Purpose of review Asthma affects more than 25 million people worldwide and continues to grow in prevalence. According to a center for disease control and prevention (CDC) report, the total annual cost of asthma in the United States between 2008 and 2013, including medical care, absenteeism, and mortality, was $81.9 billion. Although the National Institute of Health guidelines recommend fixed inhaled corticosteroid (ICS) dosing, the 2008–2010 Medical Expenditure Panel Survey showed that asthma is still poorly controlled. Single inhaler maintenance and reliever therapy (SMART) offers a possible alternative management plan. This is a review of SMART vs. current treatment guidelines. Recent findings SMART addresses variable inflammation with symptom-driven dosing of ICS. It relies on a combination inhaler that has a long-acting β-agonist, which has an immediate onset of action to provide quick relief, in combination with an ICS. Recent studies show that SMART decreases the frequency and severity of asthma exacerbations when compared to fixed ICS dosing. In addition, intermittent use of ICS gave a reduced effect on growth and permitted a lower total amount of ICS to be delivered. Summary SMART appears to outperform treatment that is based on current guidelines in the United States. As inhalers capable of being used for SMART are already approved, what is needed is Food and Drug Administration approval of the SMART strategy. Correspondence to Jay M. Portnoy, MD, Section of Allergy, Asthma and Immunology, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA. Tel: +1 816 960-8885; fax: +1 816 960-8888; e-mail: jportnoy@cmh.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
http://bit.ly/2D6QXbv
Παρασκευή 11 Ιανουαρίου 2019
Phenotypes of wheezing and asthma in preschool children
Purpose of review The purpose of this review is to provide an overview of the identified phenotypes of preschool wheezing. Recent findings Early life wheezing patterns have been described in multiple populations, with several commonalities found between cohorts. Early life environmental exposures have been found to be differentially associated with preschool wheezing phenotypes and their future trajectories. These include allergen and microbe exposure, environmental tobacco smoke exposure, and maternal stress and depression. Elevated IgE in early life may also influence future asthma risk. Summary Preschool wheezing phenotypes are heterogeneous and complex, with trajectories that are related to factors including environmental exposures. More research is needed to characterize these relationships, hopefully leading to targeted prevention strategies. Correspondence to Leonard B. Bacharier, MD, Campus Box 8116, 660 S. Euclid Ave., St. Louis, MO 63110, USA. Tel: +1 314 454 2694; e-mail: Bacharier_l@wustl.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
http://bit.ly/2QGvlpU
http://bit.ly/2QGvlpU
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
Patient Phenotyping in OSA
Abstract
Purpose of Review
OSA treatment paradigms are evolving from a "one treatment for all" philosophy to personalised therapeutic options based on anatomical and physiological phenotypes. Understanding these different phenotypes will become vital for clinicians as OSA testing and treatment become more targeted.
Recent Findings
Phenotyping of the pharynx and upper airway is vital to inform anatomical treatment options such as surgery and mandibular advancement splints. Manipulated CPAP testing allows determination of traits such as arousal threshold, muscular responsiveness and ventilatory control. Targeted therapies of each of these physiological traits have shown promise in selected patients in the research context.
Summary
Current treatment paradigms are based on anatomical therapies (CPAP, MAS, surgery); the limitations of which may be particularly evident in patients with physiological contributors to their OSA. Physiological phenotyping is an area of ongoing research into non-anatomical traits which contribute to airway obstruction.
http://bit.ly/2SOXZqL
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
Is there enough evidence to refute the antiviral therapy in vestibular neuritis: A best evidence review
Indian Journal of Otology 2018 24(3):135-138
Background: Recent research has provided extended support on the viral etiology of vestibular neuritis (VN); however, antiviral therapy is considered non-beneficial helpful in VN, contrary to its role in other similar viral-induced inflammatory conditions. The objective of this review is to segregate the available literature on antiviral therapy in VN and to evaluate and analyze the results of all those studies to know whether the antiviral therapy helps in VN patients or not. Materials and Methods: Electronic databases searched include PubMed, Scopus, Web of science, IndMED, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane library. Study Selection: Prospective randomized controlled trials (RCTs) comparing the outcomes of any form of antiviral therapy in VN, with that of placebo or any form of steroid or any other alternative therapy. Data Extraction and Data Synthesis: Among 581 screened articles, only one RCT was found on this topic, precluding the meaningful statistical analysis. However, this study did not consider the symptomatic improvement after antiviral therapy but only reported caloric response which is of less clinical relevance. No other controlled prospective study on antiviral therapy in VN has been published. Conclusions: The available evidence is not sufficient to disregard the beneficial effect of antiviral therapy in VN. Further randomized trials with better and clinically relevant study design are required to answer the question.
http://bit.ly/2Rn5Teb
Mastoid cavity obliteration using bone pate and ribbon-like temporalis muscle flap: Our experience
Indian Journal of Otology 2018 24(3):194-198
Objective: The aim of this study was to elucidate a mix of bone pate with ribbon-like temporalis muscle flap for mastoid cavity obliteration after mastoid surgery to avoid mastoid cavity problems. Materials and Methods: In 54 patients of unsafe chronic suppurative otitis media, canal wall down mastoidectomy was done, size of the cavity assessed and ribbon-like temporalis muscle flap with bone pate used for mastoid cavity obliteration. Follow-up was done at 3 weeks, 3 months and then at 6 months. Results: Dry cavity with success rate of 83% is achieved with temporalis muscle flap technique of mastoid cavity obliteration. Conclusion: A mix of bone pate to obliterate the small spaces in the mastoid cavity along with a ribbon-like temporalis muscle flap is effective method of mastoid cavity obliteration as it gives a dry ear, is not bulky and most importantly maintains the canal.
http://bit.ly/2Ck7FSP
The relative contribution of visual cues and acoustic enhancement strategies in improving speech perception of individuals with auditory neuropathy spectrum disorders
Indian Journal of Otology 2018 24(3):139-147
Background and Objectives: The present study aimed to assess the relative benefits of visual cue supplementation and acoustic enhancement in improving speech perception of individuals with Auditory Neuropathy Spectrum Disorders (ANSD). Methods: The study utilized repeated measure research design. Based on the purposive sampling 40 participants with ANSD were selected. They were assessed for their speech identification of monosyllables in auditory only (A), visual only (V), and auditory-visual (AV) modalities. In the A and AV modalities, the perception of the primary, temporally enhanced, and spectrally enhanced syllables were assessed in quiet as well as 0 dB signal to noise ratio (SNR) conditions. The identification scores were compared across modalities, stimuli, and conditions to derive the relative benefits of visual cues and acoustic enhancement on speech perception of individuals with ANSD. Results: The group data showed a significant effect of modality with the mean identification score being the maximum in AV modality. This was true both in quiet and 0 dB SNR. The mean identification scores in quiet were significantly higher compared to that in 0 dB SNR. However, acoustic enhancement of speech did not significantly enhance speech perception. When acoustic enhancement and visual cues were simultaneously provided, speech perception was determined only by visual cues. The evidence from individual data showed that most of the individuals benefit from AV modality. Conclusions: The findings indicate that both auditory and visual modality needs to be facilitated in ANSD to enhance speech perception. The acoustic enhancements in the current form have negligible influence. However, the inference shall be restricted to the perception of stop consonants.
http://bit.ly/2RlJgHd
Evaluation of the hearing results after mastoidotympanoplasty operation with or without ossiculoplasty: A percentage change versus absolute change; a different methodology
Indian Journal of Otology 2018 24(3):148-156
Purpose: Our article provides a comprehensive review of parameters of percentage change of the results regarding the documented hearing results (not based on any particular classification) in ear surgeries in chronic suppurative otitis media (CSOM) cases. Materials and Methods: Our series is a prospective cohort observational study in 230 cases of CSOM from 2009 to 2016 wherein we have evaluated the hearing improvement with a parameter of percentage change of hearing improvement between preoperative and postoperative period in various types of ear surgeries. Statistics and Results: A statistically significant difference was seen in 4 out of the 14 surgical groups, namely, in mastoidotympanoplasty, modified radical mastoidectomy (MRM), and MRM with tympanoplasty and in tympanoplasty. The rest of the 10 surgical groups had <10 cases, and therefore, the P significance could not be determined; however, these groups still showed hearing improvement. Conclusion: The superiority of the surgical techniques such as mastoidotympanoplasty, MRM, MRM with tympanoplasty and in tympanoplasty as demonstrated in our study aims to find an ideal surgical procedure in CSOM which gives the best chance to improve or preserve the hearing with complete eradication of the disease.
http://bit.ly/2RmyC2B
Preauricular iatrogenic epidermoid cyst through middle-ear surgery
Indian Journal of Otology 2018 24(3):204-206
Iatrogenic implantation of squamous epithelium during middle-ear surgery may cause epidermoid cyst (EC) development. These cysts may arise in different localizations of the head and neck following otological surgery. In this rare case, a giant EC with a size of 56 mm × 30 mm, which appeared in the preauricular area growing in the past 1 year in a 40-year-old male patient who underwent type 1 tympanomastoidectomy due to chronic otitis media without cholesteatoma 8 years ago, was discussed with the literature in terms of clinical findings and differential diagnosis.
http://bit.ly/2Cc6Zik
The role of parental hearing status in theory of mind after cochlear implant surgery
Indian Journal of Otology 2018 24(3):157-161
Introduction: Theory of mind (ToM), or the understanding of others' thoughts and feelings and their behavioral consequences, has been extensively studied in hearing typically developing preschool children over several decades, including research demonstrating the influence of ToM on preschool children's social lives. Hearing impairment is common type of sensory loss in children. Literature indicates that children with hearing impairment deficit in social, cognitive, and communicate skills. Aim: This study performed to compare ToM of cochlear-implanted first- and second-generation deaf children. Methodology: This research is causal comparative. All 15 deaf children with deaf parent selected from Baqiyatallah Cochlear Implant (CI) Center. Hence, 15 cochlear-implanted children paired with them by purposive sampling. Results: Findings showed that t-test (t = −4.52, P < 0.01) was statistically significant. According to t-test, the second-generation children was significantly higher than the first-generation children in ToM. Conclusion: We can assume that the second-generation children were joined with their family in sign language, lead to the use of primary experience before of implant. So, it is recommended to use the sign language before cochlear implantation.
http://bit.ly/2RnfdPm
A prospective study of outcome of boomerang-shaped chondroperichondrial graft in Type i tympanoplasty
Indian Journal of Otology 2018 24(3):179-183
Context: Cartilage has proven to be an excellent graft material inside the middle ear. The use of cartilage for tympanic membrane grafting may provide additional benefits in some difficult situations. Aims: The study was planned to evaluate the graft uptake and hearing after placement of "boomerang-shaped chondroperichondrial graft" in Type I tympanoplasty. Settings and Design: The prospective study was conducted on 40 patients having chronic suppurative otitis media with no active disease at least for last 6 weeks in a tertiary care center of North India. Patients having cholesteatoma and ossicular erosion/or necrosis were excluded from the study.Subjects and Methods: Those patients underwent tympanoplasty Type I by postaural approach and underlay grafting using "boomerang-shaped chondroperichondrial graft" from tragal cartilage and were followed up for 3 months. Hearing evaluation was performed preoperatively and postoperatively after 3 months. Statistical Analysis Used: The mean, range, and standard deviation of air conduction and air-bone gap were calculated and compared with preoperative findings. Results: The mean age of study group was 26.23 ± 12.46 years. Ear discharge (100%) and hearing impairment (87.5%) were the chief presenting complaints. The mean duration of ear discharge was 6.67 ± 6.75 years. Type I tympanoplasty was performed in all cases using "boomerang-shaped chondroperichondrial graft" harvested from tragal cartilage. Graft was taken up at the 3rd month in all patients. The preoperative mean air conduction was 43.21 ± 7.17 dB, which at the 3rd month improved to 36.49 ± 6.60 (P = 0.00004). Preoperative mean air-bone gap was 25.45 ± 8.44 dB which was improved to 19.31 ± 8.18 dB postoperatively at the 3rd month (P = 0.0014). Conclusions: Boomerang-shaped chondroperichondrial graft has excellent "take rate" in Type I tympanoplasty.
http://bit.ly/2Ch5ZcN
Subjective visual vertical in different peripheral vestibular disorders
Indian Journal of Otology 2018 24(3):162-167
Context: The subjective visual vertical (SVV) is considered to be a functional measure of otolith-mediated verticality perception. Aims: This study aims to detect the normative data of SVV and to analyze SVV changes in peripheral vestibular disorders. Settings and Design: This was a observational, cross-sectional study. Subjects and Methods: Forty-five adult patients with chronic peripheral vestibular disorders endolymphatic hydrops, vestibular neuritis, and benign paroxysmal positional vertigo and 20 normal individuals were included in this study. After full history taken, SVV deviations and caloric tests were completed. Statistical Analysis Used: Independent Student's t-test for independent sample when comparing 2 groups. ANOVAs test compared three or more means for statistical significance. Tukey's test compared the means of every treatment to the means of every other treatment. Chi-square test was performed. Normal cutoff value was calculated by mean +2 standard deviation (SD) as high limit and mean −2 SD as low limit. Results: The normative data of SVV ranged from −0.2° to 1.26° in clockwise direction and from −0.04° to 0.95° in the counterclockwise direction. SVV in counterclockwise direction were significantly deviated among the three groups of Peripheral vestibular disorder (PVD) patients when compared with controls. It revealed a significant deviation in counterclockwise tilt between left diseased ears in relation to controls. Conclusions: Normal adults displayed a narrow range of one-degree SVV deviation (1.06° and 0.91°) in clockwise and counterclockwise direction, respectively. The three vestibular disorders significantly deviate the SVV in counterclockwise direction compared to control with no gender difference. SVV test alone cannot differentiate between different PVD.
http://bit.ly/2RkFFsE
Comparative study of clinical and audiological outcome between anterior tucking and circumferential flap methods of type I tympanoplasty in large central perforation
Indian Journal of Otology 2018 24(3):190-193
Background: Tympanoplasty is a common operation performed by otolaryngologists worldwide. During the last 100 years various modifications in this surgical technique have come up because of continued efforts made by otologists all over the world to achieve the best surgical outcome. Objective: The aim of this study is to compare the surgical and audiological outcomes of anterior tucking and circumferential flap methods of type 1 tympanoplasty. Materials and Methods: This prospective randomized study included 100 patients who presented in the ENT outpatient Department of Bangalore Medical College and Research Institute with chronic otitis medialarge central perforation in an inactive stage. Patients were randomly allocated to two groups of 50 cases each. Group A contained 50 patients who underwent Type I tympanoplasty by circumferential flap method, and Group B contained 50 patients who underwent Type I tympanoplasty by anterior tucking method. Patients were followed up at the 3rd month postoperatively by otomicroscopy and pure tone audiometry (PTA), graft uptake and hearing gain were assessed. Results: There was a statistically significant mean hearing gain postoperatively compared to preoperative PTA in both techniques, among the two techniques, there was no statistically significant difference regarding hearing gain and graft uptake. Conclusion: Anterior tucking and circumferential flap methods of type 1 tympanoplasty are good regarding graft placement, graft uptake, and audiological outcome for chronic otitis media with large central perforation, especially with little or no anterior remnant of pars tensa.
http://bit.ly/2Ce9FMG
Comparison of tragal perichondrium and temporal fascia grafts in tympanoplasties
Indian Journal of Otology 2018 24(3):168-171
Objective: The objective of this study was to compare the anatomic and functional outcomes of the different graft materials used in tympanoplasty. Settings and Design: This was an observational, cross-sectional study. Patients and Methods: The study included 243 patients operated at Tertiary Care University Hospital, from January 2011 to December 2015. The study excluded patients who had previous ear surgery and patients with cholesteatoma and nose and paranasal sinuses diseases. Tympanoplasty was done under general anesthesia. The retroauricular approach was primarily used. All grafts were placed using the underlay technique. Audiological testing of all patients was done preoperatively and postoperatively. Statistical Analysis Used: All data were entered into Excel and analyzed using MedCalc Statistical Software version 15.8 (MedCalc Software bvba, Ostend, Belgium). Descriptive statistics was used. Audiological findings were compared using a paired t-test. The value of P < 0.05 was considered statistically significant. Results: The temporal fascia was used as the graft material in 160 patients, and tragal perichondrium was used in 83 patients. Improvement of audiological outcome in patients with temporal fascia amounted 62.5% and in patients with perichondrium amounted 60.24%. The graft success rate 3 months postoperatively was 92.5% in the fascia group whereas it was 95.18% in the perichondrium group. Conclusion: Improvement of audiological outcome was slightly better (62.5%) in the fascia group while graft acceptance in the postoperative period was slightly better (95.18%) in the perichondrium group.
http://bit.ly/2Rqis8w
Vestibular dysfunction and glycemic control in diabetes mellitus: Is there a correlation?
Indian Journal of Otology 2018 24(3):199-203
Objectives: The aim of this study is to evaluate and find the proportion of patients with Type-II diabetes mellitus (DM) with sensorineural hearing loss (SNHL) and vestibular dysfunction (VD) and association with glycemic control. Materials and Methods: An observational cross-sectional study was carried out in 100 patients (age group: 30–60 years) diagnosed with Type-II DM coming to the outpatient department of our Rural Tertiary Care Teaching Hospital, fulfilling the inclusion criteria. Prior approval of the Institutional Ethics Committee and written informed consent was obtained. All patients were subjected to investigations to assess their diabetes control, hearing, and vestibular function. The findings were subjected to statistical analysis. Results: Out of 100 patients, 62 were male and 38 were female between the age group of 30 and 60 years. The mean hemoglobin A1c (HbA1c) level was 9.16 ± 2.4. The patients were divided into three groups depending on HbA1c level, to denote control, good (≤7%), moderate (>7, ≤12%), and poor (>12%). There were a total of 69 patients with SNHL and 70 patients with VD. SNHL was present in 57.6% of good control group, 66.1% of moderate control group, and 100% of poor control group. Analysis with Chi-square test for correlation between glycemic control and SNHL was statistically significant. Out of the 70 patients with VD, 51.4% had right vestibulopathy, 41.4% had left vestibulopathy, and 7.2% had a bilateral vestibulopathy. Twenty-two patients had benign paroxysmal positional vertigo. VD was present in 42.3% of good control group, 74.5% of moderate control group, and 100% of poor control group. Chi-square test was statistically significant. Conclusion: There is a significant association between Type II DM, and SNHL and VD, especially with worsening of glycemic control. Screening for these debilities should be a part of the routine workup of a diabetic patient. VD is a potential cause for imbalance and vertigo in DM.
http://bit.ly/2Cr8Ekz
Does postural instability in type 2 diabetes relate to vestibular function?
Indian Journal of Otology 2018 24(3):172-178
Introduction: Diabetes mellitus (DM) can lead to complications including postural instability that may be related to impaired function of the vestibular system. Aims and Objectives: This study aims to measure vestibular and balance function in adults diagnosed with type 2 noninsulin-dependent diabetes mellitus (NIDDM) and to compare their findings with healthy age-matched control group. Materials and Methods: This is an experimental cross-sectional study, using purposive sampling method. Eight NIDDM patients (mean age = 36.8 ± 11.4 years) and eight age-matched healthy controls (mean age = 34.6 ± 11.0 years) were recruited. Vestibular end organs (i.e., saccule, utricle, and semicircular canals) were assessed using cervical and ocular vestibular-evoked myogenic potentials (cVEMPs and oVEMPs) and video head impulse test. Upright stance postural stability was assessed using force plate in four testing conditions, i.e., standing on firm or foam surface with eyes opened or closed. Dynamic stability was measured using Timed Up and Go (TUG) and functional gait assessment (FGA). Results: There was no statistically significant difference for all vestibular tests between groups. However, reduced p13-n23 interamplitudes (for cVEMPs) and n10 amplitudes (for oVEMPs) were observed in NIDDM patients. Upright stance postural stability was not significantly worse in patients. For dynamic postural stability, NIDDM patients demonstrated significantly poor performance in TUG and FGA than the healthy controls. Functionally, NIDDM patients walked significantly slower and less stable, and this is evident from poor performance in both TUG and FGA results. Conclusion: Our findings showed significant reduction in dynamic postural stability in NIDDM patients. However, we did not find any significant abnormal vestibular function in the patients as reported by previous studies. Further research studies are advocated.
http://bit.ly/2Rqws2f
Bilateral bullous myringitis in a teenager
Indian Journal of Otology 2018 24(3):207-208
Bullous myringitis is commonly encountered in otorhinolaryngology clinic. The most common presenting symptoms are otalgia, reduced hearing, and tinnitus. It can affect patients of any age in spite of the fact that children are frequently affected. In our recent encounter in our clinic, a teenager presented with bilateral otalgia with reduced hearing. Otoscopic findings revealed bilateral bullous myringitis that is indeed rare. He responded well with antibiotic treatment and recovered completely.
http://bit.ly/2CeOBWn
Water Waves to Sound Waves: Using Zebrafish to Explore Hair Cell Biology
Abstract
Although perhaps best known for their use in developmental studies, over the last couple of decades, zebrafish have become increasingly popular model organisms for investigating auditory system function and disease. Like mammals, zebrafish possess inner ear mechanosensory hair cells required for hearing, as well as superficial hair cells of the lateral line sensory system, which mediate detection of directional water flow. Complementing mammalian studies, zebrafish have been used to gain significant insights into many facets of hair cell biology, including mechanotransduction and synaptic physiology as well as mechanisms of both hereditary and acquired hair cell dysfunction. Here, we provide an overview of this literature, highlighting some of the particular advantages of using zebrafish to investigate hearing and hearing loss.
http://bit.ly/2AGIGcm
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 (SUVmax) 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 SUVmax 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
Oral Challenge Outcomes in Children with Adverse Aminopenicillin Reactivity
Tables: 1
http://bit.ly/2ClkNXU
Concomitant hypersensitivity pneumonitis and occupational asthma caused by two different etiological agents.
Figures: 1
http://bit.ly/2RpHhBC
Another Look at Cyclosporine for Treating Antihistamine-Resistant Chronic Spontaneous Urticaria
There are only two treatments with demonstrated efficacy in randomized placebo controlled clinical trials for antihistamine-resistant chronic spontaneous urticaria (CSU), cyclosporine1 and omalizumab.2 The latter is a commercial product that was well studied to obtain FDA approval for marketing as a treatment for CSU within the past 5 years. Cyclosporine is a generic drug that was first demonstrated in a randomized placebo controlled trial to be an effective treatment for CSU almost 20 years ago,1
http://bit.ly/2Ch1H5b
Psoriasis and IBD: Is This Comorbidity for Real?
Psoriasis vulgaris seems to be linked not only with RA and CVD but also with IBD.
Medscape Dermatology
https://wb.md/2M6FGKV
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
Water Waves to Sound Waves: Using Zebrafish to Explore Hair Cell Biology
Abstract
Although perhaps best known for their use in developmental studies, over the last couple of decades, zebrafish have become increasingly popular model organisms for investigating auditory system function and disease. Like mammals, zebrafish possess inner ear mechanosensory hair cells required for hearing, as well as superficial hair cells of the lateral line sensory system, which mediate detection of directional water flow. Complementing mammalian studies, zebrafish have been used to gain significant insights into many facets of hair cell biology, including mechanotransduction and synaptic physiology as well as mechanisms of both hereditary and acquired hair cell dysfunction. Here, we provide an overview of this literature, highlighting some of the particular advantages of using zebrafish to investigate hearing and hearing loss.
http://bit.ly/2AGIGcm
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
Do helminth infections underpin urban‐rural differences in risk factors for allergy‐related outcomes?
Abstract
Background
It is proposed that helminth exposure protects against allergy‐related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses.
Objective
We aimed to assess how helminth exposure influences rural‐urban differences in risk factors for allergy‐related outcomes in tropical low‐ and middle‐income countries.
Methods
In cross‐sectional surveys in Ugandan rural Schistosoma mansoni (Sm)‐endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen‐specific skin prick test [SPT] reactivity and IgE [asIgE] sensitisation) and clinical allergy‐related outcomes (wheeze, urticaria, rhinitis, visible flexural dermatitis), and effect‐modification by Sm exposure.
Results
Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitisation among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma‐specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non‐Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural versus urban) was an effect modifier for risk factors including Sm and Schistosoma‐specific IgG4. In both surveys, the dominant risk factors for asIgE sensitisation were Schistosoma‐specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitisation among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural‐urban differences in risk factors.
Conclusions and clinical relevance
Risk factors for allergy‐related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly.
This article is protected by copyright. All rights reserved.
http://bit.ly/2TPupSb
Is CT or MRI the optimal imaging investigation for the diagnosis of large vestibular aqueduct syndrome and large endolymphatic sac anomaly?
Abstract
Background and purpose
We explored whether there was a difference between measurements obtained with CT and MRI for the diagnosis of large vestibular aqueduct syndrome or large endolymphatic sac anomaly, and whether this influenced diagnosis on the basis of previously published threshold values (Valvassori and Cincinnati). We also investigated whether isolated dilated extra-osseous endolymphatic sac occurred on MRI. Secondary objectives were to compare inter-observer reproducibility for the measurements, and to investigate any mismatch between the diagnoses using the different criteria.
Materials/methods
Subjects diagnosed with large vestibular aqueduct syndrome or large endolymphatic sac anomalies were retrospectively analysed. For subjects with both CT and MRI available (n = 58), two independent observers measured the midpoint and operculum widths. For subjects with MRI (± CT) available (n = 84), extra-osseous sac widths were also measured.
Results
There was no significant difference between the width measurements obtained with CT versus MRI. CT alone diagnosed large vestibular aqueduct syndrome or large endolymphatic sac anomalies in 2/58 (Valvassori) and 4/58 (Cincinnati), whilst MRI alone diagnosed them in 2/58 (Valvassori). There was 93% CT/MRI diagnostic agreement using both criteria. Only 1/84 demonstrated isolated extra-osseous endolymphatic sac dilatation. The MRI-based LVAS/LESA diagnosis was less dependent on which criteria were used. Midpoint measurements are more reproducible between observers and between CT/MR imaging modalities.
Conclusion
Supplementing MRI with CT results in additional diagnoses using either criterion, however, there is no net increased diagnostic sensitivity for CT versus MRI when applying the Valvassori criteria. Isolated enlargement of the extra-osseous endolymphatic sac is rare.
http://bit.ly/2CgzdIN
Early onset oral tongue squamous cell carcinoma: Associated factors and patient outcomes
Abstract
Background
Incidence of oral tongue squamous cell carcinoma (OTC) is rising among those under age 50 years. The etiology is unknown.
Methods
A total of 395 cases of OTC diagnosed and/or treated at Vanderbilt University Medical Center between 2000 and 2017 were identified. Of those, 113 (28.6%) were early onset (age < 50 years). Logistic regression was used to identify factors associated with early onset OTC. Cox proportional hazards models evaluated survival and recurrence.
Results
Compared to typical onset patients, patients with early onset OTC were more likely to receive multimodality treatment (surgery and radiation; adjusted odds ratio [aOR], 2.7; 95% confidence interval [CI], 1.2‐6.3) and report a history of snuff use (aOR, 5.4; 95% CI, 1.8‐15.8) and were less likely to report a history of cigarette use (aOR, 0.5; 95% CI, 0.2‐0.9). Early onset patients had better overall survival (adjusted hazard ratio, 0.6).
Conclusions
This is the largest study to evaluate factors associated with early onset OTC and the first to report an association with snuff.
http://bit.ly/2M4jxgu
Ultraviolet light‐related DNA damage mutation signature distinguishes cutaneous from mucosal or other origin for head and neck squamous cell carcinoma of unknown primary site
Abstract
Background
Head and neck squamous cell carcinoma of unknown primary site (HNSCCUP) is a diagnostic challenge. Identification of an ultraviolet (UV) light‐related DNA damage signature using next‐generation sequencing (NGS) can classify the primary site of origin as cutaneous.
Methods
A 62‐year‐old male was seen with 2 months of left neck swelling. He was a lifetime nonsmoker but had a history of cutaneous squamous cell carcinoma (SCC) of the left helix. He was also found to have left hilar adenopathy. He had a p16‐negative HNSCCUP on fine needle aspiration (FNA) biopsy of the left neck.
Results
NGS of the FNA specimen revealed a high number of somatic mutations that were mostly C to T transitions, indicating a UV mutation signature and confirming the diagnosis of cutaneous SCC.
Conclusions
Identification of a UV DNA damage signature with NGS distinguishes HNSCCUP of cutaneous vs mucosal or other squamous cell carcinoma origin.
http://bit.ly/2snUhZG
Intratumoral generation of 2‐fluoroadenine to treat solid malignancies of the head and neck
Abstract
This report describes treatment of locoregional head and neck squamous cell carcinoma (HNSCC) by an innovative, experimental strategy involving generation of a robust anti‐cancer agent (2‐fluoroadenine [F‐Ade]) following transduction by Escherichia coli purine nucleoside phosphorylase (PNP) in a small number of tumor cells. F‐Ade works by a unique mechanism of action (ablation of RNA and protein synthesis) and confers tumor regressions of otherwise refractory HNSCC in human subjects. Clinical studies have now advanced to a pivotal (registration‐directed) trial involving locoregional HNSCC, with plans to begin subject enrollment late in 2018. The present review is the first to summarize use of PNP in the context of HNSCC, and provides background regarding this emerging anti‐cancer approach.
http://bit.ly/2M3D8NG
Treatment modalities and outcomes of Fanconi anemia patients with head and neck squamous cell carcinoma: A series of 9 cases and review of the literature
Abstract
Background
Fanconi anemia (FA) is associated with an increased risk of developing head and neck squamous cell cancer (HNSCC) and presents a treatment dilemma due to concerns of increased toxicities from chemotherapy and radiation therapy (RT).
Methods
We reviewed the literature on HNSCC in FA patients and report on our experience treating 9 FA patients with HNSCC.
Results
Surgery was generally well‐tolerated and surgery alone resulted in durable local control for 2 patients. Four patients received adjuvant RT that was tolerable in most cases, although 1 patient required a treatment break and early cessation of RT. Three of the irradiated patients received concurrent cetuximab.
Conclusions
In patients with adverse features, adjuvant radiation with concurrent cetuximab may be feasible with careful monitoring, although local disease control is infrequent. Early detection via screening permitting a surgery‐alone approach represents the best opportunity for cure in FA patients with HSNCC.
http://bit.ly/2spWzHn
Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma
Abstract
Background
Factors involved in neck lymph node metastasis (NLM) and prognosis of early tongue squamous cell carcinoma (SCC) remain unknown.
Methods
We analyzed disease‐specific survival (DSS) and NLM including tumor budding grade (TBG) among 64 patients with cT1/2N0 tongue SCC.
Results
Univariate analysis of DSS of primary lesions uncovered significant differences in new cT, pT, new pT, pDiameter, venous infiltration, and TBG. Multivariate analysis selected only TBG3 as a predictor of NLM (odds ratio, 9.55; 95% confidence interval [CI], 1.80‐50.8; P = .008), and a prognostic factor for DSS (hazard ratio, 4.41; 95% CI, 1.34‐14.5; P = .02).
Conclusion
The sole predictor of NLM and the prognosis of early tongue SCC was TBG, indicating that it might help to select overwhelming risk patients.
http://bit.ly/2M9myME
Preoperative neutrophil lymphocyte ratio but not platelet lymphocyte ratio predicts survival and early relapse in patients with oral, pharyngeal, and lip cancer
Abstract
Background
To evaluate the prognostic value of preoperative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in oral, pharyngeal, and lip cancer for survival and relapse.
Methods
Clinic‐pathologic and hematological records were retrospectively retrieved. Patients completed follow‐up period were included for survival and relapse analysis.
Results
The preoperative NLR value was a prognostic factor for both overall survival and relapse‐free survival. The high NLR group demonstrated higher total relapse rate, higher local relapse rate, and higher relapse rate within 12 months. However, the preoperative PLR did not associate with survival or relapse.
Conclusions
The preoperative NLR, not PLR, is an independent prognostic indicator of survival. It also exhibits predictive value for relapse, particularly early relapse within 12 months. The preoperative NLR value might be recommended as a useful tool for predicting the outcomes and stratifying patients for different management strategies.
http://bit.ly/2slXtVk
Paraganglioma of the head and neck region, treated with radiation therapy, a Rare Cancer Network study
Abstract
Background
Paraganglioma of the head and neck (HNPGL) are rare often benign tumors. Surgery and radiation therapy (RT) are the main treatment choices. We present an analysis of outcome and toxicity after RT from 13 institutions of the Rare Cancer Network.
Methods
Data were collected using a questionnaire concerning patients' characteristics, treatment, and outcome. A total of 81 patients with 82 HNPGL were analyzed.
Results
The median follow‐up was 48 months (1‐456). Sixty‐two lesions were treated with conventional RT and 20 lesions with stereotactic RT. Local control (LC) was achieved in 69 out of 77 lesions. Late toxicity occurred in 17 patients. Patients treated with stereotactic RT experienced neither disease progression nor late toxicity. Four patients with a follow‐up longer than 20 years experienced disease progression.
Conclusion
RT for HNPGL offered good local control with acceptable toxicity. Stereotactic RT might offer better results. Long‐term follow‐up is required.
http://bit.ly/2M3VD4v
Impact of extent of parotidectomy on early and long‐term complications: A prospective multicenter cohort trial
Abstract
Background
In this prospective nonrandomized multicenter trial, we analyze the incidence of early and late complications after parotidectomy in correlation to the extent of dissection.
Methods
A total of 148 patients underwent a parotidectomy for a benign lesion in the superficial lobe. The number of intraoperatively dissected main facial nerve branches was photo‐documented and defined the extent of tissue dissection. Early postoperative complications including sialocele were evaluated until 4 weeks after surgery. Late complications as facial nerve palsy, Frey´s syndrome (FS) and the outcome of the scar and substance loss were furthermore assessed after 6 and 12 months.
Results
Early complications occurred in 22 patients (14%) and did not depend on the extent of facial nerve dissection (all P > .05). However, patients with higher number of intraoperatively dissected facial nerve branches showed significantly higher palsy scores on the first postoperative day (P = .026). FS occurred with incidence of 69% and correlated significantly to the extent of dissection (P = .003). Appearance of the scar and substance loss improved significantly during the follow‐up (P < .001 and P < ,005, respectively) without significant correlation to the extent of dissection (P > .05 for both variables after 12 months).
Conclusions
Less extensive tissue dissection resulted in better postoperative facial nerve function on the first postoperative day and in lower incidence of FS after 12 months. However, incidence of early complications did not depend on the extent of surgery.
The study was registered in the German Clinical Trials Register prior to conducting the research. DRKS‐ID: DRKS00008967, URL:http://apps.who.int/trialsearch/.
http://bit.ly/2M9FmLG
Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance
Abstract
T cell responses are crucial for anti-tumor immunity. In chronic viral infections, anti-tumor T cell responses can be compromised due to various immunological mechanisms, including T cell exhaustion. To study mechanisms of anti-tumor immunity during a chronic viral infection, we made use of the well-established Friend virus (FV) mouse model. Chronically FV-infected mice are impaired in their ability to reject FBL-3 cells—a virus-induced tumor cell line of C57BL/6 origin. Here we aimed to explore therapeutic strategies to overcome the influence of T cell exhaustion during chronic viral infection, and reactivate effector CD8+ and CD4+ T cells to eliminate tumor cells. For T cell stimulation, agonistic antibodies against the tumor necrosis factor receptor (TNFR) superfamily members CD137 and CD134 were used, because they were reported to augment the cytotoxic program of T cells. αCD137 agonistic therapy, but not αCD134 agonistic therapy, resulted in FBL-3 tumor elimination in chronically FV-infected mice. CD137 stimulation significantly enhanced the cytotoxic activity of both CD4+ and CD8+ T cells, which were both required for efficient tumor control. Our study suggests that agonistic antibodies to CD137 can efficiently enhance anti-tumor immunity even in the setting of chronic viral infection, which might have promising therapeutic applications.
http://bit.ly/2SRknjk
Histogenesis of cutaneous malignant melanoma: The vast majority do not develop from melanocytic nevus but arise de novo as melanoma in situ
Abstract
It has been considered that most cutaneous malignant melanomas arise from pre‐existing melanocytic nevus. Many clinical and histopathological studies seem to support this concept. Dysplastic nevus originally proposed by Clark's group is a key entity of the intermediate lesion between benign nevus and melanoma. The latest edition of the WHO Classification of Skin Tumours (2018) has excluded Clark nevus (dysplastic nevus of mild atypia) from dysplastic nevus, the latter being now classified into the low‐ and high‐grade by the degrees of nuclear atypia. The World Health Organization classification regards dysplastic nevus of both grades as the intermediate lesion between common acquired nevus and the radial growth‐phase melanoma. An extensive genetic study recently performed by Bastian's group indicated the existence of intermediate lesions between nevus and melanoma. In spite of these findings, some investigators doubt the concept of the intermediate lesions including dysplastic nevus and insist that the majority of melanomas arise de novo as melanoma in situ, not in association with a preceding nevus. The concept of de novo genesis of melanoma may be supported by a recent meta‐analysis study revealing that 71% of melanomas likely arose de novo and 29% from pre‐existing nevus. In this review article, from the viewpoint of de novo genesis of melanoma, the author critically discusses the relevant findings of melanoma genesis and proposes a new framework to interpret the morphological and genetic data alternatively. Clarification of the oncogenic process of melanoma has great impact not only on clinical dermatology but also on basic oncology.
http://bit.ly/2SKwgHD
Colonic lymphangioma presenting with intermittent pain and intussusception
Abstract
Background
Cystic lymphangiomas are rare benign tumours and their actual incidence in the colon is unclear. Within the large bowel, these lesions are often submucosal and are incidental findings on colonoscopy. Case report
A 43-year-old man with colonic lymphangioma presented with a 7-month history of abdominal pain and altered bowel habits. Computed tomography showed a cystic mass lesion at the distal descending colon. Colonoscopy revealed a smooth, polypoid mass, initially thought as an inverting diverticulum. He underwent laparoscopic high anterior resection. The pathological analysis revealed the descending colon mass to be a lymphangioma with no evidence of diverticulosis. Conclusion
There is increasing incidence in lymphangioma due to the increasing accessibility to colonoscopy, particularly for asymptomatic or subacute disease. Although colonoscopic excision, sclerotherapy and use of steroids or fibrin glue have been advocated as possible modes of treatment, surgical excision is still considered to be the treatment of choice.http://bit.ly/2M4AhUK
Acne relapses: impact on quality of life and productivity
Abstract
Background
Acne is a common skin disease that mostly affects teenagers, with a negative impact on quality of life. Recently, adult acne and acne relapses have increased in frequency, for yet unknown reasons.
Objective
This non‐interventional, real‐life study sought to investigate the rate of acne relapses, and their impact on quality of life and productivity (loss/absenteeism) among teenagers and adults.
Methods
An online self‐administered questionnaire was proposed to ≥15‐year‐olds suffering from acne who spontaneously consulted their dermatologist. To ensure homogeneous assessment of acne severity, the Global Acne Severity (GEA) scale was applied. Quality of life was assessed via Cardiff Acne Disability Index (CADI), SF12‐physical score (PS), and SF12‐mental score (MS) questionnaires. Productivity loss or absenteeism in middle/high school was estimated based on the number of days off work or school over the last 30 days.
Results
Overall, 1,048 questionnaires were considered assessable, with 448 (43%) mild acne, 434 (41%) moderate acne, and 166 (16%) severe acne. Overall, 755 (72%) participants were in middle/high school, 267 (25%) employed, and 26 (3%) with no professional activity. Considering the population by age groups, 68% (n = 716) were ≤20‐year‐olds and 32% (n = 332) >20‐year‐olds, with a mean age of 20.26 (SD: 7.43) years. Acne relapses were reported by 44% of respondents. Analyses revealed that poorer quality of life scores were observed in acne relapsers versus non‐relapsers, with a significant difference for CADI scores (p <0.01) in >20‐year‐olds. Acne‐related absenteeism was recorded in 5.7% of cases. On multivariate analyses, after adjusting for other variables, acne relapse was proven a significant determinant of absenteeism/productivity loss.
Conclusion
This real‐life study first demonstrated acne relapse rates of 44%, which appeared to be generation‐dependent, affecting 39.9% of ≤20‐year‐olds versus 53.3% of >20‐year‐olds. Acne relapses were significantly associated with impaired quality of life and productivity loss/absenteeism.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VO4sDY
Methyl aminolevulinate daylight‐photodynamic therapy applied at home for non‐hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany
Abstract
Background
The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL‐PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies.
Objective
To evaluate patient reported outcomes, effectiveness and tolerability of patient self‐applied MAL DL‐PDT.
Patients and methods
An open study was conducted in Germany in patients with thin or non‐hyperkeratotic and non‐pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL‐PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post‐treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded.
Results
Patients (n=50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain, and skin burning sensation).
Conclusions
Patient self‐application of MAL DL‐PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.
This article is protected by copyright. All rights reserved.
http://bit.ly/2QIWSak
Trichoscopic signs in systemic lupus erythematosus: a comparative study with 109 patients and 305 healthy controls
Abstract
Background
Hair and scalp involvement in systemic lupus erythematosus (SLE) can manifest as scarring alopecia, non‐scarring alopecia or scalp/hair shaft changes without apparent hair loss. While trichoscopic signs in chronic cutaneous lupus are well estabished, data on SLE patients with normal‐looking or non‐scarring scalp are limited.
Objectives
To investigate trichoscopic features of SLE patients without chronic cutaneous scalp lesions and compare the findings with normal controls, as well as determine which feature associates with systemic disease. Furthermore, we aim to explore different clinical presentations of the scalp in SLE patients and their association with disease activity.
Methods
Trichoscopic photographs were taken from patients and healthy controls and evaluated by one blinded hair specialist. For SLE patients, their clinical presentations and evaluations for cutaneous, extracutaneous involvement; and SLE Activity Index 2000 (SLEDAI‐2K) score were documented.
Results
109 SLE patients and 305 healthy controls were included. Hair shaft changes were significantly more common in SLE and associated with higher SLEDAI‐2K (P<0.05). The most common feature was prominent arborizing blood vessels (60.6% vs. 18.4%, P<0.001), followed by thick arborizing blood vessels (57.8% vs. 10.2%, P<0.001), black dots (47.7% vs. 2%, P<0.001), brown scattered pigmentation (5.5% vs. 0.7%, P=0.005) and blue grey speckled pigmentation (44% vs.0.3%, P<0.001). When hair loss is diffuse and severe, there were associations with haematologic (P=0.002) and renal involvement (P=0.027 for proteinuria>500 mg/day, P=0.004 for proteinuria>1g/day).
Conclusions
Trichoscopic examination is a valuable tool for SLE diagnosis and monitoring. Severe diffuse non‐scarring alopecia most likely indicates active disease.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VInls4
Crossed looks on the dermatologist's position and the patient's preoccupations as to psoriasis and pregnancy: preliminary results of the PREGNAN‐PSO study
Abstract
Background
While some information on psoriasis impact on pregnancy is available, very little is known on the preoccupations of women afflicted by the disease or on the dermatologists' (D) positioning as to psoriasis and pregnancy. The "Objectifs Peau" project demonstrated a 4.7% prevalence of psoriasis in women aged 18‐45 years in France.
Objective
This project sought to further address these issues in view of a targeted action plan.
Methods
A questionnaire was made available to 361 D of different types.
Results
Overall, 152 D answered the questionnaire, 50.7% working in private or mixed practice and 49.3% in hospitals, with 63% females (DF) and 37% males (DM). Over the last 3 months, the mean percentage of women of child‐bearing age seen by these D was 28.6%. The main issue addressed by D upon psoriasis diagnosis was the patient's wish to become pregnant in the short‐term (84%), while the compatibility of drug treatment with pregnancy was the issue prioritized by patients (64%). Among DM and DF, 46% and 29% reported having been confronted with an unplanned pregnancy, with their reaction mainly dependent on the treatment taken in 66%. Regarding follow‐up, 26% D declared having shared their decision‐making with gynecologists, while 56% considered the first pregnancy trimester to be the highest risk period. Only 28% D were familiar with existing recommendations, with only 21% of them considering them appropriate.
Conclusion
Overall, 26.2% of French psoriasis women are of child‐bearing potential, in line with our dataset (28.6%). Only 56% D considered the 1st pregnancy trimester to be the highest risk period, with only one‐third familiar with existing recommendations. The gap between recommendations and actual practices must be addressed through policies that take women's preoccupations better into account.
This article is protected by copyright. All rights reserved.
http://bit.ly/2QFC8jp
HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa
Abstract
Background
Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses, and fistulas located in apocrine gland–bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used.
Objective
The objective of this study was to demonstrate the validity, reliability, and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome.
Methods
A multicenter, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires (Skindex‐16, Dermatology Life Quality Index [DLQI], Work Productivity and Activity Impairment–General Health [WPAI:GH]) and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS‐PGA).
Results
140 patients (59% women; mean age 34.9±11.0 years) were enrolled in 27 dermatologic centers. HIDRAdisk showed a strong correlation with Skindex‐16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651, and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS‐PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test–retest reliability (Spearman correlation coefficient, 0.8331; p<0.0001), and responsiveness to changes were demonstrated.
Conclusion
Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VLzXib
Demographics, health care utilization, and drug use in children and adults with atopic dermatitis in Denmark: a population‐based cross‐sectional study
Abstract
Background
Atopic dermatitis (AD) is a common inflammatory skin condition. While previous publications have examined health care expenses, large data regarding patient demographics, health care use and drug prescriptions are limited.
Objective
To examine demographics, health care use, and drug prescriptions in children and adults with hospital‐diagnosed AD.
Methods
Danish nationwide registries were cross‐linked to access demographic, healthcare, and drug prescription data on children and adults with hospital‐diagnosed AD (ICD‐10 code L20). The diagnostic code for AD used in this study was validated by reviewing medical charts.
Results
We identified 9704 children (time period 1997 to 2012) and 5558 adults (time period 1997 to 2007) with hospital‐diagnosed AD. The diagnostic code L20 had a positive predictive value of 95%. Among children with AD, a larger proportion came from less resourceful families and had immigrant parents from non‐European countries. In adults, we observed an opposite tendency. Topical and systemic antibiotics were used relatively frequent in both children and adults with AD. The use of prednisolone and other systemic anti‐inflammatory therapy was substantially higher in adults with AD than in children.
Limitations
We were unable to identify and describe patients treated by general and private practitioners.
Conclusion
There exist significant differences in social predictors for AD and the use of AD medication between children and adults with hospital‐diagnosed AD in Denmark. The diagnostic code for AD appears to be valid in Danish registries.
This article is protected by copyright. All rights reserved.
http://bit.ly/2QFlalk
Juvenile ecthyma gangrenosum caused by Pseudomonas aeruginosa revealing an underlying neutropenia: case report and review of the literature
Abstract
Background
Ecthyma gangrenosum (EG) is characterized by the occurrence of erythematous, violaceous or hemorrhagic macules and/or vesicles, often evolving into necrotic ulcers, with a central gray‐black eschar. It is a rare skin condition, usually occurring in immunocompromised patients suffering from bacterial sepsis caused by Pseudomonas aeruginosa. However, seemingly healthy children have been diagnosed with this skin disease as well.
Objectives
We report the work‐up of a case of vulvar EG caused by Pseudomonas aeruginosa in a toddler, which led to a diagnosis of an underlying neutropenia. Moreover, we provide a brief literature review on those cases of EG where an underlying primary immunodeficiency, neutropenia in particular, was eventually diagnosed.
Methods
A one‐and‐a‐half year old girl presented with a history of recurrent (respiratory) infections and the sporadic occurrence of purpuric, vulvar ulcers. Work‐up consisted of microbiological and haematological investigations, including repeated blood analyses.
Results
Bacterial swabs from the vulvar ulcers showed the growth of Pseudomonas aeruginosa. No concomitant sepsis was present, but laboratory investigations pointed towards a cyclic neutropenia, coinciding with the occurrence of the EG lesions. Topical gentamicine ointment allowed the skin lesions to heal faster. Following the administration of granulocyte‐colony stimulating factor (GCS‐F), the girl experienced less infections in general and had no recurrence of EG lesions in particular. Treatment with GCS‐F could eventually be stopped, and the neutropenia, ultimately transient in nature, completely resolved.
Conclusion
Children presenting with (anogenital) EG should always alert a physician to consider a potentially underlying immunodeficiency, neutropenia in particular.
This article is protected by copyright. All rights reserved.
http://bit.ly/2VHWlJg
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
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 xC− 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
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