AHNS Series: Do you know your guidelines? Guideline recommendations for head and neck cancer of unknown primary site

Abstract

This article reviews the clinical practice guidelines for head and neck oncology focusing on the management of head and neck cancers of unknown primary (CUP). The primary purpose of this series is to raise awareness of the current guidelines in head and neck oncology by reviewing the recommendations and the evidence supporting such recommendations, particularly those published by the National Comprehensive Cancer Network (NCCN). We review the importance of a thorough history and physical examination, the impact of the American Joint Committee on Cancer (AJCC) eighth edition changes and the importance of immunohistochemistry, the timing and type of imaging, the role of panendoscopy and tonsillectomy (palatine and lingual), and the role of surgery, radiation, and chemotherapy in the primary management of these tumors.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zn3nf0

Clinical diagnosis and treatment outcomes for parapharyngeal space schwannomas: A single-institution review of 21 cases

Abstract

Background

Because the incidence of schwannoma arising from the parapharyngeal space (PPS) is very low, no studies have analyzed extirpation methods and postoperative neurological complications exclusively in PPS schwannomas.

Methods

The preoperative diagnosis and clinical outcomes of surgical treatment in 21 patients with PPS schwannoma who underwent surgery were investigated.

Results

Neurological deficit of the involved nerve developed in all patients regardless of the extirpation method used. However, the incidence of first bite syndrome in sympathetic chain schwannoma was significantly lower after intracapsular enucleation (40%) than after total resection (100%; P = .045). Furthermore, the incidence of postoperative complications unrelated to the involved nerve was lower after intracapsular enucleation (0%) than after total resection (42.9%; P = .055).

Conclusion

Although postoperative neurological deficit of the involved nerve was unavoidable in PPS schwannoma, intracapsular enucleation could be beneficial by reducing its severity and the incidence of complications unrelated to the involved nerve.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mNnBIL

Table of Contents

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iAJBCe

Editorial Board

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AZ93Z7

Prevalence of type I sensitization to alpha-gal in forest service employees and hunters: Is the blood type an overlooked risk factor in epidemiological studies of the α-Gal syndrome?

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iCqw2x

An Analysis of Malpractice Litigation in Plastic Surgery

A new study examines the trends in malpractice litigation in plastic surgery and discusses the importance of expert witness testimony.
ePlasty, Open Access Journal of Plastic Surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zUsdST

Psoas Muscle Area as a Prognostic Factor for Survival in Patients with an Asymptomatic Infrarenal Abdominal Aortic Aneurysm: A Retrospective Cohort Study

Publication date: Available online 20 November 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Reza Indrakusuma, Jendé L. Zijlmans, Hamid Jalalzadeh, R. Nils Planken, Ron Balm, Mark J.W. Koelemay
ObjectivesLoss of muscle mass has been associated with poor survival in several surgical patient populations, including those with an abdominal aortic aneurysm (AAA). We wanted to replicate these findings and assesse the association between psoas muscle area (PMA) and survival in patients with an asymptomatic AAA.MethodsPatients with an asymptomatic infrarenal AAA who underwent computed tomography (CT) scanning between January 1, 2007, and December 31, 2013, were included in this single-centre retrospective cohort study. PMA was measured with thresholding on an axial image at the centre level of the third lumbar vertebra. The lowest tertile of PMA in all patients was used as a cutoff value for a low PMA. Then, in separate analyses for conservatively and surgically managed patients, survival was estimated with the Kaplan–Meier method. Differences in survival between patients with and without a low PMA were tested with the log-rank test.ResultsOf 228 patients, 104 were managed conservatively and 124 underwent AAA repair. Seventy-seven patients (62%) had an endovascular repair. In these 228 patients, the median PMA was 16.83 cm², while the cutoff value for low PMA was 14.56 cm². Patients who were managed conservatively were more often classified as having low PMA (45/104, 43%, vs. 31/124, 25%; p = .004) and were significantly older (mean 73.44 ± 9.05 years vs. 69.03 ± 7.46 years; p < .001). Low PMA was not associated with survival, either in patients managed conservatively, or in those who underwent AAA repair (p = .512 and p = .311, respectively).ConclusionsThe association between low PMA and poor survival could not be replicated; in this study, low PMA was not associated with survival in patients with an asymptomatic AAA. Further research is recommended before PMA can be used for pre-operative risk stratification.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hQlMJG

“Economies of Experience”—Disambiguation of Degraded Stimuli Leads to a Decreased Dispersion of Eye-Movement Patterns

Abstract

We demonstrate "economies of experience" in eye-movement patterns—that is, optimization of eye-movement patterns aimed at more efficient and less costly visual processing, similar to the priming-induced formation of sparser cortical representations or reduced reaction times. Participants looked at Mooney-type, degraded stimuli that were difficult to recognize without prior experience, but easily recognizable after exposure to their undegraded versions. As predicted, eye-movement dispersion, velocity, and the number of fixations decreased with each stimulus presentation. Further analyses showed that this effect was contingent on recognition, and the selection of information from the stimulus could be informed by the identity of the presented object. Finally, our study demonstrates that after exposure to the undegraded version of the stimulus, eye-movement patterns associated with its degraded and undegraded versions become more similar. This suggests that eye-movement patterns can evolve to facilitate the optimal processing of a given stimulus via experience-driven perceptual learning.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zmHA7k

Context Effects and Spoken Word Recognition of Chinese: An Eye-Tracking Study

Abstract

This study examined the time-course of context effects on spoken word recognition during Chinese sentence processing. We recruited 60 native Mandarin listeners to participate in an eye-tracking experiment. In this eye-tracking experiment, listeners were told to listen to a sentence carefully, which ended with a Chinese homophone, and look at different visual probes (Chinese characters or different line-drawing pictures) presented concurrently on the computer screen naturally. Different types of context and probe types were manipulated in the experiment. The results showed that (1) preceding sentence context had an early effect on spoken word recognition processes and (2) phonological information of the distracters had only a negligible effect on the spoken word recognition processes. Finally, the patterns of eye-tracking results seemed to favor an interactive approach in spoken word recognition.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mJVryq

Evaluating the mechanism and therapeutic potential of PTC-028, a novel inhibitor of BMI-1 function in ovarian cancer

BMI-1, also known as a stem cell factor, is frequently upregulated in several malignancies. Elevated expression of BMI-1 correlates with poor prognosis and is therefore considered a viable therapeutic target in a number of malignancies including ovarian cancer. Realizing the immense pathological significance of BMI-1, small molecule inhibitors against BMI1 are recently being developed. In the current study, we functionally characterize PTC-028, an orally bioavailable compound that decreases BMI-1 levels by post-translational modification We report that PTC-028 treatment selectively inhibits cancer cells in clonal growth and viability assays whereas normal cells remain unaffected. Mechanistically, hyper-phosphorylation mediated depletion of cellular BMI-1 by PTC-028 coupled with a concurrent temporal decrease in ATP and a compromised mitochondrial redox balance potentiates caspase-dependent apoptosis. In vivo, orally administered PTC-028, as a single agent exhibits significant antitumor activity comparable to the standard cisplatin/paclitaxel therapy in an orthotopic mouse model of ovarian cancer. Thus, PTC-028 has the potential to be used as an effective therapeutic agent in patients with epithelial ovarian cancer, where treatment options are limited.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zXHG23

Comparative oncology evaluation of intravenous recombinant oncolytic Vesicular Stomatitis Virus therapy in spontaneous canine cancer

Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single shot systemic therapy with a VSV-IFNβ-NIS, a novel recombinant oncolytic Vesicular stomatitis virus (VSV), can induce curative remission in tumor bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models. Dogs spontaneously develop cancer with comparable etiology, clinical progression and response to therapy as human malignancies. A comparative oncology study was carried out to investigate feasibility and tolerability of intravenous oncolytic VSV-IFNβ-NIS therapy in pet dogs with spontaneous cancer. Nine dogs with various malignancies were treated with a single intravenous dose of VSV-IFNβ-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid but transient remission of disseminated disease and transient hepatotoxicity that resolved spontaneously. There was no shedding of infectious virus. Correlative pharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogs with measurable disease remission. This is the first evaluation of intravenous oncolytic virus therapy for spontaneous canine cancer, demonstrating that VSV-IFNβ-NIS is well-tolerated and safe in dogs with advanced or metastatic disease. This approach has informed clinical translation, including dose and target indication selection, leading to a clinical investigation of intravenous VSV-IFNβ-NIS therapy, and provided preliminary evidence of clinical efficacy, and potential biomarkers that correlate with therapeutic response.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2j9Poy0

Molecular basis for necitumumab inhibition of EGFR variants associated with acquired cetuximab resistance.

Acquired resistance to cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR), impacts clinical benefit in head and neck, and colorectal cancers (CRC). One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab resistance substitution, S468R (or S492R, depending on the amino acid numbering system). We determined an X-ray crystal structure to 2.8 Å resolution of the necitumumab Fab bound to an S468R variant of EGFR domain III. The arginine is accommodated in a large, pre-existing cavity in the necitumumab paratope. We predict that this paratope shape will be permissive to other epitope substitutions, and show that necitumumab binds to most cetuximab- and panitumumab-resistance EGFR variants. We find that a simple computational approach can predict with high success which EGFR epitope substitutions abrogate antibody binding. This computational method will be valuable to determine whether necitumumab will bind to EGFR as new epitope resistance variants are identified. This method could also be useful for rapid evaluation of the effect on binding of alterations in other antibody/antigen interfaces. Together these data suggest that necitumumab may be active in patients who are resistant to cetuximab or panitumumab through EGFR epitope mutation. Further, our analysis leads us to speculate that antibodies with large paratope cavities may be less susceptible to resistance due mutations mapping to the antigen epitope.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zZ0mhS

Treatment of Richter’s Syndrome

Opinion statement

Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter's syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50–60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a ¹⁸FDG PET/CT and a biopsy are recommended to confirm RS. A ¹⁸FDG PET/CT showing low uptake is helpful to rule out RS and avoid unnecessary risks and costs of performing a biopsy. A ¹⁸FDG PET/CT showing a high uptake is not diagnostic of RS but may help in the choice of the site where the biopsy is to be performed. In the setting of the diffuse large B-cell lymphoma (DLBCL) variant of RS, the definition of a clonal relationship between RS and the underlying CLL may guide the choice of treatment. If a clonal relationship is confirmed (the most common situation), rituximab-CHOP-like treatment does not guarantee long-lasting remissions, and should be used as induction therapy followed by consolidation with a stem cell transplant in physically fit patients. If the CLL and RS are clonally unrelated (the less common situation), the management should be that of a de novo DLBCL. In the setting of the rare Hodgkin lymphoma variant of RS, which is usually clonally unrelated to the CLL, ABVD with or without radiotherapy may be curative of the aggressive lymphoma.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2izD4ba

Clinicopathologic Predictive Factors of Cervical Lymph Node Metastasis in Differentiated Thyroid Cancer

Publication date: Available online 20 November 2017
Source:Acta Otorrinolaringológica Española
Author(s): Ronghao Sun, Hua Zhang, Kun Liu, Jinchuan Fan, Guojun Li, Xicheng Song, Chao Li
BackgroundCervical lymph node metastasis (LNM) has been proven to be a predictor for locoregional recurrence in differentiated thyroid carcinoma (DTC). Clinicopathological features could be effective predictive factors for central and lateral LNM of DTC, and provide references to surgeons for cervical neck dissection.MethodsRetrospective analysis of clinicopathological data was performed on 420 patients who underwent initial surgery from 2010 to 2015.ResultsThe incidence of central and lateral LNM was calculated. Of 420 patients, 247 (58.8%) exhibited central LNM, and 185 (44.1%) exhibited lateral LNM. There were 29 (6.9%) cases confirmed to have skip metastasis. Univariate and multivariate analysis revealed that tumour location, tumour size, multifocality, capsular invasion, affected lobes, and age were independent predictors of central LNM. Tumour location, capsular invasion, affected lobes, and tumour size were independent predictors of lateral LNM.ConclusionsOur findings suggest that tumour location, affected lobes, capsular invasion, age, tumour size and multifocality may be taken as predictive factors for cervical LNM of DTC. Meticulous perioperative evaluation of cervical LNM and prophylactic cervical lymph node dissection that aims to remove the occult lymph nodes may be an option for DTC with risk factors.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jHAMtW

Effects of Intrathecal Injection of the Conditioned Medium from Bone Marrow Stromal Cells on Spinal Cord Injury in Rats

Journal of Neurotrauma , Vol. 0, No. 0.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AY6Ay7

Repeated Exposure to Experimental Pain Differentiates Combat Traumatic Brain Injury with and without Post-Traumatic Stress Disorder

Journal of Neurotrauma , Vol. 0, No. 0.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AY6x5p

Sequential occurrence of small cell and non-small lung cancer in a male patient: Is it a transformation?

.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXXXDn

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma

.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iCMHpA

Inactivation of miR-100 combined with arsenic treatment enhances the malignant transformation of BEAS-2B cells via stimulating epithelial -mesenchymal transition

.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AY6mHh

Three-dimensional printing modeling: application in maxillofacial and hand fractures and resident training

Abstract

Background

Imaging techniques in reconstructive surgery are of great assistance not only in diagnosis but also in preoperative planning; however, they are often limited to interpreting three-dimensional structures on flat surfaces. Three-dimensional (3D) printing has made it possible to overcome these limitations by allowing the creation of customized 3D anatomical models. We set out to create 3D printed models to demonstrate its application in maxillofacial and hand fractures and resident training.

Methods

Ten patients with hand and craniofacial fractures of different types were studied. Computed tomography was performed; the image files were processed digitally, and 3D models were subsequently printed. The quality and accuracy of the obtained models were rigorously evaluated, and the models were then used by plastic surgery teachers and residents in the preoperative planning.

Results

The comparative measurements confirmed that the models are at real scale with a 1:1 ratio; the pre-cast osteosynthesis plates were perfectly matched to the patient's anatomy intraoperatively, and the lengths of the pre-selected screws were accurate. The anesthetic surgical time was reduced by 20%. Teachers and residents were satisfied with the use of models for clinical discussions of patients and for preoperative planning and the advantages of manipulating physical models were highlighted.

Conclusions

We have created low-cost, good quality, reliable, and accurate 3D printed models for the preoperative planning of reconstructive surgeries of maxillofacial and hand fractures, reducing the operative times and providing a new academic teaching tool in the training of residents of plastic surgery.

Level of Evidence: Level IV, therapeutic study.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B8Tv5N

Specific Organ Targeted Vestibular Physiotherapy: The Pivot in the Contemporary Management of Vertigo and Imbalance

Abstract

Introduction

Advancements in our understanding of vestibular physiology and how it is changes in different diseases have established that of the three therapeutic approaches to treat disorders of the vestibular system viz. pharmacotherapy, surgery and physical therapy, it is the later i.e., physical therapy which is the most efficacious modality in the management of balance disorders. The futility of vestibular sedatives in the correction of vestibular disorders and in the restoration of balance and the very limited role of surgery has now been recognised. Advancements in vestibulometry now enable us to localise any lesion in the vestibular system with utmost precision and also determine the exact cause of the balance disorder. The site of lesion and the specific organ that is defective can now be very precisely identified. Treatment modalities especially that for physical therapy hence have to be organ specific, and if possible, also disease specific.

Aims and Objectives

The study aims at evaluating the efficacy of physiotherapy in the management of balance disorders and also assesses the efficacy of organ targeted physical therapy, a new concept in restoring balance after vestibulometry has identified the offending organ.

Materials and Methods

The study was conducted in the specialised physical therapy unit for balance and gait disorder patients which is a part of Vertigo and Deafness Clinic in Kolkata, India. Special instruments for physical therapy devised by the first author were used for stimulation of specific sense organs in the vestibular labyrinth that were found to be defective in vestibulometry. Specially made Virtual reality programs were used in patients suffering from psychogenic balance disorders. The pre and post therapy status was evaluated by different standard scales to assess balance and dizziness.

Results

Very promising results were obtained. Organ targeted physiotherapy where defective sense organs were specifically stimulated showed remarkable improvement in different measures. Virtual reality exercises too showed very promising results in patients of psychogenic vertigo.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mMCqLY

Polysialylated Neural Cell Adhesion Molecule Supports Regeneration of Neurons in the Nucleus Ambiguus After Unilateral Recurrent Laryngeal Nerve Avulsion in Adult Rats

A correlation appears to exist between the expression of the polysialic acid neural cell adhesion molecule (PSA-NCAM) and repair in central nervous system (CNS) diseases. However, the expression of PSA-NCAM in the CNS after peripheral nerve injury remains unclear. This study aimed to evaluate the expression of PSA-NCAM in the ipsilateral nucleus ambiguus (NA) after unilateral recurrent laryngeal nerve (RLN) avulsion.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jbMx7V

Enhanced recovery in patients having free tissue transfer for head and neck cancer: does it make a difference?

Programmes for Enhanced Recovery after Surgery (ERAS) accelerate recovery, reduce morbidity, and shorten hospital stay in a wide range of surgical specialties. We established a standardised multimodal ERAS pathway for patients who were being treated by free tissue transfer for head and neck cancer to evaluate its benefit. Our primary outcome was duration of hospital stay, and secondary outcomes included complications, number of days to first mobilisation, and readmission rates. We compared 100 consecutive patients who followed the ERAS programme with a control group of 40 consecutive patients who had free tissue transfer before the ERAS programme was introduced.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jc9pEp

Are patients satisfied with the head and neck skin cancer service? An evaluation of outpatient services with a review of published reports

Scientific publications place much emphasis on postoperative outcomes such as recurrence, but little attention to patients' satisfaction. The purpose of this evaluation was to find out patients' reported outcomes after their initial consultation, treatment, and follow-up appointments for non-melanoma skin cancer of the head and neck. We used an adapted version of the European Organisation for Research and Treatment of Cancer (EORTC) validated questionnaire for patients' satisfaction to collect data prospectively from consenting patients between September and December 2015.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zYwuCl

The glucocorticoid receptor is a key player for prostate cancer cell survival and a target for improved anti-androgen therapy.

Purpose: The major obstacle in the management of advanced prostate cancer (PCa) is the occurrence of resistance to endocrine-therapy. Although the androgen receptor (AR) has been linked to therapy failure, the underlying escape mechanisms have not been fully clarified. Being closely related to the AR, the glucocorticoid receptor (GR) has been suggested to play a role in enzalutamide and docetaxel resistance. Given that glucocorticoids are frequently applied to PCa patients, it is essential to unravel the exact role of the GR in PCa progression. Experimental Design: Assessment of GR expression and functional significance in tissues from 177 PCa patients, including 14 lymph-node metastases, as well as in several human PCa models including androgen-dependent, androgen-independent, and long-term anti-androgen-treated cell lines. Results: While GR expression is reduced in primary PCa tissue, it is restored in metastatic lesions. Relapse patients with high GR experience shortened progression-free survival. GR is significantly increased upon long-term abiraterone or enzalutamide treatment in the majority of preclinical models, thus identifying GR upregulation as an underlying mechanism for cells to bypass AR-blockade. Importantly, GR inhibition by RNA-interference or chemical blockade results in impaired proliferation and 3D-spheroid formation in all tested cell lines. Conclusions: upregulation seems to be a common mechanism during anti-androgen treatment and supports the notion that targeting the GR pathway combined with anti-androgen medication may further improve PCa therapy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mKO2ip

CAR-T cell Therapies in Glioblastoma: a first look

Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, immunosuppressive microenvironment and partially permissive anatomical blood brain barrier (BBB). Results from three first-in-man CAR-T cell trials targeting IL13Rα2, Her2/CMV and EGFRvIII have recently been reported. Each one of these trials addresses important questions, such as T cell trafficking to CNS, engraftment and persistence, tumor microenvironment (TME) remodeling, and monitoring of glioma response to chimeric antigen receptor (CAR) T cells. Objective radiological responses have been reported. Here, we discuss and summarize the results of these trials and suggest opportunities for the field.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2znafsU

Comorbidities in a community sample of narcolepsy

To assess comorbidities in a community-based cohort of narcolepsy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jFlKoi

Association between Nighttime Sleep Duration, Midday Naps and Glycemic Levels in Japanese Patients with Type 2 Diabetes

To clarify the relationship between nighttime sleep duration, midday naps and glycemic control in Japanese patients diagnosed with type 2 diabetes (n=355) or impaired glucose tolerance (n=43).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hQG3yK

Evaluation of a Low Risk Mild Traumatic Brain Injury and Intracranial Hemorrhage Emergency Department Observation Protocol

Abstract

Objectives

Among emergency physicians, there is wide variation in admitting practices for patients who suffered a mild traumatic brain injury (TBI) with an intracranial hemorrhage (ICH). The purpose of this study was to evaluate the effects of implementing a protocol in the emergency department (ED) observation unit for patients with mild TBI and ICH.

Methods

This retrospective cohort study was approved by the Institutional Review Board. Study subjects were patients ≥18 years of age with an International Classification of Diseases (ICD) code corresponding to a traumatic IC, and admitted to an ED observation unit (EDOU) of an urban, academic level 1 trauma center between February 1, 2015 and January 31, 2017. Patient data and discharge disposition were abstracted from the electronic health record; imaging data from the final neuroradiologist report. To measure kappa, two abstractors independently collected data for presence of neuro deficit from a 10% random sample of the medical charts. Using a multivariable logistic regression model with a propensity score of the probability of placement in the EDOU pre-post protocol implementation as a covariate, we sought to determine the pre-post effects of implementing a protocol on the composite outcome of admission to the floor, intensive care unit (ICU), or operating room (OR) from the EDOU, and the proportion of patients with worsening findings on repeat CT head scan in the EDOU.

Results

A total of 379 patients were identified during the study period; 83 were excluded as they were found to have no ICH on chart review. Interrater reliability kappa statistic was 0.63 for 30 charts. Among the 296 patients who remained eligible and comprised the study population, 143 were in the pre-protocol period; 153 post-protocol. The EDOU protocol was associated with an independently statistically significant decreased odds ratio (OR) for admission or worsening ICH on repeat CT scan (OR 0.45, 95% confidence interval [CI] 0.25, 0.82, p=0.009) in the observation unit. After a stay in the EDOU, 26% (37/143) of patients required an inpatient admission pre-implementation of the protocol and 13% (20/153) of patients required an inpatient admission post-protocol implementation. There was no statistically significant difference in log transformed EDOU length of stay (LOS) between the groups after adjusting for propensity score (p=0.34).

Conclusions

While there was no difference in EDOU LOS, implementing a low risk mild traumatic brain injury and intracranial hemorrhage protocol in the EDOU may decrease the rate of inpatient admissions from the EDOU. A protocol driven observation unit may help physicians by standardizing eligibility criteria and by providing guidance on management. As the propensity score method limits our ability to create a straightforward predictive model, a future larger study should validate the results.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mMt6rk

A Randomized Double Blind Trial of Needle-free Injected Lidocaine Versus Topical Anesthesia for Infant Lumbar Puncture

Abstract

Objectives

Lumbar punctures (LPs) are commonly performed in febrile infants to evaluate for meningitis, and local anesthesia increases the likelihood of LP success. Traditional methods of local anesthesia require injection which may be painful or topical application which is not effective immediately. Recent advances in needle-free jet injection may offer a rapid alternative to these modalities. We compared a needle-free jet-injection system (J-Tip^™) with 1% buffered lidocaine to topical anesthetic (TA) cream for local anesthesia in infant LPs.

Methods

Single center randomized double-blind trial of J-Tip versus TA for infant LPs in an urban tertiary care Children's Hospital Emergency Department. A computer randomization model was used to allocate patients to either intervention. Patients aged 0-4 months were randomized to J-Tip syringe containing 1% lidocaine and a placebo topical anesthetic cream, or J-Tip syringe containing saline and TA. The primary outcome was the difference between the neonatal faces coding scale (NFCS) pre-procedure and during LP needle insertion. Secondary outcomes included changes in heart rate (HR) and NFCS throughout the procedure, difficulty with LP, number of LP attempts, provider impression of pain control, additional use of lidocaine, skin changes at LP site, and LP success.

Results

We enrolled 66 subjects, 32 were randomized to J-Tip with lidocaine and 34 to EMLA. 6 participants were excluded from the final analysis due to age greater than 4 months, and the remaining 58 were analyzed in their respective groups (32 J-Tip, 34 TA). There was no difference detected in NFCS between the two treatment groups pre-procedure and during needle insertion for the LP (p=0.58, p=0.37). Neither HR nor NCFS differed among the groups throughout the procedure. Median perception of pain control by the provider and the need for additional lidocaine were comparable across groups. LPs performed with a J-Tip were twice as likely to be successful as compared to those performed using TA (RR 2.0; 95% CI 1.01, 3.93; p=0.04) with no difference in level of training or number of prior LPs performed by providers.

Conclusions

In a randomized controlled trial of two modalities for local anesthesia in infant lumbar punctures, J-Tip is not superior to topical anesthetic cream as measured by pain control or physiologic changes. Infant LPs performed with J-Tip were twice as likely to be successful.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zkZ43L

Synaptic phosphorylated α-synuclein in dementia with Lewy bodies

Abstract

Dementia with Lewy bodies is characterized by the accumulation of Lewy bodies and Lewy neurites in the CNS, both of which are composed mainly of aggregated α-synuclein phosphorylated at Ser129. Although phosphorylated α-synuclein is believed to exert toxic effects at the synapse in dementia with Lewy bodies and other α-synucleinopathies, direct evidence for the precise synaptic localization has been difficult to achieve due to the lack of adequate optical microscopic resolution to study human synapses. In the present study we applied array tomography, a microscopy technique that combines ultrathin sectioning of tissue with immunofluorescence allowing precise identification of small structures, to quantitatively investigate the synaptic phosphorylated α-synuclein pathology in dementia with Lewy bodies. We performed array tomography on human brain samples from five patients with dementia with Lewy bodies, five patients with Alzheimer's disease and five healthy control subjects to analyse the presence of phosphorylated α-synuclein immunoreactivity at the synapse and their relationship with synapse size. Main analyses were performed in blocks from cingulate cortex and confirmed in blocks from the striatum of cases with dementia with Lewy bodies. A total of 1 318 700 single pre- or postsynaptic terminals were analysed. We found that phosphorylated α-synuclein is present exclusively in dementia with Lewy bodies cases, where it can be identified in the form of Lewy bodies, Lewy neurites and small aggregates (<0.16 µm³). Between 19% and 25% of phosphorylated α-synuclein deposits were found in presynaptic terminals mainly in the form of small aggregates. Synaptic terminals that co-localized with small aggregates of phosphorylated α-synuclein were significantly larger than those that did not. Finally, a gradient of phosphorylated α-synuclein aggregation in synapses (pre > pre + post > postsynaptic) was observed. These results indicate that phosphorylated α-synuclein is found at the presynaptic terminals of dementia with Lewy bodies cases mainly in the form of small phosphorylated α-synuclein aggregates that are associated with changes in synaptic morphology. Overall, our data support the notion that pathological phosphorylated α-synuclein may disrupt the structure and function of the synapse in dementia with Lewy bodies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jaLhSz

CLIPPERS, a possible symptomatic lymphohistiocytic immune reaction

Sir,

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zXtd6f

Reply: CLIPPERS, a possible symptomatic lymphohistiocytic immune reaction

Sir,

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2j9DdRO

Laryngeal candidiasis: our experience from sixty biopsy specimens

Persistent throat symptoms, such as dysphonia, globus and throat pain, are highly prevalent and are a significant cause of morbidity¹. In a number of cases a clear cause of these symptoms is not identified and many patients are treated empirically with lifestyle advice and/or anti-reflux medication².

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AYh68u

Symptomatic benign distal biliary stricture in setting of anomalous pancreaticobiliary junction treated with metal biliary and temporary plastic pancreatic stents

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zVmvjt

Successful Repair of Duodenal Perforation With Endoscopic Vacuum Therapy

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hIu4zF

Spiral valves of Heister as per direct cystic ductoscopy

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zTLBPE

In Vitro Study of the Effects of Denosumab on Giant Cell Tumor of Bone: Comparison with Zoledronic Acid

Abstract

Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor that contains numerous osteoclasts formed from marrow-derived precursors through receptor activator of nuclear factor κ-B ligand (RANKL), an osteoclast differentiation factor expressed in neoplastic cells of GCTB. Denosumab, a fully human monoclonal antibody targeting RANKL, has recently been used for the treatment of GCTB, and superior treatment effects have been reported. The aim of this work was to elucidate the mechanism of action of denosumab, and the differences between denosumab and zoledronic acid at the level of GCTB cells. We isolated GCTB cells from 3 patients and separated them into osteoclasts, osteoclast precursors and proliferating spindle-shaped stromal cells (the true neoplastic component), and examined the action of denosumab on differentiation, survival and bone resorption activity of osteoclasts. Denosumab and zoledronic acid inhibited osteoclast differentiation from mononuclear cells containing osteoclast precursors. Zoledronic acid inhibited osteoclast survival, whereas an inhibitory effect of denosumab on osteoclast survival was not observed. The inhibitory effect on bone resorption by both agents was confirmed in culture on dentin slices. Furthermore, zoledronic acid showed dose-dependent inhibition of cell growth of neoplastic cells whereas denosumab had no inhibitory effect on these cells. Denosumab has an inhibitory effect on osteoclast differentiation, but no inhibitory effects on survival of osteoclasts or growth of neoplastic cells in GCTBs.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hEbl8i

Letter from the Guest Editor

The field of Breast Imaging is constantly evolving and has seen rapid advances in technology over the last two decades. Controversies surrounding breast cancer screening have also been gaining ground, despite unequivocal benefits and a decline in mortality of nearly 30%. There is talk of a paradigm shift in thinking from "population –based" screening to "personalized risk based" screening.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z78X0K

Sensation, mechanoreceptor and nerve fiber function after nerve regeneration

Abstract

Objective: Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis and mechanoreceptor and sensory fiber function after nerve regeneration.

Methods: Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique including tactile stimulation of mechanoreceptors were followed for 2 years, and results were compared to non-injured hands.

Results: At both repair methods, touch thresholds at the finger tips recovered to 81±3% and tactile gnosis only to 20±4% (P<0.001) of control. The sensory action potentials (SNAPs) remained dispersed and areas recovered to 23±2% and the amplitudes only to 7±1% (P<0.001). The areas of SNAPs after tactile stimulation recovered to 61±11% and remained slowed. Touch sensation correlated with SNAP areas (P<0.005) and was negatively related to the prolongation of tactile latencies (P<0.01); tactile gnosis was not related to electrophysiological parameters.

Interpretation: The recovered function of regenerated peripheral nerve fibers and reinnervated mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the CNS, which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis. This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B80Tyc

A comparative study of cone beam computed tomography and conventional radiography in diagnosing the extent of root resorptions

Root resorptions are assessed and diagnosed using different radiographical techniques. A comparison of the ability to assess resorptions on two-dimensional (2D) and three-dimensional (3D) radiographs is, hithe...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hQx94i

Comparative analysis of vestibular ecomorphology in birds

Abstract

The bony labyrinth of vertebrates houses the semicircular canals. These sense rotational accelerations of the head and play an essential role in gaze stabilisation during locomotion. The sizes and shapes of the semicircular canals have hypothesised relationships to agility and locomotory modes in many groups, including birds, and a burgeoning palaeontological literature seeks to make ecological interpretations from the morphology of the labyrinth in extinct species. Rigorous tests of form–function relationships for the vestibular system are required to support these interpretations. We test the hypothesis that the lengths, streamlines and angles between the semicircular canals are related to body size, wing kinematics and flying style in birds. To do this, we applied geometric morphometrics and multivariate phylogenetic comparative methods to a dataset of 64 three-dimensional reconstructions of the endosseous labyrinth obtained using micro-computed tomography scanning of bird crania. A strong relationship between centroid size of the semicircular canals and body size indicates that larger birds have longer semicircular canals compared with their evolutionary relatives. Wing kinematics related to manoeuvrability (and quantified using the brachial index) explain a small additional portion of the variance in labyrinth size. We also find strong evidence for allometric shape change in the semicircular canals of birds, indicating that major aspects of the shape of the avian labyrinth are determined by spatial constraints. The avian braincase accommodates a large brain, a large eye and large semicircular canals compared with other tetrapods. Negative allometry of these structures means that the restriction of space within the braincase is intense in small birds. This may explain our observation that the angles between planes of the semicircular canals of birds deviate more strongly from orthogonality than those of mammals, and especially from agile, gliding and flying mammals. Furthermore, we find little support for relationships between labyrinth shape and flying style or wing kinematics. Overall, our results suggest that the topological problem of fitting long semicircular canals into a spatially constrained braincase is more important in determining the shape of the avian labyrinth than the specifics of locomotory style or agility. Our results tentatively indicate a link between visual acuity and proportional size of the labyrinth among birds. This suggests that the large labyrinths of birds compared with other tetrapods may result from their generally high visual acuities, and not directly from their ability to fly. The endosseous labyrinths of extinct birds and their close dinosaurian relatives may allow broad inferences about flight or vision, but so far provide few specific insights into detailed aspects of locomotion.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zm6WCf

Fetal Exposure to Maternal Pregnancy Complications and Respiratory Health in Childhood

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AY7Fpl

Bilateral early activity in the hip flexors associated with Falls in Stroke Survivors: Preliminary evidence from laboratory-induced falls

Stroke is the leading cause of disability in the US with an additional 800,000 incidents occurring each year (CDC, 2012). Falls present a major risk for stroke survivors, 40% of whom experience a serious fall within their first year (Persson et al., 2011). Up to 69% of falls by stroke survivors result in injuries. Despite the importance of the problem, there is surprisingly little information about what factors contribute to falls in stroke survivors. With few exceptions, the literature has focused on relating metrics of post-stroke static balance (where stepping did not occur) and impairment (clinical scores) to fall outcomes in the acute care setting or in the community (Divani et al., 2011; Ikai et al., 2003; Marigold et al., 2004; Marigold and Eng, 2006; Persson et al., 2011; Weerdesteyn et al., 2008).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jI8hMK

Fasciculation potentials and decremental responses in amyotrophic lateral sclerosis

Clinically-observed fasciculations and fasciculation potentials (FPs) in needle EMG are characteristic findings of amyotrophic lateral sclerosis (ALS) (Wilbourn, 1998) and have been postulated to reflect the hyperexcitability of the lower motor neuron (Bostock et al., 1995). Decremental responses (hereafter abbreviated as "decrement") in repetitive nerve stimulation (RNS) are also frequently observed in ALS patients (Mulder et al., 1959; Iwanami et al., 2011; Hatanaka et al., 2017). These are usually thought to reflect immature nerve terminals in newly-formed sprouts (Stålberg et al., 1975), although the precise mechanism is yet to be clarified.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hNh8Mo

Detection radius of EMG for fasciculations: empiric study combining ultrasonography and electromyography

Fasciculation potentials are defined by spontaneous activity derived from one whole single motor unit or from part of it (Denny-Brown and Pennybacker 1938; Trojaborg and Buchthal 1965). The same fasciculations potentials may appear repetitively in the same location of a muscle. Occurring at a low intensity in most people, they may also present in "benign fasciculation syndrome" or as a symptom of a wide range of other types of motor neuron lesion (Scheel et al. 1997; Fermont et al. 2010; de Carvalho et al.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jGyGdJ

High-resolution ultrasound in patients with Wartenberg’s migrant sensory neuritis, a case-control study

Wartenberg's migrant sensory neuritis (WMSN) is a rare and exclusively sensory neuropathy of unknown etiology, characterized by sudden numbness of one or multiple cutaneous nerves. Numbness may be preceded by pain in the area of distribution of the involved nerve. In some patients stretching of the affected nerve or moving the limb causes pain in the distribution of the involved nerve.(Nicolle et al., 2001; Stork et al., 2010, Wartenberg, 1958) Although any cutaneous sensory nerve can be involved, deficits most commonly reported involve the sensory branches of the peroneal nerve, the digital branches in the hands, the superficial radial nerve and the sural nerve.(Nicolle et al., 2001; Stork et al., 2010) The disease course is generally benign, usually recurrent, and the impact on daily life being limited.(Nicolle et al., 2001; Stork et al., 2010) An auto-immune etiology has been suggested, although patients who received immunomodulating treatment did not improve.(Nicolle et al., 2001; Simmad et al., 1999)

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hNgXkc

Innate Immune Activation by cGMP-AMP Nanoparticles Leads to Potent and Long-Acting Antiretroviral Response against HIV-1 [INFECTIOUS DISEASE AND HOST RESPONSE]

HIV-1 evades immune detection by the cGAS-STING cytosolic DNA-sensing pathway during acute infection. STING is a critical mediator of type I IFN production, and STING agonists such as cGMP-AMP (cGAMP) and other cyclic dinucleotides elicit potent immune and antitumor response. In this article, we show that administration of cGAMP, delivered by an ultra–pH-sensitive nanoparticle (NP; PC7A), in human PBMCs induces potent and long-acting antiretroviral response against several laboratory-adapted and clinical HIV-1 isolates. cGAMP-PC7A NP requires endocytosis for intracellular delivery and immune signaling activation. cGAMP-PC7A NP-induced protection is mediated through type I IFN signaling and requires monocytes in PBMCs. cGAMP-PC7A NPs also inhibit HIV-1 replication in HIV⁺ patient PBMCs after ex vivo reactivation. Because pattern recognition receptor agonists continue to show more clinical benefits than the traditional IFN therapy, our data present important evidence for potentially developing cGAMP or other STING agonists as a new class of immune-stimulating long-acting antiretroviral agents.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hIt0vC

Critical Functions of IRF4 in B and T Lymphocytes [PILLARS OF IMMUNOLOGY]

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hEGNDd

In This Issue [IN THIS ISSUE]

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zV5XIj

Pillars Article: Requirement for the Transcription Factor LSIRF/IRF4 for Mature B and T Lymphocyte Function. Science. 1997. 275: 540-543 [PILLARS OF IMMUNOLOGY]

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zUHW3S

The Structural Basis for Complement Inhibition by Gigastasin, a Protease Inhibitor from the Giant Amazon Leech [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. Complement is activated by three pathways: classical, lectin, and alternative. The classical and lectin pathways are initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases. Given the role of complement in disease, there is a requirement for inhibitors to control the initiating proteases. In this article, we show that a novel inhibitor, gigastasin, from the giant Amazon leech, potently inhibits C1s and MASP-2, whereas it is also a good inhibitor of MASP-1. Gigastasin is a poor inhibitor of C1r. The inhibitor blocks the active sites of C1s and MASP-2, as well as the anion-binding exosites of the enzymes via sulfotyrosine residues. Complement deposition assays revealed that gigastasin is an effective inhibitor of complement activation in vivo, especially for activation via the lectin pathway. These data suggest that the cumulative effects of inhibiting both MASP-2 and MASP-1 have a greater effect on the lectin pathway than the more potent inhibition of only C1s of the classical pathway.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hFrNF8

Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation [BRIEF REVIEWS]

Regulatory signals provide negative input to immunological networks promoting resolution of acute and chronic inflammation. Galectin-1 (Gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and proresolving activities by targeting multiple immune cell types. Within the innate immune compartment, Gal-1 acts as a resolution-associated molecular pattern by counteracting the synthesis of proinflammatory cytokines, inhibiting neutrophil trafficking, targeting eosinophil migration and survival, and suppressing mast cell degranulation. Likewise, this lectin controls T cell and B cell compartments by modulating receptor clustering and signaling, thus serving as a negative-regulatory checkpoint that reprograms cellular activation, differentiation, and survival. In this review, we discuss the central role of Gal-1 in regulatory programs operating during acute inflammation, autoimmune diseases, allergic inflammation, pregnancy, cancer, and infection. Therapeutic strategies aimed at targeting Gal-1–glycan interactions will contribute to overcome cancer immunosuppression and reinforce antimicrobial immunity, whereas stimulation of Gal-1–driven immunoregulatory circuits will help to mitigate exuberant inflammation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hH1QW0

Complement Regulatory Protein Factor H Is a Soluble Prion Receptor That Potentiates Peripheral Prion Pathogenesis [INFECTIOUS DISEASE AND HOST RESPONSE]

Several complement proteins exacerbate prion disease, including C3, C1q, and CD21/35. These proteins of the complement cascade likely increase uptake, trafficking, and retention of prions in the lymphoreticular system, hallmark sites of early prion propagation. Complement regulatory protein factor H (fH) binds modified host proteins and lipids to prevent C3b deposition and, thus, autoimmune cell lysis. Previous reports show that fH binds various conformations of the cellular prion protein, leading us to question the role of fH in prion disease. In this article, we report that transgenic mice lacking Cfh alleles exhibit delayed peripheral prion accumulation, replication, and pathogenesis and onset of terminal disease in a gene-dose manner. We also report a biophysical interaction between purified fH and prion rods enriched from prion-diseased brain. fH also influences prion deposition in brains of infected mice. We conclude from these data and previous findings that the interplay between complement and prions likely involves a complex balance of prion sequestration and destruction via local tissue macrophages, prion trafficking by B and dendritic cells within the lymphoreticular system, intranodal prion replication by B and follicular dendritic cells, and potential prion strain selection by CD21/35 and fH. These findings reveal a novel role for complement-regulatory proteins in prion disease.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hG6CD1

Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice [CUTTING EDGE]

Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti–TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti–TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti–TIM-3–treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice. Anti–TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen deposition, and TGF-β1 production in lungs. TIM-3 expression was only detected on alveolar macrophages that protect against fibrosis by apoptotic cell clearance. Treatment with anti–TIM-3 mAb inhibited the phagocytic ability of alveolar macrophages in vivo, resulting in the defective clearance of apoptotic cells in lungs. In summary, anti–TIM-3 mAb treatment might cause pneumonitis and it should be used with caution in clinical settings.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zVbe2q

Palmitate Conditions Macrophages for Enhanced Responses toward Inflammatory Stimuli via JNK Activation [INNATE IMMUNITY AND INFLAMMATION]

Obesity is associated with low-grade inflammation and elevated levels of circulating saturated fatty acids, which trigger inflammatory responses by engaging pattern recognition receptors in macrophages. Because tissue homeostasis is maintained through an adequate balance of pro- and anti-inflammatory macrophages, we assessed the transcriptional and functional profile of M-CSF–dependent monocyte-derived human macrophages exposed to concentrations of saturated fatty acids found in obese individuals. We report that palmitate (C16:0, 200 μM) significantly modulates the macrophage gene signature, lowers the expression of transcription factors that positively regulate IL-10 expression (MAFB, AhR), and promotes a proinflammatory state whose acquisition requires JNK activation. Unlike LPS, palmitate exposure does not activate STAT1, and its transcriptional effects can be distinguished from those triggered by LPS, as both agents oppositely regulate the expression of CCL19 and TRIB3. Besides, palmitate conditions macrophages for exacerbated proinflammatory responses (lower IL-10 and CCL2, higher TNF-α, IL-6, and IL-1β) toward pathogenic stimuli, a process also mediated by JNK activation. All of these effects of palmitate are fatty acid specific because oleate (C18:1, 200 μM) does not modify the macrophage transcriptional and functional profiles. Therefore, pathologic palmitate concentrations promote the acquisition of a specific polarization state in human macrophages and condition macrophages for enhanced responses toward inflammatory stimuli, with both effects being dependent on JNK activation. Our results provide further insight into the macrophage contribution to obesity-associated inflammation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hG6zXR

Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN [AUTOIMMUNITY]

Type I IFN and nucleic acid–sensing TLRs are both strongly implicated in the pathogenesis of lupus, with most patients expressing IFN-induced genes in peripheral blood cells and with TLRs promoting type I IFNs and autoreactive B cells. About a third of systemic lupus erythematosus patients, however, lack the IFN signature, suggesting the possibility of type I IFN–independent mechanisms. In this study, we examined the role of type I IFN and TLR trafficking and signaling in xenobiotic systemic mercury-induced autoimmunity (HgIA). Strikingly, autoantibody production in HgIA was not dependent on the type I IFN receptor even in NZB mice that require type I IFN signaling for spontaneous disease, but was dependent on the endosomal TLR transporter UNC93B1 and the endosomal proton transporter, solute carrier family 15, member 4. HgIA also required the adaptor protein-3 complex, which transports TLRs from the early endosome to the late endolysosomal compartments. Examination of TLR signaling pathways implicated the canonical NF-B pathway and the proinflammatory cytokine IL-6 in autoantibody production, but not IFN regulatory factor 7. These findings identify HgIA as a novel type I IFN–independent model of systemic autoimmunity and implicate TLR-mediated NF-B proinflammatory signaling from the late endocytic pathway compartments in autoantibody generation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hG6J1p

CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral Immune Responses in Rainbow Trout [MUCOSAL IMMUNOLOGY]

Chemokines and chemokine receptors have rapidly diversified in teleost fish but their immune functions remain unclear. We report in this study that CCL19, a chemokine known to control lymphocyte migration and compartmentalization of lymphoid tissues in mammals, diversified in salmonids leading to the presence of six CCL19-like genes named CK10a, CK10b, CK12a, CK12b, CK13a, and CK13b. Salmonid CCL19-like genes all contain the DCCL-conserved motif but share low amino acid sequence identity. CK12 (but not CK10 or CK13) is constitutively expressed at high levels in all four trout MALT. Nasal vaccination with a live attenuated virus results in sustained upregulation of CK12 (but not CK10 or CK13) expression in trout nasopharynx-associated lymphoid tissue. Recombinant His-tagged trout CK12a (rCK12a) is not chemotactic in vitro but it increases the width of the nasal lamina propria when delivered intranasally. rCK12a delivered intranasally or i.p. stimulates the expression of CD8α, granulysin, and IFN- in mucosal and systemic compartments and increases nasal CD8α⁺ cell numbers. rCK12a is able to stimulate proliferation of head kidney leukocytes from Ag-experienced trout but not naive controls, yet it does not confer protection against viral challenge. These results show that local nasal production of CK12a contributes to antiviral immune protection both locally and systemically via stimulation of CD8 cellular immune responses and highlight a conserved role for CK12 in the orchestration of mucosal and systemic immune responses against viral pathogens in vertebrates.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hG6xPJ

Thymic-Specific Serine Protease Limits Central Tolerance and Exacerbates Experimental Autoimmune Encephalomyelitis [AUTOIMMUNITY]

The genetic predisposition to multiple sclerosis (MS) is most strongly conveyed by MHC class II haplotypes, possibly by shaping the autoimmune CD4 T cell repertoire. Whether Ag-processing enzymes contribute to MS susceptibility by editing the peptide repertoire presented by these MHC haplotypes is unclear. Thymus-specific serine protease (TSSP) is expressed by thymic epithelial cells and thymic dendritic cells (DCs) and, in these two stromal compartments, TSSP edits the peptide repertoire presented by class II molecules. We show in this article that TSSP increases experimental autoimmune encephalomyelitis severity by limiting central tolerance to myelin oligodendrocyte glycoprotein. The effect on experimental autoimmune encephalomyelitis severity was MHC class II allele dependent, because the lack of TSSP expression conferred protection in NOD mice but not in C57BL/6 mice. Importantly, although human thymic DCs express TSSP, individuals segregate into two groups having a high or 10-fold lower level of expression. Therefore, the level of TSSP expression by thymic DCs may modify the risk factors for MS conferred by some MHC class II haplotypes.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zTmQ6a

IFN-{lambda}4 Attenuates Antiviral Responses by Enhancing Negative Regulation of IFN Signaling [INFECTIOUS DISEASE AND HOST RESPONSE]

Type III IFNs are important mediators of antiviral immunity. IFN-4 is a unique type III IFN because it is produced only in individuals who carry a dG allele of a genetic variant rs368234815-dG/TT. Counterintuitively, those individuals who can produce IFN-4, an antiviral cytokine, are also less likely to clear hepatitis C virus infection. In this study, we searched for unique functional properties of IFN-4 that might explain its negative effect on hepatitis C virus clearance. We used fresh primary human hepatocytes (PHHs) treated with recombinant type III IFNs or infected with Sendai virus to model acute viral infection and subsequently validated our findings in HepG2 cell line models. Endogenous IFN-4 protein was detectable only in Sendai virus–infected PHHs from individuals with the dG allele, where it was poorly secreted but highly functional, even at concentrations < 50 pg/ml. IFN-4 acted faster than other type III IFNs in inducing antiviral genes, as well as negative regulators of the IFN response, such as USP18 and SOCS1. Transient treatment of PHHs with IFN-4, but not IFN-3, caused a strong and sustained induction of SOCS1 and refractoriness to further stimulation with IFN-3. Our results suggest unique functional properties of IFN-4 that can be important in viral clearance and other clinical conditions.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zVb9f8

Transient BAFF Blockade Inhibits Type 1 Diabetes Development in Nonobese Diabetic Mice by Enriching Immunoregulatory B Lymphocytes Sensitive to Deletion by Anti-CD20 Cotherapy [AUTOIMMUNITY]

In NOD mice and also likely humans, B lymphocytes play an important role as APC-expanding autoreactive T cell responses ultimately causing type 1 diabetes (T1D). Currently, humans at high future T1D risk can only be identified at late prodromal stages of disease indicated by markers such as insulin autoantibodies. When commenced in already insulin autoantibody⁺ NOD mice, continuous BAFFR-Fc treatment alone or in combination with anti-CD20 (designated combo therapy) inhibited T1D development. Despite eliciting broader B lymphocyte depletion, continuous combo therapy afforded no greater T1D protection than did BAFFR-Fc alone. As previously observed, late disease stage–initiated anti-CD20 monotherapy did not inhibit T1D, and in this study was additionally found to be associated with development of drug-blocking Abs. Promisingly, NOD mice given transient late disease stage BAFFR-Fc monotherapy were rendered T1D resistant. However, combo treatment abrogated the protective effect of transient BAFFR-Fc monotherapy. NOD mice receiving transient BAFF blockade were characterized by an enrichment of regulatory B lymphocytes that inhibit T1D development through IL-10 production, but this population is sensitive to deletion by anti-CD20 treatment. B lymphocytes from transient BAFFR-Fc–treated mice suppressed T cell proliferation to a greater extent than did those from controls. Proportions of B lymphocytes expressing CD73, an ecto-enzyme operating in a pathway converting proinflammatory ATP to anti-inflammatory adenosine, were also temporarily increased by transient BAFFR-Fc treatment, but not anti-CD20 therapy. These collective studies indicate transient BAFFR-Fc–mediated B lymphocyte depletion elicits long-term T1D protection by enriching regulatory B lymphocytes that are deleted by anti-CD20 cotherapy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hG6Iun

Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen Streptococcus pyogenes [INFECTIOUS DISEASE AND HOST RESPONSE]

Bacteria can cause life-threatening infections, such as pneumonia, meningitis, or sepsis. Antibiotic therapy is a mainstay of treatment, although antimicrobial resistance has drastically increased over the years. Unfortunately, safe and effective vaccines against most pathogens have not yet been approved, and thus developing alternative treatments is important. We analyzed the efficiency of factor H (FH)6-7/Fc, a novel antibacterial immunotherapeutic protein against the Gram-positive bacterium Streptococcus pyogenes. This protein is composed of two domains of complement inhibitor human FH (FH complement control protein modules 6 and 7) that bind to S. pyogenes, linked to the Fc region of IgG (FH6-7/Fc). FH6-7/Fc has previously been shown to enhance complement-dependent killing of, and facilitate bacterial clearance in, animal models of the Gram-negative pathogens Haemophilus influenzae and Neisseria meningitidis. We hypothesized that activation of complement by FH6-7/Fc on the surface of Gram-positive bacteria such as S. pyogenes will enable professional phagocytes to eliminate the pathogen. We found that FH6-7/Fc alleviated S. pyogenes–induced sepsis in a transgenic mouse model expressing human FH (S. pyogenes binds FH in a human-specific manner). Furthermore, FH6-7/Fc, which binds to protein H and selected M proteins, displaced FH from the bacterial surface, enhanced alternative pathway activation, and reduced bacterial blood burden by opsonophagocytosis in a C3-dependent manner in an ex vivo human whole-blood model. In conclusion, FH-Fc chimeric proteins could serve as adjunctive treatments against multidrug-resistant bacterial infections.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zTEAOy

Anti-CD20 Antibody Prevents Red Blood Cell Alloimmunization in a Mouse Model [IMMUNOTHERAPY AND VACCINES]

Alloimmunization against RBCs can cause life-threatening delayed hemolytic transfusion reactions. Anti-CD20 Ab has recently been used to prevent alloimmunization. However, its effects remain unclear, particularly in lymphoid organs. We investigated the impact of murine anti-CD20 Ab in the blood and spleen. We assessed protocols for preventing primary alloimmunization and for abolishing established alloimmunization. Prophylactic protocols prevented alloimmunization. However, anti-CD20 treatment could only limit the further amplification of established alloimmunization. Residual B cell subtype distribution was disrupted in the spleen, but adoptive transfer studies indicated that these cells were neither plasma nor memory cells. Anti-CD20 Ab had a major effect on alloreactive CD4⁺ T cells, increasing the expansion of this population and its CD40 expression, while lowering its CD134 expression, thereby confirming its role in alloimmunization. In conclusion, this study shows that anti-CD20 immunotherapy can prevent RBC Ab development. However, this immunotherapy is limited by the increase in alloreactive CD4⁺ T lymphocytes. Nevertheless, treatment with anti-CD20 Abs should be considered for patients requiring transfusion with a very high risk of alloimmunization and life-threatening complications.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zWqIDp

IL-17A-Induced PLET1 Expression Contributes to Tissue Repair and Colon Tumorigenesis [INNATE IMMUNITY AND INFLAMMATION]

This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC–dependent manner. PLET1 expression was induced in LGR5⁺ colon epithelial cells after DSS treatment. LGR5⁺PLET1⁺ marks a highly proliferative cell population with enhanced expression of IL-17A target genes. PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium and reduced tumor formation in an azoxymethane/DSS model of colitis-associated cancer. Our results suggest that IL-17A–induced PLET1 expression contributes to tissue repair and colon tumorigenesis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zVb6Qu

{gamma}{delta} T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations [IMMUNOTHERAPY AND VACCINES]

Whole-sporozoite vaccines confer sterilizing immunity to malaria-naive individuals by unknown mechanisms. In the first PfSPZ Vaccine trial ever in a malaria-endemic population, V2 T cells were significantly elevated and V9/V2 transcripts ranked as the most upregulated in vaccinees who were protected from Plasmodium falciparum infection. In a mouse model, absence of T cells during vaccination impaired protective CD8 T cell responses and ablated sterile protection. T cells were not required for circumsporozoite protein–specific Ab responses, and T cell depletion before infectious challenge did not ablate protection. T cells alone were insufficient to induce protection and required the presence of CD8α⁺ dendritic cells. In the absence of T cells, CD8α⁺ dendritic cells did not accumulate in the livers of vaccinated mice. Altogether, our results show that T cells were essential for the induction of sterile immunity during whole-organism vaccination.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hG6Gmf

Orchestrating Role of Apoptosis Inhibitor of Macrophage in the Resolution of Acute Lung Injury [INNATE IMMUNITY AND INFLAMMATION]

Appropriate resolution of inflammation is known to be essential in tissue homeostasis. In this study, we evaluated the significance of a macrophage-derived soluble protein, apoptosis inhibitor of macrophage (AIM), in LPS-induced lung injury in mice. After oropharyngeal administration of LPS, the level of free-form serum AIM increased on days 2–4, accompanied by the resolution of inflammation, which was observed in the cellular profile of bronchoalveolar lavage fluid. In an experiment using wild-type (WT) and AIM^–/– mice, the resolution of inflammation was accelerated in AIM^–/– mice when compared with the WT mice, which was reversed when recombinant AIM protein was administered. The changes in the histopathological findings and inflammatory mediators followed similar trends, and the ratio of apoptotic cells was increased in AIM^–/– mice when compared with the WT mice. In vitro analysis showed that macrophage phagocytosis of apoptotic neutrophils was suppressed in the presence of AIM, indicating that anti-resolution property of AIM involves efferocytosis inhibition. In lipidomic analysis of lung tissues, the levels of several lipid mediators increased markedly when LPS was given to WT mice. However, in AIM^–/– mice, the concentrations of these lipid mediators were not significantly upregulated by LPS. These data reflect the significant role of AIM in lipid metabolism; it may suppress lipid metabolites at baseline, and then produce an inflammatory/pathologic pattern in the event of LPS-induced lung injury. Taken together, AIM may play an orchestrating role in the resolution process of inflammation by altering the profile of pulmonary lipid mediators in mice.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zV5VAb

Listeria monocytogenes Replicate in Bone Marrow-Derived CD11c+ Cells but Not in Dendritic Cells Isolated from the Murine Gastrointestinal Tract [INFECTIOUS DISEASE AND HOST RESPONSE]

Recent fate-mapping studies and gene-expression profiles suggest that commonly used protocols to generate bone marrow–derived cultured dendritic cells yield a heterogeneous mixture, including some CD11c^hi cells that may not have a bona fide counterpart in vivo. In this study, we provide further evidence of the discordance between ex vivo–isolated and in vitro–cultured CD11c⁺ cells by analyzing an additional phenotype, the ability to support cytosolic growth of the facultative intracellular bacterial pathogen Listeria monocytogenes. Two days after foodborne infection of mice with GFP-expressing L. monocytogenes, a small percentage of CD103^neg and CD103⁺ conventional dendritic cells (cDC) in the intestinal lamina propria and mesenteric lymph nodes were GFP⁺. However, in vitro infection of the same subsets of cells harvested from naive mice resulted in inefficient invasion by the bacteria (<0.1% of the inoculum). The few intracellular bacteria detected survived for only a few hours. In contrast, cultured CD103^negCD11c⁺ cells induced by GM-CSF readily supported exponential growth of L. monocytogenes. Flt3 ligand–induced cultures yielded CD103⁺CD11c⁺ cells that more closely resembled cDC, with only a modest level of L. monocytogenes replication. For both culture protocols, the longer the cells were maintained in vitro, the more readily they supported intracellular growth. The results of this study suggest that cDC are not a niche for intracellular growth of L. monocytogenes during intestinal infection of mice.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zTmqfX

An open-source method to analyze optokinetic reflex responses in larval zebrafish

Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Seth D. Scheetz, Enhua Shao, Yangzhong Zhou, Clinton L. Cario, Qing Bai, Edward A. Burton
BackgroundOptokinetic reflex (OKR) responses provide a convenient means to evaluate oculomotor, integrative and afferent visual function in larval zebrafish models, which are commonly used to elucidate molecular mechanisms underlying development, disease and repair of the vertebrate nervous system.New methodWe developed an open-source MATLAB-based solution for automated quantitative analysis of OKR responses in larval zebrafish. The package includes applications to: (i) generate sinusoidally-transformed animated grating patterns suitable for projection onto a cylindrical screen to elicit the OKR; (ii) determine and record the angular orientations of the eyes in each frame of a video recording showing the OKR response; and (iii) analyze angular orientation data from the tracking program to yield a set of parameters that quantify essential elements of the OKR. The method can be employed without modification using the operating manual provided. In addition, annotated source code is included, allowing users to modify or adapt the software for other applications.ResultsWe validated the algorithms and measured OKR responses in normal larval zebrafish, showing good agreement with published quantitative data, where available.Comparison with existing method(s)We provide the first open-source method to elicit and analyze the OKR in larval zebrafish. The wide range of parameters that are automatically quantified by our algorithms significantly expands the scope of quantitative analysis previously reported.ConclusionsOur method for quantifying OKR responses will be useful for numerous applications in neuroscience using the genetically- and chemically-tractable zebrafish model.

Graphical abstract

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXrL3e

Language-specific strategy for programming hearing aids — A double-blind randomized controlled crossover study

Voice-aligned compression (VAC) is a method used in Oticon's hearing aids to provide more comfortable hearing without sacrificing speech discrimination. The complex, non-linear compression curve for the VAC strategy is designed based on the frequency profile of certain spoken Western languages. We hypothesized that hearing aids could be further customized for Japanese-speaking users by modifying the compression curve using the frequency profile of spoken Japanese.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zWq2xR

Pediatric type 1 cartilage tympanoplasty outcomes: A comparison of short and long term hearing results

Tympanoplasty is a commonly used procedure in children as in adults. The purposes of this study were to evaluate and report the long term results of type 1 cartilage tympanoplasty in pediatric population. Short term and long term hearing outcomes were compared according to age and perforation location.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hDRFBs

Impact of chemotherapy-induced neurotoxicities on adult cancer survivors’ symptom burden and quality of life

Abstract

Purpose

Limited information is available on the impact of chemotherapy (CTX)-induced neurotoxicity on adult survivors' symptom experience and quality of life (QOL). Purposes were to describe occurrence of hearing loss and tinnitus and evaluate for differences in phenotypic characteristics and measures of sensation, balance, perceived stress, symptom burden, and QOL between survivors who received neurotoxic CTX and did (i.e., neurotoxicity group) and did not (i.e., no neurotoxicity group) develop neurotoxicity. Neurotoxicity was defined as the presence of chemotherapy-induced neuropathy (CIN), hearing loss, and tinnitus. Survivors in the no neurotoxicity group had none of these conditions.

Methods

Survivors (n = 609) completed questionnaires that evaluated hearing loss, tinnitus, stress, symptoms, and QOL. Objective measures of sensation and balance were evaluated.

Results

Of the 609 survivors evaluated, 68.6% did and 31.4% did not have CIN. Of the survivors without CIN, 42.4% reported either hearing loss and/or tinnitus and 48.1% of the survivors with CIN reported some form of ototoxicity. Compared to the no neurotoxicity group (n = 110), survivors in the neurotoxicity group (n = 85) were older, were less likely to be employed, had a higher comorbidity burden, and a higher symptom burden, higher levels of perceived stress, and poorer QOL (all p < .05).

Conclusions

Findings suggest that CIN, hearing loss, and tinnitus are relatively common conditions in survivors who received neurotoxic CTX.

Implications for cancer survivors

Survivors need to be evaluated for these neurotoxicities and receive appropriate interventions. Referrals to audiologists and physical therapists are warranted to improve survivors' hearing ability, functional status, and QOL.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hIxcvr

Mannose-binding lectin deficiency associated with numerous paraspinal neurofibromas

Mannose-binding lectin (MBL) is a protein found in plasma that is part of the innate immune system and can activate the complement cascade.1 It is typically involved with antimicrobial and proinflammatory functions.2

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B7CRU0

The association of maternal prenatal vitamin D levels and child current wheeze

Wheezing is common in early childhood and is associated with subsequent asthma and decreased lung function.1 Prenatally, vitamin D influences immune system and lung development; a role in consequent child wheeze and asthma has been hypothesized.2,3 Previous research has reported associations between 25-dihydroxyvitamin D [25(OH)D] levels and respiratory or atopic outcomes potentially inconsistent by race.4 In this study we examine associations between maternal second trimester and delivery 25(OH)D levels and child current wheeze in the third year of life by maternal race.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z5NZ2s

Hydroxychloroquine as a steroid-sparing agent in an infant with chronic urticaria

Hydroxychloroquine is an antimalarial drug frequently used to reduce inflammation in autoimmune and inflammatory conditions.1,2 In adults, hydroxychloroquine can be used as an alternative agent to treat antihistamine-refractory chronic spontaneous urticaria (CSU).3 It is unknown whether hydroxychloroquine is safe and effective for treating antihistamine-refractory CSU in children. We present the case of a 9-month-old male infant with 5 months of recurrent, unprovoked hives and swelling who was treated safely and successfully with hydroxychloroquine.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B6rtrr

Schnitzler syndrome with IgG gammopathy and elevated IL-1β and IL-17 in skin biopsy

Schnitzler syndrome is a rare disorder known for chronic urticarial rash, systemic inflammation, and monoclonal gammopathy.1 Historically it has been associated with immunoglobulin M (IgM), but in the past 20 years new cases have been described that include variants with an immunoglobulin G (IgG) gammopathy. We report a case of Schnitzler syndrome associated with IgG gammopathy and increased expression of interleukin (IL)-1β and IL-17 by immunohistochemistry at skin biopsy examination.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z8d2Sj

Advances in rhinitis—models and mechanisms

To summarize studies highlighting recent advances in rhinitis-related research in the past 2 years.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B7CDME

Dexamethasone for inpatient childhood asthma exacerbations is as effective as short-acting corticosteroid treatment

Acute asthma exacerbations result in over 130,000 childhood hospitalizations in the United States annually.1 Systemic corticosteroids (SCS) are a fundamental component of exacerbation management and reduce relapse rates after hospital discharge.2 Use of prednisolone or other short-acting SCS during hospitalization may require continuation of this medication after hospital discharge, yet a recent study demonstrated that only about half of these prescriptions are filled within 3–7 days of discharge.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z4zSu4

The Perception of Breathiness in the Voices of Pediatric Speakers

The perception of pediatric voice quality has been investigated using clinical protocols developed for adult voices and acoustic analyses designed to identify important physical parameters associated with normal and dysphonic pediatric voices. Laboratory investigations of adult dysphonia have included sophisticated methods, including a psychoacoustic approach that involves a single-variable matching task (SVMT), characterized by high inter- and intra-listener reliability, and analyses that include bio-inspired models of auditory perception that have provided valuable information regarding adult voice quality.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zmt8Mx

Diffuse Liver Diseases: Role of imaging

Nowadays the most common imaging techniques allow to study focal liver lesions with high diagnostic accuracy but a relatively recent emerging field of interest is represented by diffuse liver disease. They include a variegated series of storage and metabolic pathologies (i.e. iron overload disorders and steatosis) requiring a precise diagnosis not always possible at imaging due to the overlapping of findings at conventional ultrasound, CT or MR studies.In recent years several imaging tecniques and specific softwares have been developed, especially for ultrasound and MR imaging, in order to identify different parameters useful in the noninvasive recognition and follow-up of these diffusely processes diffusely involving the liver.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zUdYgr

Effect of left lateral tilt-down position on cecal intubation time: a 2-center, pragmatic, randomized controlled trial

Colonoscopy insertion is technically challenging, time-consuming and painful, especially for the sigmoid. Several pilot studies indicated (left) tilt-down position could facilitate insertion procedure, but no formal trials have been published to demonstrate its efficacy. We performed the study to verify the benefits of left lateral tilt-down position (LTDP) on insertion process.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zWHiRB

Prognostic factors affecting outcomes in patients with malignant GI bleeding treated with a novel endoscopically delivered hemostatic powder

Endoscopic hemostatic techniques remain poorly effective for GI tumor bleeding. We assessed Tc-325 (Hemospray) for this indication and determined possible predictors of decreased recurrent bleeding and improved 6-month survival in affected patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jbQn0H

Dissection-enabled scaffold-assisted resection (DeSCAR): a novel technique for resection of residual or non-lifting GI neoplasia of the colon (with video)

Due to previous manipulation or submucosal invasion, GI lesions referred for endoscopic mucosal resection (EMR) frequently have flat areas of visible tissue that cannot be snared. Current methods for treating residual tissue may lead to incomplete eradication or not allow complete tissue sampling for histologic evaluation. Our aim is to describe dissection-enabled scaffold-assisted resection (DeSCAR), a new technique combining circumferential ESD with EMR for removal of superficial non-lifting or residual "islands" with suspected submucosal involvement/fibrosis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zXizfH

Comparing eye movements during position tracking and identity tracking: No evidence for separate systems

Abstract

There is an ongoing debate as to whether people track multiple moving objects in a serial fashion or with a parallel mechanism. One recent study compared eye movements when observers tracked identical objects (Multiple Object Tracking—MOT task) versus when they tracked the identities of different objects (Multiple Identity Tracking—MIT task). Distinct eye-movement patterns were found and attributed to two separate tracking systems. However, the same results could be caused by differences in the stimuli viewed during tracking. In the present study, object identities in the MIT task were invisible during tracking, so observers performed MOT and MIT tasks with identical stimuli. Observer were able to track either position and identity depending on the task. There was no difference in eye movements between position tracking and identity tracking. This result suggests that, while observers can use different eye-movement strategies in MOT and MIT, it is not necessary.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jFAweR

Endometrial Cancer Incidence Rising in the US and Worldwide

Diagnoses of endometrial cancer have increased worldwide in recent years, with rates rising in more than half of the 43 countries studied during the decade ending around 2010, a team of international researchers has shown.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AX7tqy

Primary extra-axial, para-articular Chordoma of the knee. A case report and the review of literaturę

Abstract

Chordoma is a rare malignant tumor demonstrating notochordal differentiation [1]. It almost invariably arises in the axial skeleton however rare examples of primary extra-axial chordomas have been reported [2-5]. We describe herein, for the first time, a primary conventional chordoma arising in the synovium of the knee joint.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AXT6SO

Reply to the Letter to the Editor: “Extracapsular dissection versus superficial parotidectomy in benign parotid gland tumors: The Vienna Medical School experience”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AX9frP

Peroxisome proliferator activated receptor-gamma stimulation for prevention of 5-fluorouracil-induced oral mucositis in mice

Abstract

Background

Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis.

Methods

C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected.

Results

The RGZ did not affect the 5-FU-induced decrease in mouse body weight. The 5-FU caused loss of epithelial architecture, collagen fiber impairment, and inflammatory infiltration. The RGZ reduced leukocyte infiltration, preserved tissue structure, and dampened the 5-FU-induced expression of p53 and matrix metalloproteinase (Mmp)-2 after 5 days, and of Mmp-2 and interleukin (Il-1β after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) proteins and restored collagen protein levels.

Conclusion

The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iykL5Y

Free gracilis muscle transfer for smile reanimation after treatment for advanced parotid malignancy

Abstract

Background

The purpose of this study was to characterize the outcomes of free gracilis muscle transfer for delayed smile reanimation after radical parotidectomy.

Methods

A retrospective chart review of patients who underwent free gracilis muscle transfer for smile reanimation after radical parotidectomy between 2003 and 2016 was performed. Patient-reported quality of life (Facial Clinimetric Evaluation Scale [FaCE]), physician-reported facial function ("eFACE" facial grading scale), and oral commissure excursion were compared preoperatively and postoperatively.

Results

Twelve patients were identified with prior surgery and adjuvant therapy (radiotherapy in 6 cases and chemoradiotherapy in 6 cases). Significant postoperative improvements were demonstrated for ipsilateral commissure excursion with smile (preoperatively: −2.2 mm [SD 2.3 mm] vs postoperatively: 7.9 mm [SD 2.5 mm]; P = .002), with meaningful smile achieved in 11 of 12 cases (91.7%). The average duration of facial paralysis before intervention was 72 months (range 12-204 months).

Conclusion

Free gracilis muscle transfer is an option for dynamic smile reanimation in select patients who have undergone treatment for advanced parotid malignancy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AWh8xu

Intensity-modulated radiotherapy for elderly patients with nasopharyngeal carcinoma

Abstract

Background

The purpose of this study was to evaluate the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for elderly patients with nasopharyngeal carcinoma (NPC).

Methods

Fifty-two patients treated with IMRT were eligible for study inclusion. Comorbidity was rated using the Adult Comorbidity Evaluation-27 (ACE-27) system.

Results

Twenty-six patients (50.0%) had an ACE-27 score of 1; and 6 (11.5%) had an ACE-27 score of 2. Eleven patients had died and 5 (45.5%) of them died of NPC. Two patients had developed local recurrence only, 1 had developed regional recurrence only, and 7 had developed distant metastasis only. The locoregional failure-free survival, distant failure-free survival, cancer-specific survival (CSS), and overall survival (OS) rates at 5 years were 92.6%, 83.7%, 84.9%, and 69.4%, respectively.

Conclusion

The results of treating elderly patients with NPC by IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for elderly patients with NPC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2izWw7r

Safety and effectiveness of endovascular embolization or stent-graft reconstruction for treatment of acute carotid blowout syndrome in patients with head and neck cancer: Case series and systematic review of observational studies

Abstract

Background

Indications for treatment and outcomes after endovascular management of carotid blowout syndrome for patients with head and neck cancer are not well defined. We investigated the safety and effectiveness of endovascular embolization and stent-graft reconstruction.

Methods

A literature review was performed for studies published between 2001 and 2015 with relevance to treatment outcomes. Our institutional database was examined to identify patients treated with endovascular techniques.

Results

A total of 266 patients were included. Rates of procedural stroke were higher after embolization of internal carotid artery (ICA)/common carotid artery (CCA) compared to stent graft (embolization 10.3%; stent graft 2.5%; P < .02). Stent graft of ICA/CCA was associated with higher rates of recurrent bleeding (embolization 9.1%; stent graft 31.9%; P < .01).

Conclusion

Both embolization and stent grafts are safe therapeutic options for acute carotid blowout syndrome. Embolization for ICA/CCA carotid blowout syndrome was associated with higher risks of procedural stroke and lower recurrent bleeding compared to stent grafts.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AX9fbj

Letter to the Editor regarding “Extracapsular dissection versus superficial parotidectomy in benign parotid gland tumors: The Vienna Medical School experience”

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B72hkA

Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer

Abstract

Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n=15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0.5% wt/wt) diet. Mice consumed these diets ad libitum throughout study and after six weeks were orthotopically injected with M-Wnt murine mammary tumor cells, a model of estrogen receptor (ER)-negative claudin-low breast cancer. Compared with controls, DIO mice displayed adipose dysregulation and metabolic perturbations including increased mammary adipocyte size, cyclooxygenase-2 (COX-2) expression, inflammatory eicosanoid levels, macrophage infiltration, and prevalence of crown-like structures (CLS). DIO mice (relative to controls) also had increased systemic inflammatory cytokines and decreased adipocyte expression of peroxisome proliferator-activated receptor gamma (PPARγ) and other adipogenesis-regulating genes. Supplementing the DIO diet with resveratrol prevented obesity-associated increases in mammary tumor growth, mammary adipocyte hypertrophy, COX-2 expression, macrophage infiltration, CLS prevalence, and serum cytokines. Resveratrol also offset the obesity-associated downregulation of adipocyte PPARγ and other adipogenesis genes in DIO mice. Our findings suggest that resveratrol may inhibit obesity-associated inflammation and claudin-low breast cancer growth by inhibiting adipocyte hypertrophy and associated adipose tissue dysregulation that typically accompanies obesity. This article is protected by copyright. All rights reserved

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2hEMZLx

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

Abstract

Background

Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese.

Objective

The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan.

Methods

The guideline was created according to the basic principles in creating the guidelines of JSGO.

Results

The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions.

Conclusion

Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mLqyK0

Cancers, Vol. 9, Pages 158: Alcohol and Cancer Stem Cells

Cancers, Vol. 9, Pages 158: Alcohol and Cancer Stem Cells

Cancers doi: 10.3390/cancers9110158

Authors: Mei Xu Jia Luo

Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and differentiation capacity, play an important role in tumor initiation, progression, metastasis, recurrence, and therapy resistance. The recent research evidence suggests that alcohol increases the CSC population in cancers, which may underlie alcohol-induced tumor promotion. This review discusses the recent progress in the research of alcohol promotion of CSC and underlying cellular/molecular mechanisms. The review will further explore the therapeutic potential of CSC inhibition in treating alcohol-induced tumor promotion.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zPW9j7

PulmCrit- APRV: Resurrection of the open-lung strategy?

APRV is often used in surgical ICUs, but not medical ICUs.  APRV may be viewed as a "new" technique by medical intensivists, whereas it's been used for decades in surgical ICUs with great results.  A fresh RCT may help resolve this.

EMCrit by Josh Farkas.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zY3oms

Novel non-alcoholic steatohepatitis model with histopathological and insulin-resistant features

Although several non-alcoholic steatohepatitis (NASH) models have been reported to date, few of these models fully reflect the histopathology and pathophysiology of human NASH. The aim of this study was to establish a novel NASH model by feeding a high-fat (HF) diet and administering both carbon tetrachloride (CCl₄) and the Liver X receptor agonist T0901317. Male C57BL/6J mice were divided into four groups (each n = 5): HF, HF + CCl₄, HF + T0901317, and the novel NASH model (HF + CCl₄ + T0901317). CCl₄ (0.1 mL/kg) and T0901317 (2.5 mg/kg) were intraperitoneally administered four times and five times, respectively. The livers of the novel NASH model group presented a whitish colour. The serum levels of TNF-α and IL-6 were significantly increased in the novel NASH model group, and mice in this group exhibited histopathological features and insulin resistance reflective of NASH, i.e., macrovesicular hepatic steatosis, ballooning hepatocytes, Mallory-Denk bodies, lobular inflammation and fibrosis. The novel NASH model group presented significantly upregulated expression levels of mRNAs related to lipogenesis, oxidative stress, fibrosis and steatosis and significantly downregulated expression levels of mRNAs related to triglyceride export. We successfully established a novel experimental NASH model that exhibits similar histopathology and pathophysiology to human NASH.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AW0MVI

Issue Cover (November 2017)

Cover image by Dr. Natalie Doig (MRC Brain Network Dynamics Unit, Department of Pharmacology, Oxford). The cover image is of a frontal section of mouse brain showing many regions of the basal ganglia. The section was triple-immunostained to reveal tyrosine hydroxylase (TH; cyan), parvalbumin (PV; green) and choline acetyltransferase (magenta).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2zj1hNd