Update on the Treatment of Anaplastic Large Cell Lymphoma

Abstract

Purpose of Review

Given the rarity of anaplastic large cell lymphoma (ALCL), studies evaluating new therapies have typically grouped ALCL together with other peripheral T cell lymphomas (PTCL). Thus, the treatment paradigm for ALCL largely mirrors that of PTCL in general. In this review, we discuss the current standard of care as well as emerging therapies, including antibody-based drugs, in systemic ALCL as well as primary cutaneous and breast implant-associated ALCL.

Recent Findings

High CD30 expression in ALCL has allowed the use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in both systemic and primary cutaneous ALCL. Recent clinical trials with brentuximab have shown substantial activity in the relapsed/refractory setting. A randomized phase III study is ongoing comparing brentuximab plus CHP (cyclophosphamide, doxorubicin, prednisone) with standard CHOP in the front-line setting.

Summary

The use of targeted therapies and other novel agents have improved outcomes for ALCL patients and in the future can complement or even replace the current standard of care and front-line treatment options.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G3qKtW

Effect of dental monomers and initiators on Streptococcus mutans oral biofilms

Publication date: Available online 6 March 2018
Source:Dental Materials
Author(s): Nancy J. Lin, Courtney Keeler, Alison M. Kraigsley, Jing Ye, Sheng Lin-Gibson
ObjectiveResin-based composites are known to elute leachables that include unincorporated starting materials. The objective of this work was to determine the effect of common dental monomers and initiators on Streptococcus mutans biofilm metabolic activity and biomass.MethodsS. mutans biofilms were inoculated in the presence of bisphenol A glycerolate dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), camphorquinone (CQ), and ethyl 4-(dimethylamino)benzoate (4E) at 0.01μg/mL up to 500μg/mL, depending on the aqueous solubility of each chemical. Biofilms were evaluated at 4h and 24h for pH (n=3–8), biomass via crystal violet (n=12), metabolic activity via tetrazolium salt (n=12), and membrane permeability for selected concentrations via confocal microscopy (n=6). Parametric and non-parametric statistics were applied.Results500μg/mL TEGDMA reduced 24h metabolic activity but not biomass, similar to prior results with leachables from undercured BisGMA-TEGDMA polymers. 50μg/mL BisGMA reduced biofilm biomass and activity, slightly delayed the pH drop, and decreased the number of cells with intact membranes. 100μg/mL CQ delayed the pH drop and metabolic activity at 4h but then significantly increased the 24h metabolic activity. 4E had no effect up to 10μg/mL.SignificanceMonomers and initiators that leach from resin composites affect oral bacterial biofilm growth in opposite ways. Leachables, which can be released for extended periods of time, have the potential to alter oral biofilm biomass and activity and should be considered in developing and evaluating new dental materials.

Graphical abstract

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G4ASmw

Changes in filaggrin degradation products and corneocyte surface texture by season

Summary

Background

During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather-exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF).

Objectives

To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults.

Methods

Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18–40 years and 40 aged ≥ 70 years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface texture was done (Dermal Texture Index, DTI). Potential confounders were registered and adjusted for.

Results

In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self-reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the summer, and female participants had higher NMF levels than male participants.

Conclusions

Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Ftn8nt

Retrospective analysis on the clinical outcomes of recombinant human soluble thrombomodulin for disseminated intravascular coagulation syndrome associated with solid tumors

Abstract

Background

Recombinant human soluble thrombomodulin (rTM) has been established and introduced in the clinic as a standard treatment for disseminated intravascular coagulation (DIC). However, the efficacy and safety of rTM for DIC associated with solid tumors (DIC-STs) have not been fully established. Here, we performed a retrospective analysis of the clinical outcomes of rTM for DIC-STs and considered a treatment strategy with rTM for DIC-STs.

Methods

Patients with DIC-STs between November 2009 and March 2016 in 2 cancer core hospitals were retrospectively analyzed. Data, including patient background, treatment course, and clinical outcomes of rTM for DIC-STs, were extracted. The clinical outcomes were evaluated by comparing the DIC score, resolution rate, and overall survival (OS) duration.

Results

The study included 123 patients with DIC-STs. The median OS in all patients was 41 days. The DIC resolution rate was 35.2%. DIC scores and DIC-related blood test data (fibrin degradation product and prothrombin time-international normalized ratio) significantly improved at the end of rTM administration (P < 0.001). The OS duration was longer in patients who were treated with chemotherapy after DIC onset than in those who were not treated with chemotherapy (median, 178 days vs. 17 days, P < 0.001). In both univariate and multivariate analyses, chemotherapy after DIC onset showed the strongest association with OS.

Conclusions

rTM can at least temporarily improve or maintain the state of DIC-STs. It is suggested that prolongation of survival can be expected when control of DIC and treatment of the underlying disease are compatible.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oOC7yD

Head and voice tremor improving with immunotherapy in an anti-NF155 positive CIDP patient

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy with NF155 antibodies (anti-NF155+) constitutes a specific chronic inflammatory demyelinating polyradiculoneuropathy subset with a high incidence of limb's tremor and poor response to conventional therapies. We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy anti-NF155+ with a severe tremor involving limbs, head and voice that responded very well to rituximab. This response correlated with a sharp decrease in the anti-NF155 titers. This case is the first report associating head and voice tremor to chronic inflammatory demyelinating polyradiculoneuropathy, reinforces the hypothesis of the cerebellar origin of this tremor and provides indirect evidence that the antibodies may be the cause of the tremor in these patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FhrAX2

Phosphodiesterase-5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Abstract

Background

Traumatic cerebrovascular injury (TCVI), a common consequence of traumatic brain injury (TBI), presents an attractive therapeutic target. Because phosphodiesterase-5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. This study aims to: (1) measure cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and change in CVR after a single dose of sildenafil (ΔCVR) in chronic TBI compared to uninjured controls; (2) examine the safety and tolerability of 8-week sildenafil administration in chronic symptomatic moderate/severe TBI patients; and as an exploratory aim, (3) assess the effect of an 8-week course of sildenafil on chronic TBI symptoms.

Methods

Forty-six subjects (31 chronic TBI, 15 matched healthy volunteers) were enrolled. Baseline CBF and CVR before and after administration of sildenafil were measured. Symptomatic TBI subjects then completed an 8-week double-blind, placebo-controlled, crossover trial of sildenafil. A neuropsychological battery and neurobehavioral symptom questionnaires were administered at each study visit.

Results

After a single dose of sildenafil, TBI subjects showed a significant increase in global CVR compared to healthy controls (P < 0.001, d = 0.9). Post-sildenafil CVR maps showed near-normalization of CVR in many regions where baseline CVR was low, predominantly within areas without structural abnormalities. Sildenafil was well tolerated. Clinical Global Impression (CGI) scale showed a trend toward clinical improvement while on sildenafil treatment.

Findings

Single-dose sildenafil improves regional CVR deficits in chronic TBI patients. CVR and ΔCVR are potential predictive and pharmacodynamic biomarkers of PDE5 inhibitor therapy for TCVI. Sildenafil is a potential therapy for TCVI.

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

Nomograms forecasting long-term overall and cancer-specific survival of patients with oral squamous cell carcinoma

Abstract

Our aim was to establish a "nomogram" model to forecast the overall survival (OS) and cancer-specific survival (CSS) of oral squamous cell carcinoma (OSCC) patients. The clinicopathological data for the 10,533 OSCC patients were collected from the Surveillance, Epidemiology and End Results (SEER) database. We used a credible random split-sample method to divide 10,533 patients into two cohorts: 7046 patients in the modeling cohort and 3487 patients in the external validation cohort (split-ratio = 2:1). The median follow-up period was 32 months (1–119 months). We developed nomograms to predict 5- and 8-year OS and CSS of OSCC patients with a Cox proportional hazards model. The precision of the nomograms was assessed by the concordance index (C-index) and calibration curves through internal and external validation. The C-indexes of internal validation regarding 5- and 8-year OS and CSS were 0.762 and 0.783, respectively. In addition, the external validation's C-indexes were 0.772 and 0.800. Based on a large-sample analysis targeting the SEER database, we established two nomograms to predict long-term OS and CSS for OSCC patients successfully, which can assist surgeons in developing a more effective therapeutic regimen and conducting personalized prognostic evaluations.

We successfully established two nomograms predicting overall survival(OS) and cancer-specific survival(CSS) of OSCC patients collected from SEER database. The validation results of the nomograms through the concordance index (C-index) and calibration curves showed that the model were credible, which can assist surgeons in developing a more effective therapeutic regimen and conducting personalized prognostic evaluations.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D7aGV3

PAK4 pathway as a potential therapeutic target in pancreatic cancer

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D5Frd3

Background and rationale of the eXalt3 trial investigating X-396 in the treatment of ALK+ non-small-cell lung cancer

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FYvCR7

B cells in multiple sclerosis therapy—A comprehensive review

For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and the disease was always regarded as a T cell-mediated disorder. Recent evidence shows that there is an antigen-driven B-cell response in the central nervous system of patients with MS, and memory B cells/plasma cells are detectable in MS lesions. The striking efficacy of B cell-depleting therapies in reducing the inflammatory activity of the disease highlights that B cells may play more pathogenetic roles than expected. B cells express several unique characteristic markers on their surface, for example, CD19, CD20 molecules, that provide selective targets for monoclonal antibodies. In this respect, several B cell-targeted therapies emerged, including anti-CD20 antibodies (rituximab, ocrelizumab, and ofatumumab), anti-CD19 antibody (inebilizumab), and agents targeting the BAFF/APRIL signaling pathway (atacicept, belimumab, and LY2127399). In this review, we discuss, in detail, the immunobiology of B cells and their protective and destructive roles in MS pathogenesis. In the second part, we list the completed and ongoing clinical trials investigating the safety and efficacy of B cell-related monoclonal antibodies in MS.

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

Interdisciplinary Approaches to Facilitate Return-to-Driving and Return-to-Work in Mild Stroke: A Position Paper

Publication date: Available online 6 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Suzanne Perea Burns, Jaclyn Schwartz, Shannon Scott, Hannes Devos, Mark Kovic, Ickpyo Hong, Abiodun Akinwuntan
Adults with mild stroke face substantial challenges resuming valued roles in the community. The term "mild" provides false representation of the lived experience for many adults with mild stroke who may continue to experience persistent challenges and unmet needs. Rehabilitation practitioners can identify and consequently intervene to facilitate improved independence, participation, and quality of life by facilitating function and reducing the burden of lost abilities among adults with mild stroke. The [blind task force] identified two important, and often interdependent, goals that frequently arise among adults living with mild stroke that must be addressed to facilitate improved community reintegration: (1) return-to-driving and (2) return-to-work. Adults with mild stroke may not be receiving adequate rehabilitative services to facilitate community reintegration for several reasons but primarily because current practice models are not designed to meet such needs of this specific population. Thus, the [blind task force] convened to review current literature and practice trends to 1) identify opportunities based on the evidence of assessment and interventions, for return-to-driving and return-to-work, and 2) identify gaps in the literature that must be addressed to take advantage of the opportunities. Based on findings, the task force proposes a new interdisciplinary practice model for adults with mild stroke that are too often discharged from the hospital to the community without needed services to enable successful return to driving and work.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D73p7z

Safety and Efficacy of Autologous Tissue-derived Mesenchymal Stem Cells for Radiation-Induced Xerostomia: A Randomized, Placebo-Controlled Phase I/II Trial (MESRIX)

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Christian Grønhøj, David H. Jensen, Peter Vester-Glowinski, Siri Beier Jensen, Allan Bardow, Roberto S. Oliveri, Lea Munthe Fog, Lena Specht, Carsten Thomsen, Sune Darkner, Michael Jensen, Vera Müller, Katalin Kiss, Tina Agander, Elo Andersen, Anne Fischer-Nielsen, Christian von Buchwald
BackgroundSalivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia.Patient and MethodsThis randomized, placebo-controlled phase I/II trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration.ResultsNo adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; p=0.048) and four months (50%; p=0.003), but not in the placebo-arm (p=0.6 and p=0.8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, p=0.035) and difficulties in eating solid foods (-2%, p=0.008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (p=0.04 and p=0.02, respectively). MRIs showed no significant differences between groups in gland size or intensity (p < 0.05).ConclusionsASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G1vHUi

The Biology of SBRT: LQ or Something New?

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): J Martin Brown




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D6e6Hy

A method for automatic selection of parameters in NTCP modelling

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Damianos Christophides, Ane L. Appelt, Arief Gusnanto, John Lilley, David Sebag-Montefiore
PurposeIn this study we present a fully automatic method to generate multiparameter normal tissue complication probability (NTCP) models and compare its results with a published model of the same patient cohort.Methods and MaterialsData were analysed from 345 rectal cancer patients treated with external radiotherapy to predict the risk of patients developing grade 1 or ≥2 cystitis. In total 23 clinical factors were included in the analysis as candidate predictors of cystitis.Principal component analysis (PCA) was used to decompose the bladder dose volume histogram (DVHs) into 8 principal components (PCs), explaining more than 95% of the variance. The dataset of clinical factors and PCs was divided into training (70%) and test (30%) datasets, with the training dataset used by the algorithm to compute an NTCP model. The first step of the algorithm was to obtain a bootstrap sample, followed by multicollinearity reduction using the variance inflation factor (VIF) and genetic algorithm optimisation to determine an ordinal logistic regression model that minimises the Bayesian information criterion (BIC). The process was repeated 100 times and the model with the minimum BIC was recorded on each iteration. The most frequent model was selected as the final 'automatically generated model' (AGM). The published model and AGM were fitted on the training datasets and the risk of cystitis was calculated.ResultsThe two models had no significant differences in predictive performance both for the training and test datasets (p-value>0.05), and found similar clinical and dosimetric factors as predictors. Both models exhibited good explanatory performance on the training dataset (p-values>0.44) which was reduced on the test datasets (p-values<0.05).ConclusionsThe predictive value of the AGM is equivalent to the expert-derived published model. It demonstrates potential in saving time, tackling problems with a large number of parameters and standardising variable selection in NTCP modelling.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G1ex98

The Resident Individual Development Plan as a Guide for Radiation Oncology Mentorship

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Huaising C. Ko, Randall J. Kimple




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FkQ3qn

Total Mesorectal Excision versus Local Excision Following Preoperative Chemoradiotherapy in Rectal Cancer with Lymph Node Metastasis: A Propensity Score-Matched Analysis

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Young Seob Shin, Jin-hong Park, Sang Min Yoon, Jin Cheon Kim, Chang Sik Yu, Seok-Byung Lim, In Ja Park, Tae Won Kim, Yong Sang Hong, Kyu-pyo Kim, Eun Kyung Choi, Seung Do Ahn, Sang-Wook Lee, Jong Hoon Kim
BackgroundLocal excision (LE) in good responders to preoperative chemoradiotherapy (PCRT), which is considered as a good alternative to total mesorectal excision (TME) in early-stage rectal cancer, is not commonly recommended for node-positive (cN+) cases. This study aimed to determine whether LE outcomes were comparable to TME outcomes in cN+ rectal cancer patients who were good responders.Materials and MethodsThis retrospective study included clinical T2-3 and cN+ low rectal cancer patient who received PCRT followed by TME or LE. Clinical stage T1 or T4 tumors, upper-to-middle rectal tumors (>7 cm from anal verge), and synchronous distant metastases were excluded. Lymph nodes ≥5 mm in size were defined as tumor-positive, and patients with metastatic lymph nodes >20 mm in size were excluded. Preoperative chemoradiotherapy comprised radiation (50–50.4 Gy/25–28 fractions over 5 weeks) with two cycles of 5-fluorouracil or oral capecitabine. Propensity scores were computed from tumor and patient variables and used for one-to-one matched analysis. Local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were compared between the two matched groups.ResultsBetween January 2007 and December 2013, 563 and 55 patients underwent TME and LE, respectively. Median follow-up period was 54 months. In propensity score-matched analysis, 48 patients were included in each group. No statistical differences were observed in 3-year LRFS (97.9% vs. 97.9%, p = 0.994), 3-year DFS (91.5% vs. 91.4%, p = 0.968), or 3-year OS (93.7% vs. 97.9%, p = 0.809) between TME and LE groups.ConclusionsIn clinical N+ rectal cancer patients, oncological outcomes of PCRT followed by LE were comparable to those of TME; this finding might be applicable only to those patients with good response in the primary tumor and small lymph node metastases.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G1hCpX

Contemporary statewide practice pattern assessment of the palliative treatment of bone metastasis

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Daniel E. Spratt, Brandon Mancini, James A. Hayman, Thomas Boike, Lori Pierce, Jean M. Moran, Michael M. Dominello, Mark Fireman, Kent Griffith, Shruti Jolly
PurposePalliative radiotherapy for bone metastases is often viewed as a single entity, despite national guidelines providing input principally only for painful uncomplicated bone metastases. Data surrounding the treatment of bone metastases is often gleaned from questionnaires of what providers would theoretically do in practice or population-based data lacking critical granular information. Herein, we investigate the real-world treatment of bone metastases with radiotherapy.Methods and MaterialsTwenty diverse institutions across the state of XXXXX had data extracted on their 10 most recent cases of radiotherapy delivered for the treatment of bone metastases at their institution between January and February of 2017. Uni- and multivariable binary logistic regression was used to assess use of single fraction (8 Gy x 1) radiotherapy.ResultsA total of 196 cases were eligible for inclusion. Twenty-eight different fractionation schedules were identified. The most common schedule was 3 Gy x 10 fractions (n=100, 51.0%), 4 Gy x 5 fractions (n=32, 16.3%), and 8 Gy x 1 (n=15, 7.7%). Significant predictors for use of single fraction radiotherapy were presence of oligometastatic disease (p=0.008), prior overlapping radiotherapy (p=0.050), and academic practice type (p=0.039). Twenty-nine cases (14.8%) received >10 fractions (median 15, range 11-20 fractions). Intensity modulated radiotherapy was used in 14 cases (7.1%), stereotactic body radiotherapy in 11 cases (5.6%), and image guidance with cone beam CT in 11 cases (5.6%). Amongst simple painful bone metastases (no prior surgery, cord compression, fracture, soft tissue extension, or overlapping prior radiotherapy; n=70), only 12.9% were treated with 8 Gy x 1.ConclusionsBone metastases represent a heterogeneous disease, and the radiotherapeutic treatment of bone metastases is similarly diverse. Future work is needed to understand barrier to single fraction use, and clinical trials are necessary to establish appropriate guidelines for the breadth of this complex disease.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D4XrEx

Scholarly Impact of Student Participation in Radiation Oncology Research

Publication date: Available online 6 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): M. Paracha, K.N. Kim, M.M. Qureshi, A. Shah, A. Agarwal, T. Sachs, S. Sarfaty, A.E. Hirsch
IntroductionLiterature evaluating student authorship has used the H-index (Hi), a measure of scholarly impact. However, student authorship over time is less well defined. In this study, we evaluated the rate of non-doctoral student authors publishing in an academic journal over time. Additionally, we analyzed the effects student authors have on the scholarly impact of corresponding authors (CA) by comparing their respective Hi.MethodsWe created a database of authors that published articles in the International Journal of Radiation Oncology Biology Physics (IJROBP) in 2006, 2010, and 2014 that included CA, degree and student author designations. CAs' Hi were obtained from Scopus (scopus.com). Student authorship rates were compared between the sampled years. The data was divided into two groups, CA publishing with student authors (SA) and those without (nSA). CAs' median and mean Hi with standard deviation (sd) and a 95% confidence interval (CI) were compared between SA and nSA.ResultsA total of 1,728 published articles were identified with 1,477 unique CA. Percentage of published articles with student authors increased from 44.4% in 2006, 52.9% in 2010 to 55.9% in 2014, p=0.0003. In overall analysis, mean Hi was higher for SA as compared to nSA (24.3 vs. 22.9), although this did not achieve statistical significance (p=0.094). Mean Hi (sd) in 2006, 2010 and 2014 were 27.9 (16.6), 23.6 (16.7) and 18.5 (14.6), respectively. Mean Hi was significantly higher for SA compared to nSA in years 2006 (29.5 vs. 26.6, p=0.048) and 2010 (24.9 vs. 21.9, p=0.038) but not in 2014 (18.5 vs. 18.4, p=0.963).ConclusionStudent authorship rates in IJROBP are increasing. The data suggest that student participation in research may benefit both corresponding and student authors. Creating and expanding research programs to integrate research into medical education may enhance students' experience and encourage interest in radiation oncology.

Teaser

Student authorship rates over time are ill defined. This is an analysis of the effects of student authorship on scholarly impact in radiation oncology by comparing the H-indices of corresponding authors in IJROBP that published with and without student authors in 2006-2014. Students are not a detriment to scholarly productivity; student authorship rates increased and corresponding authors publishing with student authors had higher H-indices compared to those that did not publish with student authors.


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

Effect of perioperative opioids on cancer-relevant circulating parameters: mu opioid receptor and TLR4 activation potential, and proteolytic profile

Purpose: To investigate the potential interplay between opioid analgesia and tumour metastasis through modulation of μ opioid receptor (MOR), Toll-like receptor 4 (TLR4) activation, and matrix degradation potential. Experimental design: Plasma samples were collected from 60 patients undergoing elective lower limb joint replacement pre-operatively and at 3, 6 and 24 h after surgery; pain scores were documented at the same time points. Opioid administration was recorded and converted into morphine IV equivalents. Plasma samples were also collected from 10 healthy volunteers. Alphascreen^TM cyclic AMP (cAMP) assay and MOR-overexpressing cells were employed to quantify MOR activation. HEK-Blue™ hTLR4 were utilised to measure TLR4 activation. Circulating matrix metalloprotease (MMP) and Tissue Inhibitor of Matrix Protease (TIMP) activities were assessed by gelatin zymography and reverse zymography, respectively. Results: Post-operative plasma samples displayed the ability to activate MOR and to inhibit LPS-induced TLR4 activation. Linear mixed model analysis revealed that MOR activation had a significant effect on inhibition of LPS-induced TLR4 activation. Furthermore, TLR4 had a significant effect to explain pain scores. Postoperative samples also displayed altered circulating matrix-degrading enzymes activity potential, but this was neither correlated to opioid administration nor to MOR activation potential. Conclusions: Our results show for the first time that (i) opioids administered to surgery patients result in modulation of ligand-induced TLR4 activation and (ii) postoperative pain is associated with increased circulating TLR4 activation potential. Our study further promotes the use of MOR activation potential rather than opioid intake in clinical studies measuring opioid exposure at a given time point.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FhcOQ1

Telatinib is an effective targeted therapy for pseudomyogenic hemangioendothelioma

Purpose: Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare locally aggressive neoplasm with endothelial differentiation, which often presents with multiple lesions. These tumors have characteristic SERPINE1-FOSB fusions. We report a 17 years old patient with advanced unresectable PHE with a durable complete remission to the multi-tyrosine kinase inhibitor telatinib. The aim of this study was to generate an in vitro model for PHE, to study the functional consequences of SERPINE1-FOSB in endothelial cells, and its interaction with telatinib, to biologically substantiate the complete response to telatinib. Experimental Design: As the fusion results in overexpression of a truncated form of FOSB, we overexpressed truncated FOSB in normal endothelial cells. Results: Truncated FOSB significantly affected tumor growth in 3D on matrigel with increased and sustained sprouting. Moreover, truncated FOSB acted as an active transcription factor capable to regulate its own transcription, as well as to upregulate PDGFRA and FLT1 expression (4-fold). Telatinib decreased proliferation and tumor growth in 3D and induced apoptosis. As expected, telatinib blocked VEGF signaling as phosphorylation of ERK was abolished. Interestingly, in FOSB overexpressing cells, telatinib specifically affected PDGFRA, FLT1 and FLT4 signaling and down-regulated SERPINE1, thereby affecting the self-regulation of the fusion gene. Conclusions: We provide a biological substantiation of a complete clinical remission that was seen in a patient with PHE, showing that telatinib indirectly interferes with the self-regulated expression of the fusion product. Thus, telatinib or any other currently available VEGFR1-4/PDGFRA inhibitor, could be a highly specific treatment option for patients with multifocal unresectable PHE.

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

Toxicity and efficacy of a novel GADD34-expressing oncolytic HSV-1 for the treatment of experimental glioblastoma.

Purpose: Glioblastoma (GBM) is the most common primary central nervous system cancer in adults. Oncolytic HSV-1 (oHSV) is the first FDA-approved gene therapy approach for the treatment of malignant melanoma. For GBM, oHSVs need to be engineered to replicate within and be toxic to the glial tumor but not to normal brain parenchymal cells. We have thus engineered a novel oHSV to achieve these objectives. Experimental Design: NG34 is an attenuated HSV-1 with deletions in the genes encoding viral ICP6 and ICP34.5. These mutations suppress virus replication in non-dividing brain neurons. NG34 expresses the human GADD34 gene under transcriptional control of a cellular Nestin gene promoter/enhancer element, whose expression occurs selectively in GBM. In vitro cytotoxicity assay and survival studies with mouse models were performed to evaluate therapeutic potency of NG34 against glioblastoma. In vivo neuro-toxicity evaluation of NG34 was tested by intracerebral inoculation. Results: NG34 replicates in GBM cells in vitro with similar kinetics as those exhibited by an oHSV that is currently in clinical trials (rQNestin34.5). Dose-response cytotoxicity of NG34 in human GBM panels was equivalent to or improved compared to rQNestin34.5. The in vivo efficacy of NG34 against two human orthotopic GBM models in athymic mice was similar to that of rQNestin34.5, whereas intracerebral injection of NG34 in the brains of immunocompetent and athymic mice showed significantly better tolerability. NG34 was also effective in a syngeneic mouse glioblastoma model. Conclusions: A novel oHSV encoding GADD34 is efficacious and relatively nontoxic in mouse models of GBM.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fh9DI8

Tissue transglutaminase regulates interactions between ovarian cancer stem cells and the tumor niche

Cancer progression and recurrence are linked to a rare population of cancer stem cells (CSC). Here we hypothesized that interactions with the extracellular matrix drive CSC proliferation and tumor-initiating capacity and investigated the functions of scaffold protein tissue transglutaminase (TG2) in ovarian CSC. Complexes formed by TG2, fibronectin (FN), and integrin β1 were enriched in ovarian CSC and detectable in tumors. A function-inhibiting antibody against the TG2 FN-binding domain suppressed complex formation, CSC proliferation as spheroids, tumor-initiating capacity, and stemness-associated Wnt/β-catenin signaling. Disruption of the interaction between TG2 and FN also blocked spheroid formation and the response to Wnt ligands. TG2 and the Wnt receptor Frizzled 7 (Fzd7) form a complex in cancer cells and tumors, leading to Wnt pathway activation. Protein docking and peptide inhibition demonstrate that the interaction between TG2 and Fzd7 overlaps with the FN binding domain of TG2. These results support a new function of TG2 in ovarian CSC, linked to spheroid proliferation and tumor-initiating capacity and mediated through direct interactions with Fzd7. We propose this complex as a new stem cell target.

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

Extracellular citrate affects critical elements of cancer cell metabolism and supports cancer development in vivo

Glycolysis and fatty acid synthesis are highly active in cancer cells through cytosolic citrate metabolism, with intracellular citrate primarily derived from either glucose or glutamine via the tricarboxylic acid cycle. We show here that extracellular citrate is supplied to cancer cells through a plasma membrane-specific variant of the mitochondrial citrate transporter (pmCiC). Metabolomic analysis revealed that citrate uptake broadly affected cancer cell metabolism through citrate-dependent metabolic pathways. Treatment with gluconate specifically blocked pmCiC and decreased tumor growth in murine xenografts of human pancreatic cancer. This treatment altered metabolism within tumors, including fatty acid metabolism. High expression of pmCiC was associated with invasion and advanced tumor stage across many human cancers. These findings support the exploration of extracellular citrate transport as a novel potential target for cancer therapy.

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

Tight junction protein claudin-2 promotes self-renewal of human colorectal cancer stem-like cells

Post-treatment recurrence of colorectal cancer (CRC), the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSCs). The tight junction (TJ) protein claudin-2 is overexpressed in human CRC where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-FU-based chemotherapy, an outcome in which CSC play an instrumental role. In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted CRC self-renewal in vitro and in multiple mouse xenograft models. Claudin-2 enhanced self-renewal of ALDHHigh CSC and increased their proportion in CRC cell populations, limiting their differentiation and promoting the phenotypic transition of non-CSC towards the ALDHHigh phenotype. Next-generation sequencing in ALDHHigh cells revealed that claudin-2 regulated expression of nine microRNAs known to control stem cell signaling. Among these, miR-222-3p was instrumental for the regulation of self-renewal by claudin-2, and enhancement of this self-renewal required activation of YAP, most likely upstream from miR-222-3p. Taken together, our results indicate that overexpression of claudin-2 promotes self-renewal within CRC stem-like cells, suggesting a potential role for this protein as a therapeutic target in CRC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D5rV9l

Loss of the nuclear pool of ubiquitin ligase CHIP/STUB1 in breast cancer unleashes the MZF1-cathepsin pro-oncogenic program

CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient survival, with loss of CHIP in two-thirds of ErbB2+ and triple-negative breast cancers and in one-third of ER+ breast cancers. Reduced CHIP expression was seen in breast cancer patient-derived xenograft tumors and in ErbB2+ and triple-negative breast cancer cell lines. Ectopic CHIP expression in ErbB2+ lines suppressed in vitro oncogenic traits and in vivo xenograft tumor growth. An unbiased screen for CHIP-regulated nuclear transcription factors identified many candidates whose DNA-binding activity was up- or down-regulated by CHIP. We characterized Myeloid Zinc Finger 1 (MZF1) as a CHIP target given its recently identified role as a positive regulator of cathepsin B/L (CTSB/L)-mediated tumor cell invasion downstream of ErbB2. We show that CHIP negatively regulates CTSB/L expression in ErbB2+ and other breast cancer cell lines. CTSB inhibition abrogates invasion and matrix degradation in vitro and halts ErbB2+ breast cancer cell line xenograft growth. We conclude that loss of CHIP remodels the cellular transcriptome to unleash critical pro-oncogenic pathways, such as the matrix-degrading enzymes of the cathepsin family, whose components can provide new therapeutic opportunities in breast and other cancers with loss of CHIP expression.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fh9ggG

Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients

Abstract

Purpose

Mycophenolate mofetil (MMF) is increasingly used among Japanese patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Because pharmacokinetic data for MMF in the Asian population are limited, we conducted this investigation.

Methods

Intravenous MMF (1000 mg/dose) was administered to 10 patients along with cyclosporine or tacrolimus for 10 days after allo-SCT; it was administered every 8 h in peripheral blood stem cell- and bone marrow-transplanted patients, and every 12 h in cord blood-transplanted patients. MMF was administered orally at the same dose from day 11. Plasma concentrations of mycophenolic acid (MPA) were measured by high-performance liquid chromatography.

Results

The MPA AUC_{0 − tau} was 31.9 ± 3.4, 26.2 ± 2.4, and 21.0 ± 2.2 µg*h/mL, the mean C_trough was 0.25, 0.35, and 0.37 µg/mL, and the C_max was 10.8, 9.2, and 5.5 µg/mL on days 2, 9, and 16, respectively. The AUC_{0 − tau} and C_max were significantly higher after intravenous MMF dosing than after oral MMF dosing. All patients exhibited successful neutrophil engraftments in a median time of 18 days. Grade II acute graft-versus-host disease (GvHD) of the skin was observed in two patients, and one patient developed limited chronic GvHD. Individual cases of transient and curable grade III oral mucositis and diarrhea were observed; however, MMF was not discontinued. No other severe complications or infections were observed.

Conclusions

Intravenously administered MMF was safe and possibly effective in achieving higher MPA plasma concentrations for GvHD prophylaxis after allo-SCT in Japanese patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fl8boc

Diagnostics and therapy of sudden hearing loss.

Related Articles

Diagnostics and therapy of sudden hearing loss.

GMS Curr Top Otorhinolaryngol Head Neck Surg. 2017;16:Doc05

Authors: Plontke SK

Abstract
This article reviews recent aspects of diagnostics, differential diagnostics, and evidence in systemic and local therapy of idiopathic sudden sensorineural hearing loss (ISSHL). Since a number of disorders can be accompanied by sudden hearing loss, a meaningful and targeted diagnostic strategy is of utmost importance. An important differential diagnosis of sudden hearing loss are intralabyrinthine schwannomas (ILS). The incidence of ILS is probably significantly underestimated. This may be due to the lack of awareness or lack of explicit search for an intralabyrinthine tumor on MRI or an inappropriate MRI technique for the evaluation of sudden hearing loss ("head MRI" instead of "temporal bone MRI" with too high slice thicknesses). Therefore, the request to the radiologist should specifically include the question for (or exclusion of) an ILS. With special MRI techniques, it is possibly today to visualize an endolymphatic hydrops. The evidence in the therapy of ISSHL is - with respect to the quality and not quantity of studies - unsatisfying. The value of systemically (low dose) or intratympanically applied corticosteroids in the primary treatment of ISSHL is still unclear. In order to investigate the efficacy and safety of high dose corticosteroids as primary therapy for ISSHL, a national, multicenter, three-armed, randomized, triple-blind controlled clinical trial is currently performed in Germany (http://ift.tt/2pZpq2Y). After insufficient recovery of the threshold with systemic therapy of ISSHL, intratympanic corticosteroid therapy appears to be associated with a significantly higher chance of an improved hearing threshold than no therapy or placebo. Both, hearing gain and final hearing threshold, however, appear to be independent from the onset of secondary therapy. Based on currently available data from clinical studies, no recommendation can be made with respect to the type of corticosteroid and specifics of the intratympanic application protocol.

PMID: 29503670 [PubMed]

from #ENT-PubMed via ola Kala on Inoreader http://ift.tt/2I6KXQx

Cochlear implant - state of the art.

Related Articles

Cochlear implant - state of the art.

GMS Curr Top Otorhinolaryngol Head Neck Surg. 2017;16:Doc04

Authors: Lenarz T

Abstract
Cochlear implants are the treatment of choice for auditory rehabilitation of patients with sensory deafness. They restore the missing function of inner hair cells by transforming the acoustic signal into electrical stimuli for activation of auditory nerve fibers. Due to the very fast technology development, cochlear implants provide open-set speech understanding in the majority of patients including the use of the telephone. Children can achieve a near to normal speech and language development provided their deafness is detected early after onset and implantation is performed quickly thereafter. The diagnostic procedure as well as the surgical technique have been standardized and can be adapted to the individual anatomical and physiological needs both in children and adults. Special cases such as cochlear obliteration might require special measures and re-implantation, which can be done in most cases in a straight forward way. Technology upgrades count for better performance. Future developments will focus on better electrode-nerve interfaces by improving electrode technology. An increased number of electrical contacts as well as the biological treatment with regeneration of the dendrites growing onto the electrode will increase the number of electrical channels. This will give room for improved speech coding strategies in order to create the bionic ear, i.e. to restore the process of natural hearing by means of technology. The robot-assisted surgery will allow for high precision surgery and reliable hearing preservation. Biological therapies will support the bionic ear. Methods are bio-hybrid electrodes, which are coded by stem cells transplanted into the inner ear to enhance auto-production of neurotrophins. Local drug delivery will focus on suppression of trauma reaction and local regeneration. Gene therapy by nanoparticles will hopefully lead to the preservation of residual hearing in patients being affected by genetic hearing loss. Overall the cochlear implant is a very powerful tool to rehabilitate patients with sensory deafness. More than 1 million of candidates in Germany today could benefit from this high technology auditory implant. Only 50,000 are implanted so far. In the future, the procedure can be done under local anesthesia, will be minimally invasive and straight forward. Hearing preservation will be routine.

PMID: 29503669 [PubMed]

from #ENT-PubMed via ola Kala on Inoreader http://ift.tt/2tk0skD

Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.

PROSPERO registration number

CRD42017055412.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G0V60a

Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques

Publication date: Available online 6 March 2018
Source:Brain Stimulation
Author(s): Gintaute Samusyte, Hugh Bostock, John Rothwell, Martin Koltzenburg
BackgroundShort-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear.ObjectiveTo compare T-SICI and its reliability with conventional A-SICI measurements.MethodsIn twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50–80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator.ResultsAcross the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7–0.3x, R² = 0.99), but there was considerable interindividual variability. At CS 60–80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81–0.92) and adequate-to-excellent interday (ICC 0.61–0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17–0.42 intraday, 0.37–0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies.ConclusionThe close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique.



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

Acute Stent Migration into the Right Ventricle in a Patient with Iliac Vein Stenting

THORAC CARDIOV SURG Reports 2018; 07: e7-e8
DOI: 10.1055/s-0038-1629898

Endovascular stent placement for chronic postthrombotic iliofemoral venous obstructive lesions is an effective therapeutic option and might be complicated by stent migration. We report a case of a venous stent that was lost from the iliac vein into the right ventricle rescued by emergent open-heart surgery.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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

Efficacy and safety of eberconazole 1% otic solution compared to clotrimazole 1% solution in patients with otomycosis

To demonstrate non-inferiority of eberconazole 1% otic solution to clotrimazole 1% solution, and to compare their safety profile in the treatment of otomycosis.

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

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC, Published online: 06 March 2018; doi:10.1038/bjc.2018.9

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fk8rQb

Hairy Vetch Incorporated as Green Manure Inhibits Sulfathiazole Uptake by Lettuce in Soil

Abstract

Veterinary antibiotics like sulfonamides are frequently detected in arable lands and they can potentially contaminate food crops. It is thus of great importance to identify strategies to reduce food crops' uptake of antibiotics. For the first time, using a pot culture experiment, sulfathiazole (STZ) uptake by lettuce (Lactuca sativa L.) grown in antibiotic-contaminated soils (10 and 100 mg STZ kg⁻¹ soil) and treated with (in)organic amendments, namely chemical fertilizer (NPK), compost, and hairy vetch, was investigated. Subsequent enhanced plant growth was witnessed when using hairy vetch treatment. The amount of antibiotic uptake was significantly reduced to 5 and 33% with hairy vetch application compared to compost or NPK application at 10 and 100 mg kg⁻¹ STZ, respectively. The total amounts of accumulated STZ in plant parts increased as the levels of STZ contaminated in soils were increased. STZ was much more abundant in the roots than the leaves. Within 30 days, the extractable STZ in the treated soils—especially with hairy vetch—diminished considerably to concentrations that are frequently detected in arable soils. We conclude that utilization of green manure (cover crop—hairy vetch) is a viable strategy for safer crop production in antibiotic-contaminated soils.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I9RRnM

Development of a Device-Assisted Nerve-Regeneration Procedure in Disruptive Lesions of the Brachial Plexus

J reconstr Microsurg
DOI: 10.1055/s-0038-1627472

Background We describe the development of a new surgical procedure to be used in the treatment of disruptive brachial plexus (BP) lesions. It is centered on an artificial device designed to assist nerve regeneration by providing a confined and protected environment. Nerve fibers can repair inside the device, while the adverse massive scar-tissue formation is limited to the outside of the device. Methods Steps in the development of the procedure were (1) definition of the rationale, (2) design of the device, (3) choice of an in vivo translational model, (4)refinement of the surgical procedure, and (5) performance of an in vivo pilot study as a proof of concept. An interdisciplinary team from several laboratories was involved in this work over a period of 6 years. Results Results showed the absence of significant scar tissue in the regenerate and the presence of myelinated fibers aligned proximodistally between the stumps. This surgical approach can be seen not only as a definitive treatment but also as an early examination and stabilization before some different surgery will be later performed. It may also be used as additional protection for traditional surgery like end-to-end coaptation. Conclusions We conclude that the availability of a suitable device-assisted early treatment, even if not to be considered definitive, could help in addressing the BP lesions at an earlier stage and this may improve the final outcome. Our evidence justifies further experimentation on this approach.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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

Donor-Site Outcomes for the Osteocutaneous Radial Forearm Free Flap

J reconstr Microsurg
DOI: 10.1055/s-0038-1635087

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

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

Initial Management of Traumatic Digit Amputations: A Retrospective Study of Functional Outcomes

J reconstr Microsurg
DOI: 10.1055/s-0038-1626692

Background Traumatic amputation of one or more digits can have a serious detrimental effect on social and economic standings which can be mitigated by successful replantation. Little has been recorded on preoperative management before replantation and how this affects the outcomes of the replanted digit. Methods A retrospective cohort study was conducted and data collected over an 18-month period. Three protocols for preoperative management were examined: minimal (basic wound management), complete Buncke (anticoagulation, dry dressing on amputate placed on indirect ice and absence of a digital block), and incomplete (any two or three criteria from complete Buncke in addition to the minimal) protocols. Data was collected on survival rate, secondary operations, and complication rate. Function was defined by sensation, range of movement, and strength. Results Seventy four of 177 digits were replanted with an overall survival rate of 86.5%. The rates for minimal, incomplete, and complete protocols were 95%, 87%, and 91%, respectively, and not significantly different. The complication rate was significantly different between the complete (20%) and minimal (60%) protocols (p = 0.0484). Differences in sensation and grip strength were statistically significant between protocols (p = 0.0465 and p = 0.0430, respectively). Anticoagulation, no digital block and dry gauze all showed reduced complication rates in comparison to their counterparts. Conclusions The Buncke protocol, which includes anticoagulation, no digital block, and dry gauze, was found to significantly reduce the complication rate which suggests that it prevents compromise of tissue integrity. Significant differences were found between protocols for sensation and grip strength. A higher-powered study is needed to investigate the effects of preoperative management on complication rates and functional outcomes.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HbSk7H

An Easy Method to Make a Microscale

J reconstr Microsurg
DOI: 10.1055/s-0038-1635089

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FsuY0D

Impact of Obesity on Outcomes in Breast Reconstruction: A Systematic Review and Meta-Analysis

J reconstr Microsurg
DOI: 10.1055/s-0038-1627449

Background Increased rates of both breast cancer and obesity have resulted in more obese women seeking breast reconstruction. Studies demonstrate that these women are at increased risk for perioperative complications. A systematic review was conducted to assess the outcomes in obese women who underwent breast reconstruction following mastectomy. Methods Cochrane, PUBMED, and EMBASE electronic databases were screened and data were extracted from included studies. The clinical outcomes assessed were surgical complications, medical complications, length of postoperative hospital stay, reoperation rate, and patient satisfaction. Results Out of 33 studies met the inclusion criteria for the review and 29 provided enough data to be included in the meta-analysis (71,368 patients, 20,061 of whom were obese). Obese women (body mass index > 30 kg/m2) were 2.29 times more likely to experience surgical complications (95% confidence interval (CI) 2.19–2.39; p < 0.00001), 2.89 times more likely to have medical complications (95% CI 2.50–3.35; p < 0.00001), and had a 1.91 times higher risk of reoperation (95% CI 1.75–2.07; p < 0.00001). The most common complication, wound dehiscence, was 2.51 times more likely in obese women (95% CI 1.80–3.52; p < 0.00001). Sensitivity analysis confirmed that obese women were more likely to experience surgical complications (risk ratio 2.36, 95% CI 2.22–2.52; p < 0.00001). Conclusions This study provides evidence that obesity increases the risk of complications in both implant-based and autologous reconstruction. Additional prospective and observational studies are needed to determine if the weight reduction prior to reconstruction reduces the perioperative risks associated with obesity.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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

Erratum to: A 35-Year Evolution of Free Flap-Based Breast Reconstruction at a Large Urban Academic Center

J reconstr Microsurg
DOI: 10.1055/s-0038-1632385

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Hc3p8O

The Impact of Vocal and Laryngeal Pathologies Among Professional Singers: A Meta-analysis

Professional singers are more likely to develop laryngeal pathologies and symptoms associated with misuse and overuse of the voice. However, different studies have shown conflicting evidence. We aim to perform a systematic review and quantitative meta-analysis to determine the prevalence and risk of laryngeal pathologies and symptoms among professional singers.

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

Contact dermatitis and patch testing for the allergist

Contact dermatitis (CD) is a common disease seen by allergists. Although underutilized, patch testing (PT) remains the gold standard in the diagnosis of allergic CD. It is not difficult to perform, however, the interpretation of the PT, proper classification of the results and determination of their relevance, need an appropriate level of expertise. The objective of this article is to provide a review of CD and its key allergens and provide updates and recommendations for the practicing allergist.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fh4lfB

Abnormal lung function at preschool age – asthma in adolescence?

Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D52WD3

Iatrogenic trigeminal post-traumatic neuropathy: a retrospective two-year cohort study

With the growing demand for dental work, trigeminal nerve injuries are increasingly common. This retrospective cohort study examined 53 cases of iatrogenic trigeminal nerve injury seen at the Department of Oral and Maxillofacial Surgery, University Hospitals of Leuven between 2013 and 2014 (0.6% among 8845 new patient visits). Patient records were screened for post-traumatic trigeminal nerve neuropathy caused by nerve injury incurred during implant surgery, endodontic treatment, local anaesthesia, tooth extraction, or specifically third molar removal.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FjTr8X

Reliability validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation

Globus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat.

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

Hearing sounds as words: Neural responses to environmental sounds in the context of fluent speech

Publication date: April 2018
Source:Brain and Language, Volume 179
Author(s): Sophia Uddin, Shannon L.M. Heald, Stephen C. Van Hedger, Howard C. Nusbaum
Environmental sounds (ES) can be understood easily when substituted for words in sentences, suggesting that linguistic context benefits may be mediated by processes more general than some language-specific theories assert. However, the underlying neural processing is not understood. EEG was recorded for spoken sentences ending in either a spoken word or a corresponding ES. Endings were either congruent or incongruent with the sentence frame, and thus were expected to produce N400 activity. However, if ES and word meanings are combined with language context by different mechanisms, different N400 responses would be expected. Incongruent endings (both words and ES) elicited frontocentral negativities corresponding to the N400 typically observed to incongruent spoken words. Moreover, sentential constraint had similar effects on N400 topographies to ES and words. Comparison of speech and ES responses suggests that understanding meaning in speech context may be mediated by similar neural mechanisms for these two types of stimuli.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D5vbkQ

Recruitment of patients into head and neck clinical trials: acceptability of studies to patients from perspective of the research team

We reviewed longitudinal recruitment data to assess recruitment into head and neck cancer trials, and to identify factors that could influence this and affect their acceptability to patients. We retrieved data from the prospective computerised database (2009–2016) to measure acceptability to patients using the recruitment:screening ratio, and compared observational with interventional studies, single specialty (or site) with multispecialty (or site) studies, and "step-up" randomisation with "non-inferiority" randomisation designs.

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

School moves up in rankings

The University of Washington School of Dentistry moved up one spot to No. 4 in the United States and retained its worldwide ranking of No. 14 in the newly released 2018 Quacquarelli Symonds (QS) World University Rankings assessment of dental schools.

The post School moves up in rankings appeared first on UW School of Dentistry.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HcOwD8

Lubricating the Insertion Funnel with Autologous Fat Tissue for Inserting Breast Implants

No abstract available

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

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome

Background: Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Methods: Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Results: Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. Conclusions: We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oTXL3L

Reconstruction of Anterior Neck Scar Contracture Using A Perforator-Supercharged Transposition Flap

Summary: Reconstruction of the anterior neck requires attention to both aesthetic and functional outcomes. In general, skin grafts are not suitable for anterior neck reconstruction in Asian patients, even when artificial dermis is used before skin grafting. Therefore, we have employed various types of thin flaps for anterior neck reconstruction, including the cervico-pectoral flap. However, we have realized that, to fully release neck contractures and therefore achieve the full range of neck extension, the skin pedicle must be sufficiently wide. Therefore, we have started reconstructing anterior neck scar contractures using wide, thin, and long flaps that are harvested from the anterior chest wall. In this article, we describe the case of a 71-year-old man who presented with a neck contracture and tracheal fistula after receiving extensive burns. A transposition flap bearing the internal mammary artery perforator was harvested from the anterior chest wall to repair the neck wounds that were left after removing the scar. At the same time, the tracheal fistula was covered by the flap. The aesthetic and functional results were acceptable. The effectiveness of supercharged transposition flaps from the anterior chest wall for reconstructing anterior neck scar contraction is discussed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I5735E

Associated Malformations in Children with Orofacial Clefts in Portugal: A 31-Year Study

Background: Orofacial clefts are among the most common congenital craniofacial malformations and may be associated with other birth defects. However, the proportion and type of additional anomalies vary greatly between studies. This study assessed the prevalence and type of associated congenital malformations in children with orofacial clefts, who attended the largest cleft lip and palate tertiary referral center in Portugal. Methods: Consecutive children with orofacial clefts who attended at least 1 consultation in our Clefts Unit between 1981 and 2012 were studied. Demographic and clinical data regarding the number and type of associated malformations were retrospectively collected and analyzed. Results: Of the 701 patients studied, 219 (31.2%) had associated congenital malformations. These malformations were more frequent in children with cleft palate (43.4%) than in children with cleft lip and palate (27.5%) or with cleft lip only (19.4%). Within the group with associated anomalies, 73 cases (33.3%) had conditions related with known chromosomal defects, monogenic syndromes or sequences, and 146 cases (66.7%) had multiple congenital anomalies of unknown origin. From those, head and neck malformations were the most common (60.3%), followed by malformations in the cardiovascular (28.3%) and musculoskeletal systems (26%). Conclusions: The overall prevalence of associated malformations of nearly 1 in 3 children with orofacial clefts stressed the need for a comprehensive evaluation of these patients by a multidisciplinary cleft team. Moreover, one-third of the children had multiple congenital anomalies of known origins. Thus, early routine screening for other malformations and genetic counseling might be valuable for orofacial clefts management.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oUS6KI

Porcine Model for Internal Mammary Vessels Harvesting: Anatomy and Technique

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I4Uwzg

Surgical Treatment for Kirner’s Deformity—Single Osteotomy through a Palmar Approach

Background: Patients with Kirner's deformity often seek medical attention for aesthetic improvement when they reach the age of approximately 10 years, when the deformity becomes evident. The operative technique described in textbooks is the palmar opening-wedge with multiple osteotomies through a mid-lateral incision, which is technically demanding. The purpose of this article was to introduce our surgical technique of a single transverse osteotomy through a palmar approach and to present the short-term outcomes of this technique. Methods: The surgical outcomes of 7 digits in 4 children were retrospectively reviewed. The deformed distal phalanx was approached with an oblique incision of the pulp, and the palmar cortex was incised at the apex of the curvature. The dorsal cortex was only partially incised and broken manually when correcting the deformity by a palmar opening-wedge. The dorsal aspect of the phalanx was not exposed, and the nail plate was left intact. The fragments were fixed with Kirschner wires. Results: There was no postoperative complication, and the osteotomy sites all healed uneventfully. None of the patients complained about scar pain or hypersensitivity of the finger pulp. The patients and their parents were satisfied with the aesthetic results. Conclusions: A single palmar opening-wedge osteotomy at the apex sufficiently corrected the main curvature, and the subtle curvature remaining at the tip of the phalanx did not affect the appearance. This technique is simple and easy; therefore, it is recommended as a reliable procedure for patients with Kirner's deformity who are approaching puberty.

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

Patient-reported Outcomes after ADM-assisted Implant-based Breast Reconstruction: A Cross-sectional Study

Background: Although the use of acellular dermal matrices (ADMs) in implant-based reconstruction increases, there is a lack of studies evaluating patient-reported outcome measures after this reconstruction method. We aim to evaluate the patient satisfaction after ADM-assisted implant-based breast reconstruction (IBBR) in 1 of the largest series of patients undergoing ADM-assisted IBBR. Methods: Patients with ADM-assisted IBBR were invited to fill out the BREAST-Q, a validated and standardized questionnaire to measure patient satisfaction after a breast reconstruction. A retrospective chart review was performed to identify patient and surgical characteristics. Results: In total, 208 patients (38.4%) responded and reported a mean satisfaction of 70.6 ± 20.2 with their breasts and 78.0 ± 20.5 with the outcome. An overall complication rate of 7.7% was noted, with 1.5% severe complications leading to hospital readmission (0.5%) and implant removal (0.5%). Patients with complications and unilateral reconstruction for oncological reasons reported overall less satisfaction rates compared with patients with bilateral, preventive surgery, and an uncomplicated postoperative course. Strongly related domains indicate the importance of patient satisfaction with their breasts and outcome on psychosocial and sexual functioning and satisfaction with information on satisfaction with breasts, outcome, and surgeon. Conclusion: There is an increased demand for patient-reported outcome measures in a changing practice to which the opinion of the patient assumes a larger role. With high satisfaction rates, ADM-assisted IBBR is a valuable reconstruction method, provided that complication rates remain low. Hence, it should only be performed in a selected group of women.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I7vJuD

Single Lymphaticovenular Anastomosis for Early-Stage Lower Extremity Lymphedema Treated by the Superior-Edge-of-the-Knee Incision Method

Background: Surgical treatment of lower extremity lymphedema (LEL) remains challenging. Application of the superior-edge-of-the-knee incision method for lymphaticovenular anastomosis (LVA) is reported to have a strong therapeutic effect in patients with LEL because lymph-to-venous flow at the anastomosis is enhanced by knee joint movement during normal walking. We investigated whether a single LVA created by this method is adequate for early LEL. Methods: The study involved 10 patients with LEL characterized by stage 2 or 3 leg dermal backflow and treated by a single LVA at the thigh via the superior-edge-of-the-knee incision method. The lymphatic vessel and direction of flow were assessed intraoperatively, and reduction in lymphedema volume was assessed postoperatively. Results: Use of our incision method yielded a single anastomosis in all patients with stage 2 leg dermal backflow and in all patients with stage 3 leg dermal backflow. The lymphatic vessel was 0.65 ± 0.08 mm in diameter (0.65 ± 0.09 and 0.65 ± 0.09 mm, respectively; P = 1.000). No venous reflux occurred in any patient. Mean follow-up was 7.70 ± 3.30 months (9.60 ± 3.29 and 5.80 ± 2.17 months, respectively; P = 0.068). Mean reduction in the LEL index was 20.160 ± 9.892 (22.651 ± 12.272 and 17.668 ± 7.353, respectively; P = 0.462). Conclusion: A single LVA created by the superior-edge-of-the-knee incision method can be expected to have a strong therapeutic effect in patients with stage 2 or 3 leg dermal backflow.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oUS6uc

A New Integrated Approach for the Treatment of Complicated Ulcers

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I7R6f1

Porcine Model for Deep Superior Epigastric Artery Perforator Flap Harvesting: Anatomy and Technique

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I6q9Ze

A Systematic Review and Meta-analysis of Free-style Flaps: Risk Analysis of Complications

Background: Free-style flaps allow surgeons to overcome anatomical variations and raise perforator flaps wherever a pulsatile signal can be detected. We performed a systematic review and meta-analysis to identify the risk factors for complications and indications for free-style flaps in soft-tissue defect reconstructions. Methods: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The databases of MEDLINE, PubMed, ScienceDirect, and Cochrane Library were searched from January 1991 to January 2017 for original articles describing free-style flaps in soft-tissue defect reconstruction. Results: A total of 17 articles met the inclusion criteria, representing 453 free-style flaps. The percentage of free-style flaps conducted after primary oncologic resection was 54.4% (246/453). Free-style flaps were mostly used in the head and neck region (35.5%), and most of them were designed as pedicled perforator flaps (96.7%). Complete flap survival was accomplished in 91.8% of the free-style flaps. Complications were found in 13.5% of cases, and 2 risk factors were identified: extremity defects (risk ratio, 2.39; P = 0.006) and single perforator flaps (risk ratio, 4.93; P = 0.002). No significant differences were found among the criteria including patients aged greater than 60 years, female gender, chronic etiology, flap size over 100 cm2, flap rotation, or perforator skeletonization. Conclusions: Free-style flaps are both reliable and advanced forms of perforator flaps for use in soft-tissue defect reconstructions. Defects located on the extremities and flaps with single perforators are risk factors for flap failure and complications.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oUSlW3

Porcine Model for Gluteal Artery Perforator Flap: Anatomy and Technique

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I6knHf

Pork Belly: A Simulation Training Model for Intramuscular Perforator Dissection

Background: Free tissue transfer has evolved from muscle flaps to fasciocutaneous flaps. Dissection of the intramuscular course of feeding vessels is technically challenging. Simulation-based microsurgery skills acquisition is moving toward nonliving training models. Living porcine model or human cadavers are currently cost-ineffective methods for the early learning curve in teaching intramuscular dissection. The aim of this study was to validate an inexpensive ex vivo porcine model simulating harvest of the deep inferior epigastric artery perforator (DIEAP) flap, specifically including perforator intramuscular dissection. Methods: An initial needs analysis and anatomical dissections (characteristics of vascular anatomy) established the necessity and surgical design (step-by-step) of the ex vivo DIEAP flap harvesting model. A pilot study utilizing objective assessment methodology (time to complete flap raising and hand motion analysis) demonstrated the surgeons' performance. A detailed feedback questionnaire was used to assess the participants' perception of this model. Results: Fifty-seven participants completed the initial needs analysis. Fifteen pork bellies were dissected and the vascular anatomical characteristics of the inferior epigastric vessels are presented. Eight surgeons performed the step-by-step flap design demonstrating construct validity in flap raising and intramuscular dissection. All surgeons completed the ex vivo DIEAP harvesting and they recommend this model as the first step in training for intramuscular dissection. Conclusions: The pork belly simulation is a cheap, easy, ethically considerate, and high-fidelity simulation model for intramuscular dissection for the DIEAP free flap. This study guides future validation trials to explore if the absence of physiological blood flow affects skills acquisition in the intramuscular dissection learning curve. The pork belly could be the first step in perforators dissection before progressing to the in vivo porcine model.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oUT9dQ

Beyond Serendipity to an Algorithmic Approach

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I9DQGG

Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

Background: The pathogenesis of Dupuytren's disease (DD) remains unclear. An embryonic stem cell (ESC)–like population in the endothelium of the microvessels around tissues that expresses components of the renin-angiotensin system (RAS) has been reported. This study investigated if this primitive population expresses cathepsins B, D, and G, that contribute to RAS bypass loops. Methods: 3,3-Diaminobenzidine immunohistochemical (IHC) staining for cathepsins B, D, and G was performed on sections of formalin-fixed paraffin-embedded DD cords (n = 10) and nodules (n = 10). Immunofluorescence IHC staining was utilized to demonstrate co-expression of these cathepsins with ESC markers. Protein and gene expression of these cathepsins was investigated in snap-frozen DD cords (n = 3) and nodules (n = 3) by Western blotting and NanoString analysis, respectively. Enzymatic activity of these cathepsins was investigated by enzymatic activity assays. Results: 3,3-Diaminobenzidine IHC staining demonstrated expression of cathepsins B, D, and G in DD cords and nodules. Gene expression of cathepsins B, D, and G was confirmed by NanoString analysis. Western blotting confirmed expression of cathepsins B and D, but not cathepsin G. Immunofluorescent IHC staining demonstrated high abundance of cathepsins B and D on the OCT4+/angiotensin converting enzyme+ endothelium and the smooth muscle layer of the microvessels. Cathepsin G was localized to trypase+ cells within the stroma in DD cords and nodules with limited expression on the microvessels. Enzyme activity assays demonstrated functional activity of cathepsins B and D. Conclusions: Cathepsins B, D, and G were expressed in the DD tissues, with cathepsins B and D localized to the primitive population in the endothelium of the microvessels, whereas cathepsin G was localized to phenotypic mast cells, suggesting the presence of bypass loops for the RAS.

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

Spindle Cell Lipoma of the Thumb

Summary: We report the case of a 34-year-old man who presented with a 4-year history of a soft tissue on the palmar aspect of the thumb. Magnetic resonance imaging demonstrated the presence of a mass with heterogeneous high intensities on T1-weighted images and high intensities on T2-weighted images. We performed excisional biopsy. Histologically, the tumor was composed of mature adipocytes and spindle cells in a collagen background. Immunohistochemically, the tumor cells showed strong expression of CD34. Therefore, we diagnosed it as spindle cell lipoma. To the best of our knowledge, only 2 cases of spindle cell lipoma of the thumb have previously been reported.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I4UveG

The Impact of Recipient Site External Expansion in Fat Grafting Surgical Outcomes

Background: The fat grafting process includes the 4 phases of tissue harvesting, processing, recipient-site preparation, and reinjection. Among them, the preparation of the recipient site has never been exhaustively reviewed. We aim to provide a comprehensive overview of the methods to prepare the recipient site through external expansion with the resulting outcomes. Methods: PubMed/Medline database was searched for studies on fat grafting recipient site preparation by applying the following algorithm: ((fat grafting) OR (lipofilling) OR (lipograft) AND (recipient site)). A priori criteria were used to review the resulting articles and identify those dealing with external expansion. Results: Fourteen studies published from 2008 through 2016 met inclusion criteria (4 case reports, 6 retrospective, and 4 prospective studies), representing 1,274 treated patients. Two devices for preexpansion were used with different protocols: BRAVA system and Kiwi VAC-6000M with a PalmPump. The 13 studies that applied the BRAVA system reported large fat volume transplantation to the breast (average > 200 cc). The most common complications were localized edema (14.2%), temporary bruising, and superficial skin blisters (11.3%), while the most serious was pneumothorax (0.5%). The majority of the studies reported enhancement of fat graft survival, which ranged between 53% and 82% at 6 months to 1 year follow-up, and high satisfaction of patients and surgeon. Conclusions: External expansion and fat grafting is a promising technique for breast reconstruction and augmentation. However, due to the overall low level of evidence of the available studies, further research is needed to validate the procedure.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oV6J0R

Oncoplastic Breast Volume Replacement with the Use of Lateral Intercostal Artery Perforator Flaps

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I98VL0

PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D3IFhe

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fi4mA0

Reliability validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation

Publication date: Available online 6 March 2018
Source:Auris Nasus Larynx
Author(s): Nao Takahashi, Kaori Mori, Hironori Baba, Takanobu Sasaki, Masaaki Ohno, Fumio Ikarashi, Naotaka Aizawa, Kunihiro Sato, Akio Tsuchiya, Hideyuki Hanazawa, Masahiko Tomita, Yamato Kubota, Yuka Morita, Kuniyuki Takahashi, Arata Horii
ObjectiveGlobus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat. It was reported that globus patients marked high scores specifically for the globus scale among three scales, indicating that GETS can be used as a valid symptom scale for globus sensation. Aims of this study were to translate GETS into Japanese and to test its reliability and validity.MethodsFifty-five patients complaining of globus sensation without abnormal endoscopic and CT findings were enrolled into the study. They were asked to answer the questions of GETS translated into Japanese (GETS-J). Reliability (internal consistency) of the questionnaire was tested using Cronbach's coefficient alpha. To test the validity, principal components analysis was used to identify the factorial structure of the questionnaire and GETS-J data were compared with those reported in the original GETS. Contribution of psychiatric comorbidities to globus sensation was also investigated by examining the correlation between Hospital Anxiety and Depression Scale (HADS) and GETS-J.ResultsReliability of the questionnaire examined by the Cronbach's coefficient alpha was satisfactory and all higher than 0.75. Principal components analysis identified following three questions as the globus scale: Q1, Feeling something stuck in the throat; Q5, Throat closing off; Q9, Want to swallow all the time. Somatic distress, i.e., patients' reaction to throat symptoms, was significantly correlated with globus scale (r=0.680). Anxiety component of HADS was significantly correlated with somatic distress but not with globus scale. These results were consistent with those of the original GETS except for the replacement of Q3 (discomfort/irritation in the throat) to Q5 (throat closing off) for globus scale in GETS-J.ConclusionTranslation of GETS into Japanese showed high reliability and validity, suggesting that translation and cross-cultural adaptation were not problematic. High correlation of globus scale of GETS-J with somatic distress indicated that GETS-J could be a useful questionnaire to identify the globus patients and evaluate the severity of the disease. Anxiety may complicate the somatic distress in patients with globus sensation.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oOd4f1

Spongiotic Gingival Hyperplasia Synchronously Involving Multiple Sites: Case Report and Review of the Literature

Abstract

Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a gingival lesion with unique clinicopathologic features that may involve synchronously multiple sites. We present a case with lesions clinically consistent with LJSGH in four jaw quadrants, confirmed by biopsy and review the English literature on multifocal LJSGH cases. A 19 year-old woman presented with circumscribed, erythematous overgrowths on the right and left maxillary and mandibular gingiva. With the provisional diagnosis of multifocal LJSGH, total excision of four maxillary lesions was performed. Clinical, microscopic and immunohistochemical examination with cytokeratin 19 confirmed the diagnosis of LJSGH in multiple sites. The excised lesions showed partial to complete recurrence after 4 months, while spontaneous regression of all but one lesion was observed after 15 months. Twenty cases with synchronous involvement of the gingiva of at least two teeth were previously reported. Their clinical features were comparable to that of solitary LJSGH. Only one case involved all four jaw quadrants. Spontaneous remission has not been documented before. The recognition of multiple lesions with clinicopathologic features diagnostic of LJSGH in the same adult patient argue against the designations "localized" and "juvenile". Recurrences are common, while remission might occur.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Iacn86

Ubiquitin Immunostaining in Thyroid Neoplasms Marks True Intranuclear Cytoplasmic Pseudoinclusions and May Help Differentiate Papillary Carcinoma from NIFTP

Abstract

Papillary thyroid carcinoma (PTC) is defined by an invasive growth pattern and classic nuclear features: enlarged, grooved, overlapping nuclei with chromatin clearing and intranuclear cytoplasmic pseudoinclusions (INCP). True INCPs are characteristic of PTC, but may infrequently be seen in noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Nuclear abnormalities that mimic INCP ("pseudo-pseudoinclusions") are common in a variety of thyroid lesions. H&E and ubiquitin-stained whole tissue sections of classic PTC (n = 25) and NIFTP (n = 35) were evaluated. On H&E, true INCPs were present in all (100%) PTCs and absent in all NIFTPs (0%). Pseudo-pseudoinclusions were present in 13 (37%) NIFTPs. In 24 (96%) PTCs, ubiquitin was strongly expressed within INCPs. In NIFTPs, optically clear nuclei or pseudo-pseudoinclusions did not express ubiquitin (0/35). Occasionally, nuclear vacuoles in NIFTP demonstrated a marginated staining pattern, in which strong ubiquitin expression was seen at the periphery of the nucleus, but the central pale area was negative. In addition, 2 NIFTPs demonstrated intrafollicular psammomatoid calcifications which were strongly ubiquitin-positive. Psammoma bodies in PTC were ubiquitin-negative in the majority of cases. We report a previously undescribed finding: strong ubiquitin expression in true INCPs in PTC, absence of true INCPs in NIFTP, and absence of ubiquitin expression in pseudo-pseudoinclusions in NIFTP. This finding supports the difference between true INCPs (found only in PTC) and pseudo-pseudoinclusions (found in NIFTP). Using strict histologic criteria and ubiquitin immunostaining, the presence of true pseudoinclusions may exclude a diagnosis of NIFTP. Caution should be exercised when interpreting nuclear vacuoles or pseudo-pseudoinclusions.

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