Concentrations of PCDD/Fs in the neighborhood of a hazardous waste incinerator: human health risks

Abstract

In 1996–1998, a wide surveillance program was initiated in the vicinity of a new hazardous waste incinerator (HWI) placed in Constantí (Catalonia, Spain), which started its regular operations in 1999. The program was aimed at assessing the environmental impact of the facility on the surrounding environment, as well as to evaluate the potential risks for the population living in the neighborhood. Since then, among other measurements, the concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) have been periodically determined in soil and herbage samples. This study shows the results, corresponding to the period 2013–2016. Data were compared with those obtained in the baseline survey (1996–1998), as well as with those of the previous survey (2011–2012). The median PCDD/F concentrations in soils were 0.44 and 0.33 ng toxic equivalent (I-TEQ)/kg in 2015 and 2016, respectively, with a significant decrease in relation to the baseline survey, and a non-significant decrease between 2015 and 2016. In turn, PCDD/F levels in vegetation showed some fluctuations over time, being the concentrations of PCDD/Fs in 2013 very similar to those found in 2012 (1.11 and 1.23 ng I-TEQ/kg, respectively). These concentrations notably decreased along the three last campaigns (0.16, 0.23, and 0.17 ng I-TEQ/kg in 2014, 2015, and 2016, respectively). These changes would be more related to a number of environmental factors rather than to a variation of PCDD/F emissions by the HWI. With respect to human health risks, exposure to PCDD/Fs in the area under potential influence of the HWI is not of concern, as the current environmental concentrations of PCDD/Fs do not mean additional carcinogenic or non-carcinogenic risks for the local population.

Valorization of biochars from pinewood gasification and municipal solid waste torrefaction as peat substitutes

Abstract

Gasification and torrefaction have both gained significant interest as bioenergy techniques. During biomass gasification together with fuel gas, carbon-rich solid substances are produced, whereas torrefaction process is mainly used to prepare a final product with higher calorific value and carbon content than the feedstock, through a low temperature pyrolysis. Both materials (carbon wastes from gasification and torrefied product) could be classified as alternatives to biochar obtained from slow pyrolysis of biomass. The use of biochar, typically from the slow pyrolysis of biomass, as soil amendment and, more recently, as growing media components has been widely researched. However, to our knowledge, no studies have compared the use of biochar from gasification and torrefaction as growing media component for growing media formulation. The objective of this work was to study the effect of two biochars on peat-based growing media: a pinewood gasification biochar (BG) and a biochar (BT) obtained by torrefaction of the organic fraction of municipal solid waste. Growing media mixing PT (peat) with 50%vol of BG or BT were prepared and characterized according to their chemical, thermal and hydrophysical properties. Phytotoxic experiments and growth of Lolium perenne were also performed. Results indicated that peat substitution in growing media by BG and BT at a 50%vol ratio improved their hydrophysical properties. Specifically, bulk density increased more than 50%, air space increased by 43%, the increment of the total porosity was 20%, and, finally, the water holding capacity increased by 18.3%. Significantly, a positive effect on plant biomass production (yield increment: 274%) was observed after addition of BT, whereas no significant differences were observed after addition of BG biochar. Therefore, it can be concluded that both BT and BG could be used as peat substitutes in growing media formulation.

Comparative effect of organic amendments on physio-biochemical traits of young and old bean leaves grown under cadmium stress: a multivariate analysis

Abstract

The current study investigated the influence of organic amendments on cadmium (Cd) uptake and its effects on biochemical attributes of young and old leaves of bean. Bean seedlings were exposed to two levels of Cd (25 and 100 μM) in the presence and absence of different levels of ethylenediaminetetraacetic acid (EDTA) and citric acid (CA). An increase in Cd concentration in growth medium significantly enhanced Cd accumulation in bean roots and shoot. Cadmium stress increased the production of H₂O₂ which resulted in lipid peroxidation and decreased chlorophyll contents. The presence of organic amendments significantly affected Cd accumulation and toxicity to bean plants. Application of EDTA alleviated Cd toxicity in terms of chlorophyll contents, H₂O₂ contents, and lipid peroxidation possibly by chelating toxic Cd ions, and as such forming Cd-EDTA complexes. The presence of CA decreased Cd toxicity by decreasing its uptake. The biochemical responses (H₂O₂ contents, lipid peroxidation, and chlorophyll contents) of bean plants were more severely affected by Cd treatments in old leaves compared to young leaves. This study shows that the effect of CA and EDTA on biochemical behavior of Cd varies greatly with applied levels of Cd and amendments as well as the age of leaves. Based on the results, it is proposed that the presence of organic amendments can greatly affect biogeochemical behavior of Cd in the soil-plant system (ecosystem).

Antiandrogen therapy with spironolactone for the treatment of hidradenitis suppurativa

Antiandrogen therapy has been reported as an effective treatment for hidradenitis suppurativa. This study evaluated both physician and patient reported hidradenitis suppurativa severity outcomes for patients treated with spironolactone. Antiandrogen therapy with spironolactone may be a useful treatment option for reducing inflammatory lesions and pain for female patients with HS.

Surgical Pearl: A Granny Sliding Knot for High Tension Closures

Topical Glycopyrronium Tosylate for the Treatment of Primary Axillary Hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 Phase 3 Randomized Controlled Trials

Current treatment options for hyperhidrosis are limited. The topical anticholinergic, glycopyrronium tosylate, results in significant reductions in sweating severity/production and favorable tolerability in two phase 3, randomized, vehicle-controlled trials in primary axillary hyperhidrosis. These results suggest glycopyrronium tosylate may provide a non-invasive, once-daily, topical treatment option for primary axillary hyperhidrosis.

Efficacy, Safety, and Comparison of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: A Systematic Review and Meta-Analysis

Sonic hedgehog inhibitors are systemic treatments for locally advanced and metastatic basal cell carcinomas. In locally advanced disease, overall response rate is similarly significant for sonidegib and vismodegib; complete response rate is significant for vismodegib only. Rates of major side effects do not differ between vismodegib and sonidegib. Patients should expect partial responses in locally advanced disease.

Ustekinumab treatment for neutrophilic dermatoses associated with Crohn’s disease: a multicenter-retrospective study

Intralesional Immunotherapy for the Treatment of Warts: A Network Meta-analysis

Although intralesional immunotherapy is commonly used for wart treatment, selection among existing immunotherapeutic modalities remains challenging. PPD and MMR are the most effective modalities for lesion clearance at primary and distant sites (along with autoinoculation), and also reduce recurrence. PPD and MMR may be considered as first-line treatments for warts.

Methotrexate for alopecia areata: a systematic review and meta-analysis

There is lack of synthesised data regarding methotrexate in AA, Good response was observed in 63% of patients and complete response in 36% of patients, Initial regrowth is observed after 3 months of treatment and takes 6-12 months to achieve complete regrowth, The pooled recurrence rate of AA was 47.7%

The ALT-70 Predictive Model Outperforms Thermal Imaging for the Diagnosis of Lower Extremity Cellulitis: A Prospective Evaluation

Point-of-care diagnostic tools may decrease misdiagnosis rates and unnecessary care associated with lower extremity cellulitis. In our prospective study, the ALT-70 predictive model for lower extremity cellulitis outperformed thermal imaging in diagnostic accuracy. The high negative predictive value of ALT-70 effectively allows clinicians to rule out lower extremity cellulitis.

Pigmentation of basal cell carcinoma is inversely associated with tumor aggressiveness in Asian patients

Drug-Induced Phototoxicity: A Systematic Review

Numerous oral drugs are implicated in phototoxicity; however, the level of evidence for most has not been assessed. Vemurafenib, NSAIDs, and antibiotics (fluoroquinolones, tetracyclines) have strongest evidence for phototoxicity. Most associations are not supported by robust evidence. Improved documentation of phototoxicity testing is required before labelling oral drugs as phototoxic.

“Comparing the eighth and the seventh editions of the ajcc staging system and the brigham and women’s hospital alternative staging system for cutaneous squamous cell carcinoma: implications for clinical practice”

The new 8th edition of the American Joint Committee on Cancer (AJCC) staging system incorporates changes regarding cutaneous squamous cell carcinoma (CSCC).

Mohs micrographic surgery (MMS) with MART-1 immunostaining for atypical intraepidermal melanocytic proliferation (AIMP)

Surgical outcomes for AIMP are unknown. Upstaging to unequivocal melanoma was identified in 18.8% of AIMP. No local recurrences occurred with a mean follow-up of 2.7 years. 23.8% of AIMP required greater than one stage of MMS. MMS may be an effective treatment option for AIMP.

Beyond JAAD - October 2018

Immunosenescence-like state is accelerated by constant light exposure and counteracted by melatonin or turmeric administration through DJ-1/Nrf2 and P53/Bax pathways

Publication date: Available online 9 July 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Hanan A. El-Bakry, Ismail Ahmed Ismail, Safaa S. Soliman

Abstract

The awareness of the interrelationship between immunosenescence and constant light exposure can provide new insights into the consequences of excessive exposure to light at night due to light pollution or shift work. Here, we investigated whether constant light exposure (LL) acts as an inducer of immunosenescence. We also determined the role of melatonin or turmeric in reversing the putative effects of constant light and explored for the first time the underlying molecular mechanisms. Young (3–4-month-old) rats were exposed daily to LL alone or in combination with each of melatonin and turmeric for 12 weeks. A group of aged rats (18-months old; n = 6) was used as a reference for natural immunosenescence. Constant light exposure resulted in remarkable pathophysiological alterations resembling those noticed in normal aged rats, manifested as apparent decreases in antioxidant activities as well as Nrf2 and DJ-1 expressions, striking augmentation in oxidative stress, proinflammatory cytokines and expression of TNFα, Bax, and p53 genes, and deleterious changes of lymphoid organs, Co-administration of melatonin or turmeric was able to reverse all alterations induced by LL through upregulation of Nrf2/DJ-1 and downregulation of p53/Bax pathways. These data suggest that LL accelerates immunosenescence via oxidative stress and apoptotic pathways. They also demonstrate for the first time that turmeric is comparable to melatonin in boosting the immune function and counteracting the LL-associated immunosenescence. These effects suggest that turmeric supplementation can be used as an inexpensive intervention to prevent circadian disruption-related immunosenescence. However, to validate the effects of turmeric on humans further studies are warranted.

In vivo photoinduced [4 + 2] dimerization of a neo-clerodane diterpene in Baccharis flabellata. ROS and RNS scavenging abilities

Publication date: Available online 9 July 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Matías Funes, Carlos E. Tonn, Marcela Kurina-Sanz

Abstract

Secondary metabolites play a major role in the adaptation of plants to the environment. Furan neo-clerodane diterpenes are characteristic secondary metabolites in Baccharis flabellata Hook. & Arn. var. flabellata. One of the main compounds is the diene ent-15,16-epoxy-19-hydroxy-1,3,13(16),14-clerodatetraen-18-oic acid (DAC). In this work a new dimeric compound (DACD) has been isolated and identified by NMR and MS techniques. The presence of other minor dimers was also observed in the same plant methanolic extracts. Assuming that they may be the products of [4 + 2] condensation of two monomeric moieties, the formation of adducts by photochemical dimerization was checked by inducing the in vitro [4 + 2] cycloaddition of DAC. Moreover, the DAC and DACD accumulation rates in aerial parts of B. flabellata specimens were analyzed monthly during a complete phenological cycle. The accumulation of monomer depends on the plant phonological stage; meanwhile the dimer proportion arises in detriment of the monomer as the solar UV radiation increases. Since plants exposed to strong UV intensities produce radical species, the scavenger properties of these compounds toward reactive nitrogen species (RNS), and reactive oxygen species (ROS), were analyzed. Albeit DAC and DACD show significant superoxide radical scavenger activities, the monomer proved to be more effective than the dimer toward ROS, while DACD was an excellent RNS scavenger.

Graphical Abstract

“No Drain, No Gain”: Simultaneous Seroma Drainage and Tissue Expansion in Pre-pectoral Tissue Expander-Based Breast Reconstruction

Abstract

Seromas represent the most frequent complication following immediate breast reconstruction surgery, in particular when acellular dermal matrix or synthetic meshes are used to add coverage to implants. Little information regarding breast seroma management is available in the literature. When seroma becomes clinically significant, current methods for its management consist of repeated needle aspiration. We report a fast, efficient, easy and riskless technique to perform serum aspiration in patients who underwent breast reconstruction with a tissue expander that allows simultaneous drainage and expansion of the implant at once. This procedure is safe, painless, does not need special supplies or additional costs and can be easily performed in ambulatory setting to manage breast seromas.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Ideals of Facial Beauty Amongst the Chinese Population: Results from a Large National Survey

Abstract

Surgical and non-surgical aesthetic treatments are very popular throughout Asia and in particular in China. With the globalisation and immigration of Chinese people to other countries where many seek treatment from Western-trained doctors, it is important to understand the ideals of beauty amongst Chinese people so as to achieve optimal results. We conducted an online survey to understand the preference of Han Chinese laypersons for facial shape, profile (straight, convex, concave), jaw angle and shape, and shape of the chin, nose, and lips. In addition, the participants were asked about their educational level, geographic location, likelihood to have cosmetic surgery, preference for surgical or non-surgical cosmetic procedures and whether "being beautiful" would affect their daily life. A total of 1417 responses were collected from 599 male and 818 female participants, the majority of them who were 25–35 years old (58.93%). The responses showed that the majority of participants preferred an oval face shape, with a smoothly tapered jaw angle for both men and women, round and pointy chin for both genders, straight to concave nose profile and full lips with well-defined cupid's bow. Most responders indicated they were not willing to undergo cosmetic surgery; however, when given a choice between surgical and non-surgical cosmetic procedures, 82.22% of the participants preferred non-surgical procedures. The majority of respondents (83%) thought that being beautiful has an effect on daily life and improves quality of life.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Correction to: Buttock Lifting Using Elastic Thread (Elasticum ® ) with a New Classification of Gluteal Ptosis

The original version of this article unfortunately contained a mistake. On page 8, in Table 2, the superscripts for the vertical and horizontal axes are incorrect. The correct information is shown below.

Muscle Insertion and Strength of the Muscle Contraction as Guidelines to Enhance Duration of the Botulinum Toxin Effect in the Upper Face

Abstract

Background

In this series of patients the cutaneous insertion and strength of voluntary contraction of the muscles in the upper third of the face were used as guidelines for botulinum toxin application named "BTA Codes."

Method

Anatomical dissection of fresh cadavers identified the shape and cutaneous insertions of the muscles in the upper third of the face. Patient voluntary contraction of the muscles in the upper third of the face created different patterns of skin lines classified by the 4-grade Facial Wrinkle Scale. For botulinum toxin application injections points followed the muscle cutaneous insertion and dose the 4-grade Facial Wrinkle Scale.

Results

Injection points ranged from 3 to 23 points per patient, average of 9.4 points. Dose per point varied from 2.5 to 7.5 U, ranging from 12.5 to 72.5 U per patient, average of 33.82 U. Skin lines resulting from the voluntary contraction of the muscle prior to toxin application were stated as baseline 1. The absence of skin lines and muscle activity on day fifteen after toxin application defined baseline 2. Skin lines resulting from the recovered voluntary contraction of the muscle after toxin application like those of baseline 1 established baseline 3. The botulinum toxin effect was the time elapsed between baselines 2 and 3, ranging from 171 to 204 days, average of 183.72 days, greater than the 3 or 4 months reported in the literature.

Conclusion

"BTA Codes" is a set of rules to apply botulinum toxin supported by muscle anatomy and degree of voluntary contraction to enhance the duration of its effect.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Chahal et al. Respond to “Physical Exertion and Placental Abruption: Public Health Implications and Future Directions”

Physical Exertion Immediately Prior to Placental Abruption: A Case-Crossover Study

Physical Exertion and Placental Abruption: Public Health implications and Future Directionss

Abstract

Chahal et al (Am J Epidemiol. XXXX;XXX(XX):XXXX–XXXX)) assessed the risk of placental abruption due to physical exertion using a case-crossover design. The authors found an increased risk of placental abruption following increased physical exertion in the hour prior to the abruption. The risk was greater among women who were primarily sedentary during pregnancy or prior to being pregnant compared to those who were more physically active. The authors utilize a case-crossover design to assess the association of an intermittent exposure on an acute event. Chahal et al address the limitations of the study including the inability to control for time-varying confounders as well as the potential for recall bias. The public health implications of the study must be carefully evaluated given that physical activity during and prior to pregnancy can lead to healthy outcomes and are likely recommended. While the current study is unable to determine the type of physical exertion associated with placental abruption, future studies are recommended to determine the type of activity that presents increased risk. Additionally, studies among larger samples and in other countries will help determine the generalizability of the results.

Maternal Exposure to DDT and Pyrethroids and Birth Outcomes Among Residents of an Area Sprayed for Malaria Control Participating in the VHEMBE Birth Cohort Study

Abstract

Although effective in controlling malaria, Indoor Residual Spraying results in elevated exposure to insecticides such as dichlorodiphenyltrichloroethane (DDT) and pyrethroids. These chemicals cross the placenta but no studies have examined their associations with birth outcomes in populations residing in indoor residual spraying areas. We investigated this question in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study of 751 South African children born between 2012 and 2013. We measured maternal peripartum serum DDT and urine pyrethroid metabolite concentrations and collected data on birth weight, length, head circumference and gestational duration. We analyzed data using marginal structural models with inverse probability of treatment weights, generalized propensity scores and standard conditional linear regression. p,p'-DDT, o,p'-DDT and, to a lesser extent, p,p'-dichlorodiphenyldichloroethylene were related to elevated birth weight, length and head circumference among girls only, using all three analytical methods. Changes in gestational duration did not mediate this relation, suggesting exposures accelerate fetal growth, which is consistent with the known estrogenic properties of o,p'-DDT and p,p'-DDT. No associations were found with pyrethroid metabolites. Results suggest prenatal exposure to DDT is related to elevated birth size. Further studies are needed to elucidate the implications of these findings.

Prevalence and Patterning of Mental Disorder in Three Cohorts of Black and White Americans Through Adolescence

Abstract

The tendency for Blacks to report similar or lower rates of mental disorder than Whites is well-established. However, whether these disparities are stable across cohorts of Black and White Americans is not well understood. In the current study, we examined Black-White differences in the lifetime prevalence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition mood, anxiety, impulse control, substance use and any disorders across 3 cohorts of Blacks and Whites aged 4 to 18. Using merged data from the National Comorbidity Survey Replication (2001-2003) and the National Comorbidity Survey Adolescent Supplement (2001-2004), we observed a change in the Black-White patterning of mental disorder between 1957 and 2004. Blacks born between 1957-1969 reported lower rates of anxiety disorders relative to their White counterparts (odds ratio (OR)=0.69, 95% confidence interval (CI): 0.52-0.91), Blacks born between 1970-1982 reported no difference in the rates of anxiety disorders relative to Whites (OR=0.97, 95% CI: 0.76-1.25), and Blacks born between 1983-1991 reported higher rates of anxiety disorders relative to Whites (OR=1.30, 95% CI: 1.18-1.43). Similar but less distinct trends were observed for mood, impulse control, and any disorders. Our results suggest that the Black-White patterning of mental disorder has changed across cohorts, to the disadvantage of Black Americans.

Why Choose the Septum-Supero-Medial (SSM)-Based Mammaplasty in Patients with Severe Breast Ptosis: An Anatomical Point of View

Abstract

Nipple–areola complex (NAC) loss is one of the most devastating complications of mastopexy or breast reduction, and it requires revisional procedures with poor aesthetic outcome. In high-risk patients, a free nipple graft could be a choice, but it is associated with the same aesthetic concerns for both patients and surgeons. We report our experience with the septum-supero-medial-based mammaplasty to treat 22 patients with severe breast ptosis (nipple-to-sternal-notch distance > 40 cm). No NAC loss was observed. The study highlights surgical technical details and discusses anatomical considerations to justify the successful result.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Spreading the message of antimicrobial resistance: A detailed account of a successful public engagement event

Abstract

The increase in Antimicrobial resistance (AMR) microorganisms has been exacerbated by exposure to antimicrobial drugs (e.g. antibiotics). A solution to AMR may require academic researchers to not only contribute to the drug discovery pipeline through laboratory research, but also to engage and inform non-specialist audiences using a variety of interventions in order to change behaviour towards our use of antibiotics. In this paper, the authors describe a hands-on public engagement event focusing on AMR. 'A Spoonful of Soil', was created by drawing on the past experiences of the delivering team (also described), with planning focusing on clear concise messages, selection of an appropriate audience and ensuring the event would be of significant interest to the audience. The event had a significant footfall of over 300 visitors. Key messages which aimed to raise awareness of AMR and educate visitors on the actions and behaviours that can help address the global issue of AMR were delivered by appropriate experts successfully, however success in reaching audience cannot be concluded from the feedback and evaluation gathered.

Discussion of Shue et al. “Fat Injection: A Systemic Review of Injection Volumes by Facial Subunit”

Empirical moral rationalism and the social constitution of normativity

Abstract

Moral rationalism has long been an attractive position within moral philosophy. However, among empirical-minded philosophers, it is widely dismissed as scientifically untenable. In this essay, I argue that moral rationalism's lack of uptake in the empirical domain is due to the widespread supposition that moral rationalists must hold that moral judgments and actions are produced by rational capacities. But this construal is mistaken: moral rationalism's primary concern is not with the relationship between moral judgments and rational capacities per se, but rather with developing a conception objectivity normativity that avoids Platonism. In light of this, I develop an alternative approach to translating moral rationalism into the empirical domain that builds on the common rationalist view that normative requirements are explained by the relationship between agents and the social structures and practices in which they are embedded. I propose that this social conception of normativity can be translated into a scientific framework by interpreting it as a claim about the importance of constraint-based explanation when accounting for norm-governed behavior. In order to develop this point more concretely and show that it is empirically tractable, I turn to research on macaque social organization that highlights the ways in which (proto)normative standards are generated by empirically observable social structures. The insights garnered from the macaque case allow me to then locate moral rationalism's core claims about the relationship between morality and the standards of practical rationality within an empirically plausible framework.

Global and Widespread Local White Matter Abnormalities in Juvenile Neuronal Ceroid Lipofuscinosis [PEDIATRICS]

BACKGROUND AND PURPOSE:

Juvenile neuronal ceroid lipofuscinosis is a progressive neurodegenerative lysosomal storage disease of childhood. It manifests with loss of vision, seizures, and loss of cognitive and motor functions leading to premature death. Previous MR imaging studies have reported cerebral and cerebellar atrophy, progressive hippocampal atrophy, thalamic signal intensity alterations, and decreased white matter volume in the corona radiata. However, conventional MR imaging findings are usually normal at younger than 10 years of age. The purpose of our study was to investigate whether diffusion MR imaging could reveal changes in white matter microstructure already present at a younger age.

MATERIALS AND METHODS:

We investigated global and local white matter abnormalities in 14 children with juvenile neuronal ceroid lipofuscinosis (mean age, 9.6 ± 3.4 years; 10 boys) and 14 control subjects (mean age, 11.2 ± 2.3 years; 7 boys). Twelve patients underwent follow-up MR imaging after 2 years (mean age, 11.4 ± 3.2 years; 8 boys). We performed a global analysis using 2 approaches: white matter tract skeleton and constrained spherical deconvolution–based whole-brain tractography. Then, we investigated local microstructural abnormalities using Tract-Based Spatial Statistics.

RESULTS:

We found globally decreased anisotropy (P = .000001) and increased diffusivity (P = .001) in patients with juvenile neuronal ceroid lipofuscinosis. In addition, we found widespread increased diffusivity and decreased anisotropy in, for example, the corona radiata (P < .001) and posterior thalamic radiation (P < .001). However, we found no differences between the first and second acquisitions.

CONCLUSIONS:

The patients with juvenile neuronal ceroid lipofuscinosis exhibited global and local abnormalities in white matter microstructure. Future studies could apply more specific microstructural models and study whether these abnormalities are already present at a younger age.

Endovascular Treatment of Dural Arteriovenous Fistulas Using Transarterial Liquid Embolization in Combination with Transvenous Balloon-Assisted Protection of the Venous Sinus [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Sinus-preserving endovascular embolization was described as a promising treatment technique for dural arteriovenous fistulas. Our aim was to report our single-center experience in patients with dural arteriovenous fistulas who were treated with transarterial liquid embolization in combination with transvenous balloon-assisted protection of the affected venous sinus.

MATERIALS AND METHODS:

A retrospective analysis of a prospectively collected data base was performed. Demographic and clinical data, angiographic features of the dural arteriovenous fistulas, procedural parameters, complications, treatment success, follow-up imaging, and clinical outcome were assessed.

RESULTS:

Twenty-two patients were treated in 25 procedures. All patients were symptomatic, of whom 81.8% presented with tinnitus; 9.1%, with ocular symptoms; and 9.1%, with headache. Most fistulas were located at the transverse and/or sigmoid sinus. The most frequent fistula type was Cognard IIa+b (40.9%), followed by Cognard I (31.8%) and Cognard IIa (27.3%)/Borden I (59.1%), followed by Borden II (40.9%). The affected sinus could be preserved in all except for 1 patient in whom it was sacrificed in a second treatment procedure by coil embolization. The overall complete occlusion rate was 86.4%. The overall complication rate was 20%, with transient and permanent morbidity and mortality of 8%, 0%, and 0%, respectively. After a mean follow-up of 18 months, most patients (68.2%) achieved complete symptom remission, 27.3% showed symptom relief, and 4.6% had stable symptoms.

CONCLUSIONS:

Transarterial liquid embolization of dural arteriovenous fistulas in combination with transvenous balloon-assisted protection of the venous sinus is feasible and safe and offers high rates of occlusion and of symptom remission.

REPLY: [reply]

Extent of Microstructural Tissue Damage Correlates with Hemodynamic Failure in High-Grade Carotid Occlusive Disease: An MRI Study Using Quantitative T2 and DSC Perfusion [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Chronic hemodynamic impairment in high-grade carotid occlusive disease is thought to cause microstructural abnormalities that might be subclinical or lead to subtle symptoms including cognitive impairment. Quantitative MR imaging allows assessing pathologic structural changes beyond macroscopically visible tissue damage. In this study, high-resolution quantitative T2 mapping combined with DSC-based PWI was used to investigate quantitative T2 changes as a potential marker of microstructural damage in relation to hemodynamic impairment in patients with unilateral high-grade carotid occlusive disease.

MATERIALS AND METHODS:

Eighteen patients with unilateral high-grade ICA or MCA stenosis/occlusion were included in the study. T2 values and deconvolved perfusion parameters, including relative CBF, relative CBV, and the relative CBF/relative CBV ratio as a potential indicator of local cerebral perfusion pressure, were determined within areas with delayed TTP and compared with values from contralateral unaffected areas after segmentation of normal-appearing hypoperfused WM and cortical regions. Hemispheric asymmetry indices were calculated for all parameters.

RESULTS:

Quantitative T2 was significantly prolonged (P < .01) in hypoperfused tissue and correlated significantly (P < .01) with TTP delay and relative CBF/relative CBV reduction in WM. Significant correlations (P < .001) between TTP delay and the relative CBF/relative CBV ratio were found both in WM and in cortical areas.

CONCLUSIONS:

Quantitative T2 can be used as a marker of microstructural tissue damage even in normal-appearing GM and WM within a vascular territory affected by high-grade carotid occlusive disease. Furthermore, the extent of damage correlates with the degree of hemodynamic failure measured by DSC perfusion parameters.

Neuroimaging in Dengue Seropositive Cases [letter]

MSVAT-SPACE-STIR and SEMAC-STIR for Reduction of Metallic Artifacts in 3T Head and Neck MRI [HEAD & NECK]

BACKGROUND AND PURPOSE:

The incidence of metallic dental restorations and implants is increasing, and head and neck MR imaging is becoming challenging regarding artifacts. Our aim was to evaluate whether multiple-slab acquisition with view angle tilting gradient based on a sampling perfection with application-optimized contrasts by using different flip angle evolution (MSVAT-SPACE)-STIR and slice-encoding for metal artifact correction (SEMAC)-STIR are beneficial regarding artifact suppression compared with the SPACE-STIR and TSE-STIR in vitro and in vivo.

MATERIALS AND METHODS:

At 3T, 3D artifacts of 2 dental implants, supporting different single crowns, were evaluated. Image quality was evaluated quantitatively (normalized signal-to-noise ratio) and qualitatively (2 reads by 2 blinded radiologists). Feasibility was tested in vivo in 5 volunteers and 5 patients, respectively.

RESULTS:

Maximum achievable resolution and the normalized signal-to-noise ratio of MSVAT-SPACE-STIR were higher compared with SEMAC-STIR. Performance in terms of artifact correction was dependent on the material composition. For highly paramagnetic materials, SEMAC-STIR was superior to MSVAT-SPACE-STIR (27.8% smaller artifact volume) and TSE-STIR (93.2% less slice distortion). However, MSVAT-SPACE-STIR reduced the artifact size compared with SPACE-STIR by 71.5%. For low-paramagnetic materials, MSVAT-SPACE-STIR performed as well as SEMAC-STIR. Furthermore, MSVAT-SPACE-STIR decreased artifact volume by 69.5% compared with SPACE-STIR. The image quality of all sequences did not differ systematically. In vivo results were comparable with in vitro results.

CONCLUSIONS:

Regarding susceptibility artifacts and acquisition time, MSVAT-SPACE-STIR might be advantageous over SPACE-STIR for high-resolution and isotropic head and neck imaging. Only for materials with high-susceptibility differences to soft tissue, the use of SEMAC-STIR might be beneficial. Within limited acquisition times, SEMAC-STIR cannot exploit its full advantage over TSE-STIR regarding artifact suppression.

REPLY: [reply]

Efficacy and Safety of Percutaneous Microwave Ablation and Cementoplasty in the Treatment of Painful Spinal Metastases and Myeloma [SPINE]

BACKGROUND AND PURPOSE:

Painful spinal metastases are a common cause of cancer-related morbidity. Percutaneous ablation presents an attractive minimally invasive alternative to conventional therapies. We performed a retrospective review of 69 patients with 102 painful spinal metastases undergoing microwave ablation and cementoplasty to determine the efficacy and safety of this treatment.

MATERIALS AND METHODS:

Procedures were performed between January 2015 and October 2016 with the patient under general anesthesia using image guidance for 102 spinal metastases in 69 patients in the following areas: cervical (n = 2), thoracic (n = 50), lumbar (n = 34), and sacral (n = 16) spine. Tumor pathologies included the following: multiple myeloma (n = 10), breast (n = 27), lung (n = 12), thyroid (n = 6), prostate (n = 5), colon (n = 4), renal cell (n = 3), oral squamous cell (n = 1), and adenocarcinoma of unknown origin (n = 1). Procedural efficacy was determined using the visual analog scale measured preprocedurally and at 2–4 weeks and 20–24 weeks postprocedure. Tumor locoregional control was assessed on follow-up cross-sectional imaging. Procedural complications were recorded to establish the safety profile.

RESULTS:

The median ablation time was 4 minutes 30 seconds ± 7 seconds, and energy dose, 4.1 ± 1.6 kJ. Median visual analog scale scores were the following: 7.0 ± 1.8 preprocedurally, 2 ± 1.6 at 2–4 weeks, and 2 ± 2.1 at 20–24 weeks. Eight patients died within 6 months following the procedure. Follow-up imaging in the surviving patients at 20–24 weeks demonstrated no locoregional progression in 59/61 patients. Two complications were documented (S1 nerve thermal injury and skin burn).

CONCLUSIONS:

Microwave ablation is an effective and safe treatment technique for painful spinal metastases. Further studies may be helpful in determining the role of microwave ablation in locoregional control of metastases.

Common Origin of Brachiocephalic and Left Common Carotid Arteries: Proposal of New Terminology [letter]

Clinical Significance of Intraplaque Hemorrhage in Low- and High-Grade Basilar Artery Stenosis on High-Resolution MRI [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Intraplaque hemorrhage within intracranial atherosclerotic plaques identified by high-resolution MR imaging has been studied as a potential marker of stroke risk. However, previous studies only examined intracranial arteries with high-grade stenosis (degree of stenosis, >50%). This study aimed to ascertain the clinical relevance of intraplaque hemorrhage in patients with low- and high-grade stenotic basilar artery plaques.

MATERIALS AND METHODS:

Patients with basilar artery stenosis (n = 126; mean age, 62 ± 10 years; 66 symptomatic and 60 asymptomatic) underwent high-resolution MR imaging. The relationship between imaging findings (intraplaque hemorrhage, contrast enhancement, degree of stenosis, minimal lumen area, and plaque burden) and symptoms was analyzed.

RESULTS:

Intraplaque hemorrhage was identified in 22 patients (17.5%), including 21 (31.8%) symptomatic patients and 1 (1.7%) asymptomatic patient. Multivariate analysis showed that intraplaque hemorrhage was the strongest independent marker of symptomatic status (odds ratio, 27.5; 95% CI, 3.4–221.5; P = .002). Contrast enhancement was also independently associated with symptomatic status (odds ratio, 9.9; 95% CI, 1.5–23.6; P = .016). Stenosis, minimal lumen area, and plaque burden were not correlated with symptoms (P > .05). Intraplaque hemorrhage was present in both low- and high-grade stenotic basilar arteries (11.3% versus 16.3%, P = .63). Diagnostic performance values of intraplaque hemorrhage for patients with acute/subacute symptomatic stroke were the following: specificity, 98.3%; sensitivity, 31.8%; positive predictive value, 95.5%; and negative predictive value, 56.7%.

CONCLUSIONS:

Intraplaque hemorrhage is present in both low- and high-grade stenotic basilar artery plaques and is independently associated with symptomatic stroke status. Intraplaque hemorrhage may identify high-risk plaque and provide new insight into the management of patient with stroke without significant stenosis.

[other]

Abnormal Blood Oxygen Level-Dependent Fluctuations in Focal Cortical Dysplasia and the Perilesional Zone: Initial Findings [FUNCTIONAL]

BACKGROUND AND PURPOSE:

Focal cortical dysplasia is a common cause of intractable epilepsy for which neurosurgery is an option. Delineations of a focal cortical dysplasia lesion on structural brain images may not necessarily reflect the functional borders of normal tissue. Our objective was to determine whether abnormalities in spontaneous blood oxygen level–dependent fluctuations arise in focal cortical dysplasia lesions and proximal regions.

MATERIALS AND METHODS:

Fourteen patients with focal cortical dysplasia–related epilepsy and 16 healthy controls underwent structural and resting-state functional MR imaging. Three known blood oxygen level–dependent measures were determined, including the fractional amplitude of low-frequency fluctuations, regional homogeneity, and wavelet entropy. These measures were evaluated in the lesion and perilesional zone and normalized to the contralateral cortex of patients with focal cortical dysplasia and healthy controls.

RESULTS:

Patients showed significantly decreased fractional amplitude of low-frequency fluctuations and increased wavelet entropy in the focal cortical dysplasia lesion and the perilesional zone (≤2 cm) relative to the contralateral homotopic cortex and the same regions in healthy controls. Regional homogeneity was significantly increased in the focal cortical dysplasia lesion compared with the contralateral homotopic cortex and healthy controls.

CONCLUSIONS:

Abnormalities in spontaneous blood oxygen level–dependent fluctuations were seen up to 2 cm distant from the radiologically visible boundary. It was demonstrated that functional boundaries go beyond structural boundaries of focal cortical dysplasia lesions. Validation is required to reveal whether this information is valuable for surgical planning and outcome evaluation of focal cortical dysplasia lesions and comparing current results with electrophysiologic analysis.

Cerebrovascular Manifestations of Neurosarcoidosis: An Underrecognized Aspect of the Imaging Spectrum [ADULT BRAIN]

SUMMARY:

Involvement of the central nervous system by sarcoidosis, also referred to as neurosarcoidosis, is seen clinically in about 5% of patients with systemic disease. CNS involvement most frequently affects the leptomeninges and cranial nerves, though the ventricular system, brain parenchyma, and pachymeninges may also be involved. Even though the involvement of the intracranial vascular structures is well-known on postmortem studies, there is scant literature on imaging manifestations secondary to the vessel wall involvement, being confined mostly to isolated case reports and small series. The authors present a review of various cerebrovascular manifestations of neurosarcoidosis, along with a brief synopsis of the existing literature.

{beta}-Hydroxybutyrate Detection with Proton MR Spectroscopy in Children with Drug-Resistant Epilepsy on the Ketogenic Diet [PEDIATRICS]

BACKGROUND AND PURPOSE:

The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of β-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with β-hydroxybutyrate serum concentrations.

MATERIALS AND METHODS:

Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated β-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum β-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate.

RESULTS:

β-hydroxybutyrate blood levels were highly correlated to brain β-hydroxybutyrate levels, referenced as either choline, creatine, or N-acetylaspartate. They were inversely but more weakly associated with N-acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated.

CONCLUSIONS:

Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable β-hydroxybutyrate, with a strong correlation to β-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum β-hydroxybutyrate levels and brain tissue N-acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet.

Deep-Learning Convolutional Neural Networks Accurately Classify Genetic Mutations in Gliomas [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation.

MATERIALS AND METHODS:

MR imaging data and molecular information were retrospectively obtained from The Cancer Imaging Archives for 259 patients with either low- or high-grade gliomas. A convolutional neural network was trained to classify isocitrate dehydrogenase 1 (IDH1) mutation status, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status. Principal component analysis of the final convolutional neural network layer was used to extract the key imaging features critical for successful classification.

RESULTS:

Classification had high accuracy: IDH1 mutation status, 94%; 1p/19q codeletion, 92%; and MGMT promotor methylation status, 83%. Each genetic category was also associated with distinctive imaging features such as definition of tumor margins, T1 and FLAIR suppression, extent of edema, extent of necrosis, and textural features.

CONCLUSIONS:

Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training.

MRI-Based Methods for Spinal Cord Atrophy Evaluation: A Comparison of Cervical Cord Cross-Sectional Area, Cervical Cord Volume, and Full Spinal Cord Volume in Patients with Aquaporin-4 Antibody Seropositive Neuromyelitis Optica Spectrum Disorders [SPINE]

BACKGROUND AND PURPOSE:

Measures for spinal cord atrophy have become increasingly important as imaging biomarkers in the assessment of neuroinflammatory diseases, especially in neuromyelitis optica spectrum disorders. The most commonly used method, mean upper cervical cord area, is relatively easy to measure and can be performed on brain MRIs that capture cervical myelon. Measures of spinal cord volume (eg, cervical cord volume or total cord volume) require longer scanning and more complex analysis but are potentially better suited as spinal cord atrophy measures. This study investigated spinal cord atrophy measures in a cohort of healthy subjects and patients with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders and evaluated the discriminatory performance of mean upper cervical cord cross-sectional area compared with cervical cord volume and total cord volume.

MATERIALS AND METHODS:

Mean upper cervical cord area, cervical cord volume, and total cord volume were measured using 3T MRIs from healthy subjects (n = 19) and patients with neuromyelitis optica spectrum disorders (n = 30). Group comparison and receiver operating characteristic analyses between healthy controls and patients with neuromyelitis optica spectrum disorders were performed.

RESULTS:

Mean upper cervical cord area, cervical cord volume, and total cord volume measures showed similar and highly significant group differences between healthy control subjects and patients with neuromyelitis optica spectrum disorders (P < .01 for all). All 3 measures showed similar receiver operating characteristic–area under the curve values (mean upper cervical cord area = 0.70, cervical cord volume = 0.75, total cord volume = 0.77) with no significant difference between them. No associations among mean upper cervical cord cross-sectional area, cervical cord volume, or total cord volume with disability measures were found.

CONCLUSIONS:

All 3 measures showed similar discriminatory power between healthy control and neuromyelitis optica spectrum disorders groups. Mean upper cervical cord area is easier to obtain compared with cervical cord volume and total cord volume and can be regarded as an efficient representative measure of spinal cord atrophy in the neuromyelitis optica spectrum disorders context.

Diffusion-Weighted Imaging and Diffusion Tensor Imaging for Differentiating High-Grade Glioma from Solitary Brain Metastasis: A Systematic Review and Meta-Analysis [ADULT BRAIN]

BACKGROUND:

Accurate diagnosis of high-grade glioma and solitary brain metastasis is clinically important because it affects the patient's outcome and alters patient management.

PURPOSE:

To evaluate the diagnostic performance of DWI and DTI for differentiating high-grade glioma from solitary brain metastasis.

DATA SOURCES:

A literature search of Ovid MEDLINE and EMBASE was conducted up to November 10, 2017.

STUDY SELECTION:

Studies evaluating the diagnostic performance of DWI and DTI for differentiating high-grade glioma from solitary brain metastasis were selected.

DATA ANALYSIS:

Summary sensitivity and specificity were established by hierarchic logistic regression modeling. Multiple subgroup analyses were also performed.

DATA SYNTHESIS:

Fourteen studies with 1143 patients were included. The individual sensitivities and specificities of the 14 included studies showed a wide variation, ranging from 46.2% to 96.0% for sensitivity and 40.0% to 100.0% for specificity. The pooled sensitivity of both DWI and DTI was 79.8% (95% CI, 70.9%–86.4%), and the pooled specificity was 80.9% (95% CI, 75.1%–85.5%). The area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84–0.89). The multiple subgroup analyses also demonstrated similar diagnostic performances (sensitivities of 76.8%–84.7% and specificities of 79.7%–84.0%). There was some level of heterogeneity across the included studies (I² = 36%); however, it did not reach a level of concern.

LIMITATIONS:

The included studies used various DWI and DTI parameters.

CONCLUSIONS:

DWI and DTI demonstrated a moderate diagnostic performance for differentiation of high-grade glioma from solitary brain metastasis.

Is Gd-DTPA Necessary in Clinical Practice for Peripheral Nerve Injury? [letter]

Quantitative Susceptibility Mapping after Sports-Related Concussion [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Quantitative susceptibility mapping using MR imaging can assess changes in brain tissue structure and composition. This report presents preliminary results demonstrating changes in tissue magnetic susceptibility after sports-related concussion.

MATERIALS AND METHODS:

Longitudinal quantitative susceptibility mapping metrics were produced from imaging data acquired from cohorts of concussed and control football athletes. One hundred thirty-six quantitative susceptibility mapping datasets were analyzed across 3 separate visits (24 hours after injury, 8 days postinjury, and 6 months postinjury). Longitudinal quantitative susceptibility mapping group analyses were performed on stability-thresholded brain tissue compartments and selected subregions. Clinical concussion metrics were also measured longitudinally in both cohorts and compared with the measured quantitative susceptibility mapping.

RESULTS:

Statistically significant increases in white matter susceptibility were identified in the concussed athlete group during the acute (24 hour) and subacute (day 8) period. These effects were most prominent at the 8-day visit but recovered and showed no significant difference from controls at the 6-month visit. The subcortical gray matter showed no statistically significant group differences. Observed susceptibility changes after concussion appeared to outlast self-reported clinical recovery metrics at a group level. At an individual subject level, susceptibility increases within the white matter showed statistically significant correlations with return-to-play durations.

CONCLUSIONS:

The results of this preliminary investigation suggest that sports-related concussion can induce physiologic changes to brain tissue that can be detected using MR imaging–based magnetic susceptibility estimates. In group analyses, the observed tissue changes appear to persist beyond those detected on clinical outcome assessments and were associated with return-to-play duration after sports-related concussion.

Prediction of Borderzone Infarction by CTA in Patients Undergoing Carotid Embolization for Carotid Blowout [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Permanent common carotid artery and/or ICA occlusion is an effective treatment for carotid blowout syndrome. Besides postoperative thromboembolic infarction, permanent common carotid artery and/or ICA occlusion may cause borderzone infarction when the collateral flow to the deprived brain territory is inadequate. In this study, we aimed to test the predictive value of CTA for post–permanent common carotid artery and/or ICA occlusion borderzone infarction in patients with carotid blowout syndrome.

MATERIALS AND METHODS:

In this retrospective study, we included 31 patients undergoing unilateral permanent common carotid artery and/or ICA occlusion for carotid blowout syndrome between May 2009 and December 2016. The vascular diameter of the circle of Willis was evaluated using preprocedural CTA, and the risk of borderzone infarction was graded as very high risk, high risk, intermediate risk, low risk, and very low risk.

RESULTS:

The performance of readers' consensus on CTA for predicting borderzone infarction was excellent, with an area under receiver operating characteristic curve of 0.938 (95% confidence interval, 0.85–1.00). We defined very high risk, high risk, and intermediate risk as positive for borderzone infarction, the sensitivity, specificity, positive predictive value, and negative predictive value of CTA for borderzone infarction were 100% (7/7), 62.5% (15/24), 43.8% (7/16), and 100% (15/15), respectively. The interobserver reliability was excellent ( = 0.807). No significant difference in the receiver operating characteristic curves was found between the 2 readers (P = .114).

CONCLUSIONS:

CTA can be used to predict borderzone infarction after permanent common carotid artery and/or ICA occlusion by measuring the collateral vessels of the circle of Willis.

Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study

Abstract

Background

Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented.

Materials and methods

Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥ 1% of tumor or stroma cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review.

Results

Median patient age in this cohort (N = 23) was 65 years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% (95% confidence interval [CI] 5.0%–38.8%); 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred.

Conclusion

Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1–positive prostate cancer, and its side effect profile was favorable.

ClinicalTrials.gov Identifier

NCT02054806

Reply to the letter to the editor “Anti-EGFR therapy in oesophagogastric cancer: precise but not enough” by M. Salati and S. Cascinu

Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies

PAROTIDECTOMY INCISIONS

The surgical approach to a parotidectomy was first described by Blair in 1912 for the resection of all parotid tumors. It has since evolved and changed into numerous permutations. The modern-day approach considers the size, location and sometimes anticipated pathology of the parotid tumor in addition to the need for a possible neck dissection. As the concern for cosmesis increases in today's society, the well-known Modified Blair incision has been revised to limit the cutaneous scar while preserving access and oncologic principles.

No effect of human presence at night on disease, body mass, or metabolism in rural and urban house finches (Haemorhous mexicanus)

Abstract

Global urban development continues to accelerate and have diverse effects on wildlife. Although most studies of anthropogenic impacts on animals have focused on indirect effects (e.g. environmental modifications like habitat change or pollution), there may also be direct effects of physical human presence and actions on wildlife stress, behavior, and persistence in cities. Most studies on how humans physically interact with wildlife have focused on the active, daytime phase of diurnal animals, rarely considering effects of our night-time activities. We hypothesized that, if night-time human presence is a stressor for wildlife that are not commonly exposed to humans, night-disturbed rural animals would show stronger physiological signs of elevated stress than would urban individuals. Specifically, we experimentally investigated the effects of human presence at night on disease, body mass, and mass-specific metabolic rates in urban- and rural-caught house finches (Haemorhous mexicanus) in captivity. Our human-presence-at-night treatment consisted of a human entering the housing room of the birds and briefly jostling the home cages of each finch as the person walked around the room for a 3-minute period on 5 randomly selected nights per week. Compared to a control (night-undisturbed) group, we found that human presence at night greatly increased the odds finches were awake for ca. 33 minutes post-disturbance, but that chronic treatment this did not alter body mass, parasitic infection by coccidian endoparasites, or mass-specific basal metabolic rates. Additionally, finches caught from urban and rural sites did not differ in their response to the treatment. Overall, our results are consistent with those showing that brief but regular human disturbances can have acute negative effects on wildlife, but carry few if any long-term metabolic or disease-related costs in fast-lived birds. However, these findings contrast with the broad, chronic physiological effects of other anthropogenic changes, such as artificial light at night, and highlight the differential impacts that various human activities (which differ in sensory stimulus type, perceived threat, duration and intensity, etc.) can have on wildlife health and behavior.

Cellular localization of the K+‐dependent Na+‐Ca2+ exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells

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

Vulvar lichen sclerosus: A single‐center retrospective study in China

The Journal of Dermatology, EarlyView.

Current and future treatment of hidradenitis suppurativa

British Journal of Dermatology, EarlyView.

A Chinese herbal medicine preparation (PTQX) for children with moderate to severe atopic eczema: a pilot RCT

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.

Methotrexate restores the function of peripheral blood regulatory T cells in psoriasis vulgaris via the CD73/AMPK/mTOR pathway

British Journal of Dermatology, EarlyView.

Perpetuating the patriarchy: misogyny and (post-)feminist backlash

Abstract

How are patriarchal regimes perpetuated and reproduced? Kate Manne's recent work on misogyny aims to provide an answer to this central question. According to her, misogyny is a property of social environments where women perceived as violating patriarchal norms are 'kept down' through hostile reactions coming from men, other women and social structures. In this paper, I argue that Manne's approach is problematically incomplete. I do so by examining a recent puzzling social phenomenon which I call (post-)feminist backlash: the rise of women-led movements reinstating patriarchal practices in the name of feminism. I focus on the example of 'raunch feminist' CAKE parties and argue that their pro-patriarchal dimension cannot be adequately explained by misogyny. I propose instead a different story that emphasizes the continued centrality of gender distinctions in our social normative life, even as gendered social meanings become increasingly contested. This triggers meaning vertigo, a distinct form of social anxiety and the reactionary impulse at the heart of (post)-feminist backlash. Meaning vertigo both complicates the answer to Manne's main question—"why is misogyny still a thing?"—and suggests the need and opportunity for a different kind of feminist political intervention.

Assessment of quality of life in Turkish children with psoriasis and their caregivers

Pediatric Dermatology, EarlyView.

Infantile hemangioma with minimal or arrested growth as the skin manifestation of PHACE syndrome

Pediatric Dermatology, EarlyView.

Solitary lesion of a newborn's foot

Pediatric Dermatology, Volume 35, Issue 4, Page 523-524, July/August 2018.

A facial cutaneous horn

Pediatric Dermatology, Volume 35, Issue 4, Page 515-516, July/August 2018.

Erosions and vesicles following the lines of Blaschko in a neonate

Pediatric Dermatology, Volume 35, Issue 4, Page 519-520, July/August 2018.

Skin‐colored to yellowish subungual flat plaque in a 16‐year‐old girl

Pediatric Dermatology, Volume 35, Issue 4, Page 521-522, July/August 2018.

An 8‐year‐old girl with a papule on her cheek

Pediatric Dermatology, Volume 35, Issue 4, Page 511-512, July/August 2018.

Painful callosities in a young boy

Pediatric Dermatology, Volume 35, Issue 4, Page 509-510, July/August 2018.

Generalized bullae and erosions in an infant

Pediatric Dermatology, Volume 35, Issue 4, Page 525-527, July/August 2018.

Facial cystic lesions and onychodystrophy

Pediatric Dermatology, Volume 35, Issue 4, Page 517-518, July/August 2018.

Patient Perspectives: What is mastocytosis?

Pediatric Dermatology, Volume 35, Issue 4, Page 507-508, July/August 2018.

Issue Information

Pediatric Dermatology, Volume 35, Issue 4, Page 423-427, July/August 2018.

Rapidly growing nodule in an adolescent girl

Pediatric Dermatology, Volume 35, Issue 4, Page 513-514, July/August 2018.

Response to “Case series study of the efficacy of compounded antibacterial, steroid, and moisturizer in atopic dermatitis”

Pediatric Dermatology, Volume 35, Issue 4, Page 539-539, July/August 2018.

What's the story? An analysis of children's books about atopic dermatitis

Pediatric Dermatology, EarlyView.

Body dysmorphic disorder in pediatric dermatology

Pediatric Dermatology, EarlyView.

Single‐nucleotide polymorphisms of VEGF‐A and VEGFR‐2 genes and risk of infantile hemangioma

International Journal of Dermatology, EarlyView.

A Janeway Lesson

International Journal of Dermatology, EarlyView.

The Solvatofluorochromism of 2,4,6‐Triarylpyrimidine Derivatives

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.

Is Proflavine Exposure Associated with Disease Progression in Women with Cervical Dysplasia? A Brief Report

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.

Photophysics of Xanthene Dyes at High Concentrations in Solid Environments: Charge Transfer Assisted Triplet Formation

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.

The Mechanism of CIRP in Regulation of STAT3 Phosphorylation and Bag‐1/S Expression Upon UVB Radiation

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.

Electronic Structure and Triplet‐Triplet Energy Transfer in Artificial Photosynthetic Antennas

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.

Double Effect Electron Transfer System in the AgBr/ZnO Composite with Enhanced Photocatalytic Degradation Performance against 3‐Cholorophenol under Visible Light Irradiation

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.

Correction to: Brevibacillus laterosporus isolated from the digestive tract of honeybees has high antimicrobial activity and promotes growth and productivity of honeybee’s colonies

The original publication of this paper contains a mistake. The correct affiliation no. 3 is shown in this paper.

Double Z plasty advancement flaps for closure of large defects on the forearm

International Wound Journal, EarlyView.

Skin closure in arthroplasty surgery: Current practice

International Wound Journal, EarlyView.

Barriers and facilitators to participant recruitment to randomised controlled trials: A qualitative perspective

International Wound Journal, EarlyView.

Negative pressure wound treatment with computer‐controlled irrigation/instillation decreases bacterial load in contaminated wounds and facilitates wound closure

International Wound Journal, EarlyView.

Lipoedema is not lymphoedema: A review of current literature

International Wound Journal, EarlyView.

New application of purse string suture in skin cancer surgery

International Wound Journal, EarlyView.

Vegetating erosive cutaneous lesions and pyogenic granuloma in the course of mucous membrane pemphigoid: a case report and review of literature

International Wound Journal, EarlyView.

An intra‐individual surgical wound comparison shows that octenidine‐based hydrogel wound dressing ameliorates scar appearance following abdominoplasty

International Wound Journal, EarlyView.

Surgical treatment and strategy in patients with multiple pressure sores

International Wound Journal, EarlyView.

A theoretical and experimental study of the temporal reduction in UV protection provided by a facial day cream

International Journal of Cosmetic Science, Volume 0, Issue ja, -Not available-.

Process optimization via response surface methodology in the physico-chemical treatment of vegetable oil refinery wastewater

Abstract

The present paper investigates the efficiency of coagulation/flocculation process using aluminum sulfate as coagulant and CHT industrial flocculent as coagulant aid/flocculent in the treatment of vegetable oil refinery wastewater (VORW). The process optimization was conducted in two steps, jar test experiments for preliminary evaluation to identify the most influencing factors and response surface methodology using Box–Behnken design to investigate the effects of three major factors and their interactions. The variables involved were the coagulant concentration (X₁), flocculent dosage (X₂), and initial pH (X₃) of water samples, while the responses were COD removal (Y1) and residual turbidity (Y2). The optimal conditions obtained by solving the quadratic regression models, as well as by analyzing the response surface contour plots, were as follows: 2.4 g/L of coagulant (aluminum sulfate), 60.05 mg/L of flocculent, and about 9.23 as initial pH. Under these conditions, the coagulation/flocculation treatment was able to achieve 99% of COD removal with total turbidity elimination (100% removal). Analysis of variance showed high variance coefficient (R²) values of 0.929 and 0.836 for COD and turbidity removals, respectively, thus ensuring a satisfactory adjustment of the second-order regression model with the experimental data. This statistical design methodology was demonstrated as an efficient and feasible approach for the optimization of coagulation/flocculation treatment.

New applied pharmacological approach/trend on utilization of agro-industrial wastes

Abstract

This study aimed to transform the locally available lignocellulosic residual palm frond (PF) and rice straw (RS) wastes into multifunction added products like methylated cellulose and sulfated and phosphorylated hemicelluloses by simple processes. Hydrolysis with 2 N sulfuric acid was the most suitable reaction for microcrystalline cellulose production. The characteristics of the prepared products were studied to obtain the optimum reaction conditions. Palm frond hemicellulose (PFHC) recorded the highest antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans (22, 22, 26 mm), respectively, and phosphorylated palm frond hemicellulose (PPFHC) exhibited the highest potential antioxidant activity of approximately 60%, suggesting a possible correlation between the two bioactivities. Most of extracted celluloses and their derivatives had a variety of promising probiotic activities which are expected to reduce the side effects of the gastric mucosa and possibly play a role in curing the gastric ulcer. Accordingly, the determination of anti-inflammatory and gastroprotective activity results revealed that methylcellulose, sulfated and phosphorylated hemicelluloses showed anti-inflammatory and gastroprotective activities and the capability of all tested compounds to ameliorate the ethanol-induced gastric ulcer in rats' stomach. All results recommended PF and RS and their derivatives to be used as a medicinal food.

CH 4 flux and methanogen community dynamics from five common emergent vegetations in a full-scale constructed wetland

Abstract

To investigate the effects of emergent plants on CH₄ efflux and elucidate the key factors responsible for these effects, annual monitoring of CH₄ emissions and methanogen community dynamics in a full-scale constructed wetland (CW) was conducted. Five emergent plants (Typha orientalis, Cyperus alternifolius, Arundo domax, Iris pseudacorus, and Thalia dealbata) commonly used in CWs were selected for investigation. The greatest CH₄ flux (annual mean 19.4 mg m⁻² h⁻¹) was observed from I. pseudacorus, while the lowest CH₄ flux (7.1 mg m⁻² h⁻¹) was observed from Thalia dealbata. The CH₄ flux from five emergent plants showed marked seasonal variation. Total nitrogen (TN) and total phosphorous (TP) were weakly correlated with CH₄ emissions, whereas total carbon (TC) and root biomass of plants were positively correlated with CH₄ emissions. Quantitative real-time PCR (q-PCR) analysis indicated that the gene abundance of eubacterial 16S rRNA, particulate methane monooxygenase (pmoA) and methyl coenzyme M reductase (mcrA) significantly differed among plant species. Differences in TC, root biomass, and dissolved oxygen (DO) caused by plant species were potential factors responsible for differences in methanogens, methanotrophs, and CH₄ emissions. Methanobacteriaceae, Methanoregulaceae, Methanomicrobiaceae, and Methanosarcinaceae were the dominant families of methanogens. The pathways of methanogenesis from the five emergent plants differed, with the main pathway being hydrogenotrophic, while both hydrogenotrophic and acetotrophic methanogens were involved in A. domax. Redundancy analysis (RDA) further indicated that emergent plant types had a profound influence on the methanogenic communities. Taken together, these results suggest emergent plant species can significantly influence CH₄ fluxes in CW through microbial communities, biochemical pathways for methanogenesis, TC, and DO. Furthermore, plant species in CWs should be considered an important factor in evaluating greenhouse gases emission. Finally, it is necessary to effectively manage CWs vegetation to maximize their environmental benefits.

Graphical abstract

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