Salivary pH and flow rate in menopausal women

OBJECTIVE: This study aims at determining pH and Flow Rate (FR) of Unstimulated Whole Saliva (UWS) in a sample of 120 (60 menopausal women and 60 healthy fertile women with similar mean age); detecting the DMFT index (Decayed, Missing, Filled Teeth index) and evaluating any correlations between pH, FR, age and DMFT.

PATIENTS AND METHODS: Concerning the day before sample collection, patients were advised to keep a relaxed attitude and not to practice sports. They were also told to not eat or drink during the hour preceding sampling procedures. Saliva was collected via "spitting" method. Each sampling session started at 11:00 a.m., lasted for 5 minutes and used a pre-weighed, dry, deionized and sterile test tube. The procedure took place under controlled environmental temperature and humidity conditions (means 23.27°C; 60.08%). FR was evaluated via weighing technique and pH was measured with a portable pH-meter.

RESULTS: There was a minimal but significant pH difference (0.11; p<0.05) between menopausal women (6.75 ± 0.34) and fertile women (6.86 ± 0.24); and a FR difference (0.19; p<0.0001) between menopausal women (0.29 ± 0.17 mL/min) and fertile women (0.48 ± 0.19 mL/min). Correlation (R2) between pH and age was 0.0135 for fertile women and 0.0055 for menopausal women; while the correlation between FR and age was 0.0673 for fertile women and 0.139 for menopausal women. Mean DMFT was 11.93 ± 7.14 in menopausal women and 12.23 ± 6.37 in fertile women.

CONCLUSIONS: We observed a minimal decrease in pH and a decrease in FR in menopausal women. Further studies will be needed to investigate the possible role of other environmental and individual variables in the determination of such values.

L'articolo Salivary pH and flow rate in menopausal women sembra essere il primo su European Review.

http://bit.ly/2SRM7HO

Untreated Giant Macroprolactinoma with Chronic Cerebrospinal Fluid Leakage: An Unusual Complication.

Related Articles

Untreated Giant Macroprolactinoma with Chronic Cerebrospinal Fluid Leakage: An Unusual Complication.

Case Rep Endocrinol. 2019;2019:4825357

Authors: Mad Naser MN, Aziz NA, Karim NKA

Abstract
Macroprolactinoma has the potential to cause base of skull erosion and often extends into the sphenoid sinus. Rapid shrinkage of this invasive tumor following dopamine agonist therapy has been postulated to cause unplugging of the eroded area, leading to cerebrospinal fluid leakage. To the best of our knowledge, the occurrence of spontaneous cerebrospinal fluid leak in treatment-naive prolactinomas is very rare, the majority of which involve undiagnosed macroprolactinomas. We describe here a lady presented late with giant macroprolactinoma, complicated by cerebrospinal fluid leakage. This case raised the dilemma in the management pertaining to the role of either pharmacotherapy or surgical intervention, or combination of both. As she strictly refused surgery, she was treated with bromocriptine which was later changed to cabergoline. On follow-up, there was cessation of cerebrospinal fluid leak, marked reduction of serum prolactin level, and imaging evidence of tumor shrinkage. The majority of patients with medically induced cerebrospinal fluid leakage will require surgical procedures to overcome this complication; however, there are isolated cases of leakage resolution on continuing dopamine agonist therapy while awaiting surgery. The use of dopamine agonist does not necessarily cause worsening of cerebrospinal fluid leakage and instead may produce spontaneous resolution as in this case.

PMID: 30766735 [PubMed]

http://bit.ly/2EdtKEV

Neuroendocrine Neoplasms Associated with Germline Pathogenic Variants in the Homologous Recombination Pathway

http://bit.ly/2DIJTAO

Fragmented Fat: A New Method for Harvesting and Processing of Lipograft

Fat transfer has been recognized as an attractive tool for gluteal and breast augmentation, but harvesting limitations still represent a drawback, especially for post bariatric patients, as massive adipose deflation makes traditional liposuction less effective. On the other hand, circumferential apronectomies usually discard considerable amounts of viable fat tissue1.

http://bit.ly/2tpmv6H

Novel digital image analysis using fractal dimension for assessment of skin radiance

Abstract

Background

Despite a strong desire to quantify skin radiance in the field of cosmetics, there does not exist a robust method to characterize it. Classical shine that quantifies the specular reflection from skin has been commonly used as the metric to characterize radiance. However, it does not always correlate with the perceived radiance as there are many other parameters that inform radiance perception including spatial distribution of shine and color homogeneity.

Materials and methods

In this work, we propose a novel method using fractal analysis to better characterize radiance by considering the spatial heterogeneity of pixel intensities as well as color evenness. A simulated image library (nine images) from very dull to very bright was created using bare face images of 20 panelists. Product images taken post‐product usage were ranked along this library by finding the image in the library that most resembles the product image by our algorithm as well as experts. Additionally, classical shine and color measurements were made as benchmarks.

Results

Our results confirm a strong correlation (R ² = 0.99) between the expert radiance rankings and the rankings by fractal dimension algorithm. The new algorithm offers an improved product differentiation compared with classical shine or color measurements.

Conclusion

Fractal dimension calculation offers higher sensitivity and resolution compared with other descriptors such as classical shine or color heterogeneity. In cases where the image rank is dominated by pixel intensities rather than color evenness, the image ranks resulting from calculating the fractal dimension is comparable with use of classical shine as the ranking parameter.

http://bit.ly/2EdXQs0

Confocal Raman Spectroscopy as a tool to measure the prevention of skin penetration by a specifically designed topical medical device

Abstract

Background/Aim

The scope of this study was to utilize confocal Raman spectroscopy in the evaluation of the degree of non‐penetration into the viable skin layers of a paraffin and petrolatum‐based product for use in the intimate areas of the skin. The formulation was purposely designed with properties to prevent undesirable skin penetration.

Methods

Product —The test product was a proprietary topical medical device comprising paraffinum liquidum, petrolatum, paraffin, and tocopheryl acetate.

Volunteers—A total of 20 healthy volunteers were recruited onto the study—17 females and three males.

Product Testing—Raman spectra were obtained at Baseline and 90 minutes after product application.

Product Penetration—Skin penetration was calculated from Raman spectra taken at skin depths of −5, 0, 5, 10, 15, and 20 μm.

Results

Raman spectra of the investigated product could be clearly differentiated from the skin spectrum. The minimum measurable concentration of the test product was determined at a detection level of 0.5%. In this study, the test product did not penetrate down to skin depths of 10 to 20 μm.

Conclusions

Within the precision range of the test method, the investigated product did not penetrate into the compact part of the stratum corneum. The study revealed Raman spectroscopy to be suitable to detect not only penetration but also non‐penetration of substances into human skin.

http://bit.ly/2UWQwqe

The tissue viability imaging system—Suitable method for discovering minimal skin changes in occupational screenings? Results of a cross‐sectional field study

Abstract

Background

For early detection of initial skin changes in occupational screenings, only few objective assessment systems are available.

Objectives

With the aim of assessing an objective measurement method for hand eczema, we trialed the application of the tissue viability imaging (TiVi) system, quantifying erythema non‐invasively by polarized light spectroscopy.

Materials and Methods

In a field study with 625 employees of a semiconductor production company, 411 were exposed to prolonged wearing of occlusive gloves in the clean room. TiVi system and Hand Eczema Score for Occupational Screenings (HEROS), a quantitative skin score for the hands, were used, supplemented by a standardized personal interview.

Results

TiVi values of 65 up to 246 for each hand (palm or back), for each participant summed to overall 289 up to 848 (median 389), were measured. Higher TiVi values were noted for men, smokers, and with increasing age. Correlation between TiVi and HEROS was only weak. Several factors like skin pigmentation, thickness of the skin, or tattoos seem to influence TiVi results.

Conclusions

The practical relevance of one‐time measurements with the TiVi system in occupational screenings seems to be limited. Specifically, the TiVi system cannot replace dermatological examinations at the workplace. Notwithstanding, the application for other scientific purposes might be useful.

http://bit.ly/2EdXOjS

Comment re Dear Dr. Dermatoethicist: Exam of the Future or Exam of Future Cheating?

Publication date: Available online 15 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Lela A. Lee, Thomas D. Horn, Erik J. Stratman

http://bit.ly/2X3opaG

Tracking changes nailfold capillary abnormalities in Dermatomyositis on treatment

Publication date: Available online 15 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Yahya Argobi, Gideon P. Smith

http://bit.ly/2S6IPfh

Clinicopathologic, misdiagnosis and survival differences between clinically amelanotic melanomas and pigmented melanomas

Publication date: Available online 15 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Stuart M. Goldsmith

http://bit.ly/2X3ojjk

Optimizing the Total Body Skin Exam: An Observational Cohort Study

Publication date: Available online 15 February 2019

Source: Journal of the American Academy of Dermatology

Author(s): Matthew F. Helm, Katherine K. Hallock, Elizabeth Bisbee, Jeffrey J. Miller

Abstract

Background

Total body skin examinations (TBSE) are commonly performed in clinical practice. There is limited research on best practices for performing a TBSE.

Objective

To optimize the TBSE.

Methods

We performed an observational cohort study by video recording 5 dermatology faculty and 5 residents conducting their regular TBSE on both a male and female standardized subject. Exam time, physician movements, subject movements, sequence of body parts examined, and body parts missed were analyzed using an analytic hierarchy process (AHP) matrix. Differences were evaluated by a t-test of unequal variance. P-values <0.05 were deemed significant.

Results

We identified a optimal format for conducting a TBSE that is efficient and accurate

Limitations

This study was conducted with only healthy examiners and standardized subjects, rather than individuals with a variety of physical and mental disabilities. The structure of the study was not hypothesis driven and assumed that engineers observing physicians performing the total body skin examination would identify the most optimal TBSE.

Conclusion

Our results indicate that a standardized process of performing a TBSE minimizes the chance of missing a body area. This could also have implications on teaching a standardized TBSE to medical students, residents, and physicians.

http://bit.ly/2S7gpl9

The effect of prism adaptation on state estimates of eye position in the orbit

Publication date: Available online 16 February 2019

Source: Cortex

Author(s): T.M. Gilligan, F. Cristino, J.H. Bultitude, R.D. Rafal

Abstract

Prism adaptation (PA) after-effects are assessed using tests that measure changes in sensorimotor systems. After-effects on pointing without feedback to a visual target (open loop pointing – OLP) are traditionally described as being larger than those measured by straight ahead pointing (SAP) with eyes closed, and the difference between them is attributed to a shift in visual localisation. However, neither differences between OLP and SAP, nor shifts in perceptual judgement of visual straight ahead (VSA), are consistently reported. Moreover, since very few studies have directly recorded direction of gaze, an effect of PA on the state estimate of gaze direction has not been reliably documented. The current research aimed to isolate the effects of PA on state estimates of eye position. We measured sensorimotor after-effects through common (OLP, SAP, and VSA) measures, and also recorded eye position and additional after-effect measures to interrogate changes to the oculomotor system and how these might relate to other measures of sensorimotor change. To ascertain if PA's effects on estimates of eye position could be attributed to eye muscle potentiation, we compared the effects of PA to sustained gaze deviation without adaptation. PA induced no effect on visual straight-ahead and no change in direction of gaze, when measured while positioning a target, looking straight ahead in the dark, or looking toward the passively positioned and occluded unexposed hand. We also found that after-effects measured by SAP with the eyes open were larger than SAP with the eyes closed and equal to those observed with OLP. The findings challenge the concept that total adaptation after-effect is a direct sum of arm proprioceptive and visual after-effects as conventionally measured, and suggest that the oculomotor system is altered by prism adaptation only in interaction with an arm motor command when vision is available.

http://bit.ly/2Ik4IrN

Counter-regulation of regulatory T cells by autoreactive CD8+ T cells in rheumatoid arthritis

Publication date: Available online 16 February 2019

Source: Journal of Autoimmunity

Author(s): Ilenia Cammarata, Carmela Martire, Alessandra Citro, Domenico Raimondo, Doriana Fruci, Ombretta Melaiu, Valentina D'Oria, Chiara Carone, Giovanna Peruzzi, Cristina Cerboni, Angela Santoni, John Sidney, Alessandro Sette, Marino Paroli, Rosalba Caccavale, Edoardo Milanetti, Mara Riminucci, Eleonora Timperi, Silvia Piconese, Antonio Manzo

Abstract

The mechanisms whereby autoreactive T cells escape peripheral tolerance establishing thus autoimmune diseases in humans remain an unresolved question. Here, we demonstrate that autoreactive polyfunctional CD8⁺ T cells recognizing self-antigens (i.e., vimentin, actin cytoplasmic 1, or non-muscle myosin heavy chain 9 epitopes) with high avidity, counter-regulate Tregs by killing them, in a consistent percentage of rheumatoid arthritis (RA) patients. Indeed, these CD8⁺ T cells express a phenotype and gene profile of effector (eff) cells and, upon antigen-specific activation, kill Tregs indirectly in an NKG2D-dependent bystander fashion in vitro. This data provides a mechanistic basis for the finding showing that AE-specific (CD107a⁺) CD8⁺ T killer cells correlate, directly with the disease activity score, and inversely with the percentage of activated Tregs, in both steady state and follow-up studies in vivo. In addition, multiplex immunofluorescence imaging analyses of inflamed synovial tissues in vivo show that a remarkable number of CD8⁺ T cells express granzyme-B and selectively contact FOXP3⁺ Tregs, some of which are in an apoptotic state, validating hence the possibility that CD8⁺ Teff cells can counteract neighboring Tregs within inflamed tissues, by killing them. Alternatively, the disease activity score of a different subset of patients is correlated with the expansion of a peculiar subpopulation of autoreactive low avidity, partially-activated (pa)CD8⁺ T cells that, despite they conserve the conventional naïve (N) phenotype, produce high levels of tumor necrosis factor (TNF)-α and exhibit a gene expression signature of a progressive activation state. Tregs directly correlate with the expansion of this autoreactive (low avidity) paCD8⁺ TN cell subset in vivo, and efficiently control their differentiation rather their proliferation in vitro. Interestingly, autoreactive high avidity CD8⁺ Teff cells or low avidity paCD8⁺ TN cells are significantly expanded in RA patients who would become non-responders or patients who would become responders to TNF-α inhibitor therapy, respectively. These data provide evidence of a previously undescribed role of such mechanisms in the progression and therapy of RA.

http://bit.ly/2GQSHYJ

Refractory diet-dependent changes in neural microstructure: Implications for microstructural endophenotypes of neurologic and psychiatric disease

Publication date: Available online 15 February 2019

Source: Magnetic Resonance Imaging

Author(s): Maribel Torres-Velázquez, Emily A. Sawin, Jacqueline M. Anderson, John-Paul J. Yu

Abstract

Alterations in gut microbiome populations via dietary manipulation have been shown to induce diet-dependent changes in white matter microstructure. The purpose of this study is to examine the durability of these diet-induced microstructural alterations. We implemented a crossover experimental design where post-weaned male rats were assigned to one of four experimental diets. Following the administration of experimental diets and again following crossover and resumption of a normal diet, brains were imaged ex-vivo with diffusion tensor imaging. Following standard image preprocessing, tract-based spatial statistics and region-of-interest measurements were then calculated for all diffusion tensor indices. Voxel-wise differences in FA were identified in the high fat diet group when compared to animals receiving a control diet. Following crossover, there were new voxel-wise changes in both FA and TR that do not correspond to the regions previously identified. Animals crossed over from the high fiber diet demonstrate widespread and global changes in the diffusion tensor that stand in stark contrast to the minimal changes identified before crossover. While no significant differences between any of the diffusion metrics were identified in the high protein group before crossover, statistically significant decreased RD values were observed following resumption of a normal diet. Diet-induced changes in neural microstructure are durable changes that are unrecoverable following the resumption of a normal diet. We further show that in certain experimental diets, resumption of a normal diet can lead to further marked and unanticipated changes in white matter microstructure.

http://bit.ly/2SEQWoj

Neuro-Oncology Diet and risk of glioma

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool Abstract Background Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985–2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors. Methods A multi-institutional retrospective institutional review board–approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively. Results The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0–1.0, 1.5–2.0, 2.5–3, and 3.5–4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively. Conclusion The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients Abstract Background Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients. Methods Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 MHC class I and 2 MHC class II peptides) i.d. and poly-ICLC i.m. After protocol amendment, IMA950 and poly-ICLC were mixed and injected s.c. (n=7) or i.m. (n=6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral CD4 and CD8 T cell responses. Results The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained Th1 CD4 T cell responses. For the entire cohort, CD8 T cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients. Conclusion We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients. Trial registration Clinicaltrials.gov NCT01920191. Recent Developments and Future Directions in Adult Lower-Grade Gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) Consensus Abstract The finding that most grade II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and CDKN2A/B deletional analysis. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein. Diet and risk of glioma: combined analysis of three large prospective studies in the UK and USA Abstract Background Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies. Methods Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis. Results The 1,262,104 participants, mean age 60.6 (SD5.5) at baseline, were followed for 15.4 million person-years (mean 12.2 years/participant), during which 2,313 incident gliomas occurred, at mean age 68.2 (SD6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fibre, and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex. Conclusions The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns, and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.

Highlights from the Literature

Forthcoming Meetings Edited by Albert H. Kim and Jennie W. Taylor

Glioblastoma: a prognostic value of AMT-PET? See the article by John et al, pp. 264–273.

Old meet new—the path to combination treatments in pediatric low-grade gliomas See the article by Poore et al, pp. 252–263.

Disparities along the glioblastoma clinical trials landscape We read with interest the recent work by Vanderbeek et al1 regarding the current clinical trials landscape for glioblastoma (GBM) patients. An unexplored dimension of their analysis centers on disparities and demographic discrepancies between clinical trial participants and the broader GBM population. We therefore examined clinical trials with published results as highlighted by the authors, totaling 51 trials.1 While most of these trials reported details regarding patient age (48/51, 94%) and gender (47/51, 92%), only 14 trials (27%) provided information regarding ethnicity and/or race in either peer-reviewed publications or ClinicalTrials.gov. The rate of reporting ethnicity/race was particularly low among phase I/II studies (9/43, 21%) compared with phase III trials (5/8, 63%, chi-squared test P = 0.02).

Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival Abstract Background Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. Methods Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined. Results A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = −0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98–31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients. Conclusions Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival.

Supratotal resection in glioma: a systematic review Abstract Background Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR) modalities in glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature. Methods EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded. All others were included. Results Three hundred and nine unique references yielded 41 studies for full-text review, with 7 included in the final analysis. Studies were mostly of Oxford Center for Evidence-Based Medicine Level 4 quality. A total of 88 patients underwent supratotal resection in a combined cohort of 492 patients (214 males and 278 females, age 18 to 82 years). Fifty-one supratotal resections were conducted on high-grade gliomas, and 37 on low-grade gliomas. Karnofsky performance status, overall survival, progression-free survival, neurological deficits postoperatively, and anaplastic transformation were the main measured outcomes. No randomized controlled trials were identified. Preliminary low-quality support was found for supratotal resection in increasing overall survival and progression-free survival for both low-grade and high-grade glioma. Conclusion The literature suggests insufficient evidence for carte blanche application of supratotal resection, particularly in lower-grade gliomas where neurological deficits can result in long-term disability. While the preliminary studies discussed here, containing data from only a few centers, have reported increased progression-free and overall survival, these claims require validation in prospective research studies involving larger patient populations with clearly defined appropriate outcome metrics in order to reduce potential bias.

Uncommon low-grade brain tumors Abstract The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I–II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.

Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose Abstract Background At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. Methods We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). Results We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4–100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub–hazard ratio, 2.3; 95% CI: 1.4–3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. Conclusion Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

Sex difference of mutation clonality in diffuse glioma evolution Abstract Background Sex differences in glioma incidence and outcome have been previously reported but remain poorly understood. Many sex differences that affect the cancer risk were thought to be associated with cancer evolution. Methods In this study, we used an integrated framework to infer the timing and clonal status of mutations in ~600 diffuse gliomas from The Cancer Genome Atlas (TCGA) including glioblastomas (GBMs) and low-grade gliomas (LGGs), and investigated the sex difference of mutation clonality. Results We observed higher overall and subclonal mutation burden in female patients with different grades of gliomas, which could be largely explained by the mutations of the X chromosome. Some well-established drivers were identified showing sex-biased clonality, such as CDH18 and ATRX. Focusing on glioma subtypes, we further found a higher subclonal mutation burden in females than males in the majority of glioma subtypes, and observed opposite clonal tendency of several drivers between male and female patients in a specific subtype. Moreover, analysis of clinically actionable genes revealed that mutations in genes of the mitogen-activated protein kinase (MAPK) signaling pathway were more likely to be clonal in female patients with GBM, whereas mutations in genes involved in the receptor tyrosine kinase signaling pathway were more likely to be clonal in male patients with LGG. Conclusions The patients with diffuse glioma showed sex-biased mutation clonality (eg, different subclonal mutation number and different clonal tendency of cancer genes), highlighting the need to consider sex as an important variable for improving glioma therapy and clinical care.

Does increased 11 β HSD‐ 1 activity induce adverse metabolic phenotype only in lean ?

Abstract

We read with interest article by Crowley et al (1). The authors a found an apparent decrease in 11 β HSD‐ 1 expression in subcutaneous adipose tissue (SAT) of deteriorators as compared to improvers. They explained it as compensatory decrease of 11 β HSD‐ 1 activity as consequence of overall adverse metabolic phenotype. It remained speculative whether visceral adipose tissue (VAT) 11 β HSD1 was increased in deteriorators. While this is consistent with recently published study by us (2), in which we found liver/portal circulation 11 β HSD1 activity to be increased in diabetics as compared to controls. However increased 11 β HSD1 activity was not seen in those who had BMI >23 m/kg2 (2). In this regard it will be interesting to know what was 11 β HSD1 expression in subgroup of those with Body Mass Index (BMI) >23 m/kg2 or >25 m/kg2 or >30 m/kg2. It is possible the difference between improvers and deteriorators was lost at higher BMI when other causative factors for diabetes (e.g. insulin resistance) exert more influence.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TRHOJD

Practice‐Based Differences in Pediatric Discoid Lupus Erythematosus

Abstract

Background

Children with discoid lupus erythematosus (DLE) are at risk for disfigurement and progression to systemic lupus erythematosus (SLE). Consensus is lacking regarding optimal care of children with DLE.

Objectives

We compared practice patterns among pediatric dermatologists/rheumatologists treating pediatric DLE.

Methods

An online survey was sent to 292 pediatric rheumatologists in the Childhood Arthritis & Rheumatology Research Alliance (CARRA) and 200 pediatric dermatologists in the Pediatric Dermatology Research Alliance (PeDRA). Consensus was defined as >70% agreement.

Results

Survey response rates were 38% (dermatology, n = 76/200) and 21% (rheumatology, n = 60/292). Both specialties agreed that screening labs should include complete blood counts with differential, urinalysis, complements, erythrocyte sedimentation rate, antinuclear antibody and other autoantibodies, hepatic function, and renal function/electrolytes. Both specialties agreed that arthritis or nephritis should prompt intensified evaluation for SLE. No other patient features achieved consensus as disease‐modifying risk factors. Hydroxychloroquine was agreed upon as first‐line systemic therapy, but consensus was lacking for second or third‐line treatment.

Conclusions

We found few areas of consensus and significant practice differences between pediatric dermatologists/rheumatologists treating DLE. Knowledge gaps include risk factors for SLE, optimal screening and treatment of refractory skin disease.

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Eczematous eruption during anti‐interleukin 17 treatment of psoriasis: an emerging condition

Abstract

Major advances in psoriasis pathogenesis gave rise to development of new effective drugs for its treatment. Particularly, biologic drugs revolutionized disease management. TNF‐α inhibitors represented the opening available biologic class since 2000. Thus, adverse cutaneous reactions to their use have been extensively investigated.

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Efficacy of fractional CO2 laser with intralesional steroid compared with intralesional steroid alone in the treatment of keloids and hypertrophic scars

Summary

Background and objective

Keloids and hypertrophic scars (HTS) are abnormal fibrous reactions that persist for prolonged periods, rarely regress without treatment and recur after excision. Many modalities of treatment have been advocated but the success rates of these have been variable. The present study is an attempt to evaluate and compare the efficacy of combination of fractional CO₂ laser (FCL) and intralesional steroid (ILS) against ILS alone in the treatment of keloids and HTS.

Methods

Patients with keloids or HTS were divided into two groups of 25 each receiving four sessions of therapy. Group 1 (FCL + ILS) received combination of FCL and intralesional triamcinolone acetonide (TAC) 10 mg/mL. Group 2 (ILS only) received intralesional TAC 10 mg/mL alone. Pretreatment measurements and photographs were taken. Two unbiased qualified dermatologists made independent evaluation of the photographs using modified Manchester quartile score (MQS). The patient's satisfaction to treatment was graded on a scale of 1‐4. Statistical analysis was done using a statistical software.

Results

Statistically significant improvement was seen in height and length of the lesions. Overall appearance criteria of modified MQS showed an improvement of more than 50% in 43.3% of the lesions by the end of four sessions. Degree of hypertrophy showed more than 50% improvement in 40% of the lesions treated. Dyschromia showed more than 50% improvement in 33.4%. Texture showed the least improvement, with only 30% of lesions showing an improvement of more than 50%. The improvement of these parameters in ILS only group was significantly lower than the improvement seen in the FCL + ILS group.

Conclusion

Combination therapy with FCL and ILS was superior in efficacy when compared to ILS alone, in the treatment of keloids and HTS.

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Parry‐Romberg syndrome treatment with fat transfer and a new bleaching formula

Summary

Parry‐Romberg syndrome is a hemifacial atrophy which can be complicated by melasma. We present two cases of Parry‐Romberg syndrome, treated by fat transfer and bleaching of the skin using a modified "Kligman's formula." The atrophy, as well as the skin dyschromia, improved, and the results were stable.

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Efficacy of microneedling with topical vitamin C in the treatment of melasma

Summary

Background

Despite the wide therapeutic options available for the treatment of melasma, including many active topical medications, technologies with lights and peelings, clinical control of this disorder is extremely challenging.

Objectives

To evaluate the effect of microneedling with topical vitamin C in the treatment of melasma.

Methods

Thirty female patients with melasma received six sessions of microneedling with addition of topical vitamin C every two weeks. At each session, photos were taken and Melasma Area and Severity Index (MASI) score was calculated to assess the clinical improvement.

Results

Mean age of the eligible patients was 33.2 ± 5.77 years. About 50% of cases were of Fitzpatrick skin type III. All patients showed improvement at the end of the sessions. Mean MASI score in the first session was 8.61 ± 4.45 and there was a gradual decline in its value till it reached a mean of 5.75 ± 4.16 in the last session (P < 0.0001).

Conclusion

Microneedling with topical vitamin C is an effective and safe treatment option for epidermal melasma especially in Fitzpatrick skin phototypes I‐III.

http://bit.ly/2S2IWZe