ORL 2018;80:221
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Τρίτη 27 Νοεμβρίου 2018
Diagnosis and Management of Immune Checkpoint Inhibitor‐Associated Neurologic Toxicity: Illustrative Case and Review of the Literature
AbstractImmune checkpoint inhibitors (ICIs) initiate antitumor immunity by blocking the action of immune inhibitor‐signaled cytotoxic proteins, such as cytotoxic T‐lymphocyte‐associated protein 4, programmed cell death protein 1, and programmed cell death ligand 1. However, in rare cases (∼1%–12% of patients), ICI treatment causes neurologic immune‐related adverse events (irAEs). These include, but are not limited to, headache, encephalitis, neuropathies, myasthenia gravis, and myositis. The symptoms associated with irAEs can range from mild (grade 1–2) to severe (grade 3–4); however, they are often challenging to diagnose because they may present as generalized symptoms, such as fatigue and weakness, that can also be caused by the cancer itself. Here, we present an illustrative case of a 67‐year‐old woman who presented with signs of a neurologic irAE, including progressive dysphagia and weakness leading to falls, which started during treatment with pembrolizumab and worsened following initiation of ipilimumab. Following neurological and pathological evaluation, she was diagnosed with myositis. She was treated with steroids and improved rapidly. In this article, we review previous literature to provide guidance to frequently asked questions concerning the diagnosis and management of neurologic irAEs in patients with advanced cancer. With prompt and effective treatment, most patients will achieve a complete recovery.Key Points. Neurologic immune‐related adverse events (irAEs) affect approximately 1% of patients treated with immune checkpoint inhibitor (ICI) monotherapy and 2%‐3% treated with combination therapy. These irAEs can affect any portion of the nervous system, although peripheral nerve system manifestations are most common. Overlap syndromes with multiple neurologic irAEs or other affected organ systems frequently exist.Diagnosis of neurologic irAEs can be challenging. Routine testing may be unremarkable and symptoms frequently mimic those from cancer or side effects of other therapies. Optimal management is currently unknown. A systematic, highly coordinated, and multidisciplinary approach is critical.Outcomes from neurologic irAEs are typically favorable with the current practice of holding the ICI and starting corticosteroids. Some patients are even successfully retreated with an ICI. A subset of patients, however, have a fulminant and potentially fatal course.Improved risk assessments and targeted therapies are needed.
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High‐Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study
AbstractBackground.High‐grade neuroendocrine carcinomas are rare in the gastrointestinal tract. However, treatment patterns and outcomes have not been well described.Subjects, Materials, and Methods.The National Cancer Database was analyzed. The primary objective was to describe the clinical outcomes and identify prognostic factors. Univariate and multivariate analyses were done to identify factors associated with patient outcome.Results.A total of 1,861 patients were identified between 2004 and 2013. The mean age was 63 years (standard deviation ±13). The majority of the patients (78.1%) were non‐Hispanic whites. The most common primary sites were pancreas (pancreatic neuroendocrine tumor [PNET] = 19.4%), large intestine (18.1%), esophagus (17.8%), and rectum (15.5%). Stage at presentation was I (6.6%), II (10.5%), III (18%) and IV (64.6%). Only 1.6% of the patients had brain metastases. Surgical resection was the primary therapy in 27.9%, and their median overall survival (OS) was 13.3 months. Patients treated with palliative chemotherapy had a median OS of 11.2 months, compared with 1.7 months for untreated patients. The median OS for high‐grade PNET was 6 months, compared with 9.9 months for other high‐grade gastrointestinal neuroendocrine carcinomas (HG GI NEC). On univariable analysis, age < 65 years (hazard ratio [HR] 0.72; 0.66–0.8; p < .001) and treatment at an academic center (HR 0.88; 0.79–0.99; p < .034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center.Conclusion.This is the largest series of HG GI NEC. Most patients present with metastatic disease, and overall survival remains poor. Treatment at an academic center, younger age, and use of chemotherapy were associated with improved survival. Multiagent chemotherapy was found to be associated with superior survival compared with single‐agent chemotherapy, which was superior to no chemotherapy. Temporal sequences of chemotherapy, surgery, and radiation administration were not found to be associated with survival differences on multivariable analysis.Implications for Practice.Management of patients with high‐grade gastrointestinal neuroendocrine carcinomas (HG GI NEC) is based on experience with small‐cell lung cancer. In this retrospective review, most patients had advanced disease and pancreatic primary had worse outcomes. Treatment at an academic center, younger age, and use of chemotherapy are associated with improved survival. Patients with early‐stage disease treated with resection alone had inferior outcomes compared with patients who received neoadjuvant or adjuvant therapy, suggesting that micrometastases contribute to poor surgical outcomes. The relatively high proportion of positive surgical margin favors downstaging with neoadjuvant therapy to improve resection and lower the risk of systemic recurrence.
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A family with PTEN mutations with malignancy and an unusually high number of offspring with autism spectrum disorder: a case report
Cowden's syndrome (OMIM:158350), a rare genetic disorder (incidence ~ 1:250,000), is caused by mutations of the tumor suppressor gene PTEN. In this report, we describe clinical manifestations of a 56-year-old pat...
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Change in endolymphatic hydrops 2 years after endolymphatic sac surgery evaluated by MRI
This study was performed to determine whether endolymphatic sac surgery improves vestibular and cochlear endolymphatic hydrops 2 years after sac surgery and to elucidate the relationship between the degree of improvement of endolymphatic hydrops and the changes in vertigo symptoms, the hearing level, and the summating potential/action potential ratio (−SP/AP ratio) by electrocochleography (ECochG) in patients with Ménière's disease (MD).
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Mycotoxins in poultry feed and feed ingredients in Nigeria
Abstract
Mycotoxins are toxic secondary fungal metabolites that can negatively affect animal productivity when ingested through feed. In order to assess mycotoxin contamination of poultry feed and feed ingredients vis-a-vis source tracking of feed contamination in Nigeria, 102 samples of feed (n = 30) and feed ingredients (n = 72) were collected from in-house mills of poultry farms across 12 states of Nigeria and analyzed for multiple mycotoxins using LC/MS-MS. One hundred and forty microbial metabolites were detected in the feed and feed ingredients. The most frequent mycotoxin in the feed was fumonisin B1, occurring in 97% of the samples at mean concentration of 1014 μg kg−1. AFB1 occurred in 83% of the feed samples at mean concentration of 74 μg kg−1 and in all feed ingredients except fish meal and other cereals (millet and rice). Feed samples analyzed in this study were contaminated with at least four mycotoxins: aflatoxins and fumonisin co-occurring in 80% of the samples. Peanut cake and maize contributed the most to the levels of aflatoxin and fumonisin, respectively, in the feed. Consequently, there is a need to explore other cereal- and protein-based ingredients for compounding feeds in order to reduce the risk associated with high mycotoxin (e.g. aflatoxin) intake in poultry.
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A Systematic Review and Meta-Analysis of Subsequent Malignant Neoplasm Risk After Radioactive Iodine Treatment of Thyroid Cancer
Thyroid, Ahead of Print.
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Role of Leucine 341 in Thyroid Hormone Receptor Beta Revealed by a Novel Mutation Causing Thyroid Hormone Resistance
Thyroid, Ahead of Print.
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How Should Thyroid-Related Quality of Life Be Assessed? Recalled Patient-Reported Outcomes Compared to Here-and-Now Measures
Thyroid, Ahead of Print.
https://ift.tt/2SaIhVW
An Age-Specific Serum Thyrotropin Reference Range for the Diagnosis of Thyroid Diseases in Older Adults: A Cross-Sectional Survey in China
Thyroid, Ahead of Print.
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Smartphone telemedical emergency department consults for screening of nonacute dizziness
Objectives/Hypothesis
Each year, the United States spends over $4 billion on emergency department visits for evaluation of dizziness. Benign paroxysmal positional vertigo (BPPV) is a common cause of dizziness that can easily be diagnosed by observing characteristic eye movements during the Dix‐Hallpike test (DHT). The DHT is easily performed; however, interpretation requires more advanced training. This may be part of the reason it is not commonly performed in emergency departments, and instead, patients undergo costly imaging tests. We evaluated whether smartphone‐based video recordings of DHT could be assessed telemedically for screening of nonacute dizziness.
Study Design
Feasibility study.
Methods
Dizzy patients underwent objective vestibular testing, but also had videos of their eye movements recorded via a smartphone during the DHT. The videos were remotely reviewed by two neuro‐otologists for BPPV screening and were compared to objective and in‐person exam findings.
Results
Overall, 30 dizzy patients were evaluated with seven cases of BPPV. The sensitivity for diagnosing BPPV via a smartphone‐recording of eye movements of the DHT was 92.86%, with a specificity of 100% and a negative predictive value of 97.87%.
Conclusions
Our initial proof‐of‐concept study shows that remote screening of BPPV is possible with high specificity. Because the DHT is easily taught, having a remote otolaryngologist interpret the resulting eye movements may increase usage of the test and may lead to cost savings.
Level of Evidence
4 Laryngoscope, 2018
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Antileukotrienes improve naso‐ocular symptoms and biomarkers in patients with NARES and asthma
Objective
The aim of our study was to analyze the montelukast effectiveness in improving oculonasal symptoms, patient‐reported outcomes (PROs), and eosinophilic biomarkers in patients with nonallergic rhinitis eosinophilic syndrome (NARES).
Methods
We enrolled prospectively 80 symptomatic patients treated with 10 mg once a day of montelukast in monotherapy for 2 months. All patients were investigated before and after treatment. Nasal symptoms (nasal obstruction, rhinorrhoea, sneezing, nasal itching), ocular symptoms (redness/puffiness, watery eyes), and other PROs (olfactory dysfunction, difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening) were scored by visual analogic scale. The following clinical scores were assessed: Total Nasal Symptom Score (T4NSS), Total Ocular Symptom Score (T2OSS), Total Symptom Score of Patient‐Reported Outcomes (TSS‐PROs), and a Composite Symptoms Score (CSS). Patients were classified as responders when a reduction of at least 50% of the CSS was observed. Before and after treatment, the eosinophilic biomarkers in nasal lavage were analyzed: nasal eosinophilia (number of eosinophils per high power field), eotaxin‐1 and eotaxin‐2.
Results
After treatment, significant reductions were observed for all the symptom scores. Forty‐two of 78 patients were considered responders. A significant reduction of eosinophils in nasal mucosa and of levels of eotaxin‐1 and eotaxin‐2 in nasal lavage were observed after treatment in responder patients. Patients with asthma had an increased probability to be responders.
Conclusion
NARES patients may benefit from treatment with montelukast. In particular, the presence of concomitant asthma may be predictive of a greater efficacy.
Level of Evidence
2. Laryngoscope, 2018
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Automated Quantification of Vocal Fold Motion in a Recurrent Laryngeal Nerve Injury Mouse Model
Objectives/Hypothesis
The goal of this study was to objectively examine vocal fold (VF) motion dynamics after iatrogenic recurrent laryngeal nerve (RLN) injury in a mouse surgical model. Furthermore, we sought to identify a method of inducing injury with a consistent recovery pattern from which we can begin to evaluate spontaneous recovery and test therapeutic interventions.
Study Design
Animal model.
Methods
The right RLN in C57BL/6J mice was crushed for 30 seconds using an aneurysm clip with 1.3‐N closing force. Transoral laryngoscopy enabled visualization of VF movement prior to surgery, immediately post‐crush, and at two endpoints: 3 days (n = 5) and 2 weeks (n = 5). VF motion was quantified with our custom motion‐analysis software. At each endpoint, RLN samples were collected for transmission electron microscopy for correlation with VF motion dynamics.
Results
Our VF tracking software permitted automated quantification of several measures of VF dynamics, such as range and frequency of motion. By 2 weeks post‐injury, the frequency of VF movement on the right (injured) side equaled the left, yet range of motion only partially recovered. These objective outcome measures enabled detection of VF dysfunction that persisted at 2 weeks post‐crush. Transmission electron microscopy images revealed RLN degeneration 3 days post‐crush and partial regeneration at 2 weeks, consistent with functional results obtained with automated VF tracking.
Conclusions
Our motion‐analysis software provides novel objective, quantitative, and repeatable metrics to detect and describe subtle VF dysfunction in mice that corresponds with underlying RLN degeneration and recovery. Adaptation of our tracking software for use with human patients is underway.
Level of Evidence
NA Laryngoscope, 2018
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Surgery of the major salivary glands and its impact on salivary flow—A review
Objective
The aim of this study was to bring attention to a rather unnoted side effect of salivary gland surgery–reduced salivary flow.
Methods
A systematic PubMed, Cochrane Library, LIVIVO, and Embase databases search was performed to identify relevant articles.
Results
Eight studies matched the inclusion criteria. All studies described an association between salivary gland surgery and reduced salivary flow. In five of the eight studies, patients reported on xerostomia after salivary gland surgery.
Conclusions
Head and neck surgeons should inform their patients more accurately about reduced salivary flow and possible xerostomia after salivary gland surgery, and focus more on conservative strategies and minimally invasive techniques. Laryngoscope, 2018
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Missing canines: a novel aetiology
Abstract
Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of one year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub‐Saharan East Africa.
This article is protected by copyright. All rights reserved.
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Patient reported outcome measures in forty‐three patients undergoing endoscopic middle ear surgery
Abstract
1.PROMs are a useful technique to assess patient experience of middle ear surgery
2.Endoscopic ear surgery patients report better scar discomfort score
3.Endoscopic and open ear surgery patients report equivalent pain scores
4.Endoscopic and open ear surgery patients report equivalent overall patient experience
This article is protected by copyright. All rights reserved.
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Induction of smell through transethmoid electrical stimulation of the olfactory bulb
Background
Anosmia has an estimated prevalence of 5% of the general population. Outside of inflammatory causes, therapeutic options are limited despite research advances. Bypassing peripheral neuronal damage through central stimulation is a potential therapeutic option that has shown success in other sensory systems, most notably with hearing. We performed a pilot study to determine the feasibility of inducing smell through artificial electrical stimulation of the olfactory bulbs in humans.
Methods
Subjects with a history of sinus surgery, including total ethmoidectomy, with intact ability to smell were enrolled. The ability to smell was confirmed with a 40‐item smell identification test. Awake subjects underwent nasal endoscopy and either a monopolar or bipolar electrode was positioned at 3 areas along the lateral lamella of the cribriform plate within the ethmoid sinus cavity. A graded stimulation current of 1–20 mA at 3.17 Hz was administered while cortical evoked potential (CEP) recordings were collected. Subjective responses of perceived smell along with reports of discomfort were recorded. Subjects with artificially induced smell underwent repeat stimulation after medically induced anosmia.
Results
Five subjects (age, 43–72 years) were enrolled. Three subjects reported smell perception smell with electrical stimulation. This was reproducible after inducing anosmia, but CEP recordings could not provide objective support. All subjects tolerated the study with minimal discomfort.
Conclusion
This is the first report of induced smell through transethmoid electrical stimulation of the olfactory bulb. These results provide a proof of concept for efforts in development of an olfactory implant system.
https://ift.tt/2BBIkEM
Therapeutic use of steroids in non–chronic rhinosinusitis olfactory dysfunction: a systematic evidence‐based review with recommendations
Background
Olfactory loss is a common and debilitating disease with limited treatment options, particularly for olfactory dysfunction not related to sinonasal inflammation. Both topical and systemic steroids have been used as treatments for olfactory loss. This study systematically reviews the literature on the efficacy of steroids for non–chronic rhinosinusitis (CRS)‐related olfactory loss and provides recommendations.
Methods
A literature search of PubMed, Ovid, EMBASE, and the Cochrane Database was performed according to Preferred Reporting Items for Systematic Review and Meta‐Analyses (PRISMA) guidelines. Inclusion criteria included original data, English‐language articles on steroid treatment (topical and systemic) for olfactory loss unrelated to sinonasal inflammation. Data was collected on study design, olfaction dysfunction etiology, clinical outcomes, and level of evidence. Two investigators reviewed all articles independently, with a third acting as a mediator for any disagreements in recommendation.
Results
Of 866 abstracts identified, only 15 studies met inclusion criteria and were systematically reviewed. Level 4 evidence suggests oral steroids can improve olfactory loss. Level 1B evidence demonstrates topical steroid rinses improve olfactory dysfunction in a select group of patients. Topical steroid sprays show no improvement across several levels of evidence.
Conclusion
There is a paucity of high‐quality studies demonstrating efficacy of either topical or oral steroids for olfactory dysfunction unrelated to sinonasal disease. The only level 1 evidence suggests using steroid rinses to improve olfactory outcomes in select patients, with weaker evidence supporting use of oral steroids. Topical steroid sprays do not improve olfactory dysfunction in this patient population and are not recommended.
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Ivacaftor improves rhinologic, psychologic, and sleep‐related quality of life in G551D cystic fibrosis patients
Background
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that improves pulmonary function in cystic fibrosis (CF) patients with at least 1 copy of the G551D CFTR mutation. The purpose of this study is to evaluate the impact of ivacaftor on chronic rhinosinusitis (CRS) symptoms in this population.
Methods
The G551D Observational (GOAL) study was a multicenter prospective cohort study enrolling CF patients ≥6 years with at least 1 G551D mutation. Subjects were provided 20‐item Sino‐Nasal Outcome Test (SNOT‐20) questionnaires prior to ivacaftor therapy and at 1, 3, and 6 months afterward. The impact on rhinologic (R), psychological (P), sleep (S), and ear/facial (E) quality of life (QOL) domains was evaluated separately.
Results
Of 153 subjects, 129 (84%) completed all questionnaires. Typical baseline symptom burden was low (75% with scores <1) and degree of improvement (ie, reduced scores) was greater with higher baseline scores. SNOT‐20 decreased, reflecting improvement, at all follow‐up intervals (1 month: [mean change ± standard deviation] –0.25 ± 0.53, p < 0.01; 3 months; –0.29 ± 0.58, p < 0.01; 6 months: –0.21 ± 0.58, p = 0.02), but less than the prespecified minimal clinically important difference (0.8). Significant improvement was observed at 1, 3, and 6 months in the R domain (1 month: –0.24, p < 0.01; 3 months: –0.34, p < 0.01; 6 months: –0.25, p < 0.01) and P domain (1 month: –0.25, p < 0.01; 3 months: –0.32, p < 0.01; 6 months: –0.26, p < 0.01), and 1 and 3 months in the S domain (1 months: –0.35, p < 0.01; 3 months: –0.32, p < 0.01; 6 months: –0.18, p = 0.07). There was no improvement in the E domain at any time point.
Conclusion
Ivacaftor improves QOL in the R, P, and S domains in G551D CF patients, although QOL instruments validated for CRS may not translate well to CF CRS patients because symptom burden was surprisingly low.
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Interleukin‐4‒induced posttranscriptional gene regulation of CCL26 by the RNA‐binding protein HuR in primary human nasal polyp‒derived epithelial cells
Background
Much attention on the pathophysiology of nasal polyp (NP) has focused on eosinophils. Interleukin (IL)‐4 and eotaxin‐3 (C‐C motif chemokine ligand 26, or CCL26) levels have been reported to be increased in eosinophilic nasal polyps. The aim of this study was to characterize CCL26 posttranscriptional regulation by the RNA‐binding protein HuR in primary human nasal polyp‒derived epithelial cells (hNPDECs) challenged with IL‐4.
Methods
A prospective, observational study was conducted. Nasal polyp tissues were obtained from eosinophilic (n = 12) and non‐eosinophilic (n = 10) NP patients, and inferior turbinate (IT) tissues were taken from control subjects (n = 9) and cultured into hNPDECs. Expression of HuR and CCL26 were measured by immunohistochemistry, Western blot analysis, enzyme‐linked immunoassay, and real‐time polymerase chain reaction (PCR). The nucleocytoplasmic shuttling of HuR in hNPDECs was detected by immunofluorescence. Posttranscriptional regulation of CCL26 by HuR was tested by ribonucleoprotein immunoprecipitation assay (RIP) and dual‐luciferase reporter assay. CCL26 mRNA stabilization was measured by quatititative PCR after treatment with actinomycin D. Student's t test and one‐way analysis of variance were used.
Results
Immunohistochemical data show that both HuR and CCL26 were highly expressed in NP tissues, especially eosinophilic NP tissues (p < 0.05). IL‐4 stimulation increased CCL26 mRNA stability, and overexpression and knockdown of HuR affected CCL26 expression. Immunofluorescence data indicate that IL‐4 altered the subcellular distribution of HuR. The RIP and dual‐luciferase reporter assay results supply strong evidence for HuR binding to CCL26.
Conclusion
Our results provide strong support for the hypothesis that IL‐4‒induced expression of CCL26 in hNPDECs relies partly on CCL26 mRNA stabilization mediated by the interaction of HuR with CCL26 3'UTR.
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Squamous cell carcinoma of the nail unit: a retrospective review of 19 cases in Asia and comparative review of Western literature
Abstract
Background
Reports regarding squamous cell carcinoma of the nail unit (SCCnu) are rare in Asia.
Objectives
To investigate the features of SCCnu in the Asian population.
Method
We performed a retrospective review of patients diagnosed with SCCnu at our institution between 2012 and 2017.
Results
Nineteen cases were included. Thirteen patients were male (68.4%). The fingers were most frequently affected (73.7%). Mean delay to diagnosis was 62.4 months. Misdiagnosis rate was high (78.9%). Frequent clinical features were subungual tumor, subungual hyperkeratosis, nail dystrophy, ulcer, and nail loss. The majority of cases were invasive SCC in 15 cases (78.9%), while SCC in situ was found in four cases (21.1%). Local recurrence was detected in two cases (10.5%) following surgical resection. However, distant metastasis was not reported.
Conclusion
This study provides data of 19 SCCnu cases in Asia. Clinical characteristics of SCCnu in this study were similar to those of reports from Western countries. However, we found a higher frequency of more invasive cases and longer delay to diagnosis in our study; this advocates the need for greater attention on nail disorders among healthcare providers, particularly in Asia.
https://ift.tt/2BAz4RB
The use of electrochemotherapy in combination with immunotherapy in the treatment of metastatic melanoma: a focused review
Abstract
Electrochemotherapy (ECT) is a treatment modality that combines low‐dose chemotherapy with electroporation, thereby enhancing cytotoxicity. ECT was first utilized in the treatment of metastatic head and neck cancer. Today it is used as a local treatment for the cutaneous and subcutaneous metastases of a variety of cancers, including melanoma. In addition, recent evidence indicates that ECT in combination with immunotherapy can lead to a systemic tumor response. This review aims to summarize the efficacy of ECT in the treatment of metastatic melanoma, with a specific focus on the combination of ECT with immunotherapy.
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Skin disorders are prominent features in primary immunodeficiency diseases: a systematic overview of current data
Abstract
Primary immunodeficiency diseases (PIDs) are characterized by an increased risk of infections, autoimmunity, autoinflammation, malignancy and allergic disorders. Skin disorders are also common clinical features in PIDs and may be among the presenting manifestations. Recognition of specific PID‐associated skin conditions in combination with other clinical features as described in the currently used warning signs could raise suspicion of an underlying PID. We aimed to provide a systematically obtained overview of skin disorders and their prevalence in PIDs. Secondary, the prevalence of Staphylococcus (S.) aureus‐associated skin disorders and atopy were reviewed, as these are the most prominent skin features in PIDs. A systematic search was performed in Embase, Medline, Web of Science, Cochrane and Google Scholar (up to May 9th 2018). All original observational and experimental human studies that address the presence of skin disorders in PIDs were selected. We rated study quality using the Institute of Health Economics Quality Appraisal Checklist for Case Series Studies. Sixty‐seven articles (5030 patients) were included. Study quality ranged from 18.2‐88.5%. A broad spectrum of skin disorders was reported in 30 PIDs, mostly in single studies with a low number of included patients. An overview of associated PIDs per skin disorder was generated. Data on S. aureus‐associated skin disorders and atopy in PIDs were limited. In conclusion, skin disorders are prominent features in PIDs. Through clustering of PIDs per skin disorder, we provide a support tool to use in clinical practice that should raise awareness of PIDs based on presenting skin manifestations.
This article is protected by copyright. All rights reserved.
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Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug exacerbated respiratory disease
Abstract
Background
Most patients with nonsteroidal anti‐inflammatory drug exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD.
Methods
We collected nasal polyp tissue from patients with NERD and from patients with aspirin‐tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2‐dimensional electrophoresis and identified several proteins, including L‐plastin, as highly expressed. We examined L‐plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L‐plastin in eosinophils, we knocked down L‐plastin expression in Eol‐1 cells by using siRNA transfection.
Results
L‐plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L‐plastin was dominantly expressed in eosinophils and L‐plastin and TF were co‐expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L‐plastin in Eol‐1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony‐stimulating factor.
Conclusions
Increased expression of L‐plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.
This article is protected by copyright. All rights reserved.
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Membrane‐enriched solute carrier family 2 member 1 (SLC2A1/GLUT1) in psoriatic keratinocytes confers sensitivity to 2‐deoxy‐D‐glucose (2‐DG) treatment
Abstract
Psoriasis is a common chronic disease with accelerated epidermal cell growth. Solute carrier family 2 member 1 (SLC2A1), also named GLUT1, transports glucose and its analogues into cells. With elevated membrane‐bound GLUT1, psoriatic keratinocytes uptake more glucose with increased glucose metabolism. Competition between glucose and its analogues can serve as a strategy to inhibit glycolysis as well as proliferation. In this study, we investigated the expression patterns of GLUT1 in keratinocytes in the human psoriasis vulgaris and imiquimod‐induced psoriasis model, and determined that the glucose metabolism inhibitor 2‐deoxyglucose (2‐DG) can relieve the psoriatic lesions. We found membrane‐enriched GLUT1 in psoriasis keratinocytes, which suggested some potential for glucose metabolic target therapy based on the glycolytic microenvironment. Furthermore, 2‐DG was able to relieve the psoriatic lesions in an in vivo animal model which provides a new possible therapeutic strategy.
This article is protected by copyright. All rights reserved.
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Student Elective Competition 2018/19: A call for entries
We are now launching the 2018/19 competition for students and interns. Write up your experiences as a global health case report and you could be the winner of a position as a Global Health Associate Editor for BMJ Case Reports.
All authors must be students or interns at the time of submission.
Your entry will undergo the same treatment that all our journal submissions do, including the peer review process, so be sure to check out our Instructions for Authors for guidance before you start writing. If you've never written a global health case report before, you may find our Global Health section useful to help you get started.
Winners will be selected for interview to become a Global Health Associate Editor. We welcome submissions from all over the world. Patients may be anyone seen on the ward or at home, in medical school or on elective. Winners will be announced in September 2019.
Global Health Associate Editors will have the chance to contribute to our global health blog, help manage our social media presence and collaborate on special global health projects.
The post Student Elective Competition 2018/19: A call for entries appeared first on BMJ Case Reports blog.
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Guselkumab in the treatment of severe Hidradenitis suppurativa
Abstract
Hidradenitis suppurativa (HS) is a chronic skin disease characterized by auto‐inflammation resulting in abscesses, nodules, fistula and scaring in the affected areas. It is known as one of the most life restricting diseases in dermatology with highly negative effects regarding the DLQI.
Despite the uprising therapeutic approaches available for HS, there is still a need for more effective medications to treat this auto‐inflammational disease.
This article is protected by copyright. All rights reserved.
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Trigger finger in a hereditary multiple exostoses disease: A unique case report
Abstract
Trigger finger is one of the most common upper extremity problems seen by hand surgeons. Lesions occupying space in the tendon bed can prevent tendon gliding. We describe a unique case of trigger finger in a patient known for a hereditary multiple exostoses disease where an exostosis in the tendon bed constricted the tendon sheath, leading to triggering and locking. Open surgical treatment was performed by removing of the exostosis which relieved the problem.
Level of Evidence: Level V, therapeutic study.
https://ift.tt/2TPDNWv
Microvascular Capillary Plexus Findings of Commotio Retinae on Optical Coherence Tomography Angiography
Optical coherence tomography (OCT) and histopathology features of commotio retinae (CR) have been established, but alterations of the microvascular macular capillary plexus on OCT angiography (OCTA) has not been previously studied. We present a 46-year-old man who sustained a tennis ball injury to the right eye with visual acuity reduction to 20/30 and grey-white deep macular discoloration, suggestive of CR. Spectral-domain OCT (SD-OCT) showed increased reflectivity and thickness of the ellipsoid zone (junction of photoreceptor inner and outer segments). OCTA revealed no apparent microvascular alterations (right versus left eye) in the foveal avascular zone superficial (0.42 vs. 0.43 mm2) and deep (0.45 vs. 0.44 mm2), superficial foveal capillary density (34.1 vs. 32.6%), and superficial parafoveal capillary density (55.2 vs. 52.2%). Deep macular capillary plexus and choriocapillaris were qualitatively comparable between the two eyes. At 2 months' follow-up, SD-OCT had normalized. CR is characterized by disruption of the ellipsoid zone without detectable alteration of the capillary plexuses.
Case Rep Ophthalmol 2018;9:473–478
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Severe vemurafenib‐induced photosensitivity in a 6‐year‐old boy
Abstract
Vemurafenib, a selective BRAF kinase inhibitor, has been found to induce several cutaneous adverse effects, ranging from a keratosis pilaris‐like reaction to squamous cell carcinoma. While photosensitivity has been well described as one of these manifestations, we report a case of a 6‐year‐old boy on vemurafenib who developed a severe blistering sunburn after only two 30‐minute episodes of sun exposure. A brief review of other common cutaneous adverse effects of vemurafenib is also provided.
https://ift.tt/2AstZsN
Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men
Abstract
Objective
Low endogenous sex hormones and low physical activity (PA) levels have been associated with CVD risk. Whether these interact to influence CVD outcomes remains unclear. We assessed whether sex hormone concentrations and PA were additively associated with lower central adiposity and CVD risk.
Patients
3,351 community‐dwelling men, mean age 77 years.
Measurements
Baseline testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) were assayed. Levels of PA were ascertained by questionnaire. Men were stratified using median splits into high hormone+high PA (H/H), high hormone+low PA (H/L); low hormone+high PA (L/H) and low hormone+low PA (L/L) groups.
Results
865 CVD events and 499 CVD deaths occurred during 10‐year mean follow‐up. Men with higher T, DHT or SHBG and higher PA had the lowest BMI, waist circumference and risk of metabolic syndrome. Men with higher T had the lowest risk of incident CVD events, irrespective of PA level. Men with higher T or DHT and higher PA had the lowest risk of dying from CVD (e.g. hazard ratios for T/PA H/H 0.76 p=0.031; H/L 0.85 p=0.222; L/H 0.80 p=0.075; L/L 1.00).
Conclusion
Higher circulating androgens and higher PA were associated with less central adiposity at baseline and fewer CVD deaths during follow‐up. These findings are consistent with a potential additive effect of androgens and PA on cardiometabolic outcomes in older men.
This article is protected by copyright. All rights reserved.
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Highlights and recent developments in airway diseases in EAACI journals (2017)
The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to supp...
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Erratum: Eingewachsene Zehennägel – Optionen für die tägliche Praxis
Erratum zu:
Hautarzt 2018
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Sehr geehrte Leserin, sehr geehrter Leser,
in der Abbildungslegende von Abb. 2 des oben genannten Beitrags fehlt leider der Copyrightverweis zu Abb. 2b.
Wir bitten Sie, den Fehler zu entschuldigen und zukünftig die korrigierte Version …
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Estrogen associated with UVB irradiation recapitulates the specific melanosome distribution observed in Caucasoid Melasma
Abstract
Melasma is characterized by light to dark brown macules that usually occur on the face. Melasma occurs in 10‐15% of pregnant women and in 10‐25% of women taking oral contraceptives. Fertile women are most likely to develop melasma. Histological examination of melasma lesional skin revealed mainly pigmentary disorders with an increased melanin deposition in all layers of the epidermis including the horny layer and a frequent presence of melanophages in the dermis. On the other hand in the upper dermis, a disruption of the basement membrane in 3.9% of cases, an abundance of elastotic material and an increased number of blood vessels and mast cells have been reported in melasma.
This article is protected by copyright. All rights reserved.
https://ift.tt/2KFvR6g
Estrogen associated with UVB irradiation recapitulates the specific melanosome distribution observed in Caucasoid Melasma
Abstract
Melasma is characterized by light to dark brown macules that usually occur on the face. Melasma occurs in 10‐15% of pregnant women and in 10‐25% of women taking oral contraceptives. Fertile women are most likely to develop melasma. Histological examination of melasma lesional skin revealed mainly pigmentary disorders with an increased melanin deposition in all layers of the epidermis including the horny layer and a frequent presence of melanophages in the dermis. On the other hand in the upper dermis, a disruption of the basement membrane in 3.9% of cases, an abundance of elastotic material and an increased number of blood vessels and mast cells have been reported in melasma.
This article is protected by copyright. All rights reserved.
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Oral benign neoplasms: A retrospective study of 790 patients over a 14-year period
Publication date: Available online 27 November 2018
Source: Acta Otorrinolaringológica Española
Author(s): Luiz Arthur Barbosa da Silva, Eduardo Alonso Cruz Monroy, Marianna Sampaio Serpa, Lélia Batista de Souza
Abstract
Introduction and objective
Oral benign neoplasms (OBNs) exhibit some features that can guide the professionals to the correct diagnosis and best treatment. Through retrospective studies, medical records can be reviewed to better describe a given population and, furthermore, help clinicians in routine practice. In this context, the objective of this paper was to analyze the cases of OBNs of an oral pathology referral department, from 2003 to 2017, in order to better understand their epidemiological and clinicopathological characteristics.
Methods
A total of 8355 histopathological reports were analyzed. Lesions diagnosed as OBNs were selected and the following variables were recorded: gender, age, histological type of the lesion, anatomical location, rate and pattern of growth, type of base, color, symptomatology and diagnostic hypotheses on clinical examination.
Results
OBNs represented 9.4% of all lesions diagnosed. The most frequent histopathological types were fibroma (39.9%), papilloma (22%), fibroblastoma (13.1%), lipoma (10.2%) and hemangioma (6.1%). Overall, most cases affected females (n = 518; 65.6%) and in the fifth decade of life (n = 148; 18.7%). The oral mucosa was the most common site (n = 265; 33.5%). The most common features of each OBN were also highlighted.
Conclusion
The most common OBNs were fibroma, papilloma, fibroblastoma, lipoma and hemangioma. Overall, the OBN presented common clinical features; however, in particular cases, there are some characteristics that can lead the professionals to the correct diagnosis. Nevertheless, in general, histopathological analysis must be performed to confirm diagnosis. Intraosseous tumors and large lesions may require imaging tests to help diagnosis.
Resumen
Introducción y objetivos
Las neoplasias benignas orales (NBO) presentan características clínico-patológicas específicas que pueden guiar al profesional al diagnóstico correcto y a un mejor tratamiento. Los estudios retrospectivos son uno de los principales recursos utilizados para conocer la situación actual de una población determinada y estimar sus necesidades para la implementación y el mantenimiento de los servicios de salud. En este contexto, el objetivo de este trabajo fue analizar los casos de NBO de un servicio de referencia en patología oral, de 2003 a 2017, para comprender mejor sus características epidemiológicas y clínico-patológicas.
Métodos
se analizaron un total de 8355 informes histopatológicos. Se seleccionaron las lesiones diagnosticadas como NBO y se registraron las siguientes variables: sexo, edad, tipo histológico de la lesión, ubicación anatómica, índice y patrón de crecimiento, tipo de base, color, sintomatología e hipótesis diagnósticas en el examen clínico.
Resultados
Las NBO representaron el 9,4% de todas las lesiones diagnosticadas. Los tipos histopatológicos más frecuentes fueron fibroma (39,9%), papiloma (22%), fibroblastoma (13,1%), lipoma (10,2%) y hemangioma (6,1%). También fueron verificados el perfil de los pacientes y las presentaciones clínicas de estas lesiones.
Conclusiones
Las NBO más comunes fueron fibroma, papiloma, fibroblastoma, lipoma y hemangioma. En general, las NBO presentaron características clínicas comunes; sin embargo, en casos particulares, existen algunas características que pueden llevar al profesional al diagnóstico correcto. Sin embargo, de forma general, el análisis histopatológico debe hacerse para confirmar el diagnóstico. Los tumores intraóseos y las lesiones de gran tamaño pueden requerir exámenes de imagen para ayudar al diagnóstico.
https://ift.tt/2RfTB35
The lncRNA H19/miR-675 axis regulates myocardial ischemic and reperfusion injury by targeting PPARα
Publication date: January 2019
Source: Molecular Immunology, Volume 105
Author(s): Hong Luo, Jing Wang, Donghai Liu, Suhua Zang, Ning Ma, Lixuan Zhao, Liang Zhang, Xin Zhang, Chenhui Qiao
Abstract
Increasing evidence has indicated that lncRNAs and miRNAs play important roles in the pathogenesis of myocardial ischemic and reperfusion (I/R) injury. This study investigated the potential roles and underlying molecular mechanisms of lncRNA H19 and H19-derived miR-675 in regulating myocardial I/R injury in vitro and in vivo. The results showed that expression of H19 and H19-derived miR-675 was upregulated in cardiomyocytes exposed to oxygen-glucose deprivation and reperfusion. Knockdown of H19 increased cell viability, reduced cell apoptosis, decreased inflammatory cytokines (IL-1β, TNF-α and IL-6), inhibited oxidative stress, downregulated p-IκB-α and p-p65, and upregulated expression of Nrf2 and HO-1. All of these effects were partly reversed by overexpression of miR-675. Furthermore, we found that PPARα was a target gene of miR-675 and that H19 negatively regulated PPARα expression via miR-675. By inhibiting PPARα, the biological effects of miR-675 or H19 inhibition on cellular functions (apoptosis, inflammation and oxidative stress) were at least partially reversed. Moreover, knockdown of H19 significantly reduced infarct size, increased left ventricular systolic pressure, and decreased left ventricular end-diastolic pressure in a mouse model of myocardial I/R. Taken together, these data indicate that H19 inhibition protects the heart against myocardial I/R injury, which may be partly attributed to regulation of the miR-675/PPARα axis.
Graphical abstract
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Genetic and environmental influences on third molar root mineralization
Publication date: Available online 26 November 2018
Source: Archives of Oral Biology
Author(s): Giedrė Trakinienė, Irena Andriuškevičiūtė, Loreta Šalomskienė, Arūnas Vasiliauskas, Tomas Trakinis, Antanas Šidlauskas
Abstract
Objective
To assess the genetic and environmental influences on the variability of human third molar (M3) root mineralization stages via a twin study.
Design
The study sample consisted of 162 same-sex twins (66 dizygotic and 96 monozygotic, mean age: 17.9 years) with normal growth and development. Panoramic radiographs were evaluated to assess root mineralization stages of the upper and lower third molars, using the method of Demirijian et al. (1973). Zygosity was established using 15 specific DNA markers.
Results
Females developed their third molar roots earlier in life than males. Monozygotic twins (MZ) demonstrated higher intra-pair correlations for M3 root development stages than did DZ twins. An ACE model with additive genes, as well as common and specific environmental factors, provided the best explanation of variation in M3 root development. The mineralization of M3 roots showed highly additive genetic determination, varying from 60 to 63%, whereas a common environment contributed from 25 to 27%, and a specific environment only accounted 14% of the total variation, at most.
Conclusions
A considerable proportion of the total variability of the third molar root mineralization rate can be attributed to additive genetic effects, while common and specific environmental effects have a smaller, yet significant, impact.
https://ift.tt/2Sit5q5
Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma
Abstract
Ependymomas are biologically and clinically heterogeneous tumors of the central nervous system that have variable clinical outcomes. The status of the tumor immune microenvironment in ependymoma remains unclear. Immune cell subsets and programmed death ligand 1 (PD-L1) expression were measured in 178 classical ependymoma cases by immunohistochemistry using monoclonal antibodies that recognized tumor-infiltrating lymphocyte subsets (TILs; CD3, CD4, CD8, FOXP3, and CD20), tumor-associated macrophages (TAMs; CD68, CD163, AIF1), indoleamine 2,3-dioxygenase (IDO)+ cells and PD-L1-expressing tumor cells. Increases in CD3+ and CD8+ cell numbers were associated with a prolonged PFS. In contrast, increased numbers of FOXP3+ and CD68+ cells and a ratio of CD163/AIF1+ cells were significantly associated with a shorter PFS. An increase in the IDO+ cell number was associated with a significantly longer PFS. To consider the quantities of TILs, TAMs, and IDO+ cells together, the cases were clustered into 2 immune cell subgroups using a k-means clustering analysis. Immune cell subgroup A, which was defined by high CD3+, low CD68+ and high IDO+ cell counts, predicted a favorable PFS compared to subgroup B by univariate and multivariate analyses. We found six ependymoma cases expressing PD-L1. All these cases were supratentorial ependymoma, RELA fusion-positive (ST-RELA). PD-L1 expression showed no prognostic significance. This study showed that the analysis of tumor-infiltrating immune cells could aid in predicting the prognosis of ependymoma patients and in determining therapeutic strategies to target the tumor microenvironment. PD-L1 expression in the ST-RELA subgroup suggests that this marker has a potential added value for future immunotherapy treatments.
https://ift.tt/2PUosFM
Vocal cord immobility as a cause of aphonia in a child with 3p13p12 deletion syndrome encompassing FOXP1 gene
Publication date: Available online 27 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Hatice Mutlu-Albayrak, Kadri Karaer
Abstract
Congenital bilateral laryngeal paralysis/immobilization is an uncommon condition and has been described as isolated or accompanying to some recognizable syndromes. Heterozygous mutations in the FOXP1 gene (605515) are related with intellectual disability and, language impairment with or without autistic features. Expressive language is more affected than receptive language and more than half of the patients experience oromotor dysfunction and/or feeding difficulties. Here we report a child with severe developmental, speech delay and aphonia which was considered due to bilaterally abductor vocal cord immobility. Interstitial 8700 kbp deletion encompassing FOXP1 gene was detected on 3p13p12 chromosomal region. Although it is known that FOXP1 defects are related to abnormalities in vocal communication, FOXP1-associated laryngomalacia or vocal cord paralysis/immobilization cases have not been reported yet. The FOXP1 defects are considered to be a cause of delay in speech, and it is suggested that vocal cord evaluation should be conducted in suspicious cases.
https://ift.tt/2QpkG6K
Pediatric Ewing Sarcoma of the Head and Neck: A Retrospective Survival Analysis
Publication date: Available online 26 November 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Elaine Martin, Shannon Radomski, Earl Harley
Abstract
Objective
To determine the demographics, treatment modalities, and overall survival of pediatric Ewing sarcoma of the head and neck.
Methods
The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify cases of pediatric Ewing sarcoma of the head and neck between 1973 and 2015. Additional variables collected included age, gender, ethnicity, tumor grade, staging, treatment modality, and follow-up time. Kaplan-Meier survival curves were generated and overall survival was calculated.
Results
One hundred and twenty-seven cases of pediatric Ewing sarcoma were identified. The majority of patients were male (52.8%), white (88.2%), and non-Hispanic (75.6%), and the mean age at diagnosis was 10.5 years. The most common tumor sites were bones and joints of the skull and face (45.5%), followed by soft tissue of the head, face, and neck (25.2%), followed by the mandible (13.4%). Most patients (69.2%) had some type of surgery, 70.0% received radiation, and 92.1% received chemotherapy as part of their treatment. Overall 1-, 5-, and 10-year survival was 91.1%, 72.9%, and 68.2%, respectively. There was no significant difference in survival based on patient gender, age, tumor location, radiation, or chemotherapy treatment.
Conclusion
This study demonstrates that pediatric patients with Ewing sarcoma of the head and neck most commonly have stage II disease, no distant metastasis, and are treated with chemotherapy, with or without radiation. One, five, and ten-year survival are 91.1%, 72.9%, and 68.2%, respectively, and age, gender, and radiation do not seem to affect prognosis.
https://ift.tt/2DQTE1J
Glucocorticoid insensitivity by staphylococcal enterotoxin B in keratinocytes of allergic dermatitis is associated with impaired nuclear translocation of the Glucocorticoid Receptor α
Publication date: Available online 26 November 2018
Source: Journal of Dermatological Science
Author(s): Ke Huang, Lei Ran, Wei Wang, Rong Zhou, Xiaowei Cai, Ran Li, Yuanchao Li, Chunli Zhou, Wei He, Rupeng Wang
Abstract
Background
staphylococcal enterotoxin plays an important role in patients with glucocorticoid (GC)-resistant atopic dermatitis (AD), but the exact mechanism is not fully understood.
Objective
The aim of this study was to investigate the mechanisms underlying the ability of staphylococcal enterotoxin B (SEB) to induce steroid insensitivity through impaired nuclear translocation of GRα in keratinocytes.
Methods
The steroid-resistant AD induced by SEB was assessed by analyzing dermatitis score, dermal thickness, scratching behavior, infiltrating cells/HPF, levels of SEB-specific IgE and IgG2a antibody. In addition, dexamethasone (DEX)-induced GRα nuclear translocation and keratinocyte-derived cytokines and chemokines were analyzed in the lesional keratinocytes of AD and in HaCaT cells. Furthermore, the expressions of immunophilins FKBP51, FKBP52 and HSP90 responsive to GC in HaCaT cells were determined in the presence of SEB.
Results
SEB dose-dependently diminished the inhibitory effect of DEX on dermatitis score, dermal thickness, scratching behavior, infiltrating cells/HPF, keratinocyte-derived cytokines and chemokines such as RANTES, MCP-1, TSLP and GM-CSF. In vivo and in vitro data showed that in the presence of DEX, SEB dose-dependently caused a marked decrease of GRα nuclear translocation in lesional keratinocytes of AD and in HaCaT cells. Importantly, in the presence of DEX, SEB increased the expression of FKBP51 and the product of keratinocyte-derived cytokines and chemokines in HaCaT cells.
Conclusion
These results demonstrate that GC insensitivity by SEB in keratinocytes of AD is associated with impaired nuclear translocation of the GRα. Increased DEX-induced FKBP51 by SEB may contribute to accumulation of the GRα in cytoplasm of keratinocytes.
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TRPV1 mediates inflammation and hyperplasia in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice
Publication date: Available online 26 November 2018
Source: Journal of Dermatological Science
Author(s): Yan Zhou, Taylor Follansbee, Xuesong Wu, Dan Han, Sebastian Yu, Dan T. Domocos, Zhenrui Shi, Mirela Carstens, Earl Carstens, Samuel T. Hwang
Abstract
Background
Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood.
Objective
To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice.
Methods
Following daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions.
Results
Compared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45+ leukocytes, mast cells as well as CD3 + T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice.
Conclusions
In summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.
https://ift.tt/2AtUVbB
7-Tesla MRI of the brain in a research subject with bilateral, total knee replacement implants: Case report and proposed safety guidelines
Publication date: Available online 27 November 2018
Source: Magnetic Resonance Imaging
Author(s): Giuseppe Barisano, Bozena Culo, Frank G. Shellock, Farshid Sepehrband, Katherin Martin, Mary Stevens, Danny J. Wang, Arthur W. Toga, Meng Law
Abstract
Recently, the first 7-T MR system was approved for clinical use in the United States. Unfortunately, relatively few metallic implants have undergone testing to determine if they are acceptable or pose hazards to research subjects and patients at this ultra-high-field strength. Therefore, in lieu of not performing a research or clinical MRI exam at 7-T, the supervising physician may make a decision to scan the individual with an untested metallic implant based on an analysis of the risks vs. the benefits. We present a case report of a research subject with bilateral, total knee replacement implants that safely underwent MRI of the brain at 7-T and provide guidelines for healthcare professionals to follow in order to ensure safety in research subjects or patients with metallic implants referred for 7-T scans.
https://ift.tt/2TPMKyX
Pigmented villonodular synovitis occurring in the temporomandibular joint
Publication date: Available online 27 November 2018
Source: Auris Nasus Larynx
Author(s): Fuminori Nomura, Yosuke Ariizumi, Yusuke Kiyokawa, Akihisa Tasaki, Yumiko Tateishi, Nobuaki Koide, Hiroaki Kawabe, Takashi Sugawara, Kentaro Tanaka, Takahiro Asakage
Abstract
Objective
Pigmented villonodular synovitis occurring in the region of the temporomandibular joint is a rare disease, requiring a review of the treatment method, follow-up period.
Method
Refer to the past literature, along with a retrospective search.
Results
An excision, including the skull base bone, was performed in all cases; however, recurrence was found in one case on which fractional excision was performed. Past reports have also indicated that en bloc resection was considered desirable.
Conclusion
It is necessary to perform en bloc resection on patients with pigmented villonodular synovitis occurring in the region of the temporomandibular joint. Furthermore, due to reported cases of recurrence after a long period of time, follow-up observations of about 10 years are considered necessary.
https://ift.tt/2Sh1mWS
What to know about hyperpigmentation
Hyperpigmentation occurs when a person develops darker patches on the skin, such as age spots or melasma. Learn about the causes, types, and treatments for hyperpigmentation here.
https://ift.tt/2P3abBp
What to know about hyperpigmentation
Hyperpigmentation occurs when a person develops darker patches on the skin, such as age spots or melasma. Learn about the causes, types, and treatments for hyperpigmentation here.
https://ift.tt/2P3abBp
Gender Disparities in Trauma Care: How Sex Determines Treatment, Behavior, and Outcome
Publication date: Available online 27 November 2018
Source: Anesthesiology Clinics
Author(s): Evie G. Marcolini, Jennifer S. Albrecht, Kinjal N. Sethuraman, Lena M. Napolitano
https://ift.tt/2QkeXzi
Evaluating a shortened interpretation criterion for intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism: A 5‐minutes criterion in primary hyperparathyroidism and intraoperative algorithm
Abstract
Background
Most criteria require a parathyroid hormone (PTH) decline of ≥50% within 10 minutes after excision of the gland during surgery for primary hyperparathyroidism. The aim was to evaluate a model allowing earlier prediction of cure.
Methods
One thousand eighteen patients with primary hyperparathyroidism were included. A ≥50% decline from baseline within 10 minutes after excision intraoperatively predicted complete removal of hypersecreting tissue. The data were reanalyzed regarding a criterion, requiring a ≥50% decline after 5 minutes. Based on the data and the present literature, an algorithm was created.
Results
Assay predicted cure in 854 patients (true‐positive; 83.89%) after 10 minutes (false‐positive [FP] in 13 patients; 1.52%). Nevertheless, only 14 (1.83%) showed persisting disease. According to the "5 minutes" criterion, 723 patients (71.02%) showed a ≥50% decline from baseline within 5 minutes and 10 (1.38%) patients had a FP decline (sensitivity 0.75, specificity 0.86).
Conclusion
Using a modified criterion, surgery can be discontinued 5 minutes earlier in 71%.
https://ift.tt/2P2Xu9J
Diagnosis and treatment of oropharyngeal dysphagia after total laryngectomy with or without pharyngoesophageal reconstruction: A systematic review
Abstract
Background
This systematic review qualitatively summarizes the current literature on diagnosis and treatment of oropharyngeal dysphagia (OD) after total laryngectomy (TLE).
Methods
Electronic databases PubMed, Embase, and the Cochrane Library were used. Two independent reviewers carried out the literature search and assessed the methodological quality of the included studies using a critical appraisal tool.
Results
Forty‐four articles met the inclusion criteria. Of these, 35 studies were on diagnosis, four on therapy, and five on both diagnosis and treatment of OD following TLE. Study aims, swallowing‐assessment methods, and main findings of the included studies were summarized and presented.
Conclusions
The reviewers found heterogeneous outcomes and serious methodological limitations, which prevented us from pooling data to identify trends that would assist in designing best clinical practice protocols for OD following TLE. Further research should focus on several remaining gaps in our knowledge on diagnosis and treatment interventions for OD following TLE.
https://ift.tt/2zsSJ4h
Exceptional responses to pertuzumab, trastuzumab, and docetaxel in human epidermal growth factor receptor‐2 high expressing salivary duct carcinomas
Background
Alterations in the human epidermal growth factor receptor‐2 (HER2) pathway have been identified in a subset of salivary duct carcinomas. Dual HER2 inhibition with trastuzumab and pertuzumab has superior antitumor efficacy to trastuzumab monotherapy in HER2‐positive breast cancer, yet its efficacy in HER2‐positive salivary duct carcinoma is unknown.
Methods
We report 2 cases of exceptional responses of HER2‐positive salivary duct carcinomas to dual HER2 blockade and docetaxel combination and their molecular characteristics.
Results
A 54‐year‐old man with recurrent metastatic HER2 expressing salivary duct carcinoma of the parotid gland after definitive concurrent chemoradiation achieved a complete response (CR) after 6 cycles of trastuzumab, pertuzumab, and docetaxel (TPH). A 42‐year‐old woman with HER2‐positive salivary duct carcinoma of the parotid gland with bone and liver metastases had CR with TPH and remains in remission on maintenance trastuzumab and pertuzumab.
Conclusion
Dual HER2 blockage resulted in CR in patients with HER expressing salivary duct carcinoma and warrants further evaluation in this patient population.
https://ift.tt/2P52BpX
Massive aneurysmal bone cyst of the skull base treated with denosumab
Abstract
Background
Aneurysmal bone cysts are rare, benign expansile tumors most commonly involving long bones and vertebrae in patients younger than age 20. Skull base involvement is rare. Aneurysmal bone cysts shares radiological and histological features with other bone tumors, posing a diagnostic challenge.
Methods/Results
We report the case of a 32‐year‐old man who presented with facial pain, epistaxis, and cranial neuropathies secondary to a massive tumor of the maxillary sinus and anterior skull base. The tumor was originally misdiagnosed as osteosarcoma. However, genomic analysis revealed a rearrangement in the USP6 gene, elucidating a diagnosis of primary aneurysmal bone cysts. The patient was treated with denosumab. Within 5 months, the patient was asymptomatic with CT showing ossification of the tumor.
Conclusions
This case highlights (1) the utility of genomic analysis in aggressive bone tumors when the diagnosis is unclear and (2) the effectiveness of denosumab as a treatment for aneurysmal bone cysts when surgical resection is unfavorable.
https://ift.tt/2zsSFl3
DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging
Background: Directional deep brain stimulation (DBS) allows steering the stimulation in an axial direction which offers greater flexibility in programming. However, accurate anatomical visualization of the lead orientation is required for interpreting the observed stimulation effects and to guide programming. Objectives: In this study we aimed to develop and test an accurate and robust algorithm for determining the orientation of segmented electrodes based on standard postoperative CT imaging used in DBS. Methods: Orientation angles of directional leads (CartesiaTM; Boston Scientific, Marlborough, MA, USA) were determined using CT imaging. Therefore, a sequential algorithm was developed that quantitatively compares the similarity of the observed CT artifacts with calculated artifact patterns based on the lead's orientation marker and a geometric model of the segmented electrodes. Measurements of seven ground truth phantoms and three leads with 60 different configurations of lead implantation and orientation angles were analyzed for validation. Results: The accuracy of the determined electrode orientation angles was –0.6 ± 1.5° (range: –5.4 to 4.2°). This accuracy proved to be sufficiently high to resolve even subtle differences between individual leads. Conclusions: The presented algorithm is user independent and provides highly accurate results for the orientation of the segmented electrodes for all angular constellations that typically occur in clinical cases.
Stereotact Funct Neurosurg
https://ift.tt/2FKD5ah
Stereotact Funct Neurosurg
https://ift.tt/2FKD5ah
Comparative Study of Robot-Assisted versus Conventional Frame-Based Deep Brain Stimulation Stereotactic Neurosurgery
Background/Aims: Technological advancements had a serious impact on the evolution of robotic systems in stereotactic neurosurgery over the last three decades and may turn robot-assisted stereotactic neurosurgery into a sophisticated alternative to purely mechanical guiding devices. Objectives: To compare robot-assisted and conventional frame-based deep brain stimulation (DBS) surgery with regard to accuracy, precision, reliability, duration of surgery, intraoperative imaging quality, safety and maintenance using a standardized setup. Methods: Retrospective evaluation of 80 consecutive patients was performed who underwent DBS surgery using either a frame-based mechanical stereotactic guiding device (n = 40) or a stereotactic robot (ROSA Brain, MedTech, Montpellier, France) (n = 40). Results: The mean accuracy of robot-assisted and conventional lead implantation was 0.76 mm (SD: 0.37 mm, range: 0.17–1.52 mm) and 1.11 mm (SD: 0.59 mm, range: 0.10–2.90 mm), respectively. We observed a statistically significant difference in accuracy (p #x3c; 0.001) when comparing lateral deviations between both modalities. Furthermore, a statistical significance was observed when investigating the proportion of values exceeding 2.00 mm between both groups (p = 0.013). In 8.75% (n = 7) of conventionally implanted leads, lateral deviations were greater than 2.0 mm. With a maximum value of 1.52 mm, this threshold was never reached during robot-guided DBS. The mean duration of DBS surgery could be reduced significantly (p #x3c; 0.001) when comparing robot-guided DBS (mean: 325.1 ± 81.6 min) to conventional lead implantation (mean: 394.8 ± 66.6 min). Conclusions: Robot-assisted DBS was shown to be superior to conventional lead implantation with respect to accuracy, precision and operation time. Improved quality control, continuous intraoperative monitoring and less manual adjustment likely contribute to the robotic system's reliability allowing high accuracy during lead implantation despite limited experience. Hence, robot-assisted lead implantation can be considered an appropriate and reliable alternative to purely mechanical devices.
Stereotact Funct Neurosurg
https://ift.tt/2r5OKWO
Stereotact Funct Neurosurg
https://ift.tt/2r5OKWO
Long-Term Outcomes of Bilateral Pallidal Deep Brain Stimulation for X-Linked Dystonia and Parkinsonism
Background: X-linked dystonia parkinsonism (XDP) causes adult-onset progressive dystonia and parkinsonism, which may not respond to pharmacotherapy. Objective: Previous case reports have reported beneficial effects from bilateral pallidal (GPi) deep brain stimulation (DBS). Here, we report the long-term clinical outcomes of 3 patients treated at our center. Methods: All patients presented with medication refractory dystonia and parkinsonism. They were followed prospectively. Clinical evaluations included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Adverse events were recorded. Results: The average length of follow-up was 45.7 months. No serious adverse events occurred. All patients experienced an immediate and sustained improvement in dystonia. Mean percentage improvement in motor subscores of BFMDRS was 63.5% at the last follow-up visit. Parkinsonism was less responsive to neuromodulation, with a mean improvement in UPDRS-III of 39.5%. Standard pallidal stimulation parameters were used. Freezing of gait developed after DBS therapy in 2 patients, stimulation-induced in one and due to disease progression in the other. Conclusion: Bilateral pallidal DBS resulted in significant and sustained improvement in dystonia and moderate improvement in parkinsonism. Pallidal DBS represents an important treatment option for XPD for the management of motor symptoms.
Stereotact Funct Neurosurg
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Stereotact Funct Neurosurg
https://ift.tt/2FVsIk3
Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia
Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.
https://ift.tt/2Shi0FK
Dermoscopy of lipidised dermatofibroma: A morphological study of 13 cases
Abstract
Background/Objectives
The aim of this study was to evaluate the morphological findings of lipidised dermatofibromas under dermoscopic observation.
Methods
Dermoscopic examination of 13 cases of lipidised dermatofibromas was performed to evaluate specific dermoscopic criteria and patterns.
Results
The most frequently occurring dermoscopic features were as follows: (i) A yellowish homogenous pigmentation in all cases (100%); this pigmentation was total in 30.7%; (ii) White structures were seen in 46.1%, most of them were central white networks (38.4%); (iii) Pigment network was observed in 53.8%, most of them were peripheral delicate pigment networks (38.4%), but two cases showed an atypical pigment network; (iv) The presence of vascular structures was common (10 cases, 77%); (v) Regarding to dermoscopic patterns, five lipidised dermatofibromas (38.4%) showed a total yellowish homogeneous pattern; 38.4% an atypical pattern and 23.2% a 'central white network + peripheral delicate pigment network' pattern.
Conclusions
The dermoscopic recognition of a total yellowish homogeneous area or a yellowish colouration in the context of a dermatofibroma can be proposed to help suspecting a lipidised dermatofibroma.
https://ift.tt/2FSaMqu
Dermoscopy of lipidised dermatofibroma: A morphological study of 13 cases
Abstract
Background/Objectives
The aim of this study was to evaluate the morphological findings of lipidised dermatofibromas under dermoscopic observation.
Methods
Dermoscopic examination of 13 cases of lipidised dermatofibromas was performed to evaluate specific dermoscopic criteria and patterns.
Results
The most frequently occurring dermoscopic features were as follows: (i) A yellowish homogenous pigmentation in all cases (100%); this pigmentation was total in 30.7%; (ii) White structures were seen in 46.1%, most of them were central white networks (38.4%); (iii) Pigment network was observed in 53.8%, most of them were peripheral delicate pigment networks (38.4%), but two cases showed an atypical pigment network; (iv) The presence of vascular structures was common (10 cases, 77%); (v) Regarding to dermoscopic patterns, five lipidised dermatofibromas (38.4%) showed a total yellowish homogeneous pattern; 38.4% an atypical pattern and 23.2% a 'central white network + peripheral delicate pigment network' pattern.
Conclusions
The dermoscopic recognition of a total yellowish homogeneous area or a yellowish colouration in the context of a dermatofibroma can be proposed to help suspecting a lipidised dermatofibroma.
https://ift.tt/2FSaMqu
Histopathological Findings and Increased D-Dimer Are Predictive Factors of Systemic Thromboses in Eosinophilic Granulomatosis With Polyangiitis
Abstract: Eosinophilic granulomatosis with polyangiitis (EGPA; ie, Churg–Strauss syndrome) is one of the antineutrophil cytoplasmic antibody–associated vasculitis syndromes. Although extravascular granulomatoses are a well-known histopathological feature, the diverse histopathologic spectrum of cutaneous lesions has not been described in detail. Thus, this study sought to investigate the possible correlation between the clinical features and histopathology of cutaneous lesions in EGPA cases, focusing on systemic thrombogenic conditions, such as visceral infarction and deep vein thrombosis. Fourteen cases of EGPA diagnosed at the Department of Dermatology in Asahikawa Medical University from 1977 to 2017 were clinically and histopathologically reviewed. In 6 (43%) cases, skin lesions were the initial manifestation of EGPA. Among the cutaneous lesions, purpura and erythema were the most common. Persistent proteinuria and macrohematuria were observed in only 2 myeloperoxidase–antineutrophil cytoplasmic antibody–positive cases. Systemic thrombotic symptoms, such as cerebral infarction and deep vein thrombosis, were detected in 5 (36%) cases, and, in 3 of those cases, thromboses in dermal or subcutaneous vessels were observed histopathologically. Elevation of plasma D-dimer level (>2.5 μg/mL) was significantly correlated with concomitant systemic thrombotic symptoms (P = 0.0152, Fischer exact test). The histopathological finding of thrombotic features and increased plasma D-dimer were predictive factors of EGPA accompanied with systemic thromboses, such as deep vein thromboses and cerebral infarction.https://ift.tt/2P3T4zy
The “Line Sign” Is a Rapid and Efficient Diagnostic “Test” for Morphea: Clinicopathological Study of 73 Cases
Abstract: Histologic clues that facilitate rapid diagnosis of morphea at scanning magnification have been described but not well studied. We examined 73 cases of morphea and 42 control cases to determine the sensitivity and specificity of a novel histopathological feature—"the line sign (LS)"—a prominent, straight interface between subcutis and adjacent collagen. The sensitivity of LS was shown to be the most sensitive feature among 4 other existing histopathological features. Its specificity, however, was not the highest among the other features and needs to be evaluated further in future studies to confirm the usefulness of LS as a diagnostic tool for morphea.https://ift.tt/2zvst9t
Impact of Dermoscopy and Reflectance Confocal Microscopy on the Histopathologic Diagnosis of Lentigo Maligna/Lentigo Maligna Melanoma
Background: Equivocal pigmented lesions of the head are usually biopsied to avoid inappropriate treatment. Clinical approach has evolved from simple visual examination to sophisticated techniques for selecting the biopsy sites. Objective: This study aimed to retrospectively evaluate the efficiency of dermoscopy (DE) and reflectance confocal microscopy (RCM) in sampling a histopathologically representative focus of lentigo maligna/lentigo maligna melanoma. Methods: Punch biopsies and surgical excisions of 72 patients, 37 men and 35 women (median age 70.6 years, range 39–90 years), affected by lentigo maligna/lentigo maligna melanoma of the head, sent from a single dermatology clinic, were reviewed for the presence of 5 histopathologic criteria: atypical junctional melanocytes, increased junctional melanocytes, follicular colonization, pagetoid spread and melanocytic junctional nests, plus other minor features. Forty-two patients were biopsied under DE and 30 under RCM guidance. Results: Accuracy of the 2 techniques in sampling a representative tissue overlapped in most cases, although RCM selected sites to biopsy with more histopathologic criteria, in particular pagetoid spread and melanocytic nests. Interestingly, with RCM, inflammation and melanophages were observed more in biopsy than in excision. False positive cases were not registered. Conclusion: Compared with the sampling at naked eye, our results show that DE and RCM help selecting the most appropriate areas for biopsies, thus allowing not only more robust histopathologic diagnoses, but also a more accurate microstaging of tumor.https://ift.tt/2P1yFLq
Expanding the Morphologic Heterogeneity of Stromal Changes in Molluscum Contagiosum Infection
No abstract availablehttps://ift.tt/2zrWXcG
Ewing-Like Sarcoma: A Case of a Primary Cutaneous Primitive Neuroectodermal Tumor With Atypical Immunohistochemistry and Lack of Fusion Oncogene Detection
Abstract: We present a 25-year-old male patient with a primary cutaneous primitive neuroectodermal tumor (cPNET) with unusual immunohistochemistry and lack of fusion oncogene generation. The lesion expressed CD99 and WT-1, and the histological features were consistent with cPNET. Differential diagnoses such as rhabdomyosarcoma, desmoplastic small round blue cell tumor, hematolymphoid neoplasm, neuroblastoma, and CIC-DUX round cell sarcoma were ruled out based on immunohistochemistry, genetic studies, and histology. Previous cPNET cases have been published detailing abnormal immunochemistry and genetic expression. However, to our knowledge, fusion oncogene negativity in cPNET tumors has only been reported in one other published case series. These reports, including this study, reinforce the fact that a high index of suspicion should be used when diagnosing these tumors, regardless of immunohistochemical and genetic variability. This case highlights that the typical genetic and immunohistochemical features of cPNET may be more variable than previously thought. Future studies are needed to better understand these variations of cPNET.https://ift.tt/2P1O8Lz
Late-Onset Facial Papular Elastorrhexis
Abstract: Papular elastorrhexis, a rare defect of dermal elastic fibers of unknown origin, usually involves the trunk and extremities of children or young adults. We report the case of a 62-year-old woman with multiple soft, skin-colored facial papules with histological findings characteristic of papular elastorrhexis. Awareness of this entity may allow for its proper identification outside the usual clinical setting.https://ift.tt/2zpOCGg
Campbell de Morgan Spots (Cherry Angiomas) Show Endothelial Proliferation
Abstract: Campbell de Morgan spots (also known as adult hemangiomas, cherry angiomas, or senile angiomas) show clinical and histopathological features that make them distinct. Despite this, they are not included as benign vascular tumors in the current classification by the International Society for Vascular Anomalies (ISSVA). In the current study, we investigated the proliferation rate (Ki67) of the endothelia of 23 cases of Campbell de Morgan spots, as well as the immunoexpression of Wilms tumor protein 1 (WT1) by these vascular anomalies. The youngest patient was 24 years old (range: 24–80; mean: 52.61). Ten patients were women (43.48%). All cases showed intense cytoplasmic expression of WT1 by the endothelia in 80%–100% of the endothelial cells. Ki67 demonstrated proliferation by the endothelia of all vascular lesions. A mean of 1077.6 nuclei were evaluated per case. Eight cases showed a very low proliferation (less than 0.5% of the nuclei). In the other 15 cases, the proliferation ranged from 0.59% to 3.59% (mean: 1.89%).https://ift.tt/2P46oDS
Oncocytic Metaplasia in Melanocytic Tumors
Oncocytic metaplasia represents a histopathologic feature that can be observed in normal tissue such as salivary and lacrimal glands but may also constitute a degenerative metaplastic process as a result of repeated oxidative damage during cellular aging. Although cutaneous oncocytic metaplasia has been considered rare, the finding was seen in over one-third of melanocytic nevi prospectively evaluated, in one study. This case series reports on a small series of oncocytic melanocytic tumors, with the aim of describing this phenomenon in varied contexts and also describing the use of a mitochondrial antigen immunostain, which has not been previously reported.https://ift.tt/2P2NFsn
Pruritic Linear Eruption in a 53-Year-Old Woman: Challenge
No abstract availablehttps://ift.tt/2ztBTm2
Plexiform Atypical Spitz Tumor With Rosette-Like Giant Cells: A Histologic and Immunohistochemical Study on a Case Suggesting Ganglioneuroblastic Differentiation Review of the Literature and Considerations on Histogenesis
Abstract: Spitz nevi, atypical Spitz tumors and Spitzoid melanoma, the three clinicopathologic forms that constitute the spectrum of the Spitz-type melanocytic lesions, share a histologic picture characterized by large spindle and/or epithelioid ganglion-like cells, with various admixtures of multinucleate bizarre cells. This remarkable cytology has always been interpreted as an unusual, as well as unexplained form of atypia. We report a case of atypical Spitz tumor with Homer Wright–like rosettes, a feature characteristic of ganglioneuroblastic proliferation. Furthermore, the ganglion-like cells of the tumor showed basophilic punctuation in the cytoplasm, reminiscent of Nissl substance, and a few cells, whether spindled or epithelioid, were positive to neuron-specific enolase and glial fibrillary acid protein. Based on our findings, we hypothesize that the outstanding similarity of the ganglion-like cells of Spitz tumors to the normal parasympathetic ganglion cells and to the cells of ganglioneuroma and ganglioneuroblastoma may not be fortuitous. Instead, it may represent the expression of a specific pattern of melanocytic differentiation, analogous to the neurotization of common and cellular blue nevi, although in this case, it would privilege the parasympathetic lineage over the Schwannian, perineural, or endoneural pathway. Our hypothesis is supported by the literature reports of rosette formation and frank ganglioneuroblastic differentiation in Spitz tumors and melanoma and by the demonstration that parasympathetic neurons take origin from the same tracts of the neural crest as other neural and melanocytic cells.https://ift.tt/2P56knw
Primary Visceral Merkel Cell Carcinoma: A Case Report and Review of the Literature
Abstract: A 63-year-old white man with no significant previous medical or surgical history presented with painless jaundice after 3 weeks of dark urine, yellow stools, and a 9-pound weight loss. Bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase were elevated, and a computed tomography scan detected a 10-cm, ill-defined mass at the porta hepatis compressing the common bile duct. He underwent endoscopic retrograde cholangiopancreatography with stenting and ultrasound-guided biopsies. Histologic sections showed a neoplastic population of small ovoid cells with a high N:C ratio, nuclear hyperchromasia, "smoky" chromatin and abundant mitotic figures, and characteristic of high-grade neuroendocrine carcinoma (HGNECA). Immunohistochemistry showed synaptophysin, chromogranin, Golgi pattern CK20 reactivity, and strong diffuse expression of Merkel cell polyomavirus, supporting a diagnosis of Merkel cell carcinoma (MCC). A metastatic workup, including complete skin examination and positron emission tomography scan, revealed no other site of disease. Although this patient fits the classic demographic pattern for MCC, he lacks cutaneous involvement and significant risk factors for MCC including immunosuppression and concurrent or previous malignancy. Histologically, the differential diagnosis in this anatomical site is primary or occult metastatic organ-based small-cell HGNECA. Although pure nodal MCC accounts for a minute subset of MCC, it is almost exclusively described in superficial and extremity-draining nodal basins (eg, axillary or inguinal regions). Primary visceral nodal MCC accounts for fewer than 5 cases ever reported. This case illustrates the importance of recognizing the morphologic features characteristic of MCC, regardless of anatomical location, and the value of immunohistochemistry in diagnosis, which aid in differentiating it from non-MCC mimics. Development of targeted therapy has made distinction between MCC and non-MCC HGNECA increasingly important. This patient initially responded to PD-L1 inhibitor therapy but ultimately died with disease 10 months after diagnosis.https://ift.tt/2zun5nf
Vulvar Tuberculosis Cutis Orificialis Concomitant to Pulmonary Tuberculosis: A Case Report
Abstract: Tuberculosis (TB) is a common condition with increasing incidence worldwide. Cutaneous TB represents a small portion of extrapulmonary TB. Health care professionals must be aware of cutaneous forms of TB to avoid delay in diagnosis and treatment. We present a case of a 59-year-old woman with vulvar TB cutis orificialis in association with pulmonary TB without any other involvement of genitourinary system. We discuss epidemiological aspects, classification, treatment, range of histopathological patterns, and use of ancillary techniques for diagnosis.https://ift.tt/2P5tE4z
Heavily Pigmented Epithelioid Melanoma With Loss of Protein Kinase A Regulatory Subunit-α Expression
Abstract: Heavily pigmented melanocytic neoplasms are genotypically and phenotypically diverse. Recently, a subset of this histopathologic spectrum was shown to harbor recurrent genetic alterations in the gene-encoding protein kinase A regulatory subunit-α (PRKAR1A). To date, no histopathologic descriptions of melanomas arising from this pathway have been described. We present a case of a darkly pigmented papule arising on the posterior neck of a 28-year-old man. Microscopically, the heavily pigmented compound melanocytic proliferation was centered in the dermis with permeation into the superficial subcutis. Tumor cells were arranged in large confluent nests and fascicles and lacked maturation with descent. The epithelioid melanocytes were characterized by enlarged vesicular nuclei with prominent nucleoli, nuclear pleomorphism, and plentiful gray-brown granular cytoplasm. Mitotic figures were readily identified. By immunohistochemistry, melanocytes were positive for mutant BRAF V600E and showed loss of Prkar1α and p16 expression. A multiplex MART-1/tyrosinase/phosophohistone-H3 immunostain demonstrated an increased mitotic index in melanocytes. The combination of highly atypical cytomorphology and architecture, increased mitoses, and p16 expression loss compelled the diagnosis of melanoma. Overall, we present the first clinicopathologic description of a PRKAR1A-inactivated melanoma to highlight morphological features and discuss mimics that may enter the differential diagnosis.https://ift.tt/2P4POnr
Trichoblastic Carcinosarcoma of the Skin: A Case Report and Literature Review
Abstract: An 83-year-old man presented to the dermatology department for an ulcerated skin lesion of the back that had been increasing in size during the past 11 years. The physical examination revealed a well-defined, fleshy, reddish plaque measuring 10 × 20 cm in diameter with erosions and black areas on the surface. The patient underwent surgical excision with margins of 10 mm followed by a skin graft. Histologic section showed a lesion composed of 2 intimately intermingled epithelial and mesenchymal components associated with a basal cell carcinoma (BCC). Immunohistochemical examination showed epithelial cells that were positive for CK AE1/AE3 and p53, whereas stromal cells were positive for vimentin, CD10, and p53. BCC was positive for CD10. On the basis of these findings, a diagnosis of trichoblastic carcinosarcoma associated with BCC was made. Given the scarcity of data available in the literature regarding this diagnosis, no standard of care exists. No adjuvant treatment was provided and after 1 year of follow-up, the patient did not experience recurrence.https://ift.tt/2P2rrXu
Is Immunohistochemical Screening of Cutaneous Leiomyomas for the Early Detection of Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome Justified?
No abstract availablehttps://ift.tt/2zun16Z
Atypical Varicella-Zoster Kaposi Varicelliform Eruption in Sézary Syndrome
Abstract: Patients with mycosis fungoides experience considerable morbidity and mortality from secondary bacterial and viral infections. Staphylococcus aureus, β-hemolytic streptococci, herpes simplex virus, and herpes zoster virus remain the most common infectious pathogens in this group of patients. With depressed cellular immunity and diminished skin barrier as the main precipitating risk factors, immunocompromised patients can often present with an atypical presentation of a common dermatologic condition. The case herein discusses a clinically atypical nonvesicular Kaposi varicelliform eruption secondary to a varicella-zoster virus in a patient with Sézary syndrome. Concurrent polypharmacy in these patients is also a risk factor for development of drug hypersensitivity reactions. However, given their immunocompromised status, first and foremost, a careful inspection should be made of every atypical skin eruption in search of an infectious etiology, and afterward, an appropriate treatment should be promptly initiated.https://ift.tt/2P736Qe
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