Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC)

Abstract

Background

Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.

Methods

We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR).

Results

We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases.

Conclusion

In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

https://ift.tt/2PNBDVk

Monoclonal Antibody Specific for Ovarian Tumor Domain-Containing Protein 1

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Volume 37, Issue 4, Page 194-194, August 2018.


https://ift.tt/2NztRwS

Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Thyroid, Ahead of Print.


https://ift.tt/2PmFzLJ

Conservative surgical management of simple monostotic fibrous dysplasia of the proximal femur in a 19-year-old basketballer: a case report

Fibrous dysplasia is a rare benign, intramedullary, fibro-osseous lesion. It is thought to be a developmental disorder of bone maturation where normal lamellar bone is replaced by irregular trabecular bone ens...

https://ift.tt/2ooz2Vp

Paraneoplastic pemphigus associated with chronic lymphocytic leukemia: a case report

Paraneoplastic pemphigus is a rare multiorgan disease of autoimmune causes, usually triggered by neoplasias, mainly of lymphoproliferative origin, such as leukemia and lymphoma. This disorder is categorized by...

https://ift.tt/2LH8W9a

Dominant dystrophic epidermolysis bullosa pruriginosa with a COL7A1 exon 87 c.6898C>T mutation

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2C4yD4g

The impact of diaper design on mitigating known causes of diaper dermatitis

Pediatric Dermatology, EarlyView.


https://ift.tt/2opYgTg

Opioid exposure safety, superglottic airways and other EMS news of the week

Our co-hosts discuss a variety of recent news items related to EMS personnel, from cardiac arrest survival tools to a DOJ video regarding accidental opioid exposure while on the job

https://ift.tt/2PlA1kO

A Modified Translaryngeal Tracheostomy Technique in the Neurointensive Care Unit. Rationale and Single-center Experience on 199 Acute Brain-damaged Patients

Background: Brain-injured patients frequently require tracheostomy, but no technique has been shown to be the gold standard for these patients. We developed and introduced into standard clinical practice an innovative bedside translaryngeal tracheostomy (TLT) technique aided by suspension laryngoscopy (modified TLT). During this procedure, the endotracheal tube is left in place until the airway is secured with the new tracheostomy. This study assessed the clinical impact of this technique in brain-injured patients. Materials and Methods: This is a retrospective analysis of prospectively collected data from adult brain-injured patients who had undergone modified TLT during the period spanning from January 2010 to December 2016 at the Neurointensive care unit, San Gerardo Hospital (Monza, Italy). The incidence of intraprocedural complications, including episodes of intracranial hypertension (intracranial pressure [ICP] >20 mm Hg), was documented. Neurological, ventilatory, and hemodynamic parameters were retrieved before, during, and after the procedure. Risk factors for complications and intracranial hypertension were assessed by univariate logistic analysis. Data are presented as n (%) and median (interquartile range) for categorical and continuous variables, respectively. Results: A total of 199 consecutive brain-injured patients receiving modified TLT were included. An overall 52% male individuals who were 66 (54 to 74) years old and who had an admission Glasgow Coma Scale of 7 (6 to 10) were included in the cohort. Intracerebral hemorrhage (30%) was the most frequent diagnosis. Neurointensivists performed 130 (65%) of the procedures. Patients underwent tracheostomy 10 (7 to 13) days after intensive care unit admission. Short (ie, 20 mm Hg were observed in 11 cases. Overall, the procedure was associated with an increase in ICP from 7 (4 to 10) to 12 (7 to 18) mm Hg (P

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Hereditary angioedema revisited

https://ift.tt/2PjqM4E

Meta-analysis of randomized controlled trials for the efficacy and safety of anti‐interleukin-13 therapy with lebrikizumab in patients with uncontrolled asthma

https://ift.tt/2wuCWRf

Cost impact of monitoring exhaled nitric oxide in asthma management

https://ift.tt/2LMeQWY

Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab

https://ift.tt/2wsPMiD

Randomized dose-ranging study of a budesonide metered-dose inhaler by using co-suspension delivery technology in asthma

https://ift.tt/2LGJsZT

Efficacy of recombinant human C1 esterase inhibitor across anatomic locations in acute hereditary angioedema attacks

https://ift.tt/2N65Ccy

Subcutaneous C1-esterase inhibitor to prevent hereditary angioedema attacks: Safety findings from the COMPACT trial

https://ift.tt/2Poylad

Factors that predict disease severity in atopic dermatitis: The role of serum basal tryptase

https://ift.tt/2N1yenm

Improved diagnostic clarity in shrimp allergic non‐dust-mite sensitized patients

https://ift.tt/2Pnljd2

Camel's milk allergy

https://ift.tt/2wqIYSU

Human factors study of a newly approved prefilled syringe of epinephrine for the treatment of anaphylaxis

https://ift.tt/2LFhAoQ

A 45-year-old man with elevated levels of immunoglobulin A

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For the Patient

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Abstracts from the Eastern Allergy Conference, May 31-June 3, 2018, Palm Beach, Florida

https://ift.tt/2wqeU9O

Update: Asthma Yardstick: Practical recommendations for a sustained step-up in asthma therapy for poorly controlled asthma

Recently Chipps and colleagues published a comprehensive update on how to conduct a sustained step up in asthma therapy for patients with not well or poorly controlled asthma – the Asthma Yardstick (1). In this document the authors focused on the use of biologic agents, including omalizumab, mepolizumab and reslizumab. Although only published a year ago, a great deal has been learned in the world of biologic agents since.

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Treatment of alopecia universalis with topical Janus kinase inhibitors – a double blind, placebo, and active controlled pilot study

International Journal of Dermatology, EarlyView.


https://ift.tt/2PTpLRY

Introduction: Allergy Special Issue

Allergy involves abnormal variations of normally protective immune responses that, in predisposed (atopic) subjects, trigger immediate hypersensitivity to normally harmless antigens. Many elements of the immune system are involved and a number of symptoms of varying seriousness can be triggered by a wide range of allergens from many sources and with different features. Although allergic responses are abnormal, they are very common and affect a considerable, and increasing, proportion of the population; for example, worldwide up to 50% of school children are sensitized to one or more common allergen. There is, thus, a clear drive for understanding the complex mechanisms involved in allergy and to find ways to combat it.

https://ift.tt/2Nzb6JM

Three-dimensional analysis of cutaneous nervous system in pruritic atopic dermatitis and psoriasis skin

Introduction: Intraepidermal nerve fiber (IENF) count in skin biopsies has been used as a reflection of the innervation density of itch-transmitting C nerve fibers in the skin. Changes in IENF densities in pruritic conditions such as eczema and psoriasis has been studied previously, but conflicting results have been reported. In these studies, IENF count is defined as the number of PGP9.5-positive nerve fibers crossing the basement membrane per unit length in 50-μm-thick histologic sections. However, this 2-dimensional approach is limited by the thickness of the section examined.

https://ift.tt/2wsHkjm

Asthma Attack | When to Go to the E.R.

Acute asthma attacks can be scary but understanding when to seek emergency medical help can help you remain calm when your child needs you the most. Many parents have the same questions when their child's asthma worsens. Should we go to the E.R.? How will their asthma be treated once we arrive? Dr. Jamie Kondis explains how to tell when your child needs medical attention and how their asthma attack will be treated in the E.R.

The post Asthma Attack | When to Go to the E.R. appeared first on ChildrensMD.

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Praxis-HNO

https://ift.tt/2Na9Xf7

Seltene Ursache für eine Schwellung im Bereich der Gl. parotis

https://ift.tt/2C18wej

Immunologie der Polyposis nasi als Grundlage für eine Therapie mit Biologicals

Zusammenfassung

Hintergrund

Die chronische Rhinosinusitis (CRS) ist eine heterogene und multifaktorielle entzündliche Erkrankung der nasalen und paranasalen Schleimhäute. Bis heute konnte keine international standardisierte einheitliche Klassifikation hierfür entwickelt werden.

Meist wird eine Phänotypklassifikation nach CRS mit (CRScNP) und ohne Polyposis (CRSsNP) vorgenommen. Durch eine Vielzahl von Studien konnte aber gezeigt werden, dass auch innerhalb dieser Phänotypen verschiedene Endotypen der CRS existieren, denen eine unterschiedliche entzündliche Pathophysiologie zugrunde liegt. In diesem Review sollen die wesentlichen immunologischen Vorgänge bei CRScNP dargestellt und hieraus abgeleitete moderne Therapiemöglichkeiten mit Biologika aufgezeigt werden.

Methoden

Das aktuelle Wissen zu den immunologischen und molekularen Prozessen der CRS, speziell der CRScNP, wurde mittels einer strukturierten Literaturanalyse durch Recherchen in Medline, PubMed sowie den nationalen und internationalen Studien- und Leitlinienregistern und der Cochrane Library zusammengestellt.

Ergebnisse

Basierend auf der derzeitigen Literatur wurden die verschiedenen immunologischen Prozesse bei CRS und nasalen Polypen herausgearbeitet. Aktuelle Studien zur Therapie eosinophiler Erkrankungen wie Asthma und Polyposis werden vorgestellt und – falls bereits vorhanden – deren Ergebnisse diskutiert.

Schlussfolgerung

Das Verständnis über die immunologischen Grundlagen der CRScNP kann dazu beitragen, neue personalisierte Therapieansätze mittels Biologika zu entwickeln.

https://ift.tt/2POm2EW

Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis

Abstract

Purpose

Neuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study.

Methods

Mice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated.

Results

Remifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS.

Conclusion

Remifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.

https://ift.tt/2PkZ1Zb

Randomized comparative study between two different techniques of intercostobrachial nerve block together with brachial plexus block during superficialization of arteriovenous fistula

Abstract

Background

This study compared proximal and distal approaches of intercostobrachial nerve block (ICBNB) combined with infraclavicular brachial plexus block (ICBPB) during superficialization of arteriovenous fistula.

Methods

Seventy adult patients were randomized to receive ICBPB and 6 ml 0.25% bupivacaine at the level of the 3rd rib in the anterior axillary line between pectoralis minor and serratus anterior muscles (group P) or subcutaneously along the medial side of the upper arm (group D). The primary outcome was the achievement of complete sensory block. Secondary outcomes were onset of analgesia, volume of local anesthetic (LA) supplementation, fentanyl administration, success rate, and conversion to general anesthesia (GA).

Results

Complete sensory block in the medial side of the upper arm was achieved in 91% of patients in group P and 51% in group D. Failure rate of ICBNB was higher in group D (49%) than group P (14%). Conversion to GA was determined by the attending anesthesiologist in 26% of patients in group D and 0% in group P. LA supplementation was required in 5 patients in group P and 11 patients in group D, and the mean volume of LA was statistically higher in group D than group P (9.5 ± 1.5, 7.5 ± 2 ml, respectively). Onset of sensory block was faster in group P than group D (8.75 ± 1.67 and 10 ± 2.14 min, respectively). No differences were observed regarding fentanyl administration.

Conclusion

ICBNB proximal approach provides a high success rate with less amount of rescue analgesia compared to the distal approach.

https://ift.tt/2wnK7KT

Preference Signaling in the National Resident Matching Program—Reply

In Reply In our Viewpoint, we proposed a "star system" to address many of the problems mentioned in the otolaryngology–head and neck surgery (Oto-HNS) literature regarding the National Resident Matching Program ("the Match"). Namely, our system has the primary goal of improving the fit between program and applicant while increasing transparency and decreasing interview congestion and time burden. We appreciate the valuable comments made by Gray et al in their letter.

https://ift.tt/2wxzqEG

Unintended Consequences of White Noise Therapy for Tinnitus

This narrative review argues that white noise exposure therapy for tinnitus induces maladaptive neuroplastic changes in the brain and discusses alternative therapeutics that drive positive, adaptive plastic changes.

https://ift.tt/2op7TS4

Preference Signaling in the National Resident Matching Program

To the Editor In their Viewpoint, Salehi et al proposed a "star system" in which otolaryngology residency applicants can indicate particular interest in programs, similar to a "rose-sending system" previously suggested in orthopedic surgery. In the economics literature, these systems are known as preference signaling mechanisms and have been successfully implemented in the American Economic Association (AEA) job market for economics graduate students since 2006. Its rationale, design, and outcomes should inform the current proposal.

https://ift.tt/2wvtdsZ

Assessment of a Statistical Algorithm for the Prediction of Benign Paroxysmal Positional Vertigo

This case series study assesses a statistical prediction algorithm with the aim of efficiently diagnosing and treating patients with dizziness.

https://ift.tt/2PTk86j

Professional and Patient Engagement, Visual Abstracts, and Applications to Otolaryngology

This Viewpoint examines the utility of social media and specific tools for disseminating information and collaborating in the field of otolaryngology.

https://ift.tt/2C3EmqY

Active Surveillance in Thyroid Microcarcinoma

This cohort study examines 57 Colombian patients with thyroid nodules classified as Bethesda categories V to VI who were treated with active surveillance.

https://ift.tt/2PTjPsb

‘Asymptomatic’ South Auckland preschool children have significant hearing loss and middle ear disease

Publication date: Available online 30 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Louise J. Dickinson, Moea Nimmo, Randall P. Morton, Suzanne C. Purdy

Abstract

Background

Seven hundred children were recalled for hearing screening at age 2–3 years due to a problem with their newborn hearing screen. They had all been well babies with no identified risk factors for hearing loss and hence were not scheduled for targeted follow-up to retest hearing.

Methods

There were 485 children (69%) that attended the recall. The average age was 36 months (SD 3.7). Family ethnicity was Pacific Island (36%), Asian (26%), NZ European (13%), and Māori (11%), and there was a high level of deprivation in the study population. Children were screened using distortion product otoacoustic emission (DPOAE) and a parent or caregiver completed a 14-item questionnaire about ear health. The children that did not pass screening were given appointments for audiology testing. Children with hearing loss and/or middle ear problems were referred for otolaryngology review and further hearing assessments.

Results

About one third (36%; n = 176) of children did not pass DPOAE screening; 82 (17%) had abnormal type B tympanograms and hearing loss; 29 underwent insertion of ventilation tubes, and one had a perforated tympanic membrane. There was a significant association between failed tympanometry and hearing loss (Chi-squared = 16.67, p < .001).

Five children had permanent sensorineural hearing loss (SNHL), two of whom required cochlear implants for idiopathic hearing loss, with no specific risk factors. Overall 380 of 485 children screened were deemed to have normal hearing (i.e. 22% failed hearing). From the questionnaire, 15% of the caregivers with no suspicion of hearing problems did have children with significant hearing loss. Regression analysis showed that Pacific/Māori ethnicity was significantly associated with risk of hearing loss, together with questionnaire items identifying hearing problems and breathing problems.

Conclusions

There is a high proportion of children in South Auckland with unsuspected hearing loss; a different approach to hearing screening is warranted for this population with high rates of middle ear disease at age 3.

https://ift.tt/2C2KcJ2

Clinical features and management of antrochoanal polyps in children: cues from a clinical series of 58 patients

Publication date: Available online 29 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Fabio Pagella, Enzo Emanuelli, Alessandro Pusateri, Daniele Borsetto, Diego Cazzador, Roberta Marangoni, Eugenia Maiorano, Alessia Zanon, Cristina Cogliandolo, Andrea Ciorba, Stefano Pelucchi

Abstract

Objective

To review the clinical features of pediatric patients affected by antrochoanal polyps (ACPs) and surgically treated at three University settings.

Methods

Retrospective study. The present research includes the clinical data of subjects affected by ACPs, aged < 18 years and referred to three ENT Departments, between January 1^st 2003 and September 30^th 2016. All patients underwent nasal endoscopy and sinonasal imaging; all subjects have been treated surgically.

Results

Fifty-eight patients underwent functional endoscopic sinus surgery (FESS) for ACPs removal, under general anesthesia. There were no major intraoperative complications. Recurrence occurred in 12 cases (20.5%).

Conclusions

FESS was the first-choice treatment for APCs in the present series; our recurrence rate was similar to that of other reports available in literature. Recurrences of ACPs in children still represent a clinical challenge; it is likely that an improved comprehension of ACPs biology could help in better understanding the pathophysiology of this disease.

https://ift.tt/2omK6SR

Cranial orthosis after cochlear implantation in an infant: Helmet modifications

Publication date: Available online 29 August 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Erynne A. Faucett, Samantha Lam-Bellissimo, Faisal Zawawi, Sharon L. Cushing, Blake C. Papsin

Abstract

We present an infant with bilateral sensorineural hearing loss caused by bacterial meningitis, and moderate/severe plagiocephaly requiring simultaneous treatment of cochlear implantation for hearing loss and cranial orthosis for plagiocephaly. A helmet modification was created, so that the infant was able to be treated for his plagiocephaly while bilateral cochlear implants were in place, bringing attention to serve needs of those patients requiring cochlear implant and cranial orthosis concurrently. While this case was the first time such a modification was required, which was due to the young age at implantation, the occurrence of the concurrent need may increase as we continue to push the boundaries of early implantation.

https://ift.tt/2wtjVh4

Protocol of economic evaluation and equity impact analysis of mHealth and community groups for prevention and control of diabetes in rural Bangladesh in a three-arm cluster randomised controlled trial

Haghparast-Bidgoli, H; Shaha, SK; Kuddus, A; Chowdhury, MAR; Jennings, H; Ahmed, N; Morrison, J; ... Fottrell, E; + view all Haghparast-Bidgoli, H; Shaha, SK; Kuddus, A; Chowdhury, MAR; Jennings, H; Ahmed, N; Morrison, J; Akter, K; Nahar, B; Nahar, T; King, C; Skordis-Worrall, J; Batura, N; Khan, JA; Mansaray, A; Hunter, R; Khan, AKA; Costello, A; Azad, K; Fottrell, E; - view fewer (2018) Protocol of economic evaluation and equity impact analysis of mHealth and community groups for prevention and control of diabetes in rural Bangladesh in a three-arm cluster randomised controlled trial. BMJ Open , 8 (8) , Article e022035. 10.1136/bmjopen-2018-022035 . Green open access

https://ift.tt/2wpCV0U

Usability Testing of a Reusable Pulse Oximeter Probe Developed for Health-Care Workers Caring for Children < 5 Years Old in Low-Resource Settings

Boyd, N; King, C; Walker, IA; Zadutsa, B; Bernstein, M; Ahmed, S; Roy, A; ... McCollum, ED; + view all Boyd, N; King, C; Walker, IA; Zadutsa, B; Bernstein, M; Ahmed, S; Roy, A; Hanif, AAM; Saha, SC; Majumder, K; Nambiar, B; Colbourn, T; Makwenda, C; Baqui, AH; Wilson, I; McCollum, ED; - view fewer (2018) Usability Testing of a Reusable Pulse Oximeter Probe Developed for Health-Care Workers Caring for Children . (In press).

https://ift.tt/2NxAAYa

National survey of imaging practice for suspected or confirmed plasma cell malignancies

Westerland, OA; Pratt, G; Kazmi, M; El-Najjar, I; Streetly, M; Yong, K; Morris, M; ... British Society of Haematology Imaging Practice Guidelines Worki, ; + view all Westerland, OA; Pratt, G; Kazmi, M; El-Najjar, I; Streetly, M; Yong, K; Morris, M; Mehan, R; Sambrook, M; Hall-Craggs, M; Silver, D; Goh, V; British Society of Haematology Imaging Practice Guidelines Worki, ; - view fewer (2018) National survey of imaging practice for suspected or confirmed plasma cell malignancies. British Journal of Radiology 10.1259/bjr.20180462 . (In press). Green open access

https://ift.tt/2MBCpa6

Nonparametric Instrumental Variable Estimation

Wilhelm, D; Kim, D; Chetverikov, D; (2018) Nonparametric Instrumental Variable Estimation. Stata Journal (In press).

https://ift.tt/2NxqRRL

Value of MRI in Medicine: More than just another test?

van Beek, EJR; Kuhl, C; Anzai, Y; Desmond, P; Ehman, RL; Gong, Q; Gold, G; ... Wang, M; + view all van Beek, EJR; Kuhl, C; Anzai, Y; Desmond, P; Ehman, RL; Gong, Q; Gold, G; Gulani, V; Hall-Craggs, M; Leiner, T; Lim, CCT; Pipe, J; Reeder, S; Reinhold, C; Smits, M; Sodickson, D; Tempany, C; Vargas, HA; Wang, M; - view fewer (2018) Value of MRI in Medicine: More than just another test? Journal of Magnetic Resonance Imaging (In press).

https://ift.tt/2MCabvQ

Response to “Vulnerability and resistance in the United Kingdom's smart meter transition”

Shipworth, D; Fell, MJ; Elam, S; (2018) Response to "Vulnerability and resistance in the United Kingdom's smart meter transition". Energy Policy 10.1016/j.enpol.2018.08.039 . (In press).

https://ift.tt/2Ny7Q1g

Light control of the nanoscale phase separation in heteroepitaxial nickelates

Mattoni, G; Manca, N; Hadjimichael, M; Zubko, P; van der Torren, AJH; Yin, C; Catalano, S; ... Caviglia, AD; + view all Mattoni, G; Manca, N; Hadjimichael, M; Zubko, P; van der Torren, AJH; Yin, C; Catalano, S; Gibert, M; Maccherozzi, F; Liu, Y; Dhesi, SS; Caviglia, AD; - view fewer (2018) Light control of the nanoscale phase separation in heteroepitaxial nickelates. Physical Review Materials , 2 (8) , Article 085002. 10.1103/PhysRevMaterials.2.085002 . Green open access

https://ift.tt/2MGZN5U

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA

Selby, NM; Blankestijn, PJ; Boor, P; Combe, C; Eckardt, K-U; Eikefjord, E; Garcia-Fernandez, N; ... Sourbron, S; + view all Selby, NM; Blankestijn, PJ; Boor, P; Combe, C; Eckardt, K-U; Eikefjord, E; Garcia-Fernandez, N; Golay, X; Gordon, I; Grenier, N; Hockings, PD; Jensen, JD; Joles, JA; Kalra, PA; Krämer, BK; Mark, PB; Mendichovszky, IA; Nikolic, O; Odudu, A; Ong, ACM; Ortiz, A; Pruijm, M; Remuzzi, G; Rørvik, J; de Seigneux, S; Simms, RJ; Slatinska, J; Summers, P; Taal, MW; Thoeny, HC; Vallée, J-P; Wolf, M; Caroli, A; Sourbron, S; - view fewer (2018) Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA. Nephrology Dialysis Transplantation , 33 (suppl_2) ii4-ii14. 10.1093/ndt/gfy152 . Green open access

https://ift.tt/2NuGHMF

Crenças religiosas e evolução: um modelo para o diálogo em aula = Religious Beliefs and Evolution: A Model for the Dialogue in Classroom

Levinson, R; Teixeira, PP; (2018) Crenças religiosas e evolução: um modelo para o diálogo em aula = Religious Beliefs and Evolution: A Model for the Dialogue in Classroom. Alexandría : Revista de Ciencias de la Información , 11 (1) pp. 195-216. 10.5007/1982-5153.2018v11n1p195 . Green open access

https://ift.tt/2wu1QAd

Writings on Political Economy, Volume III: Preventive Police

Bentham, J; (2018) Writings on Political Economy, Volume III: Preventive Police. [Book]. The Collected Works of Jeremy Bentham. Bentham Project: London, UK. (In press). Green open access

https://ift.tt/2NxDhsP

Manufacturing of graded titanium scaffolds using a novel space holder technique

Chen, Y; Kent, D; Bermingham, M; Dehghan-Manshadi, A; Wang, G; Wen, C; Dargusch, M; (2017) Manufacturing of graded titanium scaffolds using a novel space holder technique. Bioactive Materials , 2 (4) pp. 248-252. 10.1016/j.bioactmat.2017.07.001 . Green open access

https://ift.tt/2wu1KZn

Comparative Analysis of Protocols Used in Measurement and Verification of Energy Performance: Dealing with Practical Issues of Data Availability and Granularity in a UK School Building

Jain, N; Burman, E; Mumovic, D; Davies, M; Tindale, A; (2018) Comparative Analysis of Protocols Used in Measurement and Verification of Energy Performance: Dealing with Practical Issues of Data Availability and Granularity in a UK School Building. In: (Proceedings) Building Simulation and Optimization 2018. IBPSA: San Francisco, CA, USA,. (In press).

https://ift.tt/2NycQmN

Modulator-free quadrature amplitude modulation signal synthesis

Liu, Z; Kakande, J; Kelly, B; O'Carroll, J; Phelan, R; Richardson, DJ; Slavik, R; (2016) Modulator-free quadrature amplitude modulation signal synthesis. In: (Proceedings) OFC 2016, Optical Fiber Communication Conference 2016, 20–22 March 2016, Anaheim, California USA. (pp. M2A.5). Optical Society of America (OSA) Green open access

https://ift.tt/2MFLi2c

Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: Results from the exploratory, controlled, randomized, international phase 2 IMPULSE study

Thomas, M; Ponce-Aix, S; Navarro, A; Riera-Knorrenschild, J; Schmidt, M; Wiegert, E; Kapp, K; ... IMPULSE study team, ; + view all Thomas, M; Ponce-Aix, S; Navarro, A; Riera-Knorrenschild, J; Schmidt, M; Wiegert, E; Kapp, K; Wittig, B; Mauri, C; Dómine Gómez, M; Kollmeier, J; Sadjadian, P; Fröhling, K-P; Huber, R; Wolf, M; IMPULSE study team, ; - view fewer (2018) Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: Results from the exploratory, controlled, randomized, international phase 2 IMPULSE study. Annals of Oncology , Article mdy326. 10.1093/annonc/mdy326 . (In press). Green open access

https://ift.tt/2NycBYV

Neurovascular sequestration in paediatric P. Falciparum malaria is visible clinically in the retina

Barrera, V; MacCormick, IJC; Czanner, G; Hiscott, PS; White, VA; Craig, AG; Beare, NAV; ... Harding, SP; + view all Barrera, V; MacCormick, IJC; Czanner, G; Hiscott, PS; White, VA; Craig, AG; Beare, NAV; Culshaw, LH; Zheng, Y; Biddolph, SC; Milner, DA; Kamiza, S; Molyneux, ME; Taylor, TE; Harding, SP; - view fewer (2018) Neurovascular sequestration in paediatric P. Falciparum malaria is visible clinically in the retina. eLife , 7 , Article e32208. 10.7554/eLife.32208 . Green open access

https://ift.tt/2MBRmc5

Human lung development: recent progress and new challenges

Nikolić, MZ; Sun, D; Rawlins, EL; (2018) Human lung development: recent progress and new challenges. Development , 145 (16) 10.1242/dev.163485 . Green open access

https://ift.tt/2NwF1CC

Clinically recorded heart rate and incidence of 12 coronary, cardiac, cerebrovascular and peripheral arterial diseases in 233,970 men and women: A linked electronic health record study

Archangelidi, O; Pujades-Rodriguez, M; Timmis, A; Jouven, X; Denaxas, S; Hemingway, H; (2018) Clinically recorded heart rate and incidence of 12 coronary, cardiac, cerebrovascular and peripheral arterial diseases in 233,970 men and women: A linked electronic health record study. European Journal of Preventive Cardiology 10.1177/2047487318785228 . (In press). Green open access

https://ift.tt/2wpBeAA

Flat-Sky Pseudo-Cls analysis for weak gravitational lensing

Asgari, M; Taylor, A; Joachimi, B; Kitching, TD; (2018) Flat-Sky Pseudo-Cls analysis for weak gravitational lensing. Monthly Notices of the Royal Astronomical Society , 479 (1) pp. 454-477. 10.1093/mnras/sty1412 . Green open access

https://ift.tt/2NybYi1

Schnitzler-Syndrom

Zusammenfassung

Das Schnitzler-Syndrom ist eine sehr seltene, erworbene Systemerkrankung, die viele Gemeinsamkeiten mit den hereditären autoinflammatorischen Syndromen aufweist. Das Exanthem und eine monoklonale Gammopathie mit IgM sind die Charakteristika der Erkrankung. Zu den klinischen Hauptmerkmalen gehören Fieber, urtikarielles Exanthem, Muskel‑, Knochen- und/oder Gelenkschmerzen und eine Lymphadenopathie. Etwa 15–20 % der Patienten mit Schnitzler-Syndrom entwickeln eine lymphoproliferative Erkrankung, und selten kann es zum Auftreten einer AA-Amyloidose kommen, wenn die Erkrankung nicht behandelt wird. Eine Aktivierung des angeborenen Immunsystems, speziell des Interleukin(IL)-1β, ist zentral in der Pathogenese der Erkrankung. Folgerichtig kann bei 80 % der Patienten eine komplette Kontrolle der Krankheitssymptome durch Behandlung mit dem IL-1-Rezeptorantagonisten Anakinra erreicht werden.

https://ift.tt/2N3Twkd

Comparison of the medical costs and effects of large traumatic eardrum perforations treatment

Publication date: Available online 29 August 2018

Source: American Journal of Otolaryngology

Author(s): Zheng-Cai Lou, Hong Wei, Zi-Han Lou

Abstract

Objective

We investigated the medical costs and effects of ofloxacin drops (OFLX), gelatin sponge patches, spontaneous healing, and endoscopic myringoplasty on healing in large tympanic membrane perforations (TMPs).

Methods

In total, 100 patients with large traumatic TMPs involving >50% of the eardrum were randomly assigned to OFLX, gelatin sponge, spontaneous healing, or endoscopic myringoplasty treatment groups. Medical costs, closure times, and closure rates were compared among groups at 6 months.

Results

The closure rates in the OFLX, gelatin sponge, spontaneous healing, and endoscopic myringoplasty groups were 95.7%, 82.6%, 58.3%, and 91.7%, respectively (P = 0.05). The mean closure time was 13.73 ± 6.14 days in the OFLX group, 15.89 ± 4.95 days in the gelatin sponge group, 48.36 ± 10.37 days in the spontaneous healing group, and 12 days in the endoscopic myringoplasty group (P < 0.001). The mean medical costs in US dollars were $15.53 ± 3.15, $103.64 ± 111.58, $11.17 ± 1.33, and $715.90 in the OFLX, gelatin sponge, spontaneous healing, and endoscopic myringoplasty groups, respectively (P < 0.001).

Conclusion

Although the gelatin sponge and myringoplasty treatments significantly shortened the closure time compared with spontaneous healing, the gelatin sponge patch did not significantly improve the closure rate, and the medical cost of myringoplasty was significantly higher than that of the other treatments. In contrast, OFLX significantly shortened closure time and had a higher closure rate than spontaneous healing, and the medical costs were lower than those of the gelatin sponge and myringoplasty procedures.

https://ift.tt/2PRsPh9

Rhinogenous optic neuritis with full recovery of vision – The role of endoscopic optic nerve decompression and a review of literature

Publication date: Available online 29 August 2018

Source: American Journal of Otolaryngology

Author(s): W.L. Neo, C.W.D. Chin, X.Y. Huang

Abstract

Background

Optic neuritis resulting from paranasal sinusitis is an infrequently described but clinically important and treatable entity. The role of optic nerve decompression has been well established in atraumatic optic neuropathies which are compressive in origin. However, its role in optic neuritis and other infective or inflammatory processes is lacking, and the role for early surgical intervention remains controversial.

Case report

In this case report, we describe a patient who presented with sudden onset of right vision loss secondary to optic neuritis from pansinusitis. He was treated with systemic antibiotics and steroids along with an urgent endoscopic sinus surgery with optic nerve decompression. Full restoration of his vision was recorded within 24 h of surgical decompression.

Conclusion

Optic neuritis secondary to paranasal sinusitis is a clinically important entity and timely diagnosis and decompression is key to vision restoration.

https://ift.tt/2C1L7cP

Correlation between vestibular neuritis and cerebrovascular risk factors

Publication date: Available online 29 August 2018

Source: American Journal of Otolaryngology

Author(s): Weiwei Han, Dongliang Wang, Yunqin Wu, Zhenyi Fan, Xu Guo, Qiongfeng Guan

Abstract

Purpose

To investigate the relationship between cerebrovascular risk factors, including carotid plaques, and vestibular neuritis (VN).

Materials and methods

According to the inclusion and exclusion criteria, this retrospective study included 90 VN patients and 74 age- and sex-matched healthy controls from January 2016 to December 2017. All subjects' records of cerebrovascular risk factors, such as age, sex, height, weight, history of hypertension and diabetes mellitus, living habits, serum levels of glucose, lipids, glycosylated haemoglobin (HbA1c), creatinine (CR), albumin (ALB), haemoglobin (HGB); and results of carotid colour Doppler ultrasound, were obtained and compared.

Results

No significant differences in age; sex ratio; body mass index; history of hypertension or diabetes mellitus; or mean serum lipids, glucose, creatinine, haemoglobin or HbA1c were found between patients with VN and healthy controls (all P > 0.05). The mean serum ALB level was significantly lower in VN patients than in healthy controls (40.65 ± 3.77 vs 42.84 ± 4.32, P = 0.001).The prevalence of carotid plaques was significantly higher in VN patients than in healthy controls (36.67% vs. 16.22%, P = 0.003). Regression analyses demonstrated that a high frequency of carotid plaques was associated with VN with an odds ratio of 2.252 (95% CI 1.165–5.458, P = 0.019).

Conclusion

A high frequency of carotid plaques may be a risk factor for VN.

https://ift.tt/2PSS7Mb

Comparison of psychosocial factors over time among HPV+ oropharyngeal cancer and tobacco-related oral cavity cancer patients

Publication date: Available online 29 August 2018

Source: American Journal of Otolaryngology

Author(s): Tyler A. Janz, Suhael R. Momin, Katherine R. Sterba, Masanari G. Kato, Kent E. Armeson, Terry A. Day

Abstract

Introduction

The role of human papilloma virus (HPV) in the pathogenesis of oropharyngeal squamous cell carcinoma (OPSCC) is well documented, as is the excellent prognosis of patients with HPV-associated disease; in contrast, oral cavity squamous cell carcinoma (OCSCC) is associated with tobacco and alcohol use and has a worse prognosis. While causative factors, staging, and treatment guidelines differ between these cancer subsets, few studies have compared psychosocial factors in these groups.

Objective

To explore differences in psychosocial factors between HPV+ OPSCC patients versus OCSCC smokers.

Methods

A prospective cohort study at a single multidisciplinary, tertiary care HNC center was completed with recruitment from 2010 to 2013 using self-administered questionnaires before treatment and at 12 months. Patients were included with a diagnosis of HPV+ OPSCC or OCSCC with a smoking history. 38 (21 HPV+ OPSCC/17 OCSCC) met criteria. The main outcomes included self-efficacy, symptom severity, cancer worry, and depression.

Results

A total of 38 (21 HPV+ OPSCC/17 OCSCC) patients (mean age: 57 [32–76], 73.7% male, 78.9% Caucasian, 71% stage IV) met inclusion criteria. OPSCC patients tended to be of male sex, Caucasian race, and single. Furthermore, OPSCC patients were more likely than OCSCC patients to have private insurance, be employed, and use alcohol and tobacco less frequently. Regarding psychosocial factors, HPV+ OPSCC patients reported lower symptom severity (2.7 versus 3.3), depression (12.0 versus 14.0) and cancer worry (2.8 versus 3.2) at baseline compared to OCSCC patients. Depression decreased significantly over time in OPSCC patients (12.0 to 9.9; effect size: −3.2 (95% CI: −5.9 to −0.4)). Although not statistically significant, cancer worry decreased in both groups (2.8 to 2.4 and 3.2 to 2.7, respectively, effect sizes: −0.3 (95% CI: −0.7–0.08) and −0.6 (95% CI: −1.2–0.05), respectively). No statistically significant differences in patterns of change over time were noted between groups.

Conclusions and relevance

This pilot study highlighted a pattern of reduced quality of life parameters in OCSCC patients at baseline with similar improvements over time compared to the OPSCC cohort. Although different in cancer etiology and treatment plans, HPV+ OPSCC and tobacco-related OCSCC patients both require multidisciplinary cancer care plans that address psychosocial concerns.

Level of evidence: 2B

https://ift.tt/2C9LO42

Patterns of tree nut sensitisation and allergy in the first 6 years of life in a population-based cohort

Publication date: Available online 30 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Vicki McWilliam, Rachel Peters, Mimi LK. Tang, Shyamali Dharmage, Anne- Louise Ponsonby, Lyle Gurrin, Kirsten Perrett, Jennifer Koplin, Katrina J. Allen, HealthNuts investigators

Abstract:

Introduction

Longitudinal population-based data regarding tree nut allergy are limited.

Objectives

To determine population prevalence of tree nut allergy at age 6 years, and explore the relationship between egg and peanut allergy at age 1 year and development of tree nut allergy at age 6 years.

Methods

A population-based sample of 5,276 children were recruited at age one and followed up at age 6 years. At age 1 allergy to egg and peanut were determined by oral food challenge and parents reported their child's history of reaction to tree nuts. Challenge-confirmed tree nut allergy was assessed at age 6.

Results

At age 1, prevalence of parent-reported tree nut allergy was 0.1% (95% CI 0.04-0.2). Only 18.5% of infants had consumed tree nuts in the first year of life. At age 6, challenge-confirmed tree nut allergy prevalence was 3.3% (95%CI 2.8-4.0), with cashew the most common (2.7%, 95% CI 2.2-3.3).

Of children with peanut allergy only at age 1, 27% (95%CI 16.1-39.7) were tree nut allergic at age 6, compared with 14% (95%CI 10.4-17.9) of those with egg allergy only and 37% (95%CI 27.2-47.4) of those with both peanut and egg allergy.

Conclusions

Tree nut allergy is uncommon in the first year of life, likely due to limited tree nut consumption. At age 6 years, tree nut allergy prevalence is similar to peanut allergy prevalence. Over a third of children with both peanut and egg allergy in infancy have tree nut allergy at age 6. Understanding how to prevent tree nut allergy should be an urgent priority for future research.

https://ift.tt/2wrvSVa

Coated microneedle based cutaneous immunotherapy prevents Der p1 induced airway allergy in mice

Publication date: Available online 30 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Akhilesh Kumar Shakya, Chang Hyun Lee, Harvinder Singh Gill

https://ift.tt/2PkRqdj

Surgical margins in head and neck cancer: Intra- and postoperative considerations

Publication date: Available online 30 August 2018

Source: Auris Nasus Larynx

Author(s): K. Thomas Robbins, Asterios Triantafyllou, Carlos Suárez, Fernando López, Jennifer L. Hunt, Primož Strojan, Michelle D. Williams, Boudewijn J.M. Braakhuis, Remco de Bree, Michael L. Hinni, Luiz P. Kowalski, Alessandra Rinaldo, Juan P. Rodrigo, Vincent Vander Poorten, Iain J. Nixon, Robert P. Takes, Carl E. Silver, Alfio Ferlito

Abstract

Objective

To provide a perspective on the significance of recent reports for optimizing cancer free surgical margins that have challenged standard practices.

Methods

We conducted a review of the recent literature (2012–2018) using the keywords surgical margin analysis, frozen and paraffin section techniques, head and neck cancer, spectroscopy and molecular markers.

Results

Of significance are the reports indicating superiority of tumor specimen directed sampling of margins compared to patient directed (tumor bed) sampling for frozen section control of oral cancers. With reference to optimal distance between tumor and the surgical margin, recent reports recommended cutoffs less than 5 mm. Employment of new technologies such as light spectroscopy and molecular analysis of tissues, provide opportunities for a "real time" assessment of surgical margins.

Conclusions

The commonly practiced method of patient directed margin sampling involving previous studies raises concern over conclusions made regarding the efficacy of frozen section margin control. The recent studies that challenge the optimal distance for clear surgical margins are retrospective and address patient cohorts with inherently confounding factors. The use of novel ancillary techniques require further refinements, clinical trial validation, and justification based on the additional resources.

https://ift.tt/2Pn6GGH

Delayed endolymphatic hydrops. Special emphasis on nystagmus associated with episodes and contribution of chemical labyrinthectomy

Publication date: Available online 29 August 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): P. Reynard, A. Karkas, M. Gavid, Y. Lelonge, P. Bertholon

Abstract

Objectives

The main objective was to describe spontaneous nystagmus characteristics during an episode of delayed endolymphatic hydrops (DEH), including an initial vertical upbeating nystagmus in one patient. The secondary objective was to highlight the contribution of chemical labyrinthectomy.

Methods

Episodic vertigo after a prolonged period of time of sensorineural hearing loss (profound or total) in one ear characterized ipsilateral DEH and was associated with the development of hearing loss in the opposite ear in contralateral DEH.

Results

Ten patients met the criteria for DEH: 7 ipsilateral and 3 contralateral. Three (all ipsilateral DEH) were examined during a vertigo episode. Two patients had a typical horizontal-torsional nystagmus beating contralaterally to the hearing loss. One patient showed atypic initial vertical upbeating nystagmus with a slight torsional component, which secondarily became horizontal-torsional beating contralaterally to the hearing loss. Four patients had disabling vertigo with unilateral total deafness (ipsilateral DEH), successfully treated by 1-3 transtympanic gentamycin (Gentalline^®) injections.

Conclusion

Nystagmus direction during vertigo episodes varies, and may initially present as vertical upbeating nystagmus, which, to our knowledge, has not been previously reported in DEH or Menière's disease. This nystagmus might reflect an inhibition of the superior semicircular canal (on the hearing-impaired side), suggesting incipient hydrops in this canal. Chemical labyrinthectomy is a simple and effective procedure in unilateral DEH, especially as the patient often suffers from total deafness.

https://ift.tt/2PRcOb9

Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis

Publication date: October 2018

Source: Oral Oncology, Volume 85

Author(s): Jie Jane Chen, Jeremy P. Harris, Christina S. Kong, John B. Sunwoo, Vasu Divi, Kathleen C. Horst, Sumaira Z. Aasi, S. Tyler Hollmig, Wendy Y. Hara

Abstract

Objectives

Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes.

Materials and methods

We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM).

Results

Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046).

Conclusion

Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.

https://ift.tt/2C14CSD

Odontogenic carcinosarcoma: A systematic review

Publication date: October 2018

Source: Oral Oncology, Volume 85

Author(s): Lauren Frenzel Schuch, José Alcides Almeida de Arruda, Leni Verônica Oliveira Silva, Lucas Guimarães Abreu, Tarcília Aparecida Silva, Ricardo Alves Mesquita

Abstract

The aim of this study was to integrate the available data published on odontogenic carcinosarcoma into a comprehensive analysis of their features, treatment and recurrence. An electronic search with no publication date or language restriction was undertaken in March 2018 in the following databases: Medline Ovid, PubMed, Web of Science, Scopus and LILACS. Eligibility criteria included publications having enough clinical, imaginological and histopathological information to confirm a definite diagnosis of the neoplasm. Data were evaluated descriptively and statistically using the MedCalc software. The Kaplan-Meier method was used for survival analysis. The systematic review detected nine articles from eight countries. Six cases with no age predilection occurred in male individuals complaining of painful swelling in the posterior mandible. Radiographically, the lesions were large, with expansive radiolucency and with ill-defined borders and seven cases were associated with preexisting odontogenic lesions. Radical surgery was the treatment of choice in the majority of cases. Recurrences (n = 6), metastasis (n = 4) and death (n = 4) were frequently observed in many cases. Odontogenic carcinosarcoma is a very aggressive neoplasm with a poor prognosis. This study provides knowledge that could help surgeons, oncologists, otorhinolaryngologists and oral maxillofacial pathologists with the diagnosis and management of these lesions.

https://ift.tt/2PQEHjp

Chemotherapy-induced apoptosis, autophagy and cell cycle arrest are key drivers of synergy in chemo-immunotherapy of epithelial ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the most lethal of all gynecological malignancies in the UK. Recent evidence has shown that there is potential for immunotherapies to be successful in treating this cancer. We have previously shown the effective application of combinations of traditional chemotherapy and CAR (chimeric antigen receptor) T cell immunotherapy in in vitro and in vivo models of EOC. Platinum-based chemotherapy synergizes with ErbB-targeted CAR T cells (named T4), significantly reducing tumor burden in mice. Here, we show that paclitaxel synergizes with T4 as well, and look into the mechanisms behind the effectiveness of chemo-immunotherapy in our system. Impairment of caspase activity using pan-caspase inhibitor Z-VAD reveals this chemotherapy-induced apoptotic pathway as an essential factor in driving synergy. Mannose-6-phosphate receptor-mediated autophagy and the arrest of cell cycle in G2/M are also shown to be induced by chemotherapy and significantly contributing to the synergy. Increased expression of PD-1 on T4 CAR T cells occurred when these were in culture with ovarian tumor cells; on the other hand, EOC cell lines showed increased PD-L1 expression following chemotherapy treatment. These findings provided a rationale to look into testing PD-1 blockade in combination with paclitaxel and T4 immunotherapy. Combination of these three agents in mice resulted in significant reduction of tumor burden, compared to each treatment alone. In conclusion, the mechanism driving synergy in chemo-immunotherapy of EOC is multifactorial. A deeper understanding of such process is needed to better design combination therapies and carefully stratify patients.

https://ift.tt/2on1ozj

Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung

Abstract

β-Glucan is a naturally occurring glucose polysaccharide with immunostimulatory activity in both infection and malignancy. β-Glucan's antitumor effects have been attributed to the enhancement of complement receptor 3-dependent cellular cytotoxicity, as well as modulation of suppressive and stimulatory myeloid subsets, which in turn enhances antitumor T cell immunity. In the present study, we demonstrate antitumor efficacy of yeast-derived β-glucan particles (YGP) in a model of metastatic-like melanoma in the lung, through a mechanism that is independent of previously reported β-glucan-mediated antitumor pathways. Notably, efficacy is independent of adaptive immunity, but requires inflammatory monocytes. YGP-activated monocytes mediated direct cytotoxicity against tumor cells in vitro, and systemic YGP treatment upregulated inflammatory mediators, including TNFα, M-CSF, and CCL2, in the lungs. Collectively, these studies identify a novel role for inflammatory monocytes in β-glucan-mediated antitumor efficacy, and expand the understanding of how this immunomodulator can be used to generate beneficial immune responses against metastatic disease.

https://ift.tt/2PkI8hr

T cell receptor sequencing of activated CD8 T cells in the blood identifies tumor-infiltrating clones that expand after PD-1 therapy and radiation in a melanoma patient

Abstract

PD-1-targeted therapy has dramatically changed advanced cancer treatment. However, many questions remain, including specificity of T cells activated by PD-1 therapy and how peripheral blood analysis correlates to effects at tumor sites. In this study, we utilized TCR sequencing to dissect the composition of peripheral blood CD8 T cells activated upon therapy, comparing it with tumor-infiltrating lymphocytes. We report on a nonagenarian melanoma patient who showed a prominent increase in peripheral blood Ki-67 + CD8 T cells following brain stereotactic radiation and anti-PD-1 immunotherapy. Proliferating CD8 T cells exhibited an effector-like phenotype with expression of CD38, HLA-DR and Granzyme B, as well as expression of the positive costimulatory molecules CD28 and CD27. TCR sequencing of peripheral blood CD8 T cells revealed a highly oligoclonal repertoire at baseline with one clonotype accounting for 30%. However, the majority of dominant clones—including a previously identified cytomegalovirus-reactive clone—did not expand following treatment. In contrast, expanding clones were present at low frequencies in the peripheral blood but were enriched in a previously resected liver metastasis. The patient has so far remained recurrence-free for 36 months, and several CD8 T cell clones that expanded after treatment were maintained at elevated levels for at least 8 months. Our data show that even in a nonagenarian individual with oligoclonal expansion of CD8 T cells, we can identify activation of tumor-infiltrating CD8 T cell clones in peripheral blood following anti-PD-1-based immunotherapies.

https://ift.tt/2on1AP3

Anergic natural killer cells educated by tumor cells are associated with a poor prognosis in patients with advanced pancreatic ductal adenocarcinoma

Abstract

Introduction

Natural killer cells (NK) are often believed to play a positive role in the antitumor immune response. However, this is not the case for patients with advanced pancreatic cancer. This study was performed to determine the unique subtype of "educated" NK cells and their prognostic value in patients with advanced pancreatic cancer.

Methods

We divided 378 eligible patients into a derivation cohort (September 2010 to December 2014, n = 239) and a validation cohort (January 2015 to April 2016, n = 139). Flow cytometry was performed to analyze NK cells. Enzyme-linked immunosorbent assay was used to detect interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. The Kaplan–Meier method and the Cox proportional hazards model were used.

Results

Survival analysis showed that a high density of NK cells accompanied by a high neutrophil-to-lymphocyte ratio was associated with reduced overall survival in both the derivation and validation cohorts. Multivariable analysis also showed that high NK infiltration (HR 1.45, 95% CI 1.17 to 1.79, p = 0.001) was an independent prognostic factor. In these patients, high NK infiltration was associated with reduced levels of IL-2, IFN-γ and TNF-α, although only IFN-γ reached statistical significance, which accounted for this unique phenomenon.

Discussion

Natural killer cells in patients with advanced pancreatic cancer are a unique subtype with anergic features. A high density of NKs predicts poor survival in these patients, possibly because an active inflammatory response and reduced secretion of IL-2, IFN-γ and TNF-α inhibit NK activation.

https://ift.tt/2NuvNXf

Circulating CD8 + T-cell repertoires reveal the biological characteristics of tumors and clinical responses to chemotherapy in breast cancer patients

Abstract

Purpose

CD8⁺ T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8⁺ T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy.

Experimental design

We applied a high-throughput TCR β-chain sequencing method to characterize the CD8⁺ T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8⁺ T-cell repertoire during chemotherapy were analyzed.

Results

We found that the HEC ratios of the CD8⁺ T-cell repertoires from HER2⁺ breast cancer patients were significantly higher than those of HER2⁻ patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8⁺ T cells. Several Vβ and CDR3 motifs preferentially used in HER2⁺ patients were identified. Besides, we found that the circulating CD8⁺ T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8⁺ T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response.

Conclusions

Although functional studies of clonally expanded CD8⁺ T-cell populations are clearly required, our results suggest that the circulating CD8⁺ T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.

https://ift.tt/2PmJXdP

Critical steps for computational inference of the 3′-end of novel alleles of immunoglobulin heavy chain variable genes - illustrated by an allele of IGHV3-7

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Linnea Thörnqvist, Mats Ohlin

Abstract

Sequencing of immunoglobulin germline gene loci is a challenging process, e.g. due to their repetitiveness and complexity, hence limiting the insight in the germline gene repertoire of humans and other species. Through next generation sequencing technology, it is possible to generate immunoglobulin transcript data sets large enough to computationally infer the germline genes from which the transcripts originate. Multiple tools for such inference have been developed and they can be used for construction of individual germline gene databases, and for discovery of new immunoglobulin germline genes and alleles. However, there are challenges associated with these methods, many of them related to the biological process through which immunoglobulin coding genes are generated. The junctional diversity introduced during rearrangement of the immunoglobulin heavy chain variable (IGHV), diversity and joining genes specifically complicates the inference of the junction regions, with implications for inference of the 3′-end of IGHV genes. With the aim of coping with such diversity, an inference software package may not be able to identify novel alleles harbouring a difference in these regions compared to their closest relatives in the starting database. In this study, we were able to computationally infer one such previously uncharacterized allele, IGHV3-7*02 A318G. However, this was possible only if a strategy was used in which different variants of IGHV3-7*02 were included in the inference-initiating database. Importantly, the presence of the novel allele, but not the standard IGHV3-7*02 sequence, in the genotype was strongly supported by the actual sequences that were assigned to the allele. We thus showed that the starting database used will impact the germline gene inference process, and that difference in the 3′-end of IGHV genes may remain undetected unless specific, non-standard procedures are used to address this matter. We suggest that inferred genes/alleles should be confirmed e.g. by examination of the nucleotide composition of the 3′-bases of the inference-supporting sequence reads.

Graphical abstract

https://ift.tt/2PNLlXI

Using plasma circRNA_002453 as a novel biomarker in the diagnosis of lupus nephritis

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Qingqing Ouyang, Qin Huang, Zhenlan Jiang, Jinjun Zhao, Guo-Ping Shi, Min Yang

Abstract

This study aimed to determine the expression of circRNAs in plasma from lupus nephritis (LN) patients to identify novel biomarkers for LN screening. We initially performed microarray screening of circRNA changes in plasma from 5 L N patients, 5 systemic lupus erythematosus (SLE) patients without LN, and 5 healthy controls. We then confirmed the selected circRNA changes in plasma from 59 SLE patients (30 with LN and 29 without LN), 26 rheumatoid arthritis (RA) patients, and 27 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction. Spearman's correlation test was performed to assess the correlation of circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. We confirmed that plasma circRNA_002453 was significantly elevated in LN patients when compared with SLE patients without LN, RA patients, and healthy controls. Plasma circRNA_002453 was also found to be upregulated in SLE patients when compared with RA patients and healthy controls. Among these LN patients, we detected no significant correlation between plasma circRNA_002453 and disease activity, including complement 3 (C3), complement 4 (C4), and SLE disease activity index 2000 (SLEDAI-2 K) score. However, its expression level was significantly and positively correlated with 24-hour proteinuria (r = 0.571, p = 0.001) and renal SLEDAI score (r = 0.640, p < 0.001). ROC analysis showed that plasma circRNA_002453 had an area under the curve of 0.906 (95% CI 0.838–0.974, p < 0.001) to discriminate LN patients from controls (SLE patients without LN, RA patients, and healthy controls) with sensitivity of 0.900 and specificity of 0.841. The highest Youden index was 0.741 and the corresponding optimal cut-off value was 0.001. This study suggests that upregulated plasma circRNA_002453 level in LN patients is associated with the severity of renal involvement and may also serve as a potential biomarker for LN patient diagnosis.

https://ift.tt/2C1GCPz

Editorial Board

Publication date: October 2018

Source: Clinical Immunology, Volume 195

Author(s):

https://ift.tt/2C0NtZq

Stress, Salivary Cortisol and Periodontitis: A Systematic Review and Meta-analysis of Observational Studies

Publication date: Available online 30 August 2018

Source: Archives of Oral Biology

Author(s): João Botelho, Vanessa Machado, Paulo Mascarenhas, João Rua, Ricardo Alves, Maria Alzira Cavacas, Ana Delgado, José João Mendes

Abstract

Objective

This meta-analysis aims to systematically assess whether periodontitis has a meaningful effect on salivary cortisol, reflecting changes on free blood cortisol levels.

Design

The Cochrane Handbook and the PRISMA statement were used as reporting guidelines. The MEDLINE-PubMed, Google Scholar, EMBASE, and CENTRAL databases were searched until September 2017 to identify eligible studies, screened by seven independent authors and verified by an eighth. Studies comparing salivary cortisol level of periodontitis cases to controls were included. Data were extracted using a predefined table and since all papers were non-randomized clinical trials they were appraised using Downs and Black tool. DerSimonian random effects meta-analysis was performed using OpenMetaAnalyst.

Results

Six cross-sectional studies were included, with 258 participants with chronic periodontitis and 72 with aggressive periodontitis, in a total of 573 participants. Overall results showed that aggressive periodontitis patients have, on average, 53% higher salivary cortisol levels than healthy controls 1.53 (1.11-2.12). Meta-regression exploring the relationship among salivary cortisol levels and periodontal measures, i.e., periodontitis severity, showed a global neutral effect, although this result requires future confirmation due to the low power of the model.

Conclusion

Observational studies results suggest that subjects with aggressive periodontitis have higher salivary cortisol levels than healthy ones or patients with chronic periodontitis. Such salivary cortisol response difference may have a negative impact on the periodontium, contributing to worse the burden of aggressive periodontitis disease. In the future, wide and well-designed longitudinal studies should be carried out in order to extensively confirm this possible effect, considering the complex nature of periodontitis and its many confounders factors that may contribute to this outcome.

https://ift.tt/2wxfBgK

The transient receptor potential cation channel subfamily V members 1 and 2, P2X purinoceptor 3 and calcitonin gene-related peptide in sensory neurons of the rat trigeminal ganglion, innervating the periosteum, masseter muscle and facial skin

Publication date: Available online 30 August 2018

Source: Archives of Oral Biology

Author(s): Maki Sato, Tadasu Sato, Takehiro Yajima, Kenichiro Shimazaki, Hiroyuki Ichikawa

ABSTRACT

Objective

Distribution of the transient receptor potential cation channel subfamily V members 1 (TRPV1) and 2 (TRPV2), and P2X purinoceptor 3 (P2 × 3) was investigated in rat trigeminal ganglion neurons innervating the periosteum, masseter muscle and facial skin.

Design

Double immunofluorescence method for TRPV1 and TRPV2 ion channels or ATP receptor P2 × 3 with calcitonin gene-related peptide (CGRP) was performed on trigeminal ganglion neurons retrogradely labeled from the mandibular periosteum, masseter muscle, or facial skin in 15 male Wistar rats.

Results

The cell size of periosteum neurons (mean ± S.D. = 810.7 ± 36.1 μ m²) was smaller than that of masseter muscle neurons (927.0 ± 75.6 μ m²), and larger than that of facial skin neurons (661.3 ± 82.2 μ m²). Periosteum neurons contained TRPV1- (26.7%), TRPV2- (47.1%) and P2 × 3-immunoreactivity (50.1%). Expression of TRPV2-immunoreactivity was more abundant among periosteum neurons than among facial skin neurons (16.1%). Regarding to TRPV1 and P2 × 3 expression, however, there was no significant difference between periosteum neurons and, masseter muscle and facial skin neurons. TRPV1- immunoreactive trigeminal ganglion neurons which innervated the periosteum, masseter muscle and facial skin mostly had small and medium-sized cell bodies, whereas TRPV2- and P2 × 3-immunoreactive trigeminal ganglion neurons innervating those tissues were of various cell body sizes. Approximately 20% of periosteum (19.2%), masseter muscle (19.2%) and facial skin (21.5%) neurons contained both TRPV1- and CGRP-immunoreactivity. Some periosteum neurons also co-expressed CGRP-immunoreactivity with TRPV2- (10.9%) or P2 × 3- immunoreactivity (11.1%). Distributions of perivascular and free nerve fibers containing CGRP and either TRPV1, TRPV2, or P2 × 3 were occasionally very similar in the mandibular periosteum.

Conclusions

The present study indicated that trigeminal ganglion nociceptors innervating the periosteum as well as those innervating the masseter muscle and facial skin have vanilloid, acidic, thermal, mechanical and ATP sensors. In some periosteum neurons, CGRP may act as inflammatory mediator through activation of TRPV1, TRPV2 and P2 × 3.

https://ift.tt/2okKBwO

Eingewachsene Zehennägel – Optionen für die tägliche Praxis

Zusammenfassung

Der eingewachsene Zehennagel ist ein häufiges, schmerzhaftes und entzündliches Erkrankungsbild v. a., aber nicht ausschließlich des jugendlichen Patienten. Zahlreiche konservative Behandlungsmethoden stehen zur Verfügung. Meist steht jedoch am Ende einer Leidenskette die operative Therapie. Zur operativen Behandlung wird immer noch die als obsolet einzustufende, sog. Emmert-Plastik eingesetzt. Als schonende Alternative kommt zunehmend die selektive Behandlung des lateralen Matrixhorns durch Resektion oder Phenolkaustik zum Einsatz. Letztere Verfahren bieten zahlreiche Vorteile mit geringem postoperativem Schmerz und schnellerer Wiedererlangung der normalen Lebensqualität.

https://ift.tt/2op8aoi

Assessing the inclusivity of three mainstream secondary schools in England: challenges and dilemmas

Dimitrellou, E; Hurry, J; Male, D; (2019) Assessing the inclusivity of three mainstream secondary schools in England: challenges and dilemmas. International Journal of Inclusive Education 10.1080/13603116.2018.1511757 . (In press).

https://ift.tt/2wrhjRA

Exploring the putative role of kallikrein-6, calpain-1 and cathepsin-D in the proteolytic degradation of α-synuclein in multiple system atrophy

Kiely, AP; Miners, S; Courtney, R; Strand, C; Love, S; Holton, JL; (2018) Exploring the putative role of kallikrein-6, calpain-1 and cathepsin-D in the proteolytic degradation of α-synuclein in multiple system atrophy. Neuropathology and Applied Neurobiology 10.1111/nan.12512 . (In press).

https://ift.tt/2PlPoK5

Modulator-free quadrature amplitude modulation signal synthesis

Liu, Z; Kakande, J; Kelly, B; O'Carroll, J; Phelan, R; Richardson, DJ; Slavik, R; (2014) Modulator-free quadrature amplitude modulation signal synthesis. Nature Communications , 5 , Article 5911. 10.1038/ncomms6911 . Green open access

https://ift.tt/2wpjp4i

Forecasting from time series subject to sporadic perturbations: Effectiveness of different types of forecasting support

De Baets, S; Harvey, N; (2018) Forecasting from time series subject to sporadic perturbations: Effectiveness of different types of forecasting support. International Journal of Forecasting , 34 (2) pp. 163-180. 10.1016/j.ijforecast.2017.09.007 .

https://ift.tt/2Plinxy

Expectations for future care provision in a population-based cohort of baby-boomers

Stafford, M; Kuh, D; (2018) Expectations for future care provision in a population-based cohort of baby-boomers. Maturitas , 116 pp. 116-122. 10.1016/j.maturitas.2018.08.004 . Green open access

https://ift.tt/2wrdXhm

A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care

Patel, P; Hossain, F; Horsfall, LU; Banh, X; Hayward, KL; Williams, S; Johnson, T; ... Powell, EE; + view all Patel, P; Hossain, F; Horsfall, LU; Banh, X; Hayward, KL; Williams, S; Johnson, T; Bernard, A; Brown, NN; Lampe, G; Buck, L; Saad, N; Russell, AW; Valery, PC; Irvine, KM; Clouston, AD; Stuart, KA; Rosenberg, W; Powell, EE; - view fewer (2018) A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care. Hepatology Communications , 2 (8) pp. 893-905. 10.1002/hep4.1208 . Green open access

https://ift.tt/2PhrSxC

Pediatric Pancreatic Tuberculosis: A Case Report and Review of the Literature

Pancreatic tuberculosis (TB) is an uncommon form of extrapulmonary TB and represents a diagnostic challenge for physicians. Pancreatic TB presents with nonspecific signs and symptoms and may mimic malignancy. However, pancreatic TB rarely occurs in children. Here, we present a case of a 5-year-old girl with pancreatic TB and markedly elevated serum cancer antigen- (CA-) 125 levels, thus raising the suspicion of malignancy, but positivity for Mycobacterium tuberculosis DNA was noted. The patient recovered after being administered standard antitubercular therapy for one year. This case suggests that clinicians should have a heightened suspicion of pancreatic TB when faced with pancreatic lesions despite the fact that increased CA-125 may indicate malignancy. Laparoscopy combined with peritoneal biopsy and polymerase chain reaction (PCR) may provide a new method to confirm the diagnosis.

https://ift.tt/2wsShBP

Outcome of Endoscopic Cerebrospinal Fluid Rhinorrhoea Repair: An Institutional Study

Abstract

Cerebrospinal fluid Rhinorrhoea is caused by an abnormal open communication between the subarachnoid space and the nasal cavity. The most common anatomic sites of such abnormal communication are found in the anterior skull base, namely, ethmoid roof, olfactory groove, roof of the sphenoid sinus and the posterior wall of the frontal sinus. It can be classified into traumatic or spontaneous. Spontaneous leaks are associated with highest recurrence rates following surgical repair. The repair of CSF Rhinorrhoea has rapidly evolved over the past 30 years. Prior to the advent of the endoscopic approach, craniotomy was used for repairs which carried a variable success rate and morbidity. The purpose of our study was to ascertain the outcome after Transnasal Endoscopic Repair of spontaneous CSF leaks. This was a prospective study conducted at the Department of ENT at Safdarjung Hospital, New Delhi between January 2015 and June 2016. The study comprised of eleven patients who presented with the complaint of watery nasal discharge and were diagnosed to have spontaneous CSF Rhinorrhoea. Proper clinical examination, nasal endoscopy and biochemical and cytological analysis of nasal secretions of the patient was done. High Resolution Computed Tomography and MRI scans of the nose and paranasal sinuses were done to identify precise location of CSF leak and the size of fistula. CT cisternography was done wherever required. Fistula was repaired via Transnasal endoscopic approach in a multi layered underlay fashion. Out of all eleven patients with spontaneous CSF leaks, most common site of leak was from left cribriform area. Four patients (36.36%) were found to have meningoencephalocele. No associated intracranial lesion was found and all patients did not have any benign intracranial hypertension. Our success rate of endoscopic repair on first attempt was 100% with recurrence in 1 patient after 4 months of repair. Endoscopic repair of CSF rhinorrhoea is safe and effective, with a very low complication rate. It has almost completely replaced the older open techniques. Accurate localization of leak site followed by multilayered closure of dural defect appear to be essential for successful endoscopic repair.

https://ift.tt/2BZScuv

IL‐33 signaling contributes to pollutant‐induced allergic airway inflammation

Clinical &Experimental Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Nxos9x

Forthcoming Meetings

Clinical &Experimental Allergy, Volume 48, Issue 9, Page 1242-1242, September 2018.


https://ift.tt/2wt5ryC

Issue Information

Clinical &Experimental Allergy, Volume 48, Issue 9, Page 1075-1077, September 2018.


https://ift.tt/2NxorCv

Selective nut‐eating in peanut or tree nut allergic children—How can molecular allergology help?

Clinical &Experimental Allergy, Volume 48, Issue 9, Page 1245-1245, September 2018.


https://ift.tt/2N3d7Rz

Cover Image

Clinical &Experimental Allergy, Volume 48, Issue 9, Page i-i, September 2018.


https://ift.tt/2Nw2WSG

Best of the Other Journals

Clinical &Experimental Allergy, Volume 48, Issue 9, Page 1243-1244, September 2018.


https://ift.tt/2N3WYLN

The benefits of allergy patient support groups

Clinical &Experimental Allergy, Volume 48, Issue 9, Page 1078-1079, September 2018.


https://ift.tt/2LE0lEc

Surgery, radiotherapy or a combined modality for jugulotympanic paraganglioma of Fisch class C and D

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PjUFS5

Outcome of Endoscopic Cerebrospinal Fluid Rhinorrhoea Repair: An Institutional Study

Abstract

Cerebrospinal fluid Rhinorrhoea is caused by an abnormal open communication between the subarachnoid space and the nasal cavity. The most common anatomic sites of such abnormal communication are found in the anterior skull base, namely, ethmoid roof, olfactory groove, roof of the sphenoid sinus and the posterior wall of the frontal sinus. It can be classified into traumatic or spontaneous. Spontaneous leaks are associated with highest recurrence rates following surgical repair. The repair of CSF Rhinorrhoea has rapidly evolved over the past 30 years. Prior to the advent of the endoscopic approach, craniotomy was used for repairs which carried a variable success rate and morbidity. The purpose of our study was to ascertain the outcome after Transnasal Endoscopic Repair of spontaneous CSF leaks. This was a prospective study conducted at the Department of ENT at Safdarjung Hospital, New Delhi between January 2015 and June 2016. The study comprised of eleven patients who presented with the complaint of watery nasal discharge and were diagnosed to have spontaneous CSF Rhinorrhoea. Proper clinical examination, nasal endoscopy and biochemical and cytological analysis of nasal secretions of the patient was done. High Resolution Computed Tomography and MRI scans of the nose and paranasal sinuses were done to identify precise location of CSF leak and the size of fistula. CT cisternography was done wherever required. Fistula was repaired via Transnasal endoscopic approach in a multi layered underlay fashion. Out of all eleven patients with spontaneous CSF leaks, most common site of leak was from left cribriform area. Four patients (36.36%) were found to have meningoencephalocele. No associated intracranial lesion was found and all patients did not have any benign intracranial hypertension. Our success rate of endoscopic repair on first attempt was 100% with recurrence in 1 patient after 4 months of repair. Endoscopic repair of CSF rhinorrhoea is safe and effective, with a very low complication rate. It has almost completely replaced the older open techniques. Accurate localization of leak site followed by multilayered closure of dural defect appear to be essential for successful endoscopic repair.

https://ift.tt/2BZScuv

Subclinical Changes in Deceased Donor Kidney Proteomes are Associated with 12-month Allograft Function Posttransplantation – a Preliminary Study

Background Cerebral injury during Donation after Brain Death (DBD) may induce systemic damage affecting long-term kidney function posttransplantation. Conventional evaluation of donor organ quality as a triage for transplantation is of limited utility. Methods We compared donor kidneys yielding opposing extremes of the continuum of posttransplantation outcomes by several common kidney biopsy evaluation techniques including Kidney Donor Profile Index (KDPI) and Remuzzi scoring, and analysed tissue from a minimal sample cohort using Label-Free Quantitation (LFQ) mass spectrometry. Further assessment of the proteomic results was performed by orthogonal quantitative comparisons of selected key proteins by immunoblotting. Results We show that common evaluation techniques of kidney biopsies were not predictive for posttransplantation outcomes. In contrast, despite the limited cohort size, the proteomic analysis was able to clearly differentiate between kidneys yielding extreme posttransplantation outcome differences. Pathway analysis of the proteomic data suggested that outcome-related variance in protein abundance associated with profibrotic, apoptosis and antioxidant proteins. Immunoblotting confirmation further supported this observation. Conclusions We present preliminary data indicating that there is scope for existing evaluation approaches to be supplemented by the analysis of proteomic differences. Furthermore, the observed outcome-related variance in a limited cohort was supported by immunoblotting and is consistent with mechanisms previously implicated in the development of injury and cytoprotection in kidney transplantation. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. + Equal contribution ◊ Equal contribution Corresponding Author: Dr. Maria Kaisar (maria.kaisar@nds.ox.ac.uk), Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 7LJ, United Kingdom AUTHORSHIP PAGE Authorship: MK, BMK and RJP designed this study. MK, AZ, NW as members of the National Management Team and the QUOD Steering Committee participated in the establishment of the QUOD biobank. RJP is the Coordinator of the QUOD consortium. Clinical evaluation of samples was performed by MK. Sample preparation for proteomic study was performed by MK, MLT and HH. Mass spectrometric analysis was performed by MLT and HH. Mass spectrometric data was processed and searched by MK and MLT. Statistical analysis of proteomic quantitation was performed by MK and PDC. Immunoblotting was performed by LvD. Remuzzi scoring was performed by AK. The paper was written by MK, PDC, BMK and RJP with input from the other authors. Disclosure: The authors declare no conflicts of interest Funding: This work was supported by research funding from NHS Blood and Transplant Trust Fund TF031 and Oxford Transplant Foundation award to M.K., a John Fell Fund 133/075 and Wellcome Trust grant 097813/Z/11/Z to B.M.K. and COPE FP7 grant award to R.J.P. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2NxOJon

Survival from a 75% TBSA thermal injury complicated by bowel ischemia presenting with pneumatosis intestinalis

Abstract

Thermal injury is associated with an increased risk of abdominal complications such as ischemia, infarction and pneumatosis intestinalis (PI). PI is characterized by gas in the intestinal wall and, when diagnosed it can signify the presence of a life-threatening condition. We present a case of a patient who survived 75% total body surface area burns complicated by ischemic bowel that initially presented as extensive PI. This patient was emergently taken to the operating room and underwent a subtotal colectomy and small bowel resection for ischemic bowel. Prompt diagnosis and successful management of the underlying condition ultimately contributed to the patient's survival. The presence of peritonitis or abdominal distension, portomesenteric venous gas and lactic acidosis should prompt immediate surgical intervention in the post-burn period.

https://ift.tt/2MB13HU

Adenocarcinoma of jejunum

Abstract

Although gastrointestinal malignancy is still the major concern of health problems in Worldwide and Thailand, but small intestinal malignancy is extremely rare. The location of small intestinal malignancy is duodenum (73.6%), jejunum (13.2%) and ileum (13.2%). The diagnosing of small intestinal malignancy usually delays due to inaccessible of esophagogastroduodenoscopy especially jejunum and ileum causing poor prognostic outcomes. We reported our case of jejunal adenocarcinoma.

https://ift.tt/2NsiuGW

Poorly differentiated signet ring cell carcinoma of pancreas masquerading as chronic pancreatitis

Abstract

Pancreatic cancer is typically arises in the context of inflammation, and a surrounding area of pancreatitis is often present within the tumor microenvironment. Signet ring cell carcinoma (SRCC) is a rare variant of pancreatic adenocarcinoma. Pathologically, it presents either as single cells or loose clusters masquerading in the background of pancreatitis. Sampling of these inflammatory cells during biopsy can result in the incorrect diagnosis of pancreatitis. We report a case of SRCC of the pancreas which the diagnosis of cancer was delayed because multiple biopsies revealed only inflammatory changes with no obvious evidence of malignancy. This case highlights the fact that negative results with endoscopic ultrasound fine needle aspiration in SRCC can be misleading. A cancer diagnosis should still be considered despite findings of inflammatory pancreatitis if the clinical presentation is concerning for cancer (mass on CT scan).

https://ift.tt/2MC1hhT

Age is nothing but a number: radical en bloc resection of colon adenocarcinoma with abdominal wall reconstruction in an 81 year old

Abstract

Colon adenocarcinoma is a common neoplasm, which rarely presents with full thickness invasion through the abdominal wall. Aggressive treatment is often reserved for younger patients, with many surgeons opting to consider elderly patients as non-operative candidates, especially in the setting of diffuse disease. We report a case of radical resection of a colon cancer, with full thickness abdominal wall invasion in an 81-year-old female. The patient presented with gradual abdominal swelling over multiple months. She had a CT scan revealing a mass eroding through her abdominal wall, up to the skin. Operative resection with adjuvant chemotherapy was chosen as therapy because the patient had no co-morbidities. The patient underwent en bloc resection of the abdominal wall with right hemicolectomy and resection of all structures attached to the mass. The patient has been disease free for 24 months and has had return to her baseline activities of daily living.

https://ift.tt/2NzwbUr

Foreign body granuloma treatment with 22‐MHz ultrasound‐guided corticoid infiltration

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2PPY0cD

Effects of four soaps on skin trans‐epidermal water loss and erythema index

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2BWDBzQ

Factors Affecting Delivery of the HPV Vaccination: A Focus Group Study With NHS School-Aged Vaccination Teams in London

Rockliffe, L; McBride, E; Heffernan, C; Forster, AS; (2018) Factors Affecting Delivery of the HPV Vaccination: A Focus Group Study With NHS School-Aged Vaccination Teams in London. Journal of School Nursing 10.1177/1059840518792078 . (In press). Green open access

https://ift.tt/2PjWApX

'Medicine doesn't cure my worries': Understanding the drivers of mental distress in older Nepalese women living in the UK

Sah, LK; Burgess, RA; Sah, RK; (2018) 'Medicine doesn't cure my worries': Understanding the drivers of mental distress in older Nepalese women living in the UK. Global Public Health 10.1080/17441692.2018.1473888 . (In press).

https://ift.tt/2oj4moC

Distributed watermarking for secure control of microgrids under replay attacks

Gallo, AJ; Turan, MS; Boem, F; Ferrari-Trecate, G; Parisini, T; (2018) Distributed watermarking for secure control of microgrids under replay attacks. In: (Proceedings) 7th IFAC Workshop on Distributed Estimation and Control in Networked Systems (NecSys18), 27-28 August 2018, Groningen, Netherlands. Elsevier (In press).

https://ift.tt/2wycNQz

Neuronatin regulates pancreatic beta cell insulin content and secretion

Millership, SJ; Xavier, GDS; Choudhury, AI; Bertazzo, S; Chabosseau, P; Pedroni, SMA; Irvine, EE; ... Withers, DJ; + view all Millership, SJ; Xavier, GDS; Choudhury, AI; Bertazzo, S; Chabosseau, P; Pedroni, SMA; Irvine, EE; Montoya, A; Faull, P; Taylor, WR; Kerr-Conte, J; Pattou, F; Ferrer, J; Christian, M; John, RM; Latreille, M; Liu, M; Rutter, GA; Scott, J; Withers, DJ; - view fewer (2018) Neuronatin regulates pancreatic beta cell insulin content and secretion. The Journal of Clinical Investigation , 128 (8) pp. 3369-3381. 10.1172/JCI120115 . Green open access

https://ift.tt/2oo4XW2

Prospective associations between measures of gross and fine motor coordination in infants and objectively measured physical activity and sedentary behavior in childhood

Lopez Sanchez, GF; Williams, G; Aggio, D; Vicinanza, D; Stubbs, B; Kerr, C; Johnstone, J; ... Smith, L; + view all Lopez Sanchez, GF; Williams, G; Aggio, D; Vicinanza, D; Stubbs, B; Kerr, C; Johnstone, J; Roberts, J; Smith, L; - view fewer (2017) Prospective associations between measures of gross and fine motor coordination in infants and objectively measured physical activity and sedentary behavior in childhood. Medicine , 96 (46) , Article e8424. 10.1097/MD.0000000000008424 . Green open access

https://ift.tt/2PfH7qW

Pre‐pregnancy weight loss in women with obesity requesting removal of their intra‐uterine contraceptive device in order to conceive: a pilot study of full meal replacement

Brackenridge, L; Finer, N; Batterham, RL; Pedram, K; Ding, T; Stephenson, J; Barry, J; Brackenridge, L; Finer, N; Batterham, RL; Pedram, K; Ding, T; Stephenson, J; Barry, J; Hardiman, P; - view fewer (2018) Pre‐pregnancy weight loss in women with obesity requesting removal of their intra‐uterine contraceptive device in order to conceive: a pilot study of full meal replacement. Clinical Obesity , 8 (4) pp. 244-249. 10.1111/cob.12252 .

https://ift.tt/2olCQXu

Physical activity levels in children with sensory problems: Cross-sectional analyses from the Millennium Cohort Study

Williams, G; Aggio, D; Stubbs, B; Pardhan, S; Gardner, B; Smith, L; (2018) Physical activity levels in children with sensory problems: Cross-sectional analyses from the Millennium Cohort Study. Disability and Health Journal , 11 (1) pp. 58-61. 10.1016/j.dhjo.2017.07.002 . Green open access

https://ift.tt/2PjDTm5

Otherness and Belonging: Integration of Practitioner-Academics into an Engineering School at a Research Intensive Institution

Nyamapfene, A; (2017) Otherness and Belonging: Integration of Practitioner-Academics into an Engineering School at a Research Intensive Institution. In: Proceedings of the 45th SEFI Annual Conference 2017 - Education Excellence for Sustainability (SEFI 2017). Instituto Superior De Engenharia Do Porto: Porto, Portugal. Green open access

https://ift.tt/2ombpN9

A tutorial on how not to over-interpret STRUCTURE and ADMIXTURE bar plots

Lawson, DJ; Van Dorp, L; Falush, D; (2018) A tutorial on how not to over-interpret STRUCTURE and ADMIXTURE bar plots. Nature Communications , 9 , Article 3258. 10.1038/s41467-018-05257-7 . Green open access

https://ift.tt/2wycIfJ

Admixture into and within sub-Saharan Africa

Busby, GBJ; Band, G; Le, QS; Jallow, M; Bougama, E; Mangano, VD; Amenga-Etego, LN; ... O'Brien, J; + view all Busby, GBJ; Band, G; Le, QS; Jallow, M; Bougama, E; Mangano, VD; Amenga-Etego, LN; Enimil, A; Apinjoh, T; Ndila, CM; Manjurano, A; Nyirongo, V; Doumba, O; Rockett, KA; Kwiatkowski, DP; Spencer, CCA; Vanderwal, A; Elzein, A; Nyika, A; Mendy, A; Miles, A; Diss, A; Kerasidou, A; Green, A; Jeffreys, AE; MacInnis, B; Hughes, C; Moyes, C; Hubbart, C; Malangone, C; Potter, C; Mead, D; Barnwell, D; Jyothi, D; Drury, E; Somaskantharajah, E; Hilton, E; Leffler, E; Maslen, G; Busby, G; Clarke, GM; Ragoussis, I; Garcia, JA; Rogers, J; deVries, J; Shelton, J; Ragoussis, J; Stalker, J; Rodford, J; O'Brien, J; - view fewer (2016) Admixture into and within sub-Saharan Africa. eLife , 5 , Article e15266. 10.7554/eLife.15266.001 . Green open access

https://ift.tt/2ojBJaK

Age- and sex-related changes in hematological parameters in healthy Malawians

Mandala, WL; Gondwe, EN; Maclennan, JM; Molyneux, ME; MacLennan, CA; (2017) Age- and sex-related changes in hematological parameters in healthy Malawians. Journal of Blood Medicine , 8 pp. 123-130. 10.2147/JBM.S142189 . Green open access

https://ift.tt/2wuVoID

Editorial

Sebastian, W; (2018) Editorial. Proceedings of the Institution of Civil Engineers: Structures and Buildings , 171 (9) pp. 659-660. 10.1680/jstbu.2018.171.9.659 .

https://ift.tt/2olzQu3

Association Between Twenty-Year Trajectories of Non-Occupational Physical Activity From Midlife to Old Age and Biomarkers of Cardiovascular Disease: A 20-Year Longitudinal Study of British Men.

Aggio, D; Papachristou, E; Papacosta, O; Lennon, LT; Ash, S; Whincup, PH; Wannamethee, SG; Aggio, D; Papachristou, E; Papacosta, O; Lennon, LT; Ash, S; Whincup, PH; Wannamethee, SG; Jefferis, BJ; - view fewer (2018) Association Between Twenty-Year Trajectories of Non-Occupational Physical Activity From Midlife to Old Age and Biomarkers of Cardiovascular Disease: A 20-Year Longitudinal Study of British Men. Am J Epidemiol 10.1093/aje/kwy157 . (In press). Green open access

https://ift.tt/2PfrBeD

Social networks and the intention to migrate

Manchin, M; Orazbayev, S; (2018) Social networks and the intention to migrate. World Development , 109 pp. 360-374. 10.1016/j.worlddev.2018.05.011 .

https://ift.tt/2omb25d

Evolution of Engineering Education Research as a Field of Inquiry in the UK

Nyamapfene, A; Williams, B; (2017) Evolution of Engineering Education Research as a Field of Inquiry in the UK. In: Proceedings of the 7th Research in Engineering Education Symposium (REES 2017). (pp. pp. 605-611). Research in Engineering Education Network: Red Hook (NY), USA.

https://ift.tt/2PfrzU3

B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome

James, K; Chipeta, C; Parker, A; Harding, S; Cockell, SJ; Gillespie, CS; Hallinan, J; ... Mewar, D; + view all James, K; Chipeta, C; Parker, A; Harding, S; Cockell, SJ; Gillespie, CS; Hallinan, J; Barone, F; Bowman, SJ; Ng, WF; Fisher, BA; Hall, F; Bacabac, EC; Frankland, H; Moots, R; Chadravarty, K; Lamabadusuriya, S; Bombardieri, M; Pitzalis, C; Sutcliffe, N; Breston, C; Gendi, N; Culfear, K; Riddell, C; Hamburger, J; Richards, A; Rauz, S; Brailsford, S; Dasgin, J; Logan, J; Mulherin, D; Andrews, J; Emery, P; McManus, A; Pease, C; Pickles, D; Booth, A; Regan, M; King, J; Holt, A; Dimitroulas, T; Kadiki, L; Kaur, D; Kitas, G; Khan, A; Cosier, T; Panthakalam, KM; Mintrim, K; Lloyd, M; Moore, L; Gordon, E; Lawson, C; Gupta, M; Hunter, J; Stirton, L; Ortiz, G; Price, E; Pelger, S; Gorman, C; Hans, B; Clunie, G; Lane, S; Rose, G; Cuckow, S; Batley, M; Einosas, R; Knight, S; Symmons, D; Jones, B; Carr, A; Edgar, S; Figuereido, F; Foggo, H; Lendrem, D; Macleod, I; Mitchell, S; Downie, C; Tarn, J; Locke, J; Al-Ali, S; Legg, S; Mirza, K; Hargreaves, B; Hetherington, L; Jones, A; Lanyon, P; Muir, A; White, P; Young-Min, S; Pugmire, S; Vadivelu, S; Cooper, A; Watkins, M; Field, A; Kaye, S; Mewar, D; - view fewer (2018) B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome. Rheumatology , 57 (7) pp. 1222-1227. 10.1093/rheumatology/key063 . Green open access

https://ift.tt/2olC5O8

Two accounts with "minus carats" figures

Gonis, N; (2018) Two accounts with "minus carats" figures. Bulletin of the American Society of Papyrologists , 55 pp. 297-300. (In press).

https://ift.tt/2PkupHo

SB 14.12098: another "curious prescript"

Gonis, N; (2018) SB 14.12098: another "curious prescript". Bulletin of the American Society of Papyrologists , 55 pp. 300-301. (In press).

https://ift.tt/2olqrmn

Novel adaptive finite element algorithms to predict bone ingrowth in additive manufactured porous implants.

Cheong, VS; Fromme, P; Mumith, A; Coathup, MJ; Blunn, GW; (2018) Novel adaptive finite element algorithms to predict bone ingrowth in additive manufactured porous implants. J Mech Behav Biomed Mater , 87 pp. 230-239. 10.1016/j.jmbbm.2018.07.019 .

https://ift.tt/2PhkimA

Inhibition of somatosensory mechanotransduction by annexin A6

Raouf, R; Lolignier, S; Sexton, JE; Millet, Q; Santana-Varela, S; Biller, A; Fuller, AM; ... Wood, JN; + view all Raouf, R; Lolignier, S; Sexton, JE; Millet, Q; Santana-Varela, S; Biller, A; Fuller, AM; Pereira, V; Choudhary, JS; Collins, MO; Moss, SE; Lewis, R; Tordo, J; Henckaerts, E; Linden, M; Wood, JN; - view fewer (2018) Inhibition of somatosensory mechanotransduction by annexin A6. Science Signaling , 11 (535) , Article eaao2060. 10.1126/scisignal.aao2060 . Green open access

https://ift.tt/2onoAO1