The roles of NADPH oxidase in modulating neutrophil effector responses

Abstract

Neutrophils are phagocytic innate immune cells essential for killing bacteria via activation of a wide variety of effector responses and generation of large amounts of reactive oxygen species (ROS). Majority of the ROS in neutrophils is generated by activation of the superoxide‐generating enzyme NADPH oxidase. Independent of their anti‐microbial function, NADPH oxidase‐derived ROS have emerged as key regulators of host immune responses and neutrophilic inflammation. Data from patients with inherited defects in the NADPH oxidase subunit alleles that ablate its enzyme function as well as mouse models demonstrate profound dysregulation of host inflammatory responses, neutrophil hyper‐activation and tissue damage in response to microbial ligands or tissue trauma. A large body of literature now demonstrates how oxidants function as essential signaling molecules that are essential for the regulation of neutrophil responses during priming, degranulation, neutrophil extracellular trap formation, and apoptosis, independent of their role in microbial killing. In this review we summarize how NADPH oxidase‐derived oxidants modulate neutrophil function in a cell intrinsic manner and regulate host inflammatory responses. In addition, we summarize studies that have elucidated possible roles of oxidants in neutrophilic responses within the oral mucosa and periodontal disease.

This article is protected by copyright. All rights reserved.

http://bit.ly/2M5gXGY

Is Targeting the Folate Receptor in Ovarian Cancer Coming of Age?

http://bit.ly/2D3CNrA

Current Treatment Options in Gastroenteropancreatic Neuroendocrine Carcinoma

AbstractPoorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first‐line treatment for GEPNECs is platinum‐based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first‐line and second‐line treatment options beyond platinum‐based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low‐ and intermediate‐grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy.Implications for Practice.There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first‐ and second‐line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.

http://bit.ly/2TJ48ow

Diagnostic performance of 68 Ga-PSMA PET/CT in the detection of prostate cancer prior to initial biopsy: comparison with cancer-predicting nomograms

Abstract

Purpose

To assess the diagnostic performance of ⁶⁸Ga-PSMA PET/CT for detecting suspected prostate cancer (PCa) and to compare it with that of two cancer-predicting nomograms.

Methods

We performed a retrospective analysis of 146 consecutive patients with suspected PCa based on symptoms or elevated total prostate-specific antigen (tPSA) levels who underwent ⁶⁸Ga-PSMA PET/CT and histopathologic examinations from April 2017 to April 2018 in a large tertiary care hospital in China. The ⁶⁸Ga-PSMA PET/CT results (PCa or benignancy) were evaluated by two experienced nuclear medicine specialists. The risk of positive PCa was evaluated using ERSPC and PCPT nomograms. The diagnostic performances of ⁶⁸Ga-PSMA PET/CT and that of the two nomograms were compared via receiver operating characteristic (ROC) curve analysis, decision curve analysis, and logistic regression.

Results

A total of 58 patients with tPSA of 0.4–50 ng/ml were included in the final analysis; PCa diagnosis was confirmed in 37 patients and excluded in 21 patients. ROC analysis showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ⁶⁸Ga-PSMA PET/CT were 91.67, 81.82, 89.19, and 85.71%, respectively, in per-patient analyses. ⁶⁸Ga-PSMA PET/CT exhibited a higher AUC (0.867) than those of ERSPC-RC3 (0.855) and PCPT-RC (0.770). The net benefit of ⁶⁸Ga-PSMA PET/CT was greatest for patients within threshold probabilities of 15–90%. Among the 58 patients, 11 (19%) biopsies suggested by ERSPC-RC3 were unnecessary and could have been avoided if judged by the ⁶⁸Ga-PSMA PET/CT results. Multivariate analysis revealed that the maximum standardised uptake value (SUV_max) and prostate volume were significant predictive factors for positive PCa results.

Conclusion

In suspected PCa patients with tPSA of 0.4–50 ng/ml, ⁶⁸Ga-PSMA PET/CT outperformed the nomograms in predicting cancer and reducing unnecessary biopsies. In addition, the risk of PCa was positively correlated with a higher SUV_max and lower prostate volume, which could help clinicians in making preliminary estimates of individual cancer risk, monitoring ⁶⁸Ga-PSMA PET/CT false-positive results and making biopsy decisions in daily medical practice.

http://bit.ly/2D4zYGJ

An application of advanced hair-save processes in leather industry as the reason of formation of keratinous waste: few peculiarities of its utilisation

Abstract

The application of more environmentally friendly hide and skin unhairing technologies in leather processing results in a significant increase in keratin waste. There are currently two most promising hair-saving unhairing methods: enzymatic and hair immunisation. The complete use of hair-saving unhairing methods in the leather industry will lead to the formation of approximately 143 thousand tons of hair/wool waste annually, which will require disposal. The disposal of keratin wastes from the leather industry has not been adequately studied, bearing in mind the possible amount of such wastes that will be produced in the future. Unfortunately, existing studies pay little attention to the method of unhairing, even though the unhairing method has a vast influence on the properties of keratin in the obtained hair/wool wastes. Accordingly, the present research is an attempt to establish how the differently obtained keratin wastes behave following disposal. The obtained results have shown that waste wool is characterised by different behaviour during burial in soil, and the behaviour depends on the method of unhairing. This proposition is valid for waste wool bioresistance as well. It was concluded that the deterioration of any sort of keratinous waste from the leather industry should be investigated thoroughly before disposal by burial in landfills.

http://bit.ly/2skmy36

Effect of electrolytes on the simultaneous electrochemical oxidation of sulfamethoxazole, propranolol and carbamazepine: behaviors, by-products and acute toxicity

Abstract

In this work, the effect of supporting electrolytes on the simultaneous electrochemical oxidation of the pharmaceuticals sulfamethoxazole (SMX), propranolol (PRO), and carbamazepine (CBZ) in aqueous solutions has been studied. Based on the identified by-products, the degradation mechanisms were proposed and the acute toxicity was evaluated for each electrolyte. Assays were carried out in batch mode in a 2 L undivided reactor using a niobium coated with boron-doped diamond (Nb/BDD) mesh anode and Ti cathode at 2.5 A in presence of different supporting electrolytes (Na₂SO₄, NaCl, or NaBr) at the same concentration of 7 mM. The degradation rates were higher in the assays with NaCl and NaBr. Reaction by-products were identified by gas chromatography–mass spectrometry. Indirect oxidation by electrogenerated reactive halogen species (RHS) was the main mechanism when halide ions were used as electrolytes. Ten by-products were detected using Na₂SO₄ as electrolyte, while 19 (12 non-halogenated and 7 halogenated) and 20 (10 non-halogenated and 10 halogenated) using NaCl and NaBr respectively. The proposed degradation pathways involve transformation (hydroxylation, deamination, desulfonation, and halogenation) and bond rupture to produce less molecular weight compounds and their further transformation until total degradation. Chlorinated and brominated by-products confirm halogenation reactions. The electrogenerated RHS presented a significant inhibition effect on Vibrio fischeri; nevertheless, acute toxicity was not presented using Na₂SO₄ as electrolyte and a pharmaceutical concentration of 5 μg/L. In this view, the role of the supporting electrolyte in electrochemical oxidation process is crucial since it strongly influence degradation rate, by-products, and acute toxicity.

http://bit.ly/2M7IOWR

Laboratory bioassays on the response of honey bee ( Apis mellifera L.) glutathione S -transferase and acetylcholinesterase to the oral exposure to copper, cadmium, and lead

Abstract

In the present study, the influence of cadmium, copper, and lead on two enzymes often used as biomarkers in toxicological analysis was investigated. Bees were fed with 1 M sucrose solution containing 10-fold serial dilutions of CuCl₂ (1000 mg L⁻¹, 100 mg L⁻¹, and 10 mg L⁻¹), CdCl₂ (0.1 mg L⁻¹, 0.01 mg L⁻¹, and 0.001 mg L⁻¹), or PbCl₂ (10 mg L⁻¹, 1 mg L⁻¹, and 0.1 mg L⁻¹) during 48 h. Our results showed that the total glutathione S-transferase activity was not changed under the influence of cadmium and lead, and it was decreased with the highest concentration of copper. The level of gene expression of the three analyzed classes of glutathione S-transferase was significantly increased with increasing concentrations of copper and cadmium. Lead did not cause significant changes in glutathione S-transferase activity and gene expression, while it showed biphasic effect on acetylcholinesterase activity: lower concentration of lead, 0.1 mg L⁻¹ inhibited and higher dose, 10 mg L⁻¹ induced acetylcholinesterase activity in honey bees. Furthermore, our results showed a significant decrease of the acetylcholinesterase activity in honey bees treated with 0.001 and 0.01 mg L⁻¹ CdCl₂. Our results indicate the influence of cadmium, copper, and lead on GST and AChE in the honey bees. These results form the basis for future research on the impact of metallic trace element pollution on honey bees.

http://bit.ly/2skmuQU

Free Tissue Transfer with the Free Rectus Abdominis Flap in High-Risk Patients above 65 Years – A Retrospective Cohort Study

Though technically feasible, free tissue transfer carries the risk of perioperative morbidity and mortality in elderly patients. In order to minimize operative treatment time and complication rates, we choose the rectus abdominis muscle (RAM) flap.

http://bit.ly/2FrjmdG

Allogenic Endothelial Progenitor Cell Transplantation Increases Flap Survival through an Upregulation of eNOs and VEGF on Venous Flap Survival in Rabbits

Endothelial progenitor cells (EPCs) are one type of bone marrow hematopoietic stromal cells which play a vital role in neovascularization and tissue repair. In this study, we investigated whether EPCs promote flap survival in a rabbit venous model.

http://bit.ly/2FlMBQ6

Perceived outcomes of Good Agricultural Practices (GAPs) technologies adoption in citrus farms of Iran (reflection of environment-friendly technologies)

Abstract

The main purpose of this study was to analyze the perceived outcomes of Good Agricultural Practices (GAPs) technologies adoption in order to sustain citrus farms in Mazandaran province, Iran. Study population consisted of all citrus growers in the villages of 12 counties of Mazandaran province, which a sample of 290 orchardmen were selected through a proportional random sampling technique. A questionnaire was designed to collect data which was both valid and reliable according to expert opinion and Cronbach's alpha coefficient respectively. The results of the factor analysis showed that "market access and safe product exports," "consumer' health and environment-friendly behavior," "safe production and public demand," and "information sharing and strengthening local associations" were the four perceived outcomes of GAPs technologies adoption in citrus farms of Iran. These factors explained 65.02% of the total variance. These four perceived outputs of GAPs support economic, environmental, and social sustainability dimensions respectively.

http://bit.ly/2D6acll

A full-scale study of external circulation sludge bed (ECSB) system for anaerobic wastewater treatment in a whiskey distillery

Abstract

Waste liquid streams from distillery were a hurdle in conventional wastewater treatment due to extreme high chemical oxygen demand (COD) and fluctuating feed conditions. A recently commissioned full-scale external circulation sludge bed (ECSB) was applied at a malt whiskey distillery in northeast Taiwan. Start-up of the new ECSB system, which has a total volume of 490 m³ with diameter of 6.55 m (ø) and height of 15.9 m (H), was performed by gradual increasing influent flow rates from zero to the design value of 300 m³ day⁻¹ in the first 90 days. In the subsequent 204 days, both influent flow rates (0–389 m³ day⁻¹) and COD concentrations (2.8–18.1 kg L⁻¹) were highly fluctuated due to diverse batches from the distillery. However, effective bioremediation (COD removal 95.1 ± 2.4%) and biogas production (1195 ± 724 L day⁻¹) were achieved in this system. Intensively, the Imhoff tests were carried out and shown the settled solids concentration by 0.5 ± 0.4 mL L⁻¹, while size distributions of granular sludge were analyzed and observed by SEM-EDS. In addition, developments of the anaerobic systems (including lab, pilot, and full scale from the simplest reactor to the latest ECSB) applied in whiskey wastewater treatment were reviewed with their operational parameters for comparing performances of various anaerobic systems. In general, real-time monitoring and feasible operation strategies were critical to successfully run the system by producing clean energy simultaneously. It provides more economically attractive and sustainable-to-adopt ECSB not only an end-of-pipe process but also a bioresource technology.

http://bit.ly/2TKcig3

A multi‐center, randomized, split face and/or neckcomparisonof 308‐nm excimer laser and0·1%tacrolimus ointmentfor stable vitiligo, plus intramuscular slow releasing betamethasone for active vitiligo

Abstract

Managing patients with vitiligo is no longer whether to treat or not to treat, but to decide what modalities are more appropriate. Both topical calcineurin inhibitors and 308‐nm excimer laser (EL) were generally accepted to treat vitiligo, and the combination of the two achieved better efficacy.However, there has been no strict comparison of the two methods in treating facial/neck vitiligo. Here we conducted a multi‐center,randomized, left‐right comparative trial in face and/or neck vitiligo,between 2012 and 2014.It was approved by medical ethics committees and official registered (ChiCTR‐TRC‐12002593). Informed consents were signed.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RHdu6z

Case Series of Cutaneous Mucormycosis in Setting of Herpesviridae Infection

Abstract

Mucormycosis is an aggressive infection caused by an angioinvasive fungus that results in significant human disease. It most commonly manifests as rhinocerebral, pulmonary, and cutaneous infections. Among healthcare‐associated mucormycosis, cutaneous manifestations are the most common, accounting for >50% of infections. Although mucormycosis can remain limited to the skin, it has the potential to disseminate hematogenously if left unrecognized or untreated, particularly in patients with multiple risk factors.

This article is protected by copyright. All rights reserved.

http://bit.ly/2H5JfSI

Dark skin phototype is associated with more severe ocular complications of Stevens‐Johnson syndrome and toxic epidermal necrolysis

Abstract

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute severe skin reactions with extensive apoptosis of the epidermis and mucous membranes. Ocular involvement occurs in up to 75% of patients at the acute phase, described as mild, moderate and severe involvement and may result in long‐term severe sequelae with dryness, photophobia, cicatrising conjunctivitis complicated with corneal vascularisation and scarring, which may result in severe visual loss. The acute management of SJS/TEN ocular complications has not been codified.

This article is protected by copyright. All rights reserved.

http://bit.ly/2RGXSjC

Effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real life practice

Abstract

Dupilumab has demonstrated efficacy in atopic dermatitis (AD)^1–3, asthma⁴, perennial allergic rhinitis⁵ and chronic sinusitis⁶. The objectives of this prospective observational, single‐centre study were to assess 1) dupilumab efficacy in real‐life practice and 2) the evolution of atopic co‐morbidities and specific immunoglobulin E (IgE) levels during dupilumab treatment.

This article is protected by copyright. All rights reserved.

http://bit.ly/2H5knKP

The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice

Abstract

Purpose

To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs).

Methods

Seventy-four patients were recruited from four NEN centers in this observational multicenter study.

Results

Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months.

Conclusions

Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

http://bit.ly/2Ha1lmK

Prospective comparison of (4 S )-4-(3- 18 F-fluoropropyl)- l -glutamate versus 18 F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study

Abstract

Purpose

(4S)-4-(3-¹⁸F-Fluoropropyl)-l-glutamate (FSPG) positron emission tomography (PET) reflects system x_C⁻ transporter (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC.

Methods

The performance of FSPG in detecting PDAC metastases was compared with that of ¹⁸F-fluorodeoxyglucose (FDG) in small-animal PET studies in seven PDAC tumour-bearing mice and in prospective PET/computed tomography (CT) studies in 23 patients with tissue-confirmed PDAC of stage III or stage IV. All PET/CT results were correlated with the results of histopathology or contrast-enhanced CT (ceCT) performed 3 and 6 months later.

Results

In the rodent model, FSPG PET consistently found more PDAC metastases earlier than FDG PET. FSPG PET showed a trend for a higher sensitivity, specificity and diagnostic accuracy than FDG PET in detecting PDAC metastases in a patient-based analysis: 95.0%, 100.0% and 95.7%, and 90.0%, 66.7% and 90.0%, respectively. In a lesion-based analysis, FSPG PET identified significantly more PDAC metastases, especially in the liver, than FDG PET (109 vs. 95; P = 0.0001, 95% CI 4.9–14.6). The tumour-to-background ratios for FSPG and FDG uptake on positive scans were similar (FSPG 4.2 ± 4.3, FDG 3.6 ± 3.0; P = 0.44, 95% CI −1.11 to 0.48), despite a lower tumour maximum standardized uptake value in FSPG-avid lesions (FSPG 4.2 + 2.3, FDG 7.7 + 5.7; P = 0.002, 95% CI 0.70–4.10). Because of the lower physiological activity of FSPG in the liver, FSPG PET images of the liver are more easy to interpret than FDG PET images, and therefore the use of FSPG improves the detection of liver metastasis.

Conclusion

FSPG PET is superior to FDG PET in detecting metastasized PDAC, especially in the liver.

http://bit.ly/2VLiqXq

Spatial and temporal distribution characteristics of different forms of inorganic nitrogen in three types of rivers around Lake Taihu, China

Abstract

In order to control nitrogen (N) pollution of Lake Taihu, China, we studied the spatial and temporal distribution characteristics of inorganic N in inflowing rivers polluted by industry, agriculture, and domestic sewage during low, moderate, and high flow periods. The results showed that dissolved total nitrogen (DTN) was the main fraction of total nitrogen (TN) input from these rivers. Inflowing rivers had distinct impacts on TN, DTN, ammonium N (NH₄⁺), and nitrate N (NO₃⁻) concentrations of Lake Taihu during the low flow period. Particulate nitrogen (PN) had an impact on Lake Taihu during the three flow periods and all the three types of rivers would increase PN concentration in the lake. Rivers polluted by agriculture had the greatest impact on Lake Taihu's TN, DTN, NO₃⁻, and dissolved inorganic N (DIN) concentrations, while rivers polluted by industry had the greatest impact on NH₄⁺ concentration. Therefore, agriculture and industry should be key targets for nutrient reductions. The in-lake N concentrations were higher than those of inflowing rivers during moderate and high flow periods.

http://bit.ly/2TGonTC

A critical review on the effects of zinc at toxic levels of cadmium in plants

Abstract

Increasing cadmium (Cd) pollution in agricultural soils has raised serious concerns worldwide. Several exogenous substances can be used to mitigate the toxic effects of Cd in plants. Zinc (Zn) is one of the essential plant micronutrients and is involved in several physiological functions in plants. Zn may alleviate Cd toxicity in plants owing to the chemical similarity of Zn with Cd. Published reports demonstrated that Zn can alleviate toxic effects of Cd in plants by increasing plant growth, regulating Cd uptake, increasing photosynthesis, and reducing oxidative stress. Literature demonstrated that the role of Zn on Cd accumulation by plants is very controversial and depends upon several factors including concentrations of Cd and Zn in the medium, exposure duration, plant species and genotypes, and growth conditions. This review highlights the role of Zn in reducing Cd toxicity in plants and provides new insight that proper level of Zn in plants may enhance plant resistance to excess Cd.

http://bit.ly/2D1bzla

The association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Silvia Martina Ferrari, Poupak Fallahi, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Salvatore Benvenga, Alessandro Antonelli

Abstract

Graves' disease (GD) and autoimmune thyroiditis (AT) are the two main clinical presentations of AITD, and their clinical hallmarks are thyrotoxicosis and hypothyroidism, respectively. GD, and AT, can be associated with other organ specific, or systemic autoimmune diseases in the same patient. However discordant results have been reported in the literature about the possible associations. Here, we review the association of GD and other autoimmune syndromes. Furthermore, we report the results of our prospective study that investigated the prevalence of other autoimmune disorders in 3209 GD patients (984 with Graves' ophthalmopathy), with respect to 1069 healthy controls, or 1069 patients with AT, or 1069 with multinodular goiter (matched by age, gender, coming from the same area, with a similar iodine intake).

On the whole, 16.7% of GD patients had another associated autoimmune disease; and the most frequently observed were: vitiligo (2.6%), chronic autoimmune gastritis (2.4%), rheumatoid arthritis (1.9%), polymyalgia rheumatica (1.3%), multiple sclerosis (0.3%), celiac disease (1.1%), diabetes (type 1) (0.9%), systemic lupus erythematosus and sarcoidosis (<0.1%), Sjogren disease (0.8%). Moreover, 1.5% patients with GD had three associated autoimmune disorders. Interestingly, patients with Graves' ophthalmopathy (GO) had another autoimmmune disorder more frequently (18.9%), with respect to GD patients without GO (15.6%). However the pattern of the associated autoimmune disorders in GD was not significantly different from that observed in AT patients.

In conclusion, we suggest GD patients who are still sick, or who develop new unspecific symptoms (even if during an appropriate treatment of hyperthyroidism) should be appropriately screened for the presence of other autoimmune disorders.

http://bit.ly/2AHu90p

Beyond medicine: Physical exercise should be always considered in patients with systemic autoimmune myopathies

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Diego Sales de Oliveira, Jean Marcos de Souza, Samuel Katsuyuki Shinjo

http://bit.ly/2SO6ORD

A review of the evidence for a natalizumab exit strategy for patients with multiple sclerosis

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Johann Sellner, Paulus Stefan Rommer

Abstract

Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS), but treatment for >2 years is associated with an increased risk of opportunistic infection and progressive multifocal leukoencephalopathy (PML). For this reason, patients and physicians may consider discontinuing natalizumab therapy. This article reviews the evidence for the various therapeutic approaches that may be taken in such patients. Stopping therapy altogether is unlikely to be appropriate for most patients, as it is associated with a high rate of relapse or rebound. Continuing natalizumab therapy with increased monitoring and vigilance for PML may be an acceptable option for some patients, while the data on extending the dosing interval of natalizumab look promising. In some patients whose pre-natalizumab disease activity was not very high and who did not relapse while on natalizumab, switching to a first-line treatment may be an option. In this case, dimethyl fumarate may carry a lower risk of relapse than interferon beta or glatiramer acetate. Fingolimod is the most studied post-natalizumab therapy, and the relapse rate appears to be higher than on natalizumab but lower than was seen before initiation of natalizumab. The evidence suggests that the washout period between natalizumab and fingolimod should not exceed 12 weeks. Finally, the limited evidence available for rituximab and alemtuzumab is promising, and further data on these and other newer therapies for RRMS are awaited.

http://bit.ly/2AHu6BL

Innate immune-responses and their role in driving autoimmunity

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Elias Toubi, Zahava Vadasz

Abstract

Autoimmunity and autoimmune diseases were always considered to be driven mainly by adaptive immune responses, namely by auto-reactive B and T cell over-activity. The continuous stimulation of dendritic cells by autoantigens increases B cell activity, driving auto-reactive B cells to increase the production of autoantibodies and of pro-inflammatory cytokines. On the other hand, a subset of dendritic cells is established being of tolerogenic properties thus becoming important in maintaining self-tolerance. However, early innate immune responses are continuously appreciated to be highly important in the development of immune-mediated inflammation in general and autoimmunity in particular. The innate immune system is a complex network of structured cells/proteins such as antigen presenting cells (macrophages and dendritic cells), the complement cascade, and many receptors/cytokines/proteins. Of these, one may mention the high expression of toll-like receptors 7 and 9 in antigen presenting cells, and B cells of systemic lupus erythematosus patients contributing to the expansion of auto-reactive B cells. C-reactive protein (CRP) and C1q are crucially important for efficient uptake of apoptotic cells. However, CRP is appreciated to have a role in maintaining anti-inflammatory responses and in altering autoimmunity. Natural killer cells (NK) are responsible for cytotoxicity responses but some of them (mainly CD56high), are important in maintaining peripheral self-tolerance, thus considered to be immune-regulatory cells. In this review we will cover most of the new data on innate immune system and discuss its importance in the development of autoimmunity. New treatments were developed following our better understanding of these pathways, the targeting of which, opened new therapeutic avenues in treating autoimmune diseases.

http://bit.ly/2SQ5OMD

Belimumab reduces antiphospholipid antibodies in SLE patients independently of hydroxychloroquine treatment

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Giacomo Emmi, Alessandra Bettiol, Boaz Palterer, Elena Silvestri, Gianfranco Vitiello, Paola Parronchi, Domenico Prisco

http://bit.ly/2AE2DAM

Effectiveness and safety of rituximab for the treatment of refractory systemic sclerosis associated calcinosis: A case series and systematic review of the literature

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Javier Narváez, Juan Pablo Pirola, Judit LLuch, Pablo Juarez, Joan Miquel Nolla, Antonia Valenzuela

Abstract

Objective

To analyze the effectiveness and safety of rituximab (RTX) for the treatment of refractory systemic sclerosis (SSc)–associated calcinosis.

Methods

We undertook an observational study of patients with this complication treated with 1 or more cycles of RTX (1 g × 2 weeks) and evaluated for at least 12 months after RTX treatment in a single center. The primary outcome measures of the study were the improvement of calcinosis symptoms (pain, signs of local inflammation, and new episodes of skin ulceration) and the radiologic evolution of the calcification(s).

Results

We treated 8 patients with refractory SSc-related calcinosis with RTX (off-label use). The main indications for RTX were complicated calcinosis unresponsive to previous therapies with concomitant arthritis in 2 patients and refractory arthritis or interstitial lung fibrosing disease in the remaining 6 patients.

The mean number of RTX cycles administered was 3.12 ± 2.1 (range, 1-7), the median duration of RTX treatment was 9 months (interquartile range [IQR], 7.5-36 months), and the median follow-up after the first infusion of RTX dose was 19 months (IQR, http://bit.ly/2SQFD8S (n.d.) 5-45 months). Four patients (50%) had a significant improvement in clinical symptoms (sustained improvement in the visual analog scale for pain of at least 50% and no new episodes of local inflammation or skin ulceration). Two of these patients (25%) also had a complete resolution or significant reduction in the size of the calcification(s) on X-ray, according with the radiographical scoring system for calcinosis developed by the Scleroderma Clinical Trials Consortium. In the remaining 4 patients (50%), RTX did not provide any significant clinical or radiologic benefit for calcinosis.

The frequency of adverse effects was low, occurring in only 1 patient (12.5%), who developed upper respiratory tract infections not requiring hospitalization.

Conclusion

Our preliminary data suggest that RTX may be helpful as a rescue therapy in selected cases of severe and refractory SSc-related calcinosis.

http://bit.ly/2AHu4tD

The changing face of chronic autoimmune atrophic gastritis: an updated comprehensive perspective

Publication date: Available online 11 January 2019

Source: Autoimmunity Reviews

Author(s): Sara Massironi, Alessandra Zilli, Alessandra Elvevi, Pietro Invernizzi

Abstract

Chronic autoimmune atrophic gastritis (CAAG) is an organ-specific autoimmune disease, which affects the corpus–fundus gastric mucosa. Although it has been described for several years, the real pathophysiological mechanisms, the natural history and the possible neoplastic complications are not completely known. Atrophy of the gastric mucosa is the endpoint of the chronic processes, with the loss of glandular cells and their replacement by intestinal-type epithelium, pyloric-type glands, and fibrous tissue. As a consequence, hydrochloric acid, pepsin and intrinsic-factor is impaired resulting in pernicious anemia. The exact causal agent is not yet known, but both genetic and environmental factors seem to play a decisive role.

Moreover, the clinical onset may assume different characteristics; differently from what previously observed, recent evidence has reported the onset of CAAG at a younger age, frequently with iron deficiency anemia or upper gastro-intestinal symptoms.

The diagnosis of CAAG might be challenging and usually requires the combination of clinical, serological and histopathologic data; moreover, CAAG patients are often misdiagnosed as refractory to HP eradication therapy, probably because achlorhydria might allow urease-positive bacteria other than H pylori to colonize the stomach, causing positive ¹³C-urea breath test results.

However, biopsy is the most reliable method to evaluate the presence of metaplastic atrophic gastritis. In order to assess the severity of gastric atrophy and intestinal metaplasia, OLGA and OLGIM staging systems have been proposed and seem to correlate with the risk of developing gastric adenocarcinoma. Indeed, CAAG represents a pre-neoplastic condition, as patients with CAAG are very likely to develop either type-1 gastric neuroendocrine tumors and gastric adenocarcinomas, as well as several other neoplastic diseases. To date, the need, the intervals and cost-effectiveness of endoscopic/histological surveillance for patients with CAAG/pernicious anemia are yet to be established.

http://bit.ly/2AHu2Sx

The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice

Abstract

Purpose

To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs).

Methods

Seventy-four patients were recruited from four NEN centers in this observational multicenter study.

Results

Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months.

Conclusions

Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

http://bit.ly/2Ha1lmK

Insecticidal potential and repellent and biochemical effects of phenylpropenes and monoterpenes on the red flour beetle, Tribolium castaneum Herbst

Abstract

The main objectives of the present study are to introduce new, ecologically safe, and natural compounds for controlling red flour beetle, Tribolium castaneum, and to understand the possible mode of action of these compounds. Therefore, the insecticidal and repellent activities of two phenylpropenes and six monoterpenes have been evaluated against the adults of T. castaneum. The inhibitory effects of these compounds on the activity of adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) were also tested. In fumigant toxicity assay, (−)-terpinen-4-ol (LC₅₀ = 20.47 μl/l air) and α-terpinene (LC₅₀ = 23.70 μl/l air) exhibited the highest toxicity without significant differences between them. Moreover, (−)-menthone and p-cymene showed strong toxicity, while (−)-citronellal, trans-cinnamaldehde, and eugenol were not active. In contact toxicity assay, the two phenylpropenes, trans-cinnamaldehde and eugenol, had the highest toxicity with same LC₅₀ value of 0.02 mg/cm². The monoterpenes and phenylpropenes showed pronounced repellent effect on the adults of T. castaneum at 0.001 mg/cm² with (−)-menthone, trans-cinnamaldehyde, and α-terpinene being the most effective after 2 h of exposure. Repellent activity depended on compound, exposure time, and concentration. On the other hand, the tested compounds exhibited strong inhibition of ATPases form the larvae of T. castaneum as their IC₅₀ values ranged between 1.74 and 19.99 mM. In addition, (−)-citronellal (IC₅₀ = 9.82 mM) and trans-cinnamaldehde (IC₅₀ = 23.93 mM) caused the highest inhibitory effect on AChE, while α-pinene (IC₅₀ = 53.86) and p-cymene (IC₅₀ = 68.97 mM) showed the weakest inhibitory effect. The results indicated that the tested phenylpropenes and monoterpenes had the potential to be developed as natural insecticides and repellents for controlling T. castaneum.

http://bit.ly/2D4axVS

Editorial Board

Publication date: April 2019

Source: Magnetic Resonance Imaging, Volume 57

Author(s):

http://bit.ly/2RnjNwX

MRI visualization of shiitake mycelium growing in woodchip blocks used for shiitake mushroom cultivation

Publication date: Available online 11 January 2019

Source: Magnetic Resonance Imaging

Author(s): Kuniyasu Ogawa, Takeshi Yashima

Abstract

In order to eliminate woodchip blocks where unwanted fungi have grown and select only blocks where shiitake mycelium are growing well, there is a need to develop a visualization technique for shiitake mycelium growing in woodchip blocks, and MRI is an obvious candidate technique. From the results of measurements of the woodchip bed in a small bottle (26 mm inside diameter) where shiitake mycelium was growing, the T₁ relaxation time constant immediately after inoculation was 77.9 ± 5.5 ms, and the value after about 10 to 20 days increased to 135.0 ± 9.8 ms (the increase rate was 73%). The T₁ maps of the wood-chip block (130 mm length, 75 mm height and 55 mm thickness) in which shiitake mycelium grew were calculated from T₁ weighted images measured by changing TR from 28 to 400 ms. From the T₁ maps of time series, it was found that the shiitake mycelium extended from the right-hand side to the left-hand side of the woodchip block in a planar manner. Furthermore, in a woodchip block in which penicillium was generated, since the T₁ relaxation time constant of only the shiitake mycelium became longer, it was possible to visualize the shiitake mycelium distinctly from penicillium.

http://bit.ly/2Cje7d8

Quantification of pathophysiological alterations in venous oxygen saturation: A comparison of global MR susceptometry techniques

Publication date: Available online 11 January 2019

Source: Magnetic Resonance Imaging

Author(s): Paula L. Croal, Jackie Leung, Charly L. Phillips, Malambing G. Serafin, Andrea Kassner

Abstract

The purpose of this study was to compare the Infinite Cylinder and Forward Field methods of quantifying global venous oxygen saturation (Y_v) in the superior sagittal sinus (SSS) from MRI phase data, and assess their applicability in systemic cerebrovascular disease.15 children with sickle cell disease (SCD) and 10 healthy age-matched controls were imaged on a 3.0 T MRI system. Anatomical and phase data around the superior sagittal sinus were acquired from a clinically available susceptibility weighted imaging sequence and converted to Y_v using the Infinite Cylinder and Forward Field methods. Y_v was significantly higher when calculated using the Infinite Cylinder method compared to the Forward Field method in both patients (p = 0.003) and controls (p < 0.001). A significant difference in Y_v was observed between patients and controls for the Forward Field method only (p = 0.006). While various implementations of Y_v quantification can be used in practice, the results can differ significantly. Simplistic models such as the Infinite Cylinder method may be easier to implement, but their dependence on broad assumptions can lead to an overestimation of Y_v, and may reduce the sensitivity to pathophysiological changes in Y_v.

http://bit.ly/2Rrtyuc

The use of a binary chelate formulation: Could gadolinium based linear contrast agents be rescued by the addition of zinc selective chelates?

Publication date: Available online 10 January 2019

Source: Magnetic Resonance Imaging

Author(s): Wendell Gibby, Wes Parish, Ray M. Merrill, Diego Fernandez, Christopher R. Anderson, Eric Merchel, Ryan Parr

Abstract

Tissue and bone retention of gadolinium based contrast agents (GBCAs) has become a clinical concern because of the potential short and long term toxic effects of free gadolinium. This is a critical problem for most open-chain agents that more readily transmetallate in vivo, in comparison to macrocyclic compounds. Gadoliniumdiethylene tri-aminepentaacetic acid bis-glucosamide (Gd-DTPA-BIGA) is an experimental, open-chain contrast agent which has a significantly increased relaxivity coefficient in comparison to other GBCAs. This results in greater signal intensity and improved contrast enhancement. These superior imaging qualities initiated a search for a solution to the transmettalation of this agent. Plasma zinc is a well-known GBCA transmettalation agent. Since the base chelate of Gadodiamide (Gd-DPTA-Bis-Methylamide or Omniscan), DTPA-Bis-Methylamide (DTPA-BMA), readily transmettalates with and binds serum zinc, we hypothesized that a plasma "zinc sink," may significantly reduce transmettalation of linear agents. 5% DTPA-BMA was added to a formulation of Gd-DTPA-BIGA, which was tested against the original formulation of Gd-DTPA-BIGA with 0.2% of the base chelate DTPA-BIGA. These formulations, including gadodiamide, were labeled with ¹⁵³GdCl₃ followed by infusion into cohorts of Sprague Dawley rats which were sacrificed at 1, 30 and 60 days. Internal organs were harvested, along with blood, skin and femur, and analyzed for residual gadolinium. A subset of tissues were also interrogated with ICP-MS. Labeled Gadodiamide and saline where used as controls.

Conclusion: The addition of 5% DTPA-BMA, as a zinc binding agent, reduced the transmetallation of the linear agent Gd-DTPA-BIGA, in comparison to its original formulation supplemented with 0.2% BIGA. This result indicates that supplementing linear GBCAs with ancillary chelates may hold promise for reducing, or eliminating the biological archiving of gadolinium in tissues. In addition, this paper provides valuable animal data on the long term retention of gadolinium from linear based contrast agents.

http://bit.ly/2CeEgtp

The impact of irradiance on UVB-induced cutaneous immunosuppression: Implications on administering most efficient phototherapy

Publication date: Available online 11 January 2019

Source: Journal of Dermatological Science

Author(s): Hsiao-Chi Lai, Chang-Shen Lin, Ching-Shuang Wu, Cheng-Che E. Lan

Abstract

Background

Ultraviolet B (UVB) is commonly used for treating dermatologic conditions. Recently, high irradiance UVB (HIUVB) has been suggested to be more effective for treating skin conditions as compared to its low irradiance (LI) counterpart. The biological impact of UVB radiation emitted at different irradiance on cutaneous immunity remains obscure.

Objective

This study aimed to explore the impacts of UVB radiation administered at equivalent fluence (mJ/cm²) but different irradiance (mW/cm²) on cutaneous immune response.

Methods

Cultured bone marrow derived dendritic cell (BMDC) were treated with equivalent fluence of UVB radiation with HIUVB or LIUVB. The phenotypic and functional alterations of BMDCs were documented. Animal models were used to validate the in vitro results in vivo and explore the mechanisms involved.

Results

After equivalent fluence of UVB radiation, the HIUVB treated BMDC showed significantly lower MHCII and CD86 expressions, reduced capacity to stimulate T cell proliferation, and enhanced activation of aryl hydrocarbon receptor (AhR)-activated genes as compared to control while their LIUVB treated counterpart showed no significant change. Using animal model, the HIUVB induced significantly higher immune suppressive effect in mice as compared to their LIUVB counterpart after equivalent fluence of UVB treatment. The superior immune suppressive effect of HIUVB over LIUVB radiation was not observed when similar experiments were performed using AhR-deficient mice.

Conclusion

We propose irradiance played an important role modulating UVB-induced cutaneous immune suppression. Future works on UVB phototherapy, both clinical and research, should incorporate this important parameter into consideration.

http://bit.ly/2Fng63Y

Dual wavelength 5-aminolevulinic acid photodynamic therapy using a novel flexible light-emitting diode unit

Publication date: Available online 10 January 2019

Source: Journal of Dermatological Science

Author(s): Hideyuki Masuda, Makoto Kimura, Akiko Nishioka, Hiroshi Kato, Akimichi Morita

Abstract

Background

Photosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm. Although only red light around 635 nm and blue light around 400 nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred.

Objective

We investigated the efficacy of a flexible light-emitting diode (LED) unit that emits multiple wavelengths to improve PDT effects.

Methods

HaCaT cells were incubated with 5-ALA and subsequently irradiated with either a single wavelength or sequentially with two wavelengths. Cell viability and reactive oxygen species were analyzed. Nude mice were implanted with COLO679 cells by subcutaneous injection into the flank. 5-ALA was subcutaneously injected into the tumor. The tumor was irradiated with 50 J/cm² (day 0) and assessed daily until day 21.

Results

The synergistic PDT effects of dual-wavelength irradiation and reactive oxygen species production were highest with the 405-nm and 505-nm wavelength combination. This dual wavelength combination was also the most effective in vivo.

Conclusion

We could therefore conclude that dual-wavelength PDT is an efficient strategy for improving the therapeutic effects of PDT. Using a flexible LED unit is expected to achieve more uniform irradiation of uneven areas.

http://bit.ly/2AIWdAn

Adherence to mediterranean diet in spanish patients with psoriasis: cardiovascular benefits?

Abstract

Several studies have evaluated the role of individual nutrients on psoriasis. Only a few of them have evaluated the benefits of healthy dietary patterns and the effect of the Mediterranean diet on psoriasis with promising results. Moderate‐severe psoriasis is associated with chronic systemic inflammation and increased cardiovascular risk. In our study we measure the adherence to the Mediterranean diet to determine the grade of association with severity of psoriasis, a cardiovascular profile and systemic inflammation. Our aim was to to determine a cut‐off point that approximates the real clinical practice by differentiating patients with systemic or biological treatment.

This article is protected by copyright. All rights reserved.

http://bit.ly/2FpWueH

The Monitor Practice Program: Implications for dentistry and dental education

Abstract

The restorative model of care, known colloquially as drilling and filling, has been challenged on the basis of its inappropriateness. The Caries Management System protocol was developed as an evidence‐based strategy for non‐surgical treatment of caries lesions and the Monitor Practice Program was designed to test the hypothesis that use of the protocol would reduce risk of dental caries experience. After 7 years, patients attending intervention practices, compared with those attending control practices, needed: 30‐50% fewer restorative interventions; 55% fewer first time restorative interventions; 32% fewer repeat restorative interventions; and were only 23% as likely to be classified as high risk. The outcome was cost‐effective and patients attending intervention practices highly valued non‐invasive care, and intervention dentists derived professional satisfaction from non‐surgical caries management. The implications of the program are that the general public will likely embrace the benefits of non‐invasive caries management, as will many current and future dental practitioners. This calls for dental practice reform including: the establishment of a clinical discipline in cariology; cariology curriculum development; revised accreditation regulations for cariology programs in dental schools; advanced training in clinical cariology leading to a specialty; support from the dental profession; and public health advocacy.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VN8Frw

General health benefits from good oral health

Abstract

I have read the editorial entitled "Opportunistic Dentistry is Harming Our Credibility" by Mark Bartold published in the Australian Dental Journal 2018; 63: 269.¹ I want to congratulate the author for this editorial and wish to make a contribution.

In the editorial, it was stated that "to date no studies have shown a causal effect between oral diseases such as periodontal disease and systemic disease".

This article is protected by copyright. All rights reserved.

http://bit.ly/2QBzECJ

Cutaneous leukocytoclastic vasculitis as the first manifestation of malignant syphilis coinfected with HIV

Malignant syphilis, also known as Lues maligna or ulceronodular syphilis, is a rare form of secondary syphilis mainly characterized by polymorphous, disseminated, and papulonodular cutaneous lesions, typically ulcerated and covered by rupioid crust ¹.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VN8FI2

Cutaneous Ganglioneuroma: A Case Report and Discussion of the Literature

Ganglioneuromas (GN) are benign tumors composed of ganglion cells in a schwannian stroma.¹ They are derived from neural crest cells that give rise to the sympathetic nervous system. Hence, GNs can be found anywhere a sympathetic ganglion is present.² In some cases, GNs are derived from immature ganglioblastomas or neuroganglioblastomas that differentiate.¹

This article is protected by copyright. All rights reserved.

http://bit.ly/2QI5yOc

MULTIPLE FACIAL PLAQUE VARIANT OF TRICHOBLASTOMA

Background

The plaque variant of trichoblastoma has been described as a solitary tumor with diffuse infiltration in the lower dermis and hypodermis with poorly defined borders. Herein, we report a new variant of multiple centrofacial trichoblastoma.

Object

To describe clinical and pathological features of a new multiple kind of plaque variant of centrofacial trichoblastoma.

Methods

Case series of patients with a multiple plaque variant of centrofacial trichoblastoma treated in our department between 2005 and 2017. We identified 8 patients with the centrofacial plaque variant of trichoblastoma treated in our department from 2005 to 2017.

Results

The final study sample comprised 13 trichoblastomas from four patients. All patients also developed at least one basal cell carcinoma. Mohs surgery was the method of treatment in the majority of the cases of trichoblastoma and in all the cases of basal cell carcinoma. We needed between 2 and 6 stages to obtain free margins in our cases of facial plaque trichoblastomas treated by Mohs surgery.

Conclusion

To the best of our knowledge, a multiple plaque variant of trichoblastoma has not been described in the literature. We suggest a genetic origin of this variant of trichoblastoma and describe its remarkable infiltrative nature, with poorly defined surgical margins.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VS8ewq

Histiocytoid Sweet Syndrome (HSS) Harboring an IDH‐1 Mutation: A Case Report and Retrospective Analysis of 29 Cases of HSS

Histiocytoid Sweet syndrome (HSS) is a rare histopathologic variant of Sweet syndrome that was first described in 2005 by Requena et al. In contrast to the dense infiltrate of mature neutrophils seen in conventional Sweet syndrome, this variant demonstrates dermal and/or subcutaneous infiltrate with a prominent component of immature myeloid cells resembling histiocytes. (1) A number of publications have since reported similar findings, sometimes in association with hematologic neoplasms. In recent years, an ever increasing number of mutations have been discovered in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), including mutations in isocitrate dehydrogenase 1 (IDH‐1) and isocitrate dehydrogenase 2 (IDH‐2).

This article is protected by copyright. All rights reserved.

http://bit.ly/2QE4zhC

Tufted angioma‐like lesion associated with VEGF and IL‐6 in TAFRO syndrome: Is it a common histological feature of multicentric Castleman disease/POEMS syndrome?

The histology of skin lesions of TAFRO (thrombocytopenia, anasarca, reticulin fibrosis/renal failure, and organomegaly) syndrome has rarely been reported. We report herein 2 cases of TAFRO syndrome with characteristic vascular skin lesions. The lesions resembled a tufted angioma (TA), although those of case 1 partially resembled a glomeruloid hemangioma, which was known as a specific lesion in POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M‐protein and skin changes), a variant of multicentric Castleman disease (MCD). The high titer of serum Vascular Endothelial Growth Factor (VEGF) and Interleukin‐6 (IL‐6) could explain common characteristic vascular lesions in both TAFRO syndrome and POEMS syndrome/MCD.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VIquIu

Low‐Grade Fibromyxoid Sarcoma of Acral Sites: Case Report and Literature Review

Low‐grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue sarcoma that usually presents as a deep‐seated tumor in young adults; however, they can occur on superficial sites, mostly documented in pediatric age groups. LGFMS presenting on acral sites is not highly emphasized in the general pathology or dermatopathology literature. The case presented is that of a 30‐year‐old male that had a mass on his foot that was removed fifteen years earlier that subsequently recurred as two masses. The first occurring between the third and fourth toes/metatarsal region and the second over the lateral tarsal region. An excisional biopsy showed a relatively circumscribed, bland spindle cell proliferation with hypocellular and hypercellular zones. The cells showed minimal pleomorphism and lacked mitotic activity. Immunohistochemical analysis showed immunoreactivity with MUC4 and break‐apart Fluorescence in situ hybridization was positive for FUS rearrangement confirming the diagnosis of LGFMS. There are multiple spindle cell tumors that occur on acral sites which usually generates a list of differential diagnoses; however, LGFMS is not usually discussed in that anatomic location. Awareness of the occurrence of LGFMS on acral sites is important to avoid misdiagnosis of this deceptively benign appearing tumor.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QEjMPL

Diagnostic utility of dual 5‐hmC/Melan‐A immunohistochemistry in differentiating nodal nevus from metastatic melanoma: An effective first‐line test for the work‐up of sentinel lymph node specimen

Background

Distinguishing benign nodal nevus from metastatic melanoma can be diagnostically challenging with important clinical consequences. Recently, the loss of epigenetic marker, 5‐Hydroxymethylcytosine (5‐hmC) expression by immunohistochemistry has been found in melanomas and atypical melanocytic neoplasms.

Methods

41 metastatic melanomas and 20 nodal nevi were retrieved. Nuclear 5‐hmC (brown) and cytoplasmic Melan‐A Red (red) double immunohistochemical staining was performed.

Results

Total or partial loss of nuclear expression of 5‐hmC was noted in 40/41 metastatic melanomas; these tumor cells were strongly positive for Melan‐A Red, except in one case of desmoplastic melanoma. All cases of nodal nevus showed uniformly retained nuclear expression of 5‐hmC accompanied by strong Melan‐A Red cytoplasmic staining. In two cases containing both nodal nevus and metastatic melanoma, all tumor cells were positive for Melan‐A Red, but a nuclear expression of 5‐hmC was selectively absent only in the melanoma tumor cells.

Conclusion

Dual 5‐hmC/Melan‐A Red immunohistochemistry is highly specific in distinguishing nodal nevus from metastatic melanoma. Our protocol for brown and red chromogens used in this study provides excellent color contrast and is easy to interpret. Furthermore, this dual staining method allows the preservation of limited tumor tissue, which could be used for potential molecular studies.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VEXrpf

Differential Expression of Phospho‐S6 in Hair Follicle Tumors: Evidence of mTOR pathway activation

Background

The role of the mammalian target of rapamycin (mTOR) in hair follicle tumorigenesis is unclear. mTOR controls cell growth and can be activated through ribosomal S6 kinase. Herein, we sought to evaluate the expression of phospho‐S6 in six different benign and malignant follicular tumor types.

Methods

Seventy‐six cases were selected [17 fibrofolliculomas, 20 trichoepitheliomas, 10 tricholemmomas, 19 pilomatricomas, 1 malignant proliferating tricholemmal tumor, 8 tricholemmal carcinomas and 1 trichoblastic carcinoma] and collected over 16 years. Immunohistochemistry with monoclonal antibody for phospho‐S6 was performed and analyzed semi‐quantitatively; statistical analysis χ² test (p<0.05).

Results

All malignant neoplasms in our series [8/8 (100%) cases of tricholemmal carcinoma, 1/1 (100%) trichoblastic carcinoma and 1/1 (100%) malignant proliferating tricholemmal tumor] demonstrated a strong and diffuse pattern of staining with phospho‐S6 involving 70‐90% of tumor cells. By contrast, a minority of benign tumors were positive for phospho‐S6 and most stained in a patchy pattern including 12/17 (71%) fibrofolliculomas, 9/20 (45%) trichoepitheliomas and 1/10 (10%) tricholemmomas, involving 30‐50%, 5‐20%, and 40‐50% of tumor cells, respectively. Most pilomatricomas [17/19 (89%)] exhibited a stronger, but distinctive staining pattern, staining mostly the basaloid cells with a multifocal distribution, involving 70‐90% of tumor cell.

Conclusions

Phospho‐S6 is differentially expressed among benign and malignant hair follicle tumors (p = 0.0044). While malignant tumors show diffuse expression, only a small subset of benign neoplasms were positive, primarily in a patchy distribution.

This article is protected by copyright. All rights reserved.

http://bit.ly/2QFoQn5

Clinical and histopathologic study of 39 patients with imported tungiasis

Background

Tungiasis is an infestation caused by the penetration in the skin of the flea Tunga penetrans. Histopathologic studies on imported tungiasis are rare and based on a limited number of cases.

Methods

We carried out a review of 39 biopsy specimens collected from 39 patients with imported tungiasis. In all patients, ethnicity, gender, age, location and clinical features of the lesions, Fortaleza classification and countries of infestation were recorded.

Results

Histopathologic study revealed hyper‐ parakeratosis and acanthosis. Fragments of the flea were located in the epidermis and upper dermis and were circumscribed by a pseudo‐cystic cavity. Inside this cavity, we observed: the exoskeleton, made up of a thickened and eosinophilic cuticle; the striated muscle; the tracheal rings and the digestive organs (observed only in some specimens); the ovaries, very rich in eggs, and an inflammatory infiltrate, made up of lymphocytes and neutrophils, with numerous eosinophils. The hypodermic layer was never observed.

Conclusions

Histopathologic examination is helpful for the correct diagnosis of tungiasis in travelers returning from Tropical and Subtropical countries in whom the infestation may be characterized by an atypical clinical presentation.

This article is protected by copyright. All rights reserved.

http://bit.ly/2VKsCQ0

The Bell Curve Buried Suture Placement Technique, A Video Walkthrough

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Brett C. Neill, Edward W. Seger, Isadore S. Tarantino, Thomas L.H. Hocker

http://bit.ly/2Fre1mU

An easy technique for the measurement calibration of a USB dermatoscope

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Mahesh Mathur, Prakash Acharya, Alina Karki

http://bit.ly/2Fmefwq

Fibrosis and stem cell epithelial-mesenchymal transition in primary cicatricial alopecias (JAAD-D-18-02229.R1)

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Matthew Harries, Hisayoshi Imanishi, Ralf Paus

http://bit.ly/2Fq3PLh

January 2019 Beyond JAAD

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Andrew Bronin

http://bit.ly/2FmsEsn

Pink or Blue? Unpacking the packaging of iPLEDGE

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Jacqueline D. Watchmaker, Lauren Watchmaker, Jamie L. Abbott

http://bit.ly/2Fq3NTF

Cutaneous nevi and risk of melanoma death in women and men: a prospective study

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Wen-Qing Li, Eunyoung Cho, Martin A. Weinstock, Suyun Li, Meir J. Stampfer, Abrar A. Qureshi

Abstract

Background

It was unclear whether increased number of common nevi (moles) predicts melanoma death.

Objective

We prospectively examined the association between number of common nevi and risk of melanoma death

Methods

Our study was based on the Nurses' Health Study (n=77,288 women) and Health Professionals Follow-up Study (n=32,455 men). Number of moles with ≥3 mm diameter on the upper extremity was asked in 1986 and was re-classified into three categories (none, 1-2, or ≥3) based on data distribution.

Results

During follow-up (1986-2012), 2,452 melanoma cases were pathologically confirmed, among whom we identified 196 deaths due to melanoma. Increased number of nevi was associated with melanoma death; the hazard ratio (HR) for ≥3 nevi compared with no nevi was 2.49 [95% confidence interval(CI): 1.50-4.12] for women and 3.97 (95%CI: 2.54-6.22) for men. Among melanoma cases, increased number of nevi was associated with melanoma death in men (≥3 nevi: HR=1.89, 95%CI: 1.17-3.05), but not in women. Similarly, number of nevi was positively associated with Breslow thickness in men only (P_trend=0.01).

Limitations

This is an epidemiologic study without examination into mechanisms.

Conclusions

Increased number of cutaneous nevi was significantly associated with melanoma death. High nevi count may serve as an independent prognostic factor, which predicts the risk of melanoma death particularly among male melanoma cases.

http://bit.ly/2Fk0IVT

A Randomized Double-Blind Placebo Controlled Trial of Autologous Platelet Rich Plasma Intradermal Injections for the Treatment of Vulvar Lichen Sclerosus

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Andrew T. Goldstein, Leia Mitchell, Vaishnavi Govind, Debra Heller

http://bit.ly/2FpE7qa

Effects of new keratinocyte carcinomas on skin-related quality of life: results from the Veterans Affairs Chemoprevention of Keratinocyte Carcinoma (VAKCC) Trial

Publication date: Available online 11 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Julia A. Siegel, Meghan Beatson, Mary-Margaret Chren, Martin A. Weinstock, VAKCC Trial group

http://bit.ly/2Fm2gik

Evaluating Dermatology Curricula in US Medical Schools

Publication date: Available online 10 January 2019

Source: Journal of the American Academy of Dermatology

Author(s): Hania K. Flaten, Stephanie Kuschel, Robert P. Dellavalle, Cory A. Dunnick

http://bit.ly/2FrdVvy

Mapping the face of young population in China: Influence of anatomical sites and gender on biophysical properties of facial skin

Abstract

Background

Facial skin exhibits unique biophysical properties, which are influenced by anatomical regions and genders. The aim of this study was to comprehensively assess the regional and gender differences in facial skin biophysical parameters among Chinese population.

Materials and Methods

The 12 skin biophysical parameters at four distinct facial skin sites (forehead, cheek, canthus and chin) were measured in a normal population (n = 212) with 42 males and 141 females aged 18‐29 years living in Beijing. These parameters consisted of skin hydration, transepidermal water loss, sebum content, erythema/melanin indices, L*a*b* color, skin gloss and elasticity, all quantifying with non‐invasive instruments.

Results

The results demonstrated that the characteristics of the facial skin were significantly different between the regions and genders. The forehead had weaker skin barrier function but secreted the most sebum content, while the cheek was the driest and brightest region on the face. The canthus was the most hydrated area and the chin displayed higher sebum secretion, darker skin color and less elastic. The females showed more hydrated, less oil, lighter and more elastic facial skin compared with males.

Conclusion

This study indicates that the young Chinese facial skin significantly varies with face anatomical regions and differs between genders.

http://bit.ly/2RlCgdd

Favorable outcomes of culture‐based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance

Abstract

Background

The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance‐associated treatment failure, the efficacy of culture‐based, susceptibility‐guided therapy was demonstrated as the first‐line eradication therapy for H pylori infection.

Aims

To evaluate the efficacy of culture‐based therapy as the first‐line eradication therapy in regions with high levels of antimicrobial resistance.

Methods

Helicobacter pylori‐positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7‐day clarithromycin‐containing PPI triple; 7‐day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7‐ or 14‐day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution‐determined MIC. Eradication, treatment compliance, and adverse events were examined.

Results

In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention‐to‐treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per‐protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies.

Conclusions

Culture‐based, susceptibility‐guided therapy is effective first‐line eradication therapy, especially in regions with high levels of antimicrobial resistance.

http://bit.ly/2TG2X9e

Characterization and source estimates of primary and secondary carbonaceous aerosols at urban and suburban atmospheres of Düzce, Turkey

Abstract

Düzce is one of the cities located in the western Black Sea region of Turkey with a population of 377,610 in 2017 (TUIK, 2017). There is no satisfying scientific information available to address the contribution of primary and secondary sources of carbonaceous aerosols to the observed PM₁₀ levels in the city. The main objective of the study is to determine the levels and sources of carbonaceous aerosols in PM₁₀. For this purpose, PM₁₀ samples were collected at urban and suburban locations in Düzce during winter and summer season in 2015. Average summer OC and EC concentrations in the urban area were 9.5 and 1.3 μg m⁻³, respectively, while the corresponding concentrations were observed as 28.5 and 2.3 μg m⁻³, respectively for winter season. Summer mean OC and EC levels at the suburban site were 5.46 and 0.37 μg m⁻³, respectively, while those for winter were found as 6.68 and 0.61 μg m⁻³.The contributions of OC and EC to measured PM₁₀ levels were found in the range of 10% to 60% and 1% to 7%, respectively, at the urban station while the associated contributions were in the range of 10% to 50% and 0.6% to 6%, respectively, at the suburban station. The concentrations measured during winter months in both areas were found to be higher than those measured during summer months. The EC tracer method was used in order to estimate the SOC contribution. The contribution of SOC concentrations to the total PM₁₀ mass was found to be higher during winter in the urban area and during summer in the suburban area.

http://bit.ly/2FpxTXk

Risankizumab versus ustekinumab for plaque psoriasis: a critical appraisal

Summary

Aim

Gordon et al investigated the efficacy and safety of risankizumab (an anti‐interleukin[IL]23p19 biologic) compared with ustekinumab (anti‐IL12/23p40) and placebo in patients with moderate‐to‐severe chronic plaque psoriasis. This is a parallel group controlled study up to 16 weeks with a planned switch of the placebo group to risankizumab at 16 weeks.

Setting and design

This study consisted of two replicate phase 3, double‐blinded randomised‐controlled trials (UltIMMa‐1 and UltIMMa‐2) conducted across 139 centres in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain and the USA.

Study exposure

Patients with a minimum 6 month history of chronic plaque psoriasis were randomly assigned to receive either 150 mg risankizumab, 45 mg or 90 mg ustekinumab or placebo. Prior to this, each group was also stratified by weight (either more than or less than 100kg) and previous exposure to tumour necrosis factor inhibitor. Those assigned to receive placebo were transitioned onto risankizumab at week 16. The study drugs were given at weeks 0, 4, 16, 28 and 40.

Outcomes

The severity of psoriasis was measured using the Psoriasis Area and Severity Index (PASI) and a static Physician's Global Assessment (sPGA). The authors additionally recorded the number of adverse events in each treatment arm, and a measure of quality of life.

Primary outcome measures

The co‐primary outcomes were the proportion of patients achieving a 90% reduction in their baseline PASI (PASI 90) and a sPGA score of 0 or 1 (clear or almost clear) at week 16.

Results

A total of 506 patients were included in UltIMMa‐1 and 491 patients in UltIMMa‐2. In UltIMMa‐1, PASI‐90 by week 16 was achieved by 75.3% of patients receiving risankizumab compared with 42.0% receiving ustekinumab and 4.9% receiving placebo (p<0.0001 vs placebo and ustekinumab). sPGA of 0 or 1 by week 16 was achieved by 87.6% of patients receiving risankizumab compared with 63.0% receiving ustekinumab and 7.8% receiving placebo (p<0.0001 vs placebo and ustekinumab). The results for UltIMMa‐2 are similar. The frequency of adverse events in the risankizumab, ustekinumab and placebo groups was similar in both studies.

Conclusions

Gordon et al conclude that risankizumab has a higher efficacy than placebo and ustekinumab in the treatment of moderate‐to‐severe chronic plaque psoriasis, and that the adverse event profiles were similar across all treatment groups.

This article is protected by copyright. All rights reserved.

http://bit.ly/2FksRfI

Persistence and Effectiveness of Non‐Biologic Systemic Therapies for Moderate‐Severe Psoriasis in Adults: a Systematic Review

Summary

Background

The persistence and effectiveness of systemic therapies for moderate‐severe psoriasis in current clinical practice are poorly characterised.

Objectives

To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate involving at least 100 adult patients with moderate‐severe psoriasis, exposed to therapy for ≥3 months.

Methods

Medline, Embase, the Cochrane Library and PubMed were searched from 01/01/2007 to 01/11/2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow‐up) or effectiveness (improvements in Psoriasis Area and Severity Index [PASI] or Physician Global Assessment [PGA]).

Results

Of 411 identified studies, 8 involving 4624 psoriasis patients were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta‐analysis being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterised, but mean discontinuation times ranged from 28‐50 months (FAE) and 7·7‐22·3 months (methotrexate). At 12 months' follow‐up, three studies reported 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ≥75% reduction in PASI and one reported 76% of FAE‐exposed patients achieved a markedly improved/clear PGA.

Conclusions

The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real‐world clinical practice in the past decade cannot be well‐described due to the inconsistency of the methods used.

This article is protected by copyright. All rights reserved.

http://bit.ly/2FovGeQ

Thyroid function in psoriasis

Abstract

Psoriasis has been associated with other autoimmune diseases, e.g. inflammatory bowel disease and autoimmune thyroid disease. These diseases may share genetic susceptibility loci and autoimmune mechanisms including interleukin‐17‐dependent pathways. However, the relationship between psoriasis and autoimmune thyroid disease remains unclear and a recent meta‐analysis of available evidence concluded that more data are needed.

This article is protected by copyright. All rights reserved.

http://bit.ly/2FhHFeQ

Three dimensional maxillary growth modeling in newborns

Abstract

Objectives

The aim of this study was to develop an accurate and intuitive semi-automatic segmentation technique to calculate an average maxillary arch and palatal growth profile for healthy newborns in their first year of life.

Materials and methods

Seventy babies born between 1985 and 1988 were included in this study. Each child had five impressions made in the first year after birth that were digitalized. A semi-automatic segmentation tool was developed and used to assess the maxillary dimensions. Finally, random effect models were built to describe the growth and build a simulation population of 10,000 newborns. The segmentation was tested for inter- and intra-observer variability.

Results

The Pearson correlation coefficient for each of the variables was between 0.94 and 1.00, indicating high inter-observer agreement. The paired sample t test showed that, except for the tuberosity distance, there were small, but significant differences in the landmark placements between observers. Intra-observer repeatability was high, with Pearson correlation coefficients ranging from 0.87 to 1.00 for all measurements, and the mean differences were not significant. A third or second degree growth curve could be successfully made for each parameter.

Conclusions

These findings indicated this method could be used for objective clinical evaluation of maxillary growth.

Clinical relevance

The resulting growth models can be used for growth studies in healthy newborns and for growth and treatment outcome studies in children with cleft lip and palate or other craniofacial anomalies.

http://bit.ly/2SIT0YE

Correction to: Influence of foraminal enlargement on the healing of periapical lesions in rat molars

Figures 2 and 3 in the published version of this article contained a mistake. CCP and DCP should have been FEG and NFEG. Correct figures are presented here.

http://bit.ly/2AGf5jv