaging

Skin Research and Technology, EarlyView.


Water adsorption with relative humidity changes for keratin and collagen as studied by infrared (IR) micro‐spectroscopy

Skin Research and Technology, EarlyView.


Want To Keep Your Brain Sharp? Take Care Of Your Eyes And Ears

Man gets hearing aid adjusted. Studies found restoring hearing and vision can stave off cognitive decline.

Two large studies show that age-related memory loss can be slowed significantly when older people promptly address hearing and vision loss.

(Image credit: Leyla B/Getty Images)

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Research Letter: Cross reactivity of latex agglutination assay complicates the identification of Burkholderia pseudomallei from soil.

Abstract
The monoclonal antibody—based latex agglutination tests targeting a high molecular weight exopolysaccharide antigen of Burkholderia pseudomallei are commercially available. The tests are primarily used in routine diagnosis of melioidosis in major hospitals in Thailand and some endemic countries. Being a rapid test, this technique was employed as a presumptive test to identify colonies of B. pseudomallei among many others grown from soil specimens collected from southern Thailand. Cross-reactivity of these tests with other soil bacteria was a concern since it complicated the identification of B. pseudomallei. Here, we describe the cross-reactivity of two commercial latex agglutination tests for melioidosis with B. territorii, B. pseudomultivorans, B. multivorans and B. cenocepacia isolates from soil.

Metabolomics approach used for understanding temperature-related pectinase activity in Bacillus licheniformis DY2

Abstract
Pectinases are enzymes that catalyze pectin degradation. There is a global demand for pectinases because of their wide utility and catalytic efficiency. Optimization of the fermentation process to increase the pectolytic enzyme activity is generally practiced to lower process costs, but whether temperature influences the metabolome, enhancing pectinase activity, is not known. Here, we developed a metabolomics approach to explore it. The activity of P-DY2 pectinase produced by Bacillus licheniformis DY2 was higher in cells grown at 30°C than those grown at 37 °C. Differential metabolome analysis revealed fluctuating tricarboxylic acid (TCA) cycle at 30 °C. Consistently, the transcripts of TCA cycle genes and activities of pyruvate dehydrogenase and α-Ketoglutaric dehydrogenase were lower at 30 °C than 37 °C. Furthermore, inhibition of pyruvate dehydrogenase and succinate dehydrogenase enhanced the activity of P-DY2, supporting the conclusion that the inactivated pyruvate metabolism and TCA cycle were required for pectinase activity, and that P-DY2 was TCA cycle-independent. Collectively, these findings indicated that fermentation temperature affected P-DY2 activity by metabolic modulation, with an inactivated TCA cycle as a characteristic feature of high P-DY2 activity. More importantly, the present study highlights an approach of promoting pectinase activity through metabolic modulation by using metabolic pathway inhibitors.

Genome analysis of lactic acid bacterial strains selected as potential starters for traditional Slovakian bryndza cheese

Abstract
Genomes of 21 strains of lactic acid bacteria isolated from Slovakian traditional cheeses were sequenced on an Illumina MiSeq platform. Subsequently, they were analysed regarding taxonomic classification, presence of genes encoding defence systems, antibiotic resistance and production of biogenic amines. Thirteen strains were found to carry genes encoding at least one bacteriocin, 18 carried genes encoding at least one restriction-modification system, all strains carried 1–6 prophages and 9 strains had CRISPR-Cas systems. CRISPR-Cas type II-A was the most common, containing 0–24 spacers. Only 10% spacers were found to be homological to known bacteriophage or plasmid sequences in databases. Two Enterococcus faecium strains and a Lactococcus lactis strain carried antibiotic resistance genes. Genes encoding for ornithine decarboxylase were detected in 4 strains and genes encoding for agmatine deiminase were detected in 4 strains. Lb. paraplantarum 251 L appeared to be the most interesting strain, as it contained genes encoding for two bacteriocins, a restriction-modification system, two CRISPR-Cas systems, four prophages and no genes connected with antibiotic resistance or production of biogenic amines.

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Epidemiology and Immunopathogenesis of Psoriasis and Its Comorbidities

Abstract

Purpose of Review

While psoriasis has traditionally been considered primarily a skin and joint disorder, there is a new appreciation that psoriasis affects multiple organs. In fact, psoriasis is associated with several comorbidities that also affect the vasculature, guts, lung, kidney, and other tissues. This review aims to summarize the epidemiology and immunopathogenesis of psoriasis and its comorbidities.

Recent Findings

We reviewed the current literature characterizing the epidemiology and immune pathways of psoriasis and its comorbidities and report common inflammatory and immune pathways implicated in the pathogenesis of psoriasis and its comorbidities.

Summary

A variety of diseases are associated with psoriasis, including psoriatic arthritis, metabolic syndrome, atherosclerosis and cardiovascular disease, nonalcoholic fatty liver disease, inflammatory bowel disease, uveitis, and chronic obstructive pulmonary disease. These comorbidities share similar inflammatory and immune pathways with those that are classically implicated in psoriasis: especially the adipokines, TH17, and TNF-α.



Advances in Immune Pathways and Pathogenesis of Atopic Dermatitis

Abstract

Purpose of Review

Atopic dermatitis (AD) is a common chronic skin inflammatory disorder characterized by recurrent eczema accompanied by an intractable itch that leads to an impaired quality of life. This review aims to summarize the advances in immune pathways and pathogenesis of AD.

Recent Findings

We review and summarize the current literature characterizing immune pathways and pathogenesis of AD. The complex interplay among skin barrier deficiency, immunological derangement, microbiome dysbiosis especially Staphylococcus aureus predominance, and pruritus contribute to the development, progression, and chronicity of the disease.

Summary

AD is a complex and multifactorial disease. The skin barrier, dysbiosis of the skin microbiome, immune dysregulation, and severe itch all play a part in the pathogenesis of AD. Based on this progress, better targeted therapies are now emerging.



Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas

Abstract
Background
Mutations in the promoter of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase 1 (IDH1) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection techniques lack sensitivity, or have long turnaround times, or high costs. We developed GliomaDx, an allele-specific, locked nucleic acid (LNA)-based qPCR assay to overcome these limitations and sensitively detect TERTp and IDH mutations.
Methods
We evaluated the performance of GliomaDx on cell line DNA and frozen tissue diffuse glioma samples with variable tumor percentage to mimic use in clinical settings and validated low percentage variants using sensitive techniques including droplet digital PCR (ddPCR) and next generation sequencing. We also developed GliomaDx Nest, which incorporates a high-fidelity multiplex pre-amplification step prior to allele-specific PCR for low-input samples such as FFPE.
Results
GliomaDx detects the TERTp and IDH1 alterations at an analytical sensitivity of 0.1% mutant allele fraction (MAF), corresponding to 0.2% tumor cellularity. GliomaDx identified TERTp/IDH1 alterations in a cohort of frozen tissue samples with variable tumor percentage of all major diffuse glioma histologic types. GliomaDx Nest is able to detect these hotspot mutations with similar sensitivity from pre-amplified samples and was successfully tested on a cohort of clinical FFPE samples. Testing of a cohort of previously identified TERTp WT-IDHWT gliomas (by Sanger sequencing) revealed that 26.3% harbored low-percentage mutations. Analysis by ddPCR and whole exome sequencing of these tumors confirmed the low mutant fraction of these alterations and overall mutation-based tumor purity.
Conclusions
Our results show that GliomaDx can rapidly detect TERTp/IDH mutations with high sensitivity, identifying cases that might be missed due to the lack of sensitivity of other techniques. This approach may facilitate more objective classification of diffuse glioma samples in clinical settings such as intraoperative diagnosis or in testing cases with low tumor purity.

The role of 13 N -ammonia in the differential diagnosis of gliomas and brain inflammatory lesions

Abstract

Objective

To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations.

Methods

13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA.

Results

29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively.

Conclusions

13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.



PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival

Pigment Cell &Melanoma Research, Volume 0, Issue ja, -Not available-.


Therapeutic approaches to pyogenic granuloma: an updated review

International Journal of Dermatology, EarlyView.


Pyoderma gangrenosum associated with dulaglutide therapy

International Journal of Dermatology, EarlyView.


Diffuse palmoplantar keratotic papules and melanosis

International Journal of Dermatology, EarlyView.


Mid borderline leprosy in type Bα Blaschko linear pattern: a rare phenomenon

International Journal of Dermatology, EarlyView.


Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families

Abstract

Introduction

The impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov).

Methods

In both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator's Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) (2–15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2–17 years). Established QoL score severity bands provided clinical context.

Results

Greater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: − 4.6 vs. − 3.0; P < 0.001; DLQI: − 5.2 vs. − 3.5; P = 0.015]. At baseline, more than half the patients had a "moderate effect" or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having "small effect" to "no effect", The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: − 3.7 vs. − 2.7; P = 0.003).

Conclusion

Crisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.

Trial Registration

AD-301: http://www.clinicaltrials.gov, NCT02118766; AD-302: http://www.clinicaltrials.gov, NCT02118792.

Funding

Anacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY.