OtoRhinoLaryngology News: 11/15/17

Τετάρτη 15 Νοεμβρίου 2017

Decisional regret and choice of breast reconstruction following mastectomy for breast cancer: A systematic review

Abstract

Objective

Women facing mastectomy for breast cancer should have the option of considering whether they would like breast reconstruction (BR), and if so, what type and when. Previous research has demonstrated some women will come to regret their decision about BR. We aim to summarise the evidence about the prevalence of decisional regret (DR) associated with BR choices and identify factors influencing vulnerability to DR.

Methods

A systematic review of the literature reporting BR-related DR published between January 1994 and February 2017 identified 254 initial search results. Thirteen publications from 12 studies (5,672 participants) met the selection criteria and were included in the final review. Each article was allocated a quality score out of 24.

Results

Overall, DR levels were reported as low and stable, although direct comparison across studies was limited by inconsistencies in measurement and reporting methods. Estimates of DR scores ranged from 9.3/100 to 5.4/20. All studies identified a relationship between higher levels of DR and an insufficient amount, inadequate quality or unclear nature of information provided to women prior to undergoing mastectomy. A major determinant of DR was new or recurrent cancer, while psychosocial characteristics including depression, distress and negative body image increased the likelihood of DR.

Conclusion

The available research is yet to provide a clear understanding of the many inter-related issues involved in DR. Given the consensus that pre-surgical information was inadequate, making standardised educational material more widely available and increasing use of breast care nurses in pre-operative patient education roles may be useful.

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Insufficienza velofaringea

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): F. Marmouset, A.G. Piller, C. Bobillier, S. Pondaven, E. Lescanne
Lo sfintere velofaringeo è formato dai muscoli velari e della parete faringea posteriore. Il suo ruolo è importante nella differenziazione fonemica e nella deglutizione. La lesione della funzione dello sfintere velofaringeo è multicausale e può rivelare una patologia cromosomica come la sindrome 22q11.2. Un'insufficienza velofaringea presente nel periodo di apprendimento, nel bambino piccolo, può causare delle conseguenze permanenti sulla parola e sull'immagine di sé. La gestione diagnostica e il bilancio preterapeutico sono necessariamente multidisciplinari. Il chirurgo ORL realizza un bilancio morfologico e funzionale mediante rinofibroscopia e diagnostica per immagini, determinando l'operabilità. Il bilancio ortofonico-foniatrico è funzionale e percettivo, differenziando l'ipernasalità dalle compensazioni inadeguate e quantificando l'insufficienza velofaringea. Nel bambino è necessario un piano terapeutico multidisciplinare a lungo termine. Il chirurgo ORL mira a ripristinare una chiusura velare con l'obiettivo di migliorare l'ipernasalità (risonanza) e la perdita nasale (perdita d'aria). L'ortofonista si dedica preferibilmente alla gestione dei meccanismi di compenso articolatori inadeguati, pur avendo un'azione sullo sfintere velofaringeo. Un sostegno e una guida familiare sono indispensabili nel bambino piccolo e altri professionisti partecipano spesso alla gestione.

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Melanomi cutanei cervicofacciali

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): A. Moya-Plana, E. Routier, C. Mateus, F. Kolb, C. Robert
I melanomi maligni cervicofacciali devono essere divisi in due gruppi distinti: i melanomi di origine cutanea e i melanomi mucosi. In effetti, queste due entità presentano importanti differenze in termini di storia naturale, epidemiologia, gestione terapeutica e prognosi. Il melanoma cutaneo è la forma predominante. La sua incidenza è in costante aumento da diversi decenni, con, in Francia, dieci nuovi casi ogni 100 000 abitanti per anno (all'origine di 1 600 decessi). Il principale fattore di rischio è l'esposizione solare, mentre le forme familiari rappresentano solo il 10% dei pazienti. Nel 30% dei casi, la localizzazione è cervicofacciale. Le particolarità anatomiche di questa regione influenzano significativamente le modalità di trattamento e la prognosi di questi pazienti, che è più riservata. Benché il trattamento resti prima di tutto chirurgico, sono stati compiuti recentemente notevoli progressi nel trattamento degli stadi avanzati con lo sviluppo di terapie mirate (anti-BRAF in particolare) e dell'immunoterapia (anti-programmed death 1 [PD-1]). Un posto importante deve essere lasciato alla prevenzione primaria e all'educazione dei pazienti, soprattutto in termini di protezione solare. Il melanoma mucoso, dal canto suo, è un tumore raro che rappresenta meno del 5% di tutti i melanomi. La sua localizzazione preferenziale è cervicofacciale, in particolare a livello nasosinusale. La prognosi del melanoma mucoso è riservata. Questa patologia è difficile da controllare a livello locale a causa del suo carattere spesso multifocale e dei vincoli anatomici della regione cervicofacciale, che rendono difficile ottenere un'exeresi oncologica soddisfacente. Inoltre, esiste un significativo rischio metastatico all'origine di un'importante mortalità precoce. Il trattamento di riferimento è la chirurgia, classicamente seguita da una radioterapia adiuvante. Nuove tecniche di radioterapia (adroterapia, ecc.) e terapie innovative (terapie mirate, ecc.) sono in corso di valutazione.

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Melanomi mucosi cervicofacciali

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): A. Moya-Plana, J. Thariat, N. Saroul, O. Casiraghi, S. Vergez, L. de Gabory, F. Janot
I melanomi maligni cervicofacciali devono essere divisi in due gruppi distinti: i melanomi di origine cutanea e i melanomi mucosi. In effetti, queste due entità presentano importanti differenze in termini di storia naturale, epidemiologia, gestione terapeutica e prognosi. Il melanoma cutaneo è la forma predominante. La sua incidenza è in costante aumento da diversi decenni, con dieci nuovi casi in Francia per 100 000 abitanti e per anno (all'origine di 1 600 decessi). Il principale fattore di rischio è l'esposizione al sole, mentre le forme familiari rappresentano solo il 10% dei pazienti. Nel 30% dei casi, la localizzazione è cervicofacciale. Le particolarità anatomiche di questa regione influenzano significativamente le modalità terapeutiche e la prognosi di questi pazienti, che è più riservata. Benché il trattamento resti prima di tutto chirurgico, sono stati compiuti recentemente progressi importanti nel trattamento degli stadi avanzati con lo sviluppo delle terapie mirate (in particolare, anti-BRAF) e dell'immunoterapia (anti-PD1). Un posto importante deve essere attribuito alla prevenzione primaria e all'educazione dei pazienti, soprattutto in termini di protezione solare. Il melanoma mucoso, dal canto suo, è un tumore raro che rappresenta meno del 5% di tutti i melanomi. La sua localizzazione preferenziale è cervicofacciale, in particolare a livello nasosinusale. La prognosi del melanoma mucoso è riservata. In effetti, questa patologia è difficile da controllare localmente a causa del suo carattere spesso multifocale e dei vincoli anatomici della regione cervicofacciale, che rendono difficile la realizzazione di un'exeresi oncologica soddisfacente. Inoltre, c'è un significativo rischio metastatico all'origine di una significativa mortalità precoce. Il trattamento di riferimento è la chirurgia tipicamente seguita da una radioterapia adiuvante. Nuove tecniche di irradiazione (adroterapia, ecc.) e terapie innovative (terapie mirate, ecc.) sono in corso di valutazione.

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Apparecchi acustici convenzionali

Publication date: December 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 4
Author(s): J.-C. Ceccato, J. Bourien, F. Venail, J.-L. Puel
Il 16% della popolazione adulta e una persona su due oltre i 75 anni soffrono di disturbi uditivi (sordità, acufeni). Visto l'aumento della speranza di vita e l'esposizione al rumore che accelera l'invecchiamento, molte persone avranno dei benefici nell'uso di apparecchi. Oggi, praticamente tutti gli apparecchi acustici sono digitali e connessi. Questi dispositivi si presentano come retroauricolari indossati sul padiglione o come intrauricolari più o meno nascosti nel condotto uditivo esterno. Il principio di questi apparecchi è di amplificare l'informazione pertinente (in particolare il discorso) per avviarla vicino al timpano. Questo articolo descrive il funzionamento e le strategie di elaborazione del segnale per adattarsi alle diverse situazioni di ascolto dei pazienti. Certamente, l'adattamento protesico si basa su un approccio scientifico, soprattutto perché si basa su un bilancio audiologico completo e su dei software di trattamento del segnale sofisticati. Tuttavia, il successo di un apparecchio si basa anche su una gestione rieducativa del paziente, così come su un supporto personalizzato e regolare per arrivare a una regolazione adeguata alla sordità, all'ambiente, alla vita e alle aspettative dell'ipoudente.

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Annals of Oncology: factors for making a real impact

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Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer; A JSMO - ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS

Abstract

The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (CSCO), Korea (KACO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

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Fine needle aspiration evaluation of pancreatic lymphoma: A retrospective study of 25 cases in a single institution

Background

Accurate diagnosis of pancreatic lymphoma is crucial for clinical management. We evaluate the role of fine-needle aspiration (FNA) in the diagnosis of pancreatic lymphoma with the aid of flow cytometry and/or immunohistochemistry on the cell block.

Methods

Cases of pancreatic lymphoma were collected by searching our pathology laboratory information system over a period of 16 years. The clinical findings, cytologic features, and immunophenotypic results were reviewed. The diagnoses of FNA were correlated with surgical specimens in a subset of FNA cases.

Results

A total of 25 FNA cases of pancreatic lymphoma were included. The most common type of pancreatic lymphoma was large B cell lymphoma followed by follicular lymphoma. With the aid of flow cytometry and immunohistochemical work-up on cell block, 72% (18/25) of the cases were diagnosed as lymphoma and 16% of the cases (4/25) were diagnosed as suspicious for lymphoma by FNA. Only two cases (8%) including one false negative and one nondiagnostic aspirate missed the lymphoma diagnosis and 1 case (4%) was indeterminate by FNA evaluation.

Conclusion

FNA demonstrated high accuracy in rendering diagnosis of pancreatic lymphoma. The overall sensitivity is 88% and the false negative and nondiagnostic rates are 4%, respectively. Further subtyping of certain lymphomas can be difficult due to the lack of architectural features of FNA specimens.

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Upregulation of Tyrosine Kinase FYN in Human Thyroid Carcinoma: Role in Modulating Tumor Cell Proliferation, Invasion, and Migration

Cancer Biotherapy & Radiopharmaceuticals Nov 2017, Vol. 32, No. 9: 320-326.

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Comparative In Vitro Study of 11C-Methionine and 11C-Deuterodeprenyl Uptake in Three Human Glioma Cell Lines

Cancer Biotherapy & Radiopharmaceuticals Nov 2017, Vol. 32, No. 9: 344-350.

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Food Allergy.

Food Allergy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):xv-xvi

Authors: Bird JA

PMID: 29132679 [PubMed - in process]

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The Quest for Food Allergy Treatments: On Course and Gaining Steam…Finally.

The Quest for Food Allergy Treatments: On Course and Gaining Steam…Finally.

Immunol Allergy Clin North Am. 2018 Feb;38(1):xiii-xiv

Authors: Tilles SA

PMID: 29132678 [PubMed - in process]

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Adjuvant Therapies in Food Immunotherapy.

Adjuvant Therapies in Food Immunotherapy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):89-101

Authors: Loh W, Tang M

Abstract
Finding an effective curative treatment for food allergy is a research priority. Although oral immunotherapy (OIT) is effective at inducing desensitization, the temporary nature of this effect and high rates of adverse reactions have highlighted a need for novel strategies to improve tolerance induction and safety. One such strategy is the use of an adjuvant together with food immunotherapy to either suppress allergic reactions and/or modulate the underlying allergic immune response. In particular, the use of bacterial adjuvants seems to be a promising means of enhancing OIT-induced sustained unresponsiveness and warrants further investigation.

PMID: 29132677 [PubMed - in process]

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Interventional Therapies for the Treatment of Food Allergy.

Interventional Therapies for the Treatment of Food Allergy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):77-88

Authors: Parrish CP, Kim EH, Bird JA

Abstract
Treatment of IgE-mediated food allergies is limited to allergen avoidance and emergency treatment on accidental ingestion, which is not uncommon. In recent years, interest in interventional therapies to treat food allergy has increased significantly. Although oral, sublingual, and epicutaneous immunotherapy have shown promise in studies, none is approved as therapy for food allergy to date and questions remain regarding efficacy, safety, dosing, and duration of therapy.

PMID: 29132676 [PubMed - in process]

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The Role of Baked Egg and Milk in the Diets of Allergic Children.

The Role of Baked Egg and Milk in the Diets of Allergic Children.

Immunol Allergy Clin North Am. 2018 Feb;38(1):65-76

Authors: Robinson ML, Lanser BJ

Abstract
Baked egg and baked milk are tolerated by most children who are allergic to hen's egg and cow's milk. Incorporating baked goods into the diets of allergic children may help them outgrow their primary allergy more quickly, with changes observed akin to immunotherapy. Benefits may also include increased quality of life and improved nutritional status. The search for a reliable biomarker to predict tolerance to baked goods is ongoing. Most children with a milk or egg allergy who are not previously tolerating egg or milk in baked goods should be offered an observed oral food challenge.

PMID: 29132675 [PubMed - in process]

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Food Allergy Management.

Food Allergy Management.

Immunol Allergy Clin North Am. 2018 Feb;38(1):53-64

Authors: Davis CM, Kelso JM

Abstract
The management of food allergies requires the cooperation of the food allergic person, physician, family, and social contacts. For children, school management of food allergies is a key component of the overall approach. Recognition of the signs and symptoms of allergic reactions and preparation to administer the appropriate treatment of mild and severe symptoms in the event of accidental exposure is necessary. Avoidance of food allergens is facilitated by label reading and dietary guidance is extremely important to minimize nutritional deficiencies. Medications and vaccines with food-derived excipients generally do not need to be avoided because, in most cases, they contain little food protein.

PMID: 29132674 [PubMed - in process]

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Diagnosis of Food Allergy.

Diagnosis of Food Allergy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):39-52

Authors: Gupta M, Cox A, Nowak-Węgrzyn A, Wang J

Abstract
Food allergy diagnosis remains challenging. Most standard methods are unable to differentiate sensitization from clinical allergy. Recognizing food allergy is of utmost importance to prevent life-threatening reactions. On the other hand, faulty interpretation of tests leads to overdiagnosis and unnecessary food avoidances. Highly predictive models have been established for major food allergens based on skin prick testing and food-specific immunoglobulin E but are lacking for most other foods. Although many newer diagnostic techniques are improving the accuracy of food allergy diagnostics, an oral food challenge remains the only definitive method of confirming a food allergy.

PMID: 29132673 [PubMed - in process]

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Oral Tolerance Development and Maintenance.

Oral Tolerance Development and Maintenance.

Immunol Allergy Clin North Am. 2018 Feb;38(1):27-37

Authors: Wambre E, Jeong D

Abstract
The gastrointestinal tract has an abundant mucosal immune system to develop and maintain oral tolerance. The oral route of administration takes advantage of the unique set of immune cells and pathways involved in the induction of oral tolerance. Food allergy results from a loss of oral tolerance toward ingested antigens. Oral immunotherapy is thought to initiate desensitization through interaction of an allergen with mucosal dendritic cells that initiate downstream immune system modulation through regulatory T cells and effector T cells.

PMID: 29132672 [PubMed - in process]

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Unproven Diagnostic Tests for Food Allergy.

Unproven Diagnostic Tests for Food Allergy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):153-163

Authors: Hammond C, Lieberman JA

Abstract
The gold standard for diagnosis of immunoglobulin E (IgE)-mediated food allergy remains the oral food challenge, with serum IgE testing and skin prick testing serving as acceptable alternatives. However, the increase in prevalence of food allergy (both physician diagnosed and patient suspected) has led patients to pursue a variety of other alternative diagnostic procedures for suspected food allergy, which are reviewed in this article. These procedures (IgG testing, electrodermal testing, cytotoxic testing, provocation/neutralization, and applied kinesiology) have largely been unproven and may lead to unnecessary elimination diets.

PMID: 29132671 [PubMed - in process]

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Food Protein-Induced Enterocolitis Syndrome.

Food Protein-Induced Enterocolitis Syndrome.

Immunol Allergy Clin North Am. 2018 Feb;38(1):141-152

Authors: Bingemann TA, Sood P, Järvinen KM

Abstract
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that usually presents in infancy. Cow's milk, soy, and grains are the most common food triggers. FPIES can present as a medical emergency with symptoms including delayed persistent emesis or diarrhea that can lead to severe dehydration and hemodynamic instability with abnormal laboratory markers. Diagnosis can often be made based on clinical history and noted improvement in symptoms once the suspected triggers have been removed from the diet, with oral food challenge as the gold standard for confirmation of diagnosis in unclear cases.

PMID: 29132670 [PubMed - in process]

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Epidemiology of Food Allergy.

Epidemiology of Food Allergy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):13-25

Authors: Dunlop JH, Keet CA

Abstract
Understanding the epidemiology of food allergy is complicated by the difficulty of identifying it on a large scale. The prevalence of food allergy is higher in younger age groups and decreases with age. Allergy to peanut and egg seems to be more common in Northern Europe, the United States, Canada and Australia compared with Southern Europe, Eastern Europe and Asia, whereas shellfish and fish allergies may be more common in Asia. The rate of transient unrecognized food allergy may be high and variable recognition of food allergy may explain some of the differences seen in food allergy prevalence.

PMID: 29132669 [PubMed - in process]

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Diagnosis and Management of Eosinophilic Esophagitis.

Diagnosis and Management of Eosinophilic Esophagitis.

Immunol Allergy Clin North Am. 2018 Feb;38(1):125-139

Authors: Wilson JM, McGowan EC

Abstract
Unlike traditional food allergies, immunoglobulin E (IgE) is not a key mediator of eosinophilic esophagitis (EoE). Nonetheless, foods antigens are important triggers of EoE, and allergists play an important role in management of this chronic disease. This review addresses insights into the diagnosis and management as it relates to our evolving understanding about the pathogenesis of EoE.

PMID: 29132668 [PubMed - in process]

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Complementary and Alternative Medicine for Treatment of Food Allergy.

Complementary and Alternative Medicine for Treatment of Food Allergy.

Immunol Allergy Clin North Am. 2018 Feb;38(1):103-124

Authors: Li XM

Abstract
The prevalence of food allergy is increasing. Food allergy can be life threatening and there is no approved treatment available. Allergen avoidance and rescue medication remain the sole management tools. Complementary and alternative medicine (CAM) use is common in the United States. However, research into safety and efficacy for food allergy is limited. Continued scientific research into food allergy herbal formula 2 (FAHF-2), refined methods of formulation, purified compounds, and other modalities are needed. Traditional Chinese medicine is the main component of CAM in the United States. Conventional doctors, CAM practitioners, and patients' families must collaborate to comanage these patients.

PMID: 29132667 [PubMed - in process]

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Prevention of Food Allergies.

Prevention of Food Allergies.

Immunol Allergy Clin North Am. 2018 Feb;38(1):1-11

Authors: Koplin JJ, Peters RL, Allen KJ

Abstract
This review summarizes the current state of play with regard to food allergy prevention. Food allergy prevention strategies focused on promoting timely introduction of allergenic foods (predominantly peanut) into the infant diet have recently been introduced in several countries. Additional prevention strategies currently under investigation include optimizing infant vitamin D levels, modulating the gut microbiota through use of probiotics, and preventing eczema to reduce the risk of food sensitization through a damaged skin barrier.

PMID: 29132666 [PubMed - in process]

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Patch testing in Israeli children with suspected allergic contact dermatitis: A retrospective study and literature review

Abstract

Background/objectives

Childhood allergic contact dermatitis is recognized as a significant clinical problem. The objective was to evaluate the rate of positive patch tests in Israeli children with clinically suspected allergic contact dermatitis, identify possible sex and age differences, compare results with those in Israeli adults, and review pediatric studies in the literature.

Methods

The study sample included 343 children and adolescents (197 female, 146 male; 1-18 years of age, mean age 11.8 years) with clinically suspected allergic contact dermatitis who underwent patch testing with a standard pediatric series of 23 allergens at a tertiary medical center from 1999 to 2012. Data on clinical characteristics and test results were collected retrospectively from the medical files.

Results

Ninety-eight subjects (28.6%) (75 girls [38.1%], 23 boys [15.8%]) had at least one positive reaction. The most frequent reactions were to nickel sulfate, followed by potassium dichromate and cobalt chloride. Nickel sulfate sensitivity was more common in girls, especially those younger than 3 years and older than 12 years. The prevalence of contact sensitization was similar in subjects with and without atopic dermatitis (50% and 51%, respectively).

Conclusion

Nickel is the most common allergen in Israeli children, especially girls. Patch testing should be performed in children with clinically suspected allergic contact dermatitis regardless of atopic background.

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Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand

Abstract

Background/Objectives

Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants.

Methods

Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm.

Results

SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity.

Conclusion

The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity.

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Imaging and imagination

Future Oncology, Volume 13, Issue 26, Page 2315-2316, November 2017.

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Durvalumab in non-small-cell lung cancer patients: current developments

Future Oncology, Ahead of Print.

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Tailored coefficients in the algorithm to assess reconstructed light extinction at urban sites: A comparison with the IMPROVE revised approach

Publication date: January 2018
Source:Atmospheric Environment, Volume 172
Author(s): S. Valentini, V. Bernardoni, D. Massabò, P. Prati, G. Valli, R. Vecchi
Estimates of light extinction and visibility are routinely performed by the U.S. Interagency Monitoring of Protected Visual Environments (IMPROVE) network using a simple algorithm which assesses light extinction coefficient (bext) at remote and rural sites from concentrations of major particulate matter (PM) species, NO2, and Rayleigh scattering from clear-air gaseous components. Following the same approach, in this paper an equation with tailored (i.e. site-specific) coefficients was implemented with the aim of reducing uncertainties and assumptions of the IMPROVE algorithm for applications at polluted urban sites. Major differences compared to IMPROVE algorithm are: 1) dry mass extinction efficiencies calculated using a discrete dipole approximation code with aerosol size distributions measured at our monitoring site as input data; 2) site-specific water growth functions computed separately for ammonium sulfate, ammonium nitrate, and organic matter; 3) fine soil evaluated using an equation previously adopted at our urban site; 4) aerosol absorption component assessed directly through filter-based optical measurements. Details about the calculations performed are reported in the paper and the comparison with the IMPROVE revised algorithm is discussed.The tailored approach here proposed to estimate reconstructed light extinction was applied to PM2.5 test samples collected on purpose in Milan (Italy), where heavy pollution episodes occur during winter periods. In addition, visual range was calculated applying the Koschmieder equation and compared to visibility measured at the nearby Milano-Linate airport obtaining a fairly good correlation.

Graphical abstract

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Contrasting aerosol optical and radiative properties between dust and urban haze episodes in megacities of Pakistan

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Muhammad Iftikhar, Khan Alam, Armin Sorooshian, Waqar Adil Syed, Samina Bibi, Humera Bibi
Satellite and ground based remote sensors provide vital information about aerosol optical and radiative properties. Analysis of aerosol optical and radiative properties during heavy aerosol loading events in Pakistan are limited and, therefore, require in-depth examination. This work examines aerosol properties and radiative forcing during Dust Episodes (DE) and Haze Episodes (HE) between 2010 and 2014 over mega cities of Pakistan (Karachi and Lahore). Episodes having the daily averaged values of Aerosol Optical Depth (AOD) exceeding 1 were selected. DE were associated with high AOD and low Ångström Exponent (AE) over Karachi and Lahore while high AOD and high AE values were associated with HE over Lahore. Aerosol volume size distributions (AVSD) exhibited a bimodal lognormal distribution with a noticeable coarse mode peak at a radius of 2.24 μm during DE, whereas a fine mode peak was prominent at a radius 0.25 μm during HE. The results reveal distinct differences between HE and DE for spectral profiles of several parameters including Single Scattering Albedo (SSA), ASYmmetry parameter (ASY), and the real and imaginary components of refractive index (RRI and IRI). The AOD-AE correlation revealed that dust was the dominant aerosol type during DE and that biomass burning and urban/industrial aerosol types were pronounced during HE. Aerosol radiative forcing (ARF) was estimated using the Santa Barbra DISORT Atmospheric Radiative Transfer (SBDART) model. Calculations revealed a negative ARF at the Top Of the Atmosphere (ARFTOA) and at the Bottom Of the Atmosphere (ARFBOA), with positive ARF within the Atmosphere (ARFATM) during both DE and HE over Karachi and Lahore. Furthermore, estimations of ARFATM by SBDART were shown to be in good agreement with values derived from AERONET data for DE and HE over Karachi and Lahore.

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Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment

Abstract

Objective

The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner.

Methods

A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case–control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan–Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models.

Results

Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0–59, standard error (SE) 15.35] versus 27 months (95% CI 22.6–31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02–5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32–11, p < 0.001] were found to be independent risk factors for decreased OS.

Conclusion

DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

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Standardized automated training of rhesus monkeys for neuroscience research in their housing environment

Teaching non-human primates the complex cognitive behavioral tasks that are central to cognitive neuroscience research is an essential and challenging endeavor. It is crucial for the scientific success that the animals learn to interpret the often complex task rules, and reliably and enduringly act accordingly. To achieve consistent behavior and comparable learning histories across animals, it is desirable to standardize training protocols. Automatizing the training can significantly reduce the time invested by the person training the animal. And self-paced training schedules with individualized learning speeds based on automatic updating of task conditions could enhance the animals' motivation and welfare. We developed a training paradigm for across-task unsupervised training (AUT) of successively more complex cognitive tasks to be administered through a stand-alone housing-based system optimized for rhesus monkeys in neuroscience research settings (Calapai et al. 2016). The AUT revealed inter-individual differences in long-term learning progress between animals, helping to characterize learning personalities, and commonalities, helping to identify easier and more difficult learning steps in the training protocol. Our results demonstrate that (1) rhesus monkeys stay engaged with the AUT over months despite access to water and food outside the experimental sessions, but with lower numbers of interaction compared to conventional fluid-controlled training; (2) with unsupervised training across sessions and task levels, rhesus monkeys can learn tasks of sufficient complexity for state-of-the art cognitive neuroscience in their housing environment; (3) AUT learning progress is primarily determined by the number of interactions with the system rather than the mere exposure time.

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Novel Ca2+-Dependent Mechanisms Regulate Spontaneous Release at Excitatory Synapses onto CA1 Pyramidal Cells

Although long thought to simply be a source of synaptic noise, spontaneous, action-potential independent release of neurotransmitter from presynaptic terminals has multiple roles in synaptic function. We explored whether and to what extent the two predominantly proposed mechanisms for explaining spontaneous release, stochastic activation of voltage-gated Ca²⁺ channels (VGCCs) or activation of Ca²⁺-sensing receptors (CaSRs) by extracelluar Ca²⁺, played a role in the sensitivity of spontaneous release to the level of extracellular Ca²⁺ concentration at excitatory synapses at CA1 pyramidal cells of the adult, male mouse hippocampus. Blocking VGCCs with Cd²⁺ had no effect on spontaneous release, ruling out stochastic activation of VGCCs. Although divalent cation agonists of CaSRs, Co²⁺ and Mg²⁺, dramatically enhanced mEPSC frequency, potent positive and negative allosteric modulators of CaSRs had no effect. Moreover, immunoblot analysis of hippocampal lysates failed to detect CaSR expression, ruling out the CaSR. Instead, the increase in mEPSC frequency induced by Co²⁺ and Mg²⁺ was mimicked by lowering postsynaptic Ca²⁺ levels with BAPTA. Together, our results suggest that a reduction in intracellular Ca²⁺ may trigger a homeostatic-like compensatory response that upregulates spontaneous transmission at excitatory synapses onto CA1 pyramidal cells in the adult hippocampus.

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Assessing TMS-induced D- and I-waves with spinal H-reflexes

Transcranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D- (direct) and I- (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D-waves, early and late I-waves from TMS. We therefore probed H-reflex facilitation at arrival times of D- and I-waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D- and different I-waves. We changed TMS intensity and current direction, and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: I) In FCR, H-reflex facilitation showed characteristic modulations with altered TMS-parameters that correspond to the changes of evoked D- and I-waves. II) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D- and I-waves.

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Response of supra oculomotor area neurons during combined saccade-vergence movements

Combined saccade-vergence movements allow humans and other primates to align their eyes with objects of interest in three-dimensions. In the absence of saccades, vergence movements are typically slow, symmetrical movements of the two eyes in opposite directions. However, combined saccade-vergence movements produce vergence velocities that exceed values observed during vergence alone. This phenomenon is often called "vergence enhancement", or "saccade-facilitated vergence," though it is important to consider that rapid vergence changes, known as "vergence transients," are also observed during conjugate saccades. We developed a visual target array that allows monkeys to make saccades in all directions between targets spaced at distances that correspond to ~1o intervals of vergence angle relative to the monkey. We recorded the activity of vergence-sensitive neurons in the supra-oculomotor area (SOA), located dorsal and lateral to the oculomotor nucleus while monkeys made saccades with vergence amplitudes ranging from 0-10o. The primary focus of this study was to test the hypothesis that neurons in the SOA fire a high frequency burst of spikes during saccades that could generate the enhanced vergence. We found that individual neurons encode vergence velocity during both saccadic and non-saccadic vergence, yet firing rates were insufficient to produce the observed enhancement of vergence velocity. Our results are consistent with the hypothesis that slow vergence changes are encoded by the SOA while fast vergence movements require an additional contribution from the saccadic system.

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The acquisition of skilled finger movements is accompanied by the reorganization of the corticospinal system

Dexterous finger movements are often characterized by highly coordinated movements. Such coordination might be derived from reorganization of the corticospinal system. In this study, we investigated 1) the manner in which finger movement covariation patterns are acquired by examining the effects of the implicit and explicit learning of a serial reaction time task (SRTT), and 2) how such changes in finger coordination are represented in the corticospinal system. The subjects learned a button press sequence in both implicit and explicit learning conditions. In the implicit conditions, they were naive about what they are learning, whereas in the explicit conditions the subjects consciously learnt the order of the sequence elements. Principal component analysis decomposed both the voluntary movements produced during the SRTT and the passive movements evoked by transcranial magnetic stimulation (TMS) over the primary motor cortex into a set of 5 finger joint covariation patterns. The structures of the voluntary and passive TMS-evoked movement patterns were reorganized by implicit learning, but not explicit learning. Furthermore, in the implicit learning conditions the finger covariation patterns derived from the TMS-evoked and voluntary movements spanned similar movement subspaces. These results provide the first evidence that skilled sequential finger movements are acquired differently through implicit and explicit learning; i.e., the changes in finger coordination patterns induced by implicit learning are accompanied by functional reorganization of the corticospinal system, whereas explicit learning results in faster recruitment of individual finger movements without causing any changes in finger coordination.

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Patterns of intermuscular inhibitory force feedback across cat hindlimbs suggest a flexible system for regulating whole limb mechanics

Prior work has suggested that Golgi tendon organ feedback, via its distributed network linking muscles spanning all joints, could be used by the nervous system to help regulate whole limb mechanics if appropriately organized. We tested this hypothesis by characterizing the patterns of intermuscular force dependent feedback between the primary extensor muscles spanning the knee, ankle and toes in decerebrate cat hindlimbs. Intermuscular force feedback was evaluated by stretching tendons of selected muscles in isolation and in pairwise combinations and then measuring the resulting force dependent intermuscular interactions. The relative inhibitory feedback between extensor muscles was examined, as well as symmetry of the interactions across limbs. Differences in the directional biases of inhibitory feedback were observed across cats, with three patterns identified as points on a spectrum: Pattern 1) directional bias of inhibitory feedback onto the ankle extensors and toe flexors, Pattern 2) convergence of inhibitory feedback onto ankle extensors and mostly balanced inhibitory feedback between V and FHL, and Pattern 3) directional bias of inhibitory feedback onto ankle and knee extensors. The patterns of inhibitory feedback, while different across cats, were symmetric across limbs of individual cats. The variable but structured distribution of force feedback across cat hindlimbs provides preliminary evidence that inhibitory force feedback could be a regulated neural control variable. We propose the directional biases of inhibitory feedback observed experimentally could provide important task dependent benefits, such as directionally appropriate joint compliance, joint coupling, and compensation for nonuniform inertia.

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Fast oscillation dynamics during hypsarrhythmia as a localization biomarker

Hypsarrhythmia in West syndrome, although hard to define, is characterized by chaotic and disorganized electrical activity of the brain and is often regarded as a generalized EEG pattern without any localization value. Using event-related spectral perturbation (ERSP), we tried to determine the brain dynamics during hypsarrhythmia. Routine 1-h scalp EEGs were retrieved from 31 patients with infantile spasms and 20 age-matched controls. Using the EEGLAB toolbox of MATLAB 2015b, the ERSPs of fast oscillations (FOs; 20-100 Hz) of selected channels were analyzed and compared among groups according to their MRI lesions. FO-ERSP cutoff values for predicting the pathologic foci were estimated. The mean FO-ERSPs across all analyzed electrodes of patients with spasms were significantly higher than those of controls. When the patients were categorized into non-lesional, focal/multifocal, or diffuse lesional groups, the FO-ERSP of patients in the focal/multifocal lesional group was significantly lower than that of those in the non-focal or diffuse lesional groups. In the focal/multifocal lesional group, seven patients (7/9, 77.8%) showed that the locations of channels with high FO-ERSPs were matched to the pathologic MRI lesions. Thus, the localization of high FO-ERSPs is closely associated with the location of pathologic brain lesions. Further research is required to prove the value of the FO-ERSP as an important quantitative localizing biomarker of West syndrome.

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Developmental changes in spinal neuronal properties, motor network configuration and neuromodulation at free-swimming stages of Xenopus frog tadpoles.

We describe a novel preparation of the isolated brainstem and spinal cord from pro-metamorphic tadpole stages of the South African clawed frog (Xenopus laevis) that permits whole cell patch-clamp recordings from neurons in the ventral spinal cord. Previous research on earlier stages of the same species has provided one of the most detailed understandings of the design and operation of a CPG circuit. Here we have addressed how development sculpts complexity from this more basic circuit. The preparation generates bouts of fictive swimming activity either spontaneously or in response to electrical stimulation of the optic tectum, allowing an investigation into how the neuronal properties, activity patterns and neuromodulation of locomotor rhythm generation change during development. We describe an increased repertoire of cellular responses compared to younger larval stages and investigate the cellular level effects of nitrergic neuromodulation as well as the development of a sodium pump-mediated ultra-slow afterhyperpolarisation (usAHP) in these free-swimming larval animals.

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Physiological and pathophysiological firing properties of single postganglionic sympathetic neurons in humans

It has long been known from microneurographic recordings in human subjects that activity of postganglionic sympathetic axons occurs as spontaneous bursts, with muscle sympathetic nerve activity (MSNA) exhibiting strong cardiac rhythmicity via the baroreflex and skin sympathetic nerve activity (SSNA) showing much weaker cardiac modulation. Here we review the firing properties of single sympathetic neurons, obtained using highly selective microelectrodes. Individual vasoconstrictor neurons supplying muscle or skin, or sudomotor neurones supplying sweat glands, always discharge with a low firing probability (~30%) and at very low frequencies (~0.5 Hz). Moreover, they usually fire only once per cardiac interval, but can fire >4 times within a burst. Modeling has shown that this pattern can best be explained by individual neurons being driven by, on average, two preganglionic inputs. Unitary recordings of muscle vasoconstrictor neurons have been made in several pathophysiological states, including heart failure, hypertension, obstructive sleep apnea, bronchiectasis, chronic obstructive pulmonary disease, depression and panic disorder. The augmented MSNA in each of these diseases features an increase in firing probability and discharge frequency of individual muscle vasoconstrictor neurons above that seen in healthy subjects, yet firing rates rarely exceed 1 Hz. However, unlike patients with heart failure, all patients with respiratory disease or panic disorder, and patients with hyperhidrosis, exhibited an increase in multiple within-burst firing, which emphasizes the different modes by which the sympathetic nervous system grades its output in pathophysiological states of high sympathetic nerve activity.

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Abnormal visual gain control and excitotoxicity in early-onset Parkinson's disease Drosophila models

The excitotoxic theory of Parkinson's disease (PD) hypothesises that a pathophysiological degeneration of dopaminergic neurons stems from neural hyperactivity at early stages of disease, leading to mitochondrial stress and cell death. Recent research has harnessed the visual system of Drosophila PD models to probe this hypothesis. Here, we investigate whether abnormal visual sensitivity and excitotoxicity occur in early-onset PD Drosophila models DJ-172, DJ1-93, and PINK15. We used an electroretinogram to record steady state visually evoked potentials driven by temporal contrast stimuli. At 1 day of age, all early-onset PD mutants had a twofold increase in response amplitudes when compared to w- controls. Further, we found that excitotoxicity occurs in older early-onset PD models after increased neural demand is applied via visual stimulation. In an additional analysis, we used a linear discriminant analysis to test whether there were subtle variations in neural gain control that could be used to classify Drosophila into their correct age and genotype. The discriminant analysis was highly accurate, classifying Drosophila into their correct genotypic class at all age groups at 50-70% accuracy (20% chance baseline). Differences in cellular processes link to subtle alterations in neural network operation in young flies - all of which lead to the same pathogenic outcome. Our data are the first to demonstrate abnormal gain control and excitotoxicity in early-onset PD Drosophila mutants. We conclude that early-onset PD mutations may be linked to more sensitive neuronal signalling in prodromal animals that may cause the expression of PD symptomologies later in life.

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Imaging and imagination

Future Oncology, Volume 13, Issue 26, Page 2315-2316, November 2017.

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Durvalumab in non-small-cell lung cancer patients: current developments

Future Oncology, Ahead of Print.

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Polyglucosan myopathy and functional characterization of a novel GYG1 mutation

Objectives

Disorders of glycogen metabolism include rare hereditary muscle glycogen storage diseases with polyglucosan, which are characterized by storage of abnormally structured glycogen in muscle in addition to exercise intolerance or muscle weakness. In this study, we investigated the etiology and pathogenesis of a late-onset myopathy associated with glycogenin-1 deficiency.

Materials and methods

A family with two affected siblings, 64- and 66-year-olds, was studied. Clinical examination and whole-body MRI revealed weakness and wasting in the hip girdle and proximal leg muscles affecting ambulation in the brother. The sister had weakness and atrophy of hands and slight foot dorsiflexion difficulties. Muscle biopsy and whole-exome sequencing were performed in both cases to identify and characterize the pathogenesis including the functional effects of identified mutations.

Results

Both siblings demonstrated storage of glycogen that was partly resistant to alpha-amylase digestion. Both were heterozygous for two mutations in GYG1, one truncating 1-base deletion (c.484delG; p.Asp163Thrfs*5) and one novel missense mutation (c.403G>A; p.Gly135Arg). The mutations caused reduced expression of glycogenin-1 protein, and the missense mutation abolished the enzymatic function as analyzed by an in vitro autoglucosylation assay.

Conclusion

We present functional evidence for the pathogenicity of a novel GYG1 missense mutation located in the substrate binding domain. Our results also demonstrate that glycogenin-1 deficiency may present with highly variable distribution of weakness and wasting also in the same family.

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Guidelines for Contributing Authors

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Editorial Board

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Oncogenic spiral by infectious pathogens: The cooperation of multiple factors in cancer development

Abstract

Chronic infection is one of the major causes of cancer, and there are several mechanisms for infection-mediated oncogenesis. Some pathogens encode gene products that behave like oncogenic factors, hijacking cellular pathways to promote the survival and proliferation of infected cells in vivo. Some of these viral oncoproteins trigger a cellular damage defense response leading to senescence; however, other viral factors hinder this suppressive effect, suggesting that cooperation of those viral factors is important for malignant transformation. Coinfection with multiple agents is known to accelerate cancer development in certain cases. For example, parasitic or bacterial infection is a risk factor for adult T-cell leukemia-lymphoma induced by human T-cell leukemia virus type 1, and Epstein-Barr virus and malaria are closely associated with endemic Burkitt lymphoma. Human immunodeficiency virus type 1 infection is accompanied by various types of infection-related cancer. These findings indicate that these oncogenic pathogens can cooperate to overcome host barriers against cancer development. In this review, the authors focus on the collaborative strategies of pathogens for oncogenesis from two different points of view: (1) the cooperation of two or more different factors encoded by a single pathogen, and (2) the acceleration of oncogenesis by coinfection with multiple agents.

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Microvascular insulin resistance in skeletal muscle and brain occurs early in the development of juvenile obesity in pigs

Background: Impaired microvascular insulin signaling may develop prior to overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex) and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase C beta (PKCβ). Methods and Results: Juvenile Ossabaw miniature swine (3.5-months of age) were divided into two groups: lean control (n=6) and obese (n=6). Obesity was induced by feeding the animals a high-fat/high-fructose corn syrup/high-cholesterol diet for 10-weeks. Juvenile obesity was characterized by excess body mass, hyperglycemia, physical inactivity (accelerometer) and marked lipid accumulation in the skeletal muscle, with no evidence of overt atherosclerotic lesions in athero-prone regions such as the abdominal aorta. Endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) vasomotor responses in the brachial and carotid arteries (wire myography) as well as in the skeletal muscle resistance and 2A pial arterioles (pressure myography) were unaltered, but insulin-induced microvascular vasodilation was impaired in the obese group. Blunted insulin-stimulated vasodilation, which was reversed with acute PKCβ inhibition (LY333-351), occurred alongside decreased tissue perfusion as well as reduced insulin-stimulated Akt signaling in the prefrontal cortex, but not the triceps. Conclusions: In the early stages of juvenile obesity development, the microvasculature and prefrontal cortex exhibit impaired insulin signaling. Such adaptations may underscore vascular and neurological derangements associated with juvenile obesity.

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Maternal circadian rhythms and the programming of adult health and disease

The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability and other environmental factors change predictably and repeatedly every 24 hours. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual's health and wellbeing. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review we outline circadian timing system ontogeny in mammals, and examine emerging research from animal models demonstrating long term negative implications for progeny health following maternal chronodisruption during pregnancy.

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Atypical G protein {beta}5 promotes cardiac oxidative stress, apoptosis, and fibrotic remodeling in response to multiple cancer chemotherapeutics

The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. We report here that, though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium, correlating with oxidative stress, myocyte apoptosis, and the accumulation of pro-inflammatory and pro-fibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII pro-apoptotic signaling cascades. In addition, Gβ5 loss allowed for maintenance of Δψm, basal MCU, and mitochondrial Ca2+ levels, effects likely to preserve functional myocyte excitation-contraction coupling. Gβ5 knockdown also reduced chemotherapy-induced release of pro-inflammatory cytokines (e.g. TNFα), hypertrophic factors (e.g. ANP), and pro-fibrotic factors (e.g. TGFβ1) from both VCM and ventricular cardiac fibroblasts (VCF), with the most dramatic reductions occurring in co-cultured cells. Intracardiac injection of Gβ5-targeted shRNA allowed for heart specific protection against the damaging impact of chronic chemotherapy. These data suggest that Gβ5 facilitates the myofibroblast transition, the persistence of which contributes to pathological remodeling and heart failure. The convergence of Gβ5-mediated, ROS-dependent signaling pathways in both cell types represents a critical etiological factor in the pathogenesis of chemotherapy-induced cardiotoxicity.

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Pharmacologic inhibition of the menin-MLL interaction leads to transcriptional repression of PEG10 and blocks hepatocellular carcinoma

Hepatocellular carcinoma (HCC) accounts for ~85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Here, we demonstrate that the menin-MLL inhibitor MI-503 shows anti-tumor activity in in vitro and in vivo models of HCC and reveal the potential mechanism of menin contribution to HCC. Treatment with MI-503 selectively kills various HCC cell lines and this effect is significantly enhanced by a combination of MI-503 with sorafenib, the standard of care therapy for HCC. Furthermore, MI-503 reduces sphere formation and cell migration in in vitro HCC models. When applied in vivo, MI-503 gives a strong anti-tumor effect both as a single agent and in combination with sorafenib in mice xenograft models of HCC. Mechanistically, treatment with MI-503 downregulates expression of several genes known to play a critical role in proliferation and migration of HCC cells, including PEG10, and displaces the menin-MLL1 complex from the PEG10 promoter, resulting in reduced H3K4 methylation and transcriptional repression. Overall, our studies reveal a mechanistic link between menin and genes involved in HCC and demonstrate that pharmacologic inhibition of the menin-MLL interaction might represent a promising therapeutic approach for HCC.

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CAT-02-106, a site-specifically conjugated anti-CD22 antibody bearing an MDR1-resistant maytansine payload yields excellent efficacy and safety in preclinical models

Hematologically-derived tumors make up ~10% of all newly-diagnosed cancer cases in the U.S. Of these, the non-Hodgkin lymphoma (NHL) designation describes a diverse group of cancers that collectively rank among the top 10 most commonly diagnosed cancers worldwide. Although long-term survival trends are improving, there remains a significant unmet clinical need for treatments to help patients with relapsed or refractory disease, one cause of which is drug efflux through upregulation of xenobiotic pumps, such as MDR1. CD22 is a clinically-validated target for the treatment of NHL, but no anti-CD22 agents have yet been approved for this indication. Recent approval of an anti-CD22 antibody-drug conjugate (ADC) for the treatment of relapsed/refractory ALL supports the rationale for targeting this protein. An opportunity exists for a next-generation anti-CD22 antibody-drug conjugate (ADC) to address unmet medical needs in the relapsed/refractory NHL population. We describe a site-specifically-conjugated antibody-drug conjugate, made using aldehyde tag technology, targeted against CD22 and bearing a noncleavable maytansine payload that is resistant to MDR1-mediated efflux. The construct was efficacious against CD22+ NHL xenografts and could be repeatedly dosed in cynomolgus monkeys at 60 mg/kg with no observed significantly adverse effects. Exposure to total ADC at these doses (as assessed by AUC0-inf) indicated that the exposure needed to achieve efficacy was below tolerable limits. Together, the data suggest that this drug has the potential to be used effectively in patients with CD22+ tumors that have developed MDR1-related resistance to prior therapies.

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Characterization of SGN-CD123A, a potent CD123-directed antibody-drug conjugate for acute myeloid leukemia

Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation. Mechanistically, SGN-CD123A induces activation of DNA damage response pathways, cell cycle changes, and apoptosis in AML cells. In vitro, SGN-CD123A mediated potent cytotoxicity of 11/12 CD123+ AML cell lines and 20/23 primary samples from AML patients, including those with unfavorable cytogenetic profiles or FLT3 mutations. In vivo, SGN-CD123A treatment led to AML eradication in a disseminated disease model, remission in a subcutaneous xenograft model, and significant growth delay in a multidrug resistance xenograft model. Moreover, SGN-CD123A also resulted in durable complete remission of a patient-derived xenograft AML model. When combined with a FLT3 inhibitor quizartinib, SGN-CD123A enhanced the activity of quizartinib against two FLT3-mutated xenograft models. Overall, these data demonstrate that SGN-CD123A is a potent anti-leukemic agent, supporting an ongoing trial to evaluate its safety and efficacy in AML patients (NCT02848248).

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JQ1 induces DNA damage and apoptosis, and inhibits tumor growth in a patient-derived xenograft model of cholangiocarcinoma

Cholangiocarcinoma (CCA) is a fatal disease with a five-year survival of <30%. For a majority of patients chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the frontline agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ~8 months. Combining this agent with cisplatin increases survival by ~3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA. We used two of these models to investigate the anti-tumor efficacy and mechanism of action of the bromodomain inhibitor JQ1, an agent that has not been evaluated for the treatment of CCA. The data show that JQ1 suppressed the growth of the CCA PDX model CCA2, and demonstrate that growth suppression was concomitant with inhibition of c-Myc protein expression. A second model (CCA1) was JQ1-insensitive, with tumor progression and c-Myc expression unaffected by exposure to this agent. Also selective to CCA2 tumors, JQ1 induced DNA damage and apoptosis, and downregulated multiple c-Myc transcriptional targets that regulate cell cycle progression and DNA repair. These findings suggest that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA.

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Indolent T-lymphoblastic proliferation concomitant to acinic cell carcinoma mimicking T-lymphoblastic lymphoma: case report and literature review

Abstract

Aims

Indolent T-lymphoblastic proliferation (iT-LBP) is a non-clonal benign condition showing extrathymic proliferation of T-lymphoblasts positive for CD3, CD4, CD8, and TdT. Isolated iT-LBP has been observed, but the majority of iT-LBP have been seen in conjunction with other disorders including Castleman disease, hepatocellular carcinoma, follicular dendritic cell tumors, angioimmunoblastic T-cell lymphoma, myasthenia gravis, and acinic cell carcinoma (ACC). The clinical course of iT-LBP is indolent, and no therapy is usually required. A major concern is misdiagnosis for T-lymphoblastic lymphoma, and a correct diagnosis of iT-LBP often requires not only pathological analysis but also a cautious monitoring of the clinical course. The aim of this report is to broaden knowledge of this yet not well recognized entity to pathologists and physicians

Methods and Results

We report a case of iT-LBP concomitant to ACC, along with a literature review of all 14 cases of iT-LBP reported to date

Conclusions

iT-LBP should always be considered as a differential diagnosis of T-lymphoblastic lymphoma as the two disorders show extremely resembling traits.

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Epigenetic down-regulation of SOX2 is an independent poor prognostic factor for hypopharyngeal cancers

Abstract

Aims

We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The present study aimed to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal or oropharyngeal squamous cell carcinomas (HPSCCs or OPSCCs, respectively).

Methods and Results

The study cohort consisted of consecutive patients with HPSCC (n=130) and OPSCC (n=65) who underwent surgery without preoperative therapy. On immunostaining, SOX2 was almost entirely negative in 10/130 HPSCCs (8%) and 7/65 OPSCCs (11%). No significant differences were observed in clinicopathological features, including the p16 status, between SOX2-positive and SOX2-negative cancers. However, patients with SOX2-negative HPSCC had significantly worse overall and recurrence-free survivals than those with SOX2-positive cancer, while such prognostic relationship was not confirmed in patients with OPSCC. In a multivariate analysis, the loss of SOX2 expression appeared to be an independent poor prognostic factor for patients with HPSCC. In a sequencing analysis, no mutation was found in SOX2. Since SOX2 is known to contain an extensive CpG island before the transcription start site, methylation-specific PCR for the SOX2 promoter was performed. Methylated alleles were found in 9/10 SOX2-negative HPSCCs but none of SOX2-retained cases.

Conclusions

Similar to oesophageal cancers, a small subset (8%) of HPSCCs characteristically almost lacking SOX2 expression appeared to be aggressive neoplasms with high recurrence rates. Promoter hypermethylation was determined to be a major mechanism underlying epigenetic SOX2 silencing.

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Primary myxoid mesenchymal tumor with intracranial location: report of a case with a EWSR1-ATF1 fusion

Abstract

About a third of soft tissue tumors are recognized by gene fusions. Some of these fusions are not histotype specific and occur in entities with totally different clinicopathological features. A good example is the fusion between EWSR1 and genes of the CREB transcription factor gene family (CREB1 or ATF1).

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Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels

The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the ex...

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EEG dynamical correlates of focal and diffuse causes of coma

Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve D...

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Quality assurance of the SCOPE 1 trial in oesophageal radiotherapy

SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims:

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Patient-derived xenograft in zebrafish embryos: a new platform for translational research in gastric cancer

Gastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored area...

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Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer

Though androgen deprivation therapy is the standard treatment for prostate cancer (PCa), most patients would inevitably progress to castration-resistant prostate cancer (CRPC) which is the main cause of PCa de...

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Psychological and Psychophysiological Effects of Recuperative Music Postexercise.

Purpose: Few studies have examined the psychological and psychophysiological effects of recuperative music following exhaustive exercise. The main purpose of the present study was to examine the effects of two music conditions compared with a no-music control on psychological and psychophysiological recovery processes post-exercise. Methods: A randomized, fully counterbalanced, crossover design was used. Core affect, salivary cortisol, heart rate, and blood pressure were measured before exhaustive exercise, immediately after, and in 10-, 20-, and 30-min intervals during passive recovery (21 women and 21 men; 20.9 +/- 1.7 yr) over three separate trials (slow, sedative music; fast, stimulative music; no-music control). The exercise task entailed incremental cycle ergometry performed at 75 rpm with a 22.5 W.min-1 increase in intensity at the end of each minute until exhaustion. Data were analyzed using mixed-model 3 (condition) x 4 (time) x 2 (gender) MANOVA/ANCOVA. Results: The largest decline in affective arousal between active and passive recovery phases was evident in the slow, sedative condition ([eta]p2 = 0.50). Women had a more pronounced reduction in arousal than men in the slow, sedative music condition. Heart rate measures showed that fast, stimulative music inhibited the return of heart rate toward resting levels ([eta]p2 = 0.06). Similarly, salivary cortisol levels tended to be lower in response to slow, sedative music ([eta]p2 = 0.11). There was a main effect of condition for affective valence indicating that the slow, sedative condition elicited more positive affective responses than the control and fast, stimulative conditions ([eta]p2 = 0.12). Conclusions: The present findings support the notion that slow, sedative music can expedite the recovery process immediately after strenuous exercise. (C) 2017 American College of Sports Medicine

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A Construct Validation Study of PLAYfun.

Introduction: PLAYfun is a measure of motor competence, comprehension and confidence which is part of a suite of scales used to assess physical literacy in children and youth. However, its measurement properties have not been reported in the published literature. The purpose of this study is to examine the factor structure of PLAYfun, in addition to variations in PLAYfun subscale results by age and sex. Method: In this study, we use a sample of children and youth aged 7 to 14 years (n=215) to test a proposed factor structure for the motor competence component of PLAYfun and to examine age and sex differences in subscale and total scores. The initial (n=128) and secondary (n=98) samples were drawn from a stratified (by geographic region), random sample of 27 afterschool programs from a larger pool of 400 programs across the province of Ontario. Seven research assistants were initially trained on the administration of PLAYfun and rated a small pilot sample of 10 children. These trained assessors then assessed the full sample.. Results: Inter-rater agreement was very good (ICC=.87). The hypothesized 5-factor structure of the scale was found to have an acceptable fit to the data (RMSEA = 0.055, 90% CI = 0.03 to 0.075; CFI = 0.95; TLI = 0.94). In general, PLAYfun scores increased with age as developmentally expected. There were few sex differences across skills, but girls did not perform as well as boys on upper and lower body object control skills. Conclusion: The factor structure and patterns of results by age and sex support PLAYfun as a measure of motor competence. Continued evaluation of the tool and other subscales of PLAY are required. (C) 2017 American College of Sports Medicine

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Isotemporal Substitution of Sedentary Behavior and Physical Activity on Function.

The amount of time spent in sedentary behaviors (SB) progressively increases with age, while reducing time spent in light (LPA) and moderate-to-vigorous physical activity (MVPA). These trajectories in PA and SB are linked to accelerated reductions in physical functioning. PURPOSE: To examine the association of substituting SB time with LPA and MVPA on physical function in older adults. METHODS: Ninety-one older adults (mean age: 70.7 +/- 10.2 yr) wore a hip-mounted accelerometer to measure SB, LPA, and MVPA time. Measures of physical function included a 400m walk test (400W), usual gait speed (UGS), and 5-time sit-to-stand (5xSTS), and the short physical performance battery (SPPB). Isotemporal substitution regression modeling was performed to assess the relationship of replacing the amount of time spent in one activity for another. RESULTS: Replacing 30 min[BULLET OPERATOR]d-1 of SB with LPA was associated with a significant improvement in 400W (p = 0.0497), while MVPA resulted in a significant improvement (p

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Associations between BMI Change and Cardiometabolic Risk in Retired Football Players.

Purpose: Elevated rates of cardiometabolic diseases have been observed in former American football players. The current study sought to determine if change in body mass index ([DELTA]BMI) following retirement influences the prevalence of coronary heart disease (CHD), diabetes, or high blood pressure (HBP) in former professional football players. Methods: Retired professional football players (n=3,729) were sent a survey with questions regarding health status, playing history, and demographic information. Self-reported BMI at the time of retirement was subtracted from current self-reported BMI to calculate [DELTA]BMI. Prevalence of CHD, diabetes, and HBP were determined by asking participants if they had ever been diagnosed by a healthcare professional. Binomial regression with a Poisson residual and robust variance estimation was used to compute crude prevalence ratios (PRs) and 95% confidence intervals (CI) for each outcome. Adjusted PRs were calculated by adjusting for BMI at the time of retirement, age, years of football experience, race, exercise habits, alcohol use, steroid history, smoking history, and playing position. Results: Complete data were available for 2,062 respondents. Prevalence of CHD increased 25-31% for each 5-point increase in [DELTA]BMI following retirement (Crude PR: 1.25; 95%CI: 1.03-1.52; p=0.026; Adjusted PR: 1.31; 95%CI: 1.11-1.55; p=0.001). Diabetes prevalence increased 69-88% for each 5-point [DELTA]BMI increase (Crude: 1.88; 95%CI: 1.45-2.44; p

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Cold-Water Ingestion Improves Exercise Tolerance of Heat-Sensitive People with MS.

Purpose: Heat intolerance commonly affects the exercise capacity of people with multiple sclerosis (MS) during bouts of hot weather. Cold-water ingestion is a simple cooling strategy but its efficacy for prolonging exercise capacity with MS remains undetermined. We sought to identify whether cold-water ingestion blunts exercise-induced rises in body temperature and improves exercise tolerance in heat-sensitive individuals with MS. Methods: On two separate occasions, 20 participants (10 relapsing-remitting MS (EDSS: 1-5); 10 age-matched healthy controls (CON)) cycled at ~40% VO2max at 30[degrees]C, 30%RH until volitional exhaustion (or a maximum of 60 min). Every 15 minutes, participants ingested 3.2 mL[middle dot]kg-1 of either 1.5[degrees]C (CLD) or 37[degrees]C (NEU) water. Rectal (Tre) temperature, mean skin (Tsk) temperature, and heart rate (HR) were measured throughout. Results: All 10 CON, but only 3 of 10 MS participants completed 60 minutes of exercise in NEU trial. The remaining 7 MS participants all cycled longer (P=0.006) in CLD (46.4+/-14.2 min) compared to NEU (32.7+/-11.5 min), despite a similar absolute Tre (NEU: 37.32+/-0.34[degrees]C; CLD: 37.28+/-0.26[degrees]C; P=0.44), change in Tre (NEU: 0.38+/-0.21[degrees]C; CLD: 0.34+/-0.24[degrees]C), absolute Tsk (NEU: 34.48+/-0.47[degrees]C; CLD: 34.44+/-0.54[degrees]C; P=0.82) and HR (NEU: 114+/-20 beats[middle dot]min-1; CLD: 113+/-18 beats[middle dot]min-1; P=0.38) for the same exercise volume. Conclusions: Cold-water ingestion enhanced exercise tolerance of MS participants in the heat by ~30% despite no differences in core and mean skin temperatures or heart rate. These findings support the use of a simple cooling strategy for mitigating heat intolerance with MS, and lend insight into the potential role of cold-afferent thermoreceptors that reside in the abdomen and oral cavity in the modulation of exercise tolerance with MS in the heat. (C) 2017 American College of Sports Medicine

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The Omental Free Flap—A Review of Usage and Physiology

J reconstr Microsurg
DOI: 10.1055/s-0037-1608008

Background The omental flap has a rich history of use over the last century, and specifically as a free flap in the last four decades. It has a wide variety of applications in reconstructive surgery and has shown itself to be a reliable donor tissue. We seek to review the properties that make the omental free flap a valuable tool in reconstruction, as well as its many surgical applications in all anatomic regions of the body. Methods We conducted a narrative review of the literature on Medline and Google Scholar. We reviewed basic science articles discussing the intrinsic properties of omental tissue, along with clinical papers describing its applications. Results The omental free flap is anatomically suitable for harvest and wound coverage and has molecular properties that promote healing and improve function at recipient sites. It has demonstrated utility in a wide variety of reconstructive procedures spanning the head and neck, extremities, and viscera and for several purposes, including wound coverage, lymphedema treatment, and vascularization. It is also occasionally employed in the thoracic cavity and chest wall, though more often as a pedicled flap. More novel uses include its use for cerebrospinal fluid leaks. Conclusions The omental free flap is a valuable option for reconstructive efforts in nearly all anatomic regions. This is a result of its inherent anatomy and vascularity, and its angiogenic, immunogenic, and lymphatic properties.
[...]

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

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

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Phalloplasty in Female-to-Male Transsexuals by Gottlieb and Levine's Free Radial Forearm Flap Technique—A Long-Term Single-Center Experience Over More than Two Decades

J reconstr Microsurg
DOI: 10.1055/s-0037-1608656

Background The free radial forearm flap phalloplasty is the most utilized method for penile reconstruction. Among the techniques described in the literature, evidence for the flap design after Gottlieb and Levine is poor. Methods From January 1993 until December 2015, 402 phalloplasties were performed in our clinic. Among the 247 free radial forearm flap phalloplasties, 232 free radial forearm flap phalloplasties were performed after Gottlieb and Levine in 229 patients. Operation and patient-specific characteristics were evaluated. Results This study presents the highest number of free radial forearm flap phalloplasties after Gottlieb and Levine. The rate of total flap failure was 3%; 46% of the patients were heavy smokers. Urinary fistulae and strictures are common. The revision rate for urinary fistulae and/or strictures was 1.3 per patient. The number of postoperative complications, such as bleeding (14.2%), thrombosis of the flap requiring revision (11.2%), or delayed wound healing (16.8%) was considering the high rate of nicotine abuse (45.9%) reasonable. Conclusion The free radial forearm phalloplasty in the design by Gottlieb and Levine is well established at our institution and has proven safe and reliable since 1993. The operative results are satisfactory for both patients and surgeons even in the presence of relevant comorbidities and heavy smoking. We acknowledge the long ordeal and psychological pressure that our patients suffer from, before presenting in our outpatient clinic.
[...]

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

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

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Thrombosis Prevention with Botulinum Toxin A after Traumatic Crush Injury in a Rat Model

J reconstr Microsurg
DOI: 10.1055/s-0037-1607437

Background Revascularized digits may fail because of vessel thrombosis. The current study aimed to develop a standard model for crush injury in the rat femoral artery to evaluate the antithrombotic effect of perivascular botulinum toxin A (BTX-A) injection. Methods We explored bilateral femoral arteries of 10 rats using a microscopic technique. The crush injury was reproduced using a bulldog clamp. One randomly chosen leg of each rat was injected with BTX-A. The other side received normal saline as its own control. After 24 hours, the femoral arteries were ligated distal to the trauma site and were divided between the traumatized and ligated sites. Results All arteries injected with BTX-A had pulsatile bleeding without thrombosis. Arteries injected with normal saline had thrombosis without bleeding, except for one with oozing. The results showed the efficacy of BTX-A and its potential use in microvascular trauma (p < 0.001). Conclusion The use of BTX-A preoperatively in the emergency department may help reduce traumatic stress and subsequent thrombosis and improve trauma management results. Complementary studies are needed to assess the ability of BTX-A to reduce thrombosis and vasospasm and improve survival of traumatized digits.
[...]

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

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

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Short-term intraindividual variability of the posterior dominant alpha frequency in the electroencephalogram

There is no general consensus on the intraindividual variability of the posterior dominant alpha frequency; some researchers posit a static individual alpha background frequency, while others believe it to be dynamic. It has been declared as a stable clinical marker over longer periods of time and robust to repetitive cognitive interventions in healthy persons (Grandy et al., 2013). Regarding short-term variability, i.e. the variability of alpha power within a single record aside of inter-record variability, one study found a high correlation between both measures and no significant short-term variability of the posterior dominant alpha frequency after three different visual conditions (Hawkes and Prescott, 1973).

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Endoscopic string clip suturing method: a prospective pilot study (with video)

We developed a suturing method with string and clips for a single-channel endoscope. The feasibility of string clip suturing method was evaluated in this prospective pilot study.

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Endoscopic Carpal Tunnel Release with and without Sedation

Background: This study evaluates outcomes and complications with endoscopic carpal tunnel release (eCTR) performed with local anesthesia (LOCAL) only versus local anesthesia with sedation (SEDATION). We hypothesize that patient outcomes and satisfaction will be equivalent in both groups irrespective of anesthesia type. Methods: One hundred fifty-four consecutive patients undergoing eCTR with either LOCAL or SEDATION protocols were prospectively enrolled in a study of satisfaction and outcomes. The patients were surveyed preoperatively and at 2-weeks and 3-months postoperatively to evaluate satisfaction, symptoms, complications, and disability using the QuickDASH survey, the Levine-Katz carpal tunnel survey, and a customized LIKERT scale. Results: The hypothesis was upheld. Both groups of patients reported high levels of satisfaction (96% in LOCAL and 93% in SEDATION groups at 3 weeks). Disability, pain, and symptom scores did not differ significantly between groups at either postoperative time point. Following surgery, patients in the SEDATION group recalled more mean preoperative anxiety (4/10 versus 2.03/10 at 3 months). If they were to undergo the surgery again, patients in the SEDATION group were likely to desire either sedation (68%) or general anesthesia (29%) while patients in the LOCAL group were likely to wish for similar local-only anesthesia (78%). There were no reoperations or epinephrine-related complications in either group. Conclusions: Patients undergoing eCTR experience similar levels of satisfaction and outcomes with LOCAL and SEDATION protocols. The findings of this study confirm that both methods of anesthesia provide excellent results and allow for surgeons and patients to choose freely between the two anesthetic techniques. Financial Disclosure Statement: The authors have nothing to disclose. No funding was received for this research. Presented at: American Society for Surgery of the Hand annual meeting 2016 in Austin, TX, USA Author contributions: Tulipan: Data gathering, data analysis, manuscript preparation Kim: Data gathering, data analysis, manuscript preparation Ilyas: Data gathering, data analysis, manuscript preparation Matzon: Data gathering, data analysis, manuscript preparation This study was approved by the institutional review board at Thomas Jefferson University *CORRESPONDING AUTHOR: Jacob Tulipan, MD, 1025 Walnut St, Suite 516 College, Philadelphia, PA, United States. (215) 955-1500, (215) 503-0530, Jacob.tulipan@gmail.com ©2017American Society of Plastic Surgeons

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Cleft-Related Orthognathic Surgery Based On Maxillary Vertical Lengthening Of the Anterior Facial Height

Background: The conventional approach during orthognathic surgery for cleft-related deformities has largely focused on restoration of maxilla retrusion, using the maxillary advancement as a standard treatment objective. However, we thought the maxillary vertical shortening and deficient incisor show could be the additional key elements of cleft-related deformities. Although slight vertical lengthening can be obtained with only maxillary advancement, it would not be enough to obtain satisfactory aesthetical results in terms of the anterior facial height. We hypothesized that vertical deficiency as well as anteroposterior maxillary retrusion exists in cleft-related deformities. Therefore, orthognathic surgery including intentional vertical lengthening and advancement would be better than the conventional simple advancement. Methods: A new approach was used to treat consecutive patients with dentofacial deformities between December 2007 and December 2016. The inclusion criterion was patients with cleft-related deformities. Results: Forty-one patients with cleft-related dentofacial deformities were included. The distance from the nasion to the incisor tip was 76.70 mm, angle of the lines connecting the sella, nasion, and point A was 74.03∘, and the incisor show was 1.02 mm. Corresponding measurements in forty patients without clefts were 81.57 mm, 80.08∘, and 3.38 mm, respectively. Postoperatively, the average vertical lengthening achieved was 0.88 mm in simple maxillary advancement group and 7.65 mm in intentional vertical lengthening accompanied by the maxillary advancement group. Conclusions: Our results suggest that simultaneous maxillary vertical lengthening with horizontal advancement is a viable approach to orthognathic surgery for cleft-related deformities given the long-term stability of outcomes demonstrated in this study. Financial Disclosure Statement: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Acknowledgment: This article was presented at 2016 EACMFS in London, England. Corresponding author: Jong Woo Choi, M.D., Ph.D., MMM, Associate Professor, Department of Plastic and Reconstructive Surgery, University of Ulsan College of Medicine, Asan Medical Center, 388-1 PungNap-2Dong, SongPa-Gu, Seoul 138-736, Korea, Phone: 82-2-3010-3604; Fax: 82-2-476-7471, E-mail: pschoi@amc.seoul.kr ©2017American Society of Plastic Surgeons

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Gender Confirmation Surgery Using the Pedicle Transverse Colon Flap for Vaginal Reconstruction: A Clinical Outcome and Sexual Function Evaluation Study

Introduction: Vaginal reconstruction and vaginoplasty are indicated in vaginal agenesis, following pelvic tumor resection, trauma and for gender confirmation surgery. Different surgical options have been described when using these techniques. Herein, we present the clinical outcomes and sexual function evaluation using the pedicle transverse colon flap (TCF) for gender confirmation surgery in transgender women. Methods: This is a retrospective chart review of all transgender women who underwent gender confirmation surgery using the pedicle TCF. Demographics, etiology, procedure specifics and surgical outcomes were recorded and analyzed. Sexual function was measured using the Female Sexual Function Index (FSFI) and the female genital self-image scale (FGSIS) one year after surgery. Results: 15 patients underwent gender confirmation surgery using the pedicle transverse colon flap. Average age was 20, (range: 18-32 years), average OR time was 10.1 hours; (8-12.5 hrs.). The average length and width of the flaps was 15 cm and 2.8 cm respectively. During a 12-year follow-up, two complications were reported: one patient had pain due to narrowing at the introitus vaginalis, which required intervention and one patient had excessive amount of secretions in the first month which subsided at the third month after surgery. The mean FSFI score was 28.6 (range 24-31). All patients achieved a normal sexual function as indicated by a FSFI score of 25 or more. For the FGSIS, the mean total score was 20.0 ± 4.5 (range: 7- 28). Conclusion: The pedicle transverse colon flap is another valuable alternative method for vaginoplasty with promising results and minor complications. Financial Disclosure:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Corresponding Author: Oscar J. Manrique M.D., Senior Associated Consultant, Assistant Professor of Surgery, Division of Plastic and Reconstructive Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, Tel: +1-507-284-3214; Fax: +1-507-284-5994, Email: manrique.oscar@mayo.edu ©2017American Society of Plastic Surgeons

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Nose and lips graft variants: a subunit anatomical study

Background. In the field of Vascularized Composite tissue Allotransplantation (VCA), the surgical design of facial subunit grafts is an evolving concept. The purpose of the present paper is to study the possibilities to divide the historical nose and lips face transplant into several morphological and functional subunit grafts, depending on their respective supply. Methods. Our study was conducted in 20 adult cadavers. The facial artery and its branches were dissected bilaterally in 16 fresh and 4 embalmed heads. Nasolabial perfusion was assessed by selective injection of methylene blue and eosin (n=2) or indian ink (n=2) in superior labial artery (SLA) and distal facial artery (DFA). Dynamic perfusion through the DFA was illustrated by fluoroscopy (n=3). Three nose-upper lip grafts were harvested and injected with barium sulfate for micro-Angio CT analysis. Finally, three isolated nasal and bilabial grafts were procured and their vascular patency assessed by fluoroscopy. Results. DFA can perfuse the entire nose, septum and upper lip, without any contribution of SLA. A dense anastomotic network indeed exists between the respective distal rami of both vessels. Furthermore, the exclusion of SLA from the harvested nasal subunit allowed safe bilabial subunit procurement, from the same specimen. Conclusions. Our results demonstrate the feasibility of harvesting nasal and labial subunits, in an isolated or a combined manner. These results can find applications in subunit autologous replantation, allotransplantation, allogenic face partial retransplantation, and in the emerging field of vascularized composite tissue engineering. Financial Disclosure Statement: The authors have no conflict of interest to disclose. This work was financially supported by a Fondation Saint-Luc Grant, FSR-UCL (Fonds Spécial de la Recherche) and Fonds Dr. Gaëtan Lagneaux. The content of the work is solely the responsibility of the authors. None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Acknowledgments: We would like to thank Mrs. Pascale Segers and Mr Walter Hudders for manuscript editing, Mrs. Michelle Cougnon and Mr Eric Legrand for administrative support, Mr. Bernard Caelen and Mrs. Maïté Van de Woestijne for assistance in cadaver procurement, Prof. Anne Bol for Micro-CT acquisition support. Conflict of interest: none. Authorships: JD Designed study, performed part of experimental manipulations, reviewed and interpreted all data, wrote article, gave approval for publication. LM Performed part of experimental manipulations, participated to data collection and analysis, gave approval for publication AG Performed part of experimental manipulations, participated to data collection and analysis, revised article, gave approval for publication MV Performed radiographic acquisition and reconstruction, reviewed and interpreted data, gave approval for publication. PG Supported experiments, reviewed and interpreted data, revised article, gave approval for publication. CB Supported experiments, reviewed and interpreted data, revised article, gave approval for publication. BL Supported experiments and designed study, reviewed data, revised article extensively, gave final approval for publication. Corresponding author: Benoît Lengelé, MD, PhD, FRCS, UCL/IREC/MORF,, Avenue E. Mounier 51, Bte B1.52.04, B-1200 Brussels (BELGIUM) Tel: +3227645251, Fax: + 3227645225, E-mail : benoit.lengele@uclouvain.be ©2017American Society of Plastic Surgeons

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Αρχειοθήκη ιστολογίου

Τετάρτη 15 Νοεμβρίου 2017

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