Cellular differentiation, bioactive and mechanical properties of experimental light-curing pulp protection materials

Publication date: Available online 16 March 2018
Source:Dental Materials
Author(s): Salvatore Sauro, Ashvin Babbar, Borzo Gharibi, Victor Pinheiro Feitosa, Ricardo Marins Carvalho, Lidiany Karla Azevedo Rodrigues, Avijit Banerjee, Timothy Watson
ObjectiveMaterials for pulp protection should have therapeutic properties in order to stimulate remineralization and pulp reparative processes. The aim of this study was to evaluate the mechanical properties, biocompatibility, cell differentiation and bioactivity of experimental light-curable resin-based materials containing bioactive micro-fillers.MethodsFour calcium-phosphosilicate micro-fillers were prepared and incorporated into a resin blend: 1) Bioglass 45S5 (BAG); 2) zinc-doped bioglass (BAG-Zn); 3) βTCP-modified calcium silicate (β-CS); 4) zinc-doped β-CS (β-CS-Zn). These experimental resins were tested for flexural strength (FS) and fracture toughness (FT) after 24h and 30-day storage in simulated body fluid (SBF). Cytotoxicity was evaluated using MTT assay, while bioactivity was evaluated using mineralization and gene expression assays (Runx-2 & ALP).ResultsThe lowest FS and FT at 24h was attained with β-CS resin, while all the other tested materials exhibited a decrease in FS after prolonged storage in SBF. β-CS-Zn maintained a stable FT after 30-day SBF aging. Incorporation of bioactive micro-fillers had no negative effect on the biocompatibility of the experimental materials tested in this study. The inclusion of zinc-doped fillers significantly increased the cellular remineralization potential and expression of the osteogenic genes Runx2 and ALP (p<0.05).SignificanceThe innovative materials tested in this study, in particular those containing β-CS-Zn and BAG-Zn may promote cell differentiation and mineralization. Thus, these materials might represent suitable therapeutic pulp protection materials for minimally invasive and atraumatic restorative treatments.

Graphical abstract

http://ift.tt/2FOoBS4

Investigation of the relationship between morphology and permeability for open-cell foams using virtual materials testing

Publication date: 5 June 2018
Source:Materials & Design, Volume 147
Author(s): Daniel Westhoff, Jakub Skibinski, Ondřej Šedivý, Bartlomiej Wysocki, Tomasz Wejrzanowski, Volker Schmidt
The effect of the morphology of open-cell foam structures on their functional properties is investigated. A stochastic microstructure model is used to generate representative 3D open-cell foam structures, where morphological properties are systematically varied. Subsequently, permeability of these virtual, but realistic microstructures is determined using the finite volume method. This procedure, which is called virtual materials testing, has recently been employed to investigate the effect of the variation of cell sizes on permeability. In the present paper, we introduce a stochastic microstructure model that can be used to generate structures with varying distribution of (open) face sizes between cells. It turns out that this characteristic strongly influences the so-called constrictivity, a measure for bottleneck effects, which, in turn, has a strong impact on the resulting permeability. Moreover, we show how the virtual materials testing approach can be applied to derive empirical formulas between descriptors of 3D morphology and functionality. Additionally, an experimental validation of the simulation results is performed by printing three of the virtual structures using selective laser melting and subsequent experimental measurement of pressure drop, which allows calculation of the permeability using Darcy's law.

Graphical abstract

http://ift.tt/2GAyQuC

Role of Virtual Touch Tissue Quantification in Hashimoto's Thyroiditis

Publication date: Available online 16 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Zi-mei Lin, Yao Wang, Chun-mei Liu, Cao-xin Yan, Pin-tong Huang
We investigated the role of the virtual touch tissue quantification (VTQ) technique in diagnosing Hashimoto's thyroiditis (HT) and in distinguishing various HT-related thyroid dysfunctions. Two hundred HT patients and 100 healthy volunteers (the control group) were enrolled. The diagnostic performance of VTQ in predicting HT was calculated as the area under the receiver operating characteristic curve (AZ). The HT patients were further classified into three subgroups on the basis of serologic tests of thyroid function: hyperthyroidism, euthyroidism and hypothyroidism. Comparisons of shear wave velocity (SWV) between three subgroups were evaluated by analysis of variance. The mean SWV of the control group was significantly lower than that of the HT group (1.93 ± 0.33 m/s vs. 2.32 ± 0.49 m/s, p < 0.001). Az was 0.734 with a cut-off value of 1.86 m/s for performance of SWV in distinguishing between HT and a healthy thyroid; the sensitivity and specificity were 82.5% and 50.0%, respectively. Mean SWV values in the three HT subgroups (hyperthyroidism [2.07 ± 0.37 cm/s] vs. euthyroidism [2.20 ± 0.40 cm/s] vs. hypothyroidism [2.49 ± 0.46 cm/s]) were significantly different (p < 0.05). Our results suggest that VTQ is a promising technique for assessing HT and HT-related thyroid dysfunction.



http://ift.tt/2pjWALf

Blocking the Glycolytic Pathway Sensitizes Breast Cancer to Sonodynamic Therapy

Publication date: Available online 16 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Lifen Xie, Xiaolan Feng, Yin Shi, Meng He, Pan Wang, Xiaobing Wang, Zeyuan Mi, Quanhong Liu, Kun Zhang
Inhibition of the increased aerobic glycolysis in cancer cells is a promising methodology for various malignant tumor therapies but is limited by systemic toxicity, at least in part. Recent studies suggest that dual restriction of glycolysis and mitochondrial function may overcome this issue. Sonodynamic therapy (SDT), a prospective therapeutic modality for cancers, has been reported to induce mitochondria-dependent cell damage. Here, we investigated the combined effect of SDT and 2-deoxyglucose (2DG), an anti-glycolytic agent, on breast cancer both in vitro and in vivo. In vitro, we found that, compared with a single treatment, SDT + 2DG co-treatment significantly decreased cell viability and increased cell apoptosis. Moreover, the generation of reactive oxygen species was enhanced and mitochondrial membrane potential (MMP) was reduced after SDT + 2DG co-treatment. Furthermore, the oxidative phosphorylation was also restrained after SDT + 2DG co-treatment, further to cause the blockage of ATP provision. In vivo, SDT + 2DG markedly reduced tumor volume and weight, consistent with the in vitro findings. Furthermore, toxicology tests concurrently indicated that the dosages of sinoporphyrin sodium and 2DG were comparatively tolerable. Generally, these results indicated that SDT + 2DG combination therapy may be an available, promising therapy for highly metastatic breast cancer.



http://ift.tt/2IvJpj5

Is Acoustic Radiation Force Impulse (ARFI) Ultrasound Elastography Valuable in the Assessment of Cervical Lymphadenopathy?

Abstract

Cervical lymphadenopathy frequently poses a diagnostic challenge as neither clinical nor imaging assessment can reliably differentiate between benign and malignant lymphadenopathy. Non-invasive differentiation between the two may help to reduce the number of FNAC or biopsy. The purpose of this study was to evaluate whether the new ARFI technique (Virtual Touch Quantification), in conjunction with gray scale sonography and Doppler, can help in the characterization and differentiation of benign from malignant cervical lymphadenopathy. Fifty adult patients with cervical lymphadenopathy were included in the study and sonoelastography was done. Sonoelastographic findings were compared to the gold standard histopathology or cytopathology. ARFI measurements in benign and malignant enlarged lymph nodes were compared using the Student t test and ROC curve was used to arrive at the Youden index, sensitivity, specificity, PPV, NPV and diagnostic accuracy. Sonographic patterns indicative of malignancy includes heterogenous echopattern, short axis/long axis ratio > 0.5, absent echogenic fatty hilum and mixed vascular pattern. Sensitivity, specificity, PPV, NPV and accuracy in differentiation between the benign and malignant lymph nodes using ARFI elastography was 79.17, 100, 100, 83.9 and 89.9% respectively. ROC curve analysis of SWVs for differentiation between the malignant and benign lymph nodes gave a cut-off value of 2.8 m/s with an area under curve of 0.892. ARFI imaging technique quantifies the tissue stiffness of the cervical lymph nodes non-invasively and aids in characterisation and differentiation of benign from malignant cervical lymphadenopathy in conjunction with conventional sonography.

http://ift.tt/2HF51YZ

Cochlear Implantation in Children with Otitis Media

Abstract

One of the concerns during the cochlear implant candidacy process is the presence of chronic otitis media which could delay the implantation process. The aim of this study was to evaluate the surgical difficulties and the long-term complications in children with otitis media and to examine whether it is necessary to delay the implantation until the infection is resolved. The study used a comparative retrospective design based on chart review of all patients who received their implant(s) from January to December of 2012. A total of 200 patients were identified and were followed for 4 years post surgery. Patients were divided into three groups based on their history of otitis media (non-otitis media, chronic otitis media with effusion, and acute otitis media). Data included long-term complications, operative time and duration from first clinical visit to the time until implantation was received. None of study participants had long-term complications during the study period. The operative time was longer in the acute otitis media group with a difference of 45 min. The average delay in cochlear implantation due to the presence of otitis media in chronic group was more than 5 months. Pediatric patients with otitis media could be implanted in one stage safely and effectively.

http://ift.tt/2pofyBp

In Reply to Güngör et al

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Wilma D. Heemsbergen, Ruud C. Wortel, Luca Incrocci, Robert Jan Smeenk, Marnix G. Witte, Floris J. Pos, Stijn Krol




http://ift.tt/2DAeA95

Somatic Frameshift Alterations in Tumor Suppressor Genes May Predict Anti-PD-1/L1 Response in Squamous Cell Carcinoma of the Head and Neck

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): G.J. Hanna, L.E. Macconaill, P. Lizotte, M. Cavanaugh, N.G. Chau, J.D. Schoenfeld, J.H. Lorch, R. Uppaluri, R.I. Haddad




http://ift.tt/2piOO5d

2018 Red Journal Conflicts of Interest and Photographs

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5





http://ift.tt/2DxBcY0

In Regard to Cahlon et al

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Jee Suk Chang, Yong Bae Kim, Jaeyong Shin




http://ift.tt/2phQY4Y

Locally Advanced Lung Cancer: Is It Time to Take Cardiac Protection Seriously in Radiation Planning?

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): James J. Urbanic, Ronald C. McGarry, Megan E. Daly, David A. Palma




http://ift.tt/2DCPxCE

Relapsing Prostate Cancer: Castrate or Cure?

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Hannah Tharmalingam, Ananya Choudhury




http://ift.tt/2pjWSTj

Live to SABR Another Day?

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Phuoc T. Tran, Felix Feng, Piet Ost




http://ift.tt/2G4vceN

Table of Contents

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5





http://ift.tt/2DA689X

Androgen Deprivation Fortified

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Prateek Mendiratta, Jorge Garcia




http://ift.tt/2pfGqTZ

Issue Highlights

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5





http://ift.tt/2Dzs7hj

Apply an Oligometastatic Paradigm for Nodal Recurrence

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Daniel Song




http://ift.tt/2G31abi

…of Radiation Oncology, Biology, and Physics

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Jay W. Burmeister, Monica W. Tracey, Sara E. Kacin, Michael M. Dominello, Michael C. Joiner




http://ift.tt/2DAeazC

In Reply to Hamstra

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Stephen A. Rosenberg, Kristin A. Bradley, Randall J. Kimple




http://ift.tt/2FYeFZx

In Reply to Garden

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): David M. Routman, Robert L. Foote, Daniel J. Ma, Samir H. Patel, Michael L. Hinni




http://ift.tt/2DA7ZeO

Erratum to: Mahmood J, Connors CQ, Alexander AA, et al. Cavernous nerve injury by radiation therapy may potentiate erectile dysfunction in rats. Int J Radiat Oncol Biol Phys 2017;99:680-688.

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5





http://ift.tt/2G0Ht3C

Comparison of 36 Gy, 20 Gy, or No Radiation Therapy After 6 Cycles of EBVP Chemotherapy and Complete Remission in Early-Stage Hodgkin Lymphoma Without Risk Factors: Results of the EORT-GELA H9-F Intergroup Randomized Trial

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): José Thomas, Christophe Fermé, Evert M. Noordijk, Franck Morschhauser, Théodore Girinsky, Isabelle Gaillard, Pieternella J. Lugtenburg, Marc André, Marnix L.M. Lybeert, Aspasia Stamatoullas, Max Beijert, Philippe Hélias, Houchingue Eghbali, Jean Gabarre, Richard W.M. van der Maazen, Jérôme Jaubert, Krimo Bouabdallah, Olivier Boulat, Judith M. Roesink, Bernard Christian, Francisca Ong, Dominique Bordessoule, Gérard Tertian, Hugo Gonzalez, Andrej Vranovsky, Philippe Quittet, Umberto Tirelli, Daphne de Jong, Josée Audouin, Berthe M.P. Aleman, Michel Henry-Amar
PurposeWhile patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy.Methods and MaterialsPatients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130).ResultsRandomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] −1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%.ConclusionsIn adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20 Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome.



http://ift.tt/2DCPuXu

A Randomized, Open-Label, Multicenter, Global Phase 2 Study of Durvalumab (D), Tremelimumab (T), or D Plus T, in Patients With PD-L1 Low/Negative Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: CONDOR

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): L. Siu, C. Even, R. Mesía, A. Daste, J. Krauss, N.F. Saba, L. Nabell, N.E. Ready, I.Brana Garcia, N. Kotecki, D.P. Zandberg, J. Gilbert, H. Mehanna, A. Jarkowski, G. Melillo, J.M. Armstrong, J. Fayette




http://ift.tt/2piXoRs

OPTIMA—A Phase 2 Trial of Induction Chemotherapy Response-Stratified Radiation Therapy Dose and Volume De-escalation for HPV+ Oropharyngeal Cancer: Efficacy, Toxicity, and HPV Subtype Analysis

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): T. Seiwert, J.M. Melotek, C.C. Foster, E.A. Blair, T.G. Karrison, N. Agrawal, L. Portugal, Z. Gooi, K.M. Stenson, R.J. Brisson, S. Arshad, A. Dekker, S. Kochanny, V. Saloura, M.T. Spiotto, V.M. Villaflor, D.J. Haraf, E.E. Vokes




http://ift.tt/2DAe9vy

Management of Borderline Resectable Pancreatic Cancer

Publication date: 1 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 5
Author(s): Diego A.S. Toesca, Amanda J. Koong, George A. Poultsides, Brendan C. Visser, Sigurdis Haraldsdottir, Albert C. Koong, Daniel T. Chang
With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.



http://ift.tt/2G3How0

Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations

Publication date: Available online 16 March 2018
Source:Journal of Autoimmunity
Author(s): Aigli G. Vakrakou, Sorina Boiu, Panayiotis D. Ziakas, Evangelia Xingi, Haralabia Boleti, Menelaos N. Manoussakis
Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls. We found that SS patients at high risk for lymphoma and those with established lymphoma display high serum cf-DNA levels, substantial extranuclear DNA accumulations in PBMC and SG tissues, a unique NLRP3 inflammasome gene signature in PBMC, and significantly increased serum IL-18 and ASC levels. In these patients, the circulating monocytes manifested NLRP3 inflammasome activation and increased response to NLRP3 stimuli, whereas SG-infiltrating macrophages exhibited signs of NLRP3 activation and pyroptosis. Cell-free nucleic acids isolated from patients' sera competently primed the activation of both NLRP3 and AIM2 inflammasomes in healthy monocytes. SS patients also manifested diminished DNaseI activity in serum and DNaseII expression in PBMC, which inversely correlated with indices of inflammasome activation. DNaseII gene-silencing in healthy monocytes led to cytoplasmic DNA deposition and activation of inflammasome-related genes and of caspase1. Our data reveal the occurrence of systemic NLRP3 inflammasome activation in severe SS, which is associated with widespread extranuclear accumulations of inflammagenic DNA and impaired DNA degradation. These findings can provide novel biomarkers and new therapeutic targets for the management of SS patients with adverse outcomes.



http://ift.tt/2FPrAKe

BRAF and RAS Mutational Status in Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features and Invasive Subtype of Encapsulated Follicular Variant of Papillary Thyroid Carcinoma in Korea

Thyroid, Ahead of Print.


http://ift.tt/2HIdHhr

A Nomogram Based on the Characteristics of Metastatic Lymph Nodes to Predict Papillary Thyroid Carcinoma Recurrence

Thyroid, Volume 28, Issue 3, Page 301-310, March 2018.


http://ift.tt/2pjfVwK

Mild Maternal Hypothyroxinemia During Pregnancy Induces Persistent DNA Hypermethylation in the Hippocampal Brain-Derived Neurotrophic Factor Gene in Mouse Offspring

Thyroid, Volume 28, Issue 3, Page 395-406, March 2018.


http://ift.tt/2HGmsZ8

Acknowledgment of Reviewers

Thyroid, Volume 28, Issue 3, Page 422-426, March 2018.


http://ift.tt/2plj3bq

Ionizing Radiation Deregulates the MicroRNA Expression Profile in Differentiated Thyroid Cells

Thyroid, Volume 28, Issue 3, Page 407-421, March 2018.


http://ift.tt/2FEQsIx

Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1 Expression in Patients with Non-Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis

Thyroid, Volume 28, Issue 3, Page 349-361, March 2018.


http://ift.tt/2piR5gI

Temporal Trends in the Presentation, Treatment, and Outcome of Medullary Thyroid Carcinoma: An Israeli Multicenter Study

Thyroid, Volume 28, Issue 3, Page 369-376, March 2018.


http://ift.tt/2HCZD8E

Is Acoustic Radiation Force Impulse (ARFI) Ultrasound Elastography Valuable in the Assessment of Cervical Lymphadenopathy?

Abstract

Cervical lymphadenopathy frequently poses a diagnostic challenge as neither clinical nor imaging assessment can reliably differentiate between benign and malignant lymphadenopathy. Non-invasive differentiation between the two may help to reduce the number of FNAC or biopsy. The purpose of this study was to evaluate whether the new ARFI technique (Virtual Touch Quantification), in conjunction with gray scale sonography and Doppler, can help in the characterization and differentiation of benign from malignant cervical lymphadenopathy. Fifty adult patients with cervical lymphadenopathy were included in the study and sonoelastography was done. Sonoelastographic findings were compared to the gold standard histopathology or cytopathology. ARFI measurements in benign and malignant enlarged lymph nodes were compared using the Student t test and ROC curve was used to arrive at the Youden index, sensitivity, specificity, PPV, NPV and diagnostic accuracy. Sonographic patterns indicative of malignancy includes heterogenous echopattern, short axis/long axis ratio > 0.5, absent echogenic fatty hilum and mixed vascular pattern. Sensitivity, specificity, PPV, NPV and accuracy in differentiation between the benign and malignant lymph nodes using ARFI elastography was 79.17, 100, 100, 83.9 and 89.9% respectively. ROC curve analysis of SWVs for differentiation between the malignant and benign lymph nodes gave a cut-off value of 2.8 m/s with an area under curve of 0.892. ARFI imaging technique quantifies the tissue stiffness of the cervical lymph nodes non-invasively and aids in characterisation and differentiation of benign from malignant cervical lymphadenopathy in conjunction with conventional sonography.

http://ift.tt/2HF51YZ

Cochlear Implantation in Children with Otitis Media

Abstract

One of the concerns during the cochlear implant candidacy process is the presence of chronic otitis media which could delay the implantation process. The aim of this study was to evaluate the surgical difficulties and the long-term complications in children with otitis media and to examine whether it is necessary to delay the implantation until the infection is resolved. The study used a comparative retrospective design based on chart review of all patients who received their implant(s) from January to December of 2012. A total of 200 patients were identified and were followed for 4 years post surgery. Patients were divided into three groups based on their history of otitis media (non-otitis media, chronic otitis media with effusion, and acute otitis media). Data included long-term complications, operative time and duration from first clinical visit to the time until implantation was received. None of study participants had long-term complications during the study period. The operative time was longer in the acute otitis media group with a difference of 45 min. The average delay in cochlear implantation due to the presence of otitis media in chronic group was more than 5 months. Pediatric patients with otitis media could be implanted in one stage safely and effectively.

http://ift.tt/2pofyBp

Is There a Moore's Law for 3D Printing?

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 53-62, March 2018.


http://ift.tt/2FFYyjW

A Conversation with Marcelo Coelho, Head of Design at Formlabs

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 1-3, March 2018.


http://ift.tt/2HIFSgf

Production Techniques for 3D Printed Inflatable Elastomer Structures: Part I—Fabricating Air-Permeable Forms and Coating with Inflatable Silicone Membranes via Spray Deposition

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 5-16, March 2018.


http://ift.tt/2FFYgcQ

3D Printed Composites of Copper–Aluminum Oxides

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 46-52, March 2018.


http://ift.tt/2HDDqaQ

Three-Dimensional Printing Antimicrobial and Radiopaque Constructs

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 29-36, March 2018.


http://ift.tt/2FGI4bh

3D-Printed Acrylonitrile Butadiene Styrene-Metal Organic Framework Composite Materials and Their Gas Storage Properties

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 63-72, March 2018.


http://ift.tt/2HGu9i3

The Value of 3D Printed Models in Understanding Acetabular Fractures

3D Printing and Additive Manufacturing, Volume 5, Issue 1, Page 37-46, March 2018.


http://ift.tt/2FHwRHL

Aberrant expression of the sFRP and WIF1 genes in invasive non-functioning pituitary adenomas

Publication date: Available online 16 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Wang Song, Liu Qian, Guo Jing, Feng Jie, Shan Xiaosong, Liu Chunhui, Li Yangfang, Li Guilin, Hua Gao, Zhang Yazhuo
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (p = 0.002, p < 0.001). Univariate analysis showed a significant correlation between tumor invasion and low expression of WIF1 and sFRP4 (p = 0.002, p < 0.001). A similar trend was observed when analyzing the mRNA and protein levels through RT-PCR and western blot experiments. Methylation of the WIF1 promoter was significantly increased in invasive NFPAs compared with the noninvasive group (p = 0.004). The average progression free survival time in the high WIF1 group was longer than that in the low WIF1 group (p = 0.025). Furthermore, RT-PCR measured the levels of 11 miRNAs targeting WIF1 according to the Targetscan database and PubMed. The levels of miRNA-137, miRNA-374a-5p and miRNA-374b-5p in the invasive group were 0.037-fold, 0.577-fold and 0.44-fold that of the noninvasive group (p = 0.003, p = 0.049 and p = 0.047). Overexpression of miRNA-137 could inhibit the proliferation and invasion of GH3 cells through cell viability and Transwell experiments (p < 0.05). Furthermore, the WIF1 level was upregulated after overexpression of miRNA-137 compared with miRNA-137-NC (control miRNA) in GH3 cells. Our data suggest that WIF1 may be potential biomarker for the aggressiveness of NFPAs. miRNA-137 plays an important role in the Wnt signaling pathway by affecting promoter methylation of WIF1.



http://ift.tt/2phSLpG

The Force Is Strong with This One: Metabolism (Over)powers Stem Cell Fate

Publication date: Available online 16 March 2018
Source:Trends in Cell Biology
Author(s): Peng Wei, Katja K. Dove, Claire Bensard, John C. Schell, Jared Rutter
Compared to their differentiated progeny, stem cells are often characterized by distinct metabolic landscapes that emphasize anaerobic glycolysis and a lower fraction of mitochondrial carbohydrate oxidation. Until recently, the metabolic program of stem cells had been thought to be a byproduct of the environment, rather than an intrinsic feature determined by the cell itself. However, new studies highlight the impact of metabolic behavior on the maintenance and function of intestinal stem cells and hair follicle stem cells. This Review summarizes and discusses the evidence that metabolism is not a mere consequence of, but rather influential on stem cell fate.



http://ift.tt/2tQRBHy

BAX and BAK at the Gates of Innate Immunity

Publication date: Available online 16 March 2018
Source:Trends in Cell Biology
Author(s): Lorenzo Galluzzi, Claire Vanpouille-Box
Large BAX/BAK pores that form during apoptosis enable mitochondrial nucleoids to access the cytosol, potentially leading to inflammatory signaling via CGAS. Under physiological conditions, however, BAX/BAK-dependent caspase activation rapidly dismantles dying cells to prevent inflammatory responses. BAX and BAK operate at the interface between apoptotic signaling and innate immunity control.



http://ift.tt/2G1K6SQ

Immune signatures predicting responses to immunomodulatory antibody therapy

Graham Pawelec

http://ift.tt/2tUCGff

Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts

Publication date: Available online 16 March 2018
Source:Brain Stimulation
Author(s): Haidar Salimi Dafsari, Jan Niklas Petry-Schmelzer, K. Ray-Chaudhuri, Keyoumars Ashkan, Luca Weis, Till A. Dembek, Michael Samuel, Alexandra Rizos, Monty Silverdale, Michael T. Barbe, Gereon R. Fink, Julian Evans, Pablo Martinez-Martin, Angelo Antonini, Veerle Visser-Vandewalle, Lars Timmermann
BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS.ObjectiveTo investigate the impact of active contact location on NMS in STN-DBS in PD.MethodsIn this prospective, open-label, multicenter study including 50 PD patients undergoing bilateral STN-DBS, we collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, motor complications, activities of daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and Bonferroni-correction for multiple comparisons. Although the STN was targeted visually, we employed an atlas-based approach to explore the relationship between active contact locations and DBS outcomes. Based on fused MRI/CT-images, we identified Cartesian coordinates of active contacts with patient-specific Mai-atlas standardization. We computed linear mixed-effects models with x-/y-/z-coordinates as independent, hemispheres as within-subject, and test change scores as dependent variables.ResultsNMSS, NMSQ, PDQ-8, motor examination, complications, and LEDD significantly improved at follow-up. Linear mixed-effect models showed that NMS and QoL improvement significantly depended on more medial (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ-8) neurostimulation. ADL improved more in posterior, LEDD in lateral neurostimulation locations. No relationship was observed for motor examination and complications scores.ConclusionsOur study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes.



http://ift.tt/2FOTnKN

Yet Another Absolute Indication for Rapid Sequence Intubation

No abstract available

http://ift.tt/2phVNdK

The ASA Committee for Neuroanesthesia and Anesthesia Quality Institute: Report for Demographic Patterns for Neurosurgical Anesthesia Practice in the United States

No abstract available

http://ift.tt/2IxPXgW

Neuroanesthesiology Update

We provide a synopsis of innovative research, recurring themes, and novel experimental findings pertinent to the care of neurosurgical patients and critically ill patients with neurological diseases. We cover the following broad topics: general neurosurgery, spine surgery, stroke, traumatic brain injury, monitoring, and anesthetic neurotoxicity.

http://ift.tt/2pk7pNs

Dexmedetomidine Reduces Perioperative Opioid Consumption and Postoperative Pain Intensity in Neurosurgery: A Meta-analysis

Background: Dexmedetomidine (DEX) has been administered to patients during neurosurgery. Some studies have found that DEX could reduce perioperative opioid consumption and postoperative pain intensity. However, no firm conclusions have been reached. The purpose of this meta-analysis was to assess the efficacy of DEX for managing pain in neurosurgical patients. Materials and Methods: A comprehensive literature review was conducted to identify randomized controlled trials (RCTs) focusing on the effects of DEX on perioperative opioid consumption and postoperative pain intensity in patients undergoing neurosurgery. PubMed, the Web of science, the Cochrane Library, and Scopus were searched. The resulting data were combined to calculate the pooled mean differences (MDs), standard MDs or odds ratios (ORs), and 95% confidence intervals (CIs), as appropriate. Heterogeneity and potential publication bias were assessed. Furthermore, a trial sequential analysis was performed to improve the precision of our findings. Results: A total of 11 published RCTs involving 674 patients undergoing neurosurgery (335 patients, 339 controls) were included in this meta-analysis. There were significant differences in postanesthesia care unit (PACU) visual analog scale scores between the groups (MD=−1.54, 95% CI, −2.33 to 0.75, I2=87%, P=0.0001). In addition, there were significant differences in PACU opioid requirements between the treatment and control groups (standard MD=−0.88, 95% CI, −1.74 to 0.02, I2=91%, P=0.05). Furthermore, intraoperative opioid consumption was significantly reduced in the treatment group (MD=−127.75, 95% CI, −208.62 to 46.89, I2=98%, P=0.002). Conclusions: DEX could reduce perioperative and PACU opioid consumption as well as postoperative pain intensity.

http://ift.tt/2phVFeg

Injury and Liability Associated With Spine Surgery

Background: Although spine surgery is associated with significant morbidity, the anesthesia liability profile for spine surgery is not known. We examined claims for spine procedures in the Anesthesia Closed Claims Project database to evaluate patterns of injury and liability. Materials and Methods: A retrospective cohort study was performed. Inclusion criteria were anesthesia claims provided for surgical procedures in 2000 to 2014. We compared mechanisms of injury for cervical spine to thoracic or lumbar spine procedures using χ2 and the Fisher exact test. Univariate and multivariate logistic regression analyses were used to determine factors associated with permanent disabling injury in spine surgery claims. Results: The 207 spine procedure (73% thoracic/lumbar; 27% cervical) claims comprised >10% of claims. Permanent disabling injuries to nerves, the spinal cord, and the eyes or visual pathways were more common with spine procedures than in nonspine procedures. Hemorrhage and positioning injuries were more common in thoracic/lumbar spine claims, whereas difficult intubation was more common in cervical spine claims. Multiple logistic regression demonstrated prone positioning (odds ratio=3.50; 95% confidence interval, 1.30-9.43) and surgical duration of ≥4 hours increased the odds of severe permanent injury in spine claims (odds ratio=2.73; 95% confidence interval, 1.11-6.72). Conclusions: Anesthesia claims related to spine surgery were associated with severe permanent disability primarily from nerve and eye injuries. Prone positioning and surgical duration of ≥4 hours were associated with permanent disabling injuries. Attention to positioning, resuscitation during blood loss, and reducing length of surgery may reduce these complications.

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Editorial

No abstract available

http://ift.tt/2IvyxBN

Effects of Hypertonic Saline and Sodium Lactate on Cortical Cerebral Microcirculation and Brain Tissue Oxygenation

Background: Hyperosmolar solutions have been used in neurosurgery to modify brain bulk. The aim of this animal study was to compare the short-term effects of equivolemic, equiosmolar solutions of hypertonic saline (HTS) and sodium lactate (HTL) on cerebral cortical microcirculation and brain tissue oxygenation in a rabbit craniotomy model. Methods: Rabbits (weight, 1.5 to 2.0 kg) were anesthetized, ventilated mechanically, and subjected to a craniotomy. The animals were allocated randomly to receive a 3.75 mL/kg intravenous infusion of either 3.2% HTS (group HTS, n=9), half-molar sodium lactate (group HTL, n=10), or normal saline (group C, n=9). Brain tissue partial pressure of oxygen (PbtO2) and microcirculation in the cerebral cortex using sidestream dark-field imaging were evaluated before, 20 and 40 minutes after 15 minutes of hyperosmolar solution infusion. Global hemodynamic data were recorded, and blood samples for laboratory analysis were obtained at the time of sidestream dark-field image recording. Results: No differences in the microcirculatory parameters were observed between the groups before and after the use of osmotherapy. Brain tissue oxygen deteriorated over time in groups C and HTL, this deterioration was not significant in the group HTS. Conclusions: Our findings suggest that equivolemic, equiosmolar HTS and HTL solutions equally preserve perfusion of cortical brain microcirculation in a rabbit craniotomy model. The use of HTS was better in preventing the worsening of brain tissue oxygen tension.

http://ift.tt/2phVxLO

Prone Position, Cerebral Oximetry, and Delirium

No abstract available

http://ift.tt/2IxZmVN

Comparison of 3% Hypertonic Saline and 20% Mannitol for Reducing Intracranial Pressure in Patients Undergoing Supratentorial Brain Tumor Surgery: A Randomized, Double-blind Clinical Trial

Background: In the present study, we hypothesized that 3% hypertonic saline (HS) is more effective than 20% mannitol to reduce intracranial pressure (ICP) and to modify brain bulk in patients undergoing an elective supratentorial craniotomy. Materials and Methods: After institutional review board approval, patients scheduled to undergo supratentorial craniotomy were enrolled into this prospective, randomized, double-blind study. The patients were monitored for routine hemodynamic parameters, depth of anesthesia, and ICP. They received 5 mL/kg 20% mannitol (n=20) or 3% HS (n=19) as infusion for 15 minutes. The patients' ICP values were monitored during hypertonic fluid infusion and throughout 30 minutes after infusion as a primary outcome. Secondary outcomes were hemodynamic variables, serum sodium value, blood gases, and surgeon brain relaxation assessment score (1=relaxed, 2=satisfactory, 3=firm, 4=bulging). In addition, the length of intensive care unit and hospital stay were recorded. Results: Demographic and tumor characteristics were similar between groups. The basal (before hypertonic infusion, ICPT0) and last (30 min after hypertonic infusion finished, ICPT45) ICP values were 13.7±3.0 and 9.5±1.9 mm Hg, respectively, for the M group, which were comparable with the corresponding levels of 14.2±2.8 and 8.7±1.1 mm Hg in the HS group (P>0.05). The median amount of ICP reduction between T0 and T45 timepoints were 4 (1 to 7) and 5 (1 to 9) mm Hg for group M and group HS, respectively (P=0.035). Baseline central venous pressure, pulse pressure variation, and serum sodium and lactate values were similar between groups, but the last measured pulse pressure variation and lactate value were lower, and sodium value was higher in group HS than in group M (P

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A Comparison of Regional Versus General Anesthesia for Lumbar Spine Surgery: An Untouched Aspect of the Meta-Analysis

No abstract available

http://ift.tt/2Iw1A89

Comparison of Anesthetic Management and Outcomes in Patients Having Either Transnasal or Transoral Endoscopic Odontoid Process Surgery

Background: Endoscopic neurosurgical procedures involving the upper cervical vertebrae are challenging due to a narrow operating field and close proximity to vital anatomical structures. Historically, transoropharyngeal (transoral) endoscopy has been the preferred approach. More recently, however, an endoscopic transnasal approach was developed as an alternative method in hopes to reduce postoperative dysphagia, a common complication following transoral neurosurgery. Methods: Twenty-two endoscopic neurosurgical cases involving the odontoid or C1 vertebra were reviewed between January 1, 2005 and December 31, 2015 (17 and 5 through transoral and transnasal approaches, respectively). Patient demographics, anesthetic technique, intraoperative course, and postoperative outcomes such as were recorded. Results: Patients who underwent transnasal odontoidectomy had a shorter length of stay and lower rates of tracheostomy compared with those having similar surgery via the transoral route. In those having transoral surgery, no patient presented to the operating room with a preexisting tracheostomy. In 16 of 17 patients within the transoral group, a tracheostomy was performed. In those having transnasal surgery, 2 of 5 patients had a preexisting tracheostomy. In the remaining 3 of 5 patients, orotracheal intubation was performed and patients were extubated after the procedure. Conclusions: The transnasal odontoid resection technique may become a more popular surgical approach without increasing rates of complications compared with those having transoral surgery. Ultimately, a larger, study is needed to further clarify these relationships.

http://ift.tt/2phVtvy

Spectrogram Analysis as a Monitor of Anesthetic Depth in a Pediatric Patient

No abstract available

http://ift.tt/2IxZmFh

Journal Club

No abstract available

http://ift.tt/2phVoIg

2017 SNACC Annual Meeting Report

No abstract available

http://ift.tt/2IyAkpQ

Thermal response test data of five quadratic cross section precast pile heat exchangers

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Maria Alberdi-Pagola
This data article comprises records from five Thermal Response Tests (TRT) of quadratic cross section pile heat exchangers. Pile heat exchangers, typically referred to as energy piles, consist of traditional foundation piles with embedded heat exchanger pipes. The data presented in this article are related to the research article entitled "Comparing heat flow models for interpretation of precast quadratic pile heat exchanger thermal response tests" (Alberdi-Pagola et al., 2018) [1]. The TRT data consists of measured inlet and outlet temperatures, fluid flow and injected heat rate recorded every 10 min. The field dataset is made available to enable model verification studies.



http://ift.tt/2G3niSH

A new SWATH ion library for mouse adult hippocampal neural stem cells

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Clarissa Braccia, Meritxell Pons Espinal, Mattia Pini, Davide De Pietri Tonelli, Andrea Armirotti
Over the last years, the SWATH data-independent acquisition protocol (Sequential Window acquisition of All THeoretical mass spectra) has become a cornerstone for the worldwide proteomics community (Collins et al., 2017) [1]. In this approach, a high-resolution quadrupole-ToF mass spectrometer acquires thousands of MS/MS data by selecting not just a single precursor at a time, but by allowing a broad m/z range to be fragmented. This acquisition window is then sequentially moved from the lowest to the highest mass selection range. This technique enables the acquisition of thousands of high-resolution MS/MS spectra per minute in a standard LC–MS run. In the subsequent data analysis phase, the corresponding dataset is searched in a "triple quadrupole-like" mode, thus not considering the whole MS/MS scan spectrum, but by searching for several precursor to fragment transitions that identify and quantify the corresponding peptide. This search is made possible with the use of an ion library, previously acquired in a classical data dependent, full-spectrum mode (Fabre et al., 2017; Wu et al., 2017) [2,3]. The SWATH protocol, combining the protein identification power of high-resolution MS/MS spectra with the robustness and accuracy in analyte quantification of triple-quad targeted workflows, has become very popular in proteomics research. The major drawback lies in the ion library itself, which is normally demanding and time-consuming to build. Conversely, through the realignment of chromatographic retention times, an ion library of a given proteome can relatively easily be tailored upon "any" proteomics experiment done on the same proteome. We are thus hereby sharing with the worldwide proteomics community our newly acquired ion library of mouse adult hippocampal neural stem cells. Given the growing effort in neuroscience research involving proteomics experiments (Pons-Espinal et al., 2017; Sarnyai and Guest, 2017; Sethi et al., 2015; Bramini et al., 2016) [4,5–7], we believe that this data might be of great help for the neuroscience community. All the here reported data (RAW files, results and ion library) can be freely downloaded from the SWATHATLAS (Deutsch et al., 2008) [8] website (http://ift.tt/2G0mn5r)



http://ift.tt/2tU9c15

Data on farm diversification decisions and farmers’ risk preferences in the Ruhr Metropolitan region (Germany)

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Manuela Meraner, Bernd Pölling, Robert Finger
On-farm non-agricultural diversification is increasingly important for many farmers to stabilize their income and to fulfill societal demand for integrated farming. Especially in peri-urban areas, where the potential for farms' expansion in terms of farm size is limited and public interest in regional products and other services provided at farms is high, the uptake of on-farm non-agricultural diversification is thus an attractive strategy for many farmers. The here presented dataset is based on an online survey conducted in March 2016 with 156 farms located in the Ruhr Metropolitan region (North Rhine-Westphalia, Germany). The survey was used to collect information on farms' and farmers' characteristics. More specifically, the dataset includes detailed information on farms' diversification decisions, location, size and general information on farms' production type and structure. Moreover, the dataset contains information on farmers' risk perception and risk preferences (collected using three different elicitation methods) and general information on farmers and households. In addition, farmers' personal assessments on agricultural production in peri-urban settings and information on the use of extension services were collected.



http://ift.tt/2tTOf6m

Ion homeostasis and ion channels in NLRP3 inflammasome activation and regulation

Publication date: June 2018
Source:Current Opinion in Immunology, Volume 52
Author(s): Iva Hafner-Bratkovič, Pablo Pelegrín
The NLRP3 inflammasome is a multiprotein platform for the activation of caspase-1, which in turn drives inflammation through the activation of proinflammatory cytokines, such as IL-1β. In contrast to the majority of pattern recognition receptors, NLRP3 inflammasome can be triggered by a plethora of pathogen-derived or endogenous activators, which perturb intracellular ion homeostasis. Here, we discuss how the complex interplay of ion fluxes contributes to canonical, non-canonical, and alternative NLRP3 activation pathways that induce IL-1β secretion from immune cells. Particular attention is given to the concrete evidence for the involvement of ion channels, which may present viable therapeutic targets for the modulation of NLRP3 inflammasome activation.



http://ift.tt/2ItYcL6

Oncolytic viruses and immunity

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Shyambabu Chaurasiya, Nanhai G Chen, Yuman Fong
Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived as the major obstacle in oncolytic virotherapy. Over the last decade, there has been a lot of debate on whether the immune system is a friend or foe of OVs. However, we are now at a stage where the initial thinking has been reversed as a result of compelling evidence that the immune system plays a critical role in the success of oncolytic virotherapy. In this review we discuss the importance of the involvement of innate and adaptive immunity for therapeutic efficacy of OVs, and the rational combination of OVs with other immunotherapies for further enhancement of overall therapeutic outcome.



http://ift.tt/2pjCy3m

Immune signatures predicting responses to immunomodulatory antibody therapy

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Graham Pawelec
Since the first immunomodulatory antibody was licensed by the FDA in 2011 for treating melanoma it has remained the case that only a certain proportion of cancer patients respond favourably to a particular therapy. Recent results from combining two or more different antibodies each targeting a different immune checkpoint indicate that the proportion of responding patients can be increased, but thus far there are no such therapies routinely yielding clinical benefit in 100% of patients in any cancer type. Therefore, predicting which patients will respond to a particular therapy remains of the utmost importance in order to maximise treatment efficacy and minimise side-effects and costs. Moreover, determining biomarkers predicting responses may provide insight into the mechanisms responsible for success or failure of that therapy. This article reviews seminal papers mostly from the past two years of progress in this area of intense investigation, and mostly in melanoma, the tumour type for which the largest body of data exists thus far.



http://ift.tt/2Iw16ik

Driving CARs on the uneven road of antigen heterogeneity in solid tumors

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Nan Chen, Xiaoyu Li, Navin K Chintala, Zachary E Tano, Prasad S Adusumilli
Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.



http://ift.tt/2pkozdJ

Immune-based identification of cancer patients at high risk of progression

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Yann-Alexandre Vano, Florent Petitprez, Nicolas A Giraldo, Wolf H Fridman, Catherine Sautès-Fridman
Tumors are highly heterogeneous structures where malignant cells interact with a large variety of cell populations, including a clinically-relevant immune component. We review and compare the most recent methods designed to analyze and quantify the composition of immune and stromal microenvironment of tumors and discuss their use in identification of patients for high risk of progression. If the impact of the various immune components on patient's relapse share common rules in most malignancies, clear cell renal cell tumors behave differently with regards to immunity. We focus on this specific pathology to show how the tumor interacts with the host's immune system and how this intricate relationship shapes the clinical outcome.



http://ift.tt/2IxX3C7

Cancer vaccines: translation from mice to human clinical trials

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Hoyoung Maeng, Masaki Terabe, Jay A Berzofsky
Therapeutic cancer vaccines have been a long-sought approach to harness the exquisite specificity of the immune system to treat cancer, but until recently have not had much success as single agents in clinical trials. However, new understanding of the immunoregulatory mechanisms exploited by cancers has allowed the development of approaches to potentiate the effect of vaccines by removing the brakes while the vaccines step on the accelerator. Thus, vaccines that had induced a strong T cell response but no clinical therapeutic effect may now reach their full potential. Here, we review a number of promising approaches to cancer vaccines developed initially in mouse models and their translation into clinical trials, along with combinations of vaccines with other therapies that might allow cancer vaccines to finally achieve clinical efficacy against many types of cancer.



http://ift.tt/2plRP3F

Induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A systematic review and meta-analysis

Publication date: Available online 16 March 2018
Source:Radiotherapy and Oncology
Author(s): Teng Hwee Tan, Yu Yang Soon, Timothy Cheo, Francis Ho, Lea Choung Wong, Jeremy Tey, Ivan W.K. Tham
PurposeTo determine if the addition of induction chemotherapy (IC) to concurrent chemoradiation (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) can improve survival.MethodsWe performed a meta-analysis of both randomized controlled trials (RCTs) and observational studies (OBS) to compare the effects of addition of IC to CCRT versus (vs) CCRT alone on overall survival (OS), progression free survival (PFS), distant metastasis-free survival (DMFS) and adverse events (AE) in LA-NPC. We searched MEDLINE for eligible studies comparing IC plus CCRT vs CCRT for LA-NPC from Jan 1996 to May 2017. We selected RCTs and OBS that included patients with non-metastatic, LA-NPC who received IC followed by CCRT or CCRT alone. Three reviewers independently assessed the abstracts for eligibility. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model. We used the GRADE approach to appraise the quality of evidence from RCTs. The primary outcome was OS; secondary outcomes included PFS, DMFS and AE.ResultsWe found six RCTs and five OBS including 2802 patients with low to moderate risk of bias in their methodological quality. There was high quality evidence from the RCTs that IC improved PFS (HR 0.69, 95% CI 0.57–0.84, P = 0.0003, I² = 0%) and OS (HR 0.77, 95% CI 0.60–0.98, P = 0.03, I² = 0%) significantly and was associated with more frequent AE. The estimates of IC effects from RCTs and OBS were similar (PFS HR 0.69 vs 0.71, interaction P (IP) = 0.92; OS HR 0.77 vs 0.58, IP = 0.27).ConclusionsIC delays disease progression and improves survival significantly for LA-NPC treated with CCRT, and was associated with more toxicity. There were no divergent results between RCTs and OBS. IC followed by CCRT can be considered one of the standard treatment options for LA-NPC.



http://ift.tt/2FNcTY4

Compliance with bladder protocol during concurrent chemoradiation for cancer of the cervix and its impact on enteritis: A prospective observational study

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Sweta Bandanatham, Janaki Manur Gururajachar, Mohan Kumar Somashekar
AimThis prospective study aims to assess the compliance with bladder protocol and the correlation with enteritis during pelvic radiation.BackgroundBladder protocol is routinely used for patients undergoing pelvic radiation to reduce radiation enteritis. It is very difficult to maintain constant volume especially in the last two weeks due to radiation enteritis and cystitis.Materials and methodsHistologically proven 35 cervical cancer patients treated with concurrent chemoradiation in a tertiary care center were the subjects of this prospective study. Following CT simulation and after every fraction, patients were asked to void urine in a calibrated urine container and the volume was documented. Patients were assessed for the highest grade of radiation enteritis weekly as per common toxicity criteria. The mean voided urine volume was correlated with the radiation enteritis.ResultsThe mean urine volume at planning CT scan was 295.85±300ml (SD) with a range of 75–650. At the end of treatment, it was reduced to 233.14±250ml (range 50–400ml), a reduction by 21% (p<0.001). The maximum grade of enteritis was grade I (11%), II (11.4%), III (3–29%) in week 1,2 and 3–5, respectively with a p value of <0.001. A mean urine volume of 230ml was associated with grade III enteritis in the third week.ConclusionsUrine output volume measured using a calibrated container is a simple, efficient and practical method to monitor bladder distension thereby reducing enteritis in cervical cancer patients treated with concurrent chemoradiation.



http://ift.tt/2phGDpG

Dosimetry of the left anterior descending coronary artery in left breast cancer patients treated with postoperative external radiotherapy

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Adela Poitevin-Chacón, Jessica Chávez-Nogueda, Rubí Ramos Prudencio, Alejandro Calvo Fernández, Alejandro Rodríguez Laguna, Jesús Linares, Julio César Martínez
AimTo evaluate the dose distribution to the left anterior descending (LAD) coronary artery in patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT).BackgroundPostoperative radiotherapy may increase the risk of heart disease, particularly in patients with left-sided breast cancer. Clinical data on doses to the LAD are limited.Materials and methodsRetrospective study of 14 patients who underwent postoperative 3DCRT for left breast cancer in 2014. All data were retrieved from medical records. Means, medians, ranges, and percentages were calculated.ResultsThe mean dose to the LAD in patients with V25<1% was 0.12cGy. Dmean, Dmax and V25 to the heart were, respectively, 3.7Gy (range, 0.9–4.18), 40.3Gy (9.28–62.9), and 1.59cGy. The mean Dmean and Dmax values in the sample were 9.71Gy and 33.2Gy, respectively. The maximum dose to the LAD (D2%) ranged from 3.66 to 53.01Gy. Due to the spacing of the CT slices (5mm), it was not possible to completely contour the entire artery. The mean dose to the heart (3.3Gy) was considered acceptable.ConclusionsThe maximum dose to the LAD was as high as 53Gy, suggesting an increased risk of cardiac morbidity. This study underscores the value of contouring the LAD and the value of the breath hold technique to reduce maximum cardiac doses. Smaller CT cuts (2.5mm) can improve contouring. Larger studies with long-term follow up are needed to determine the radiation tolerance dose for the LAD.



http://ift.tt/2FHWk3N

Thymic tumors and results of radiotherapy

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Sureyya Sarıhan, Ahmet Sami Bayram, Cengiz Gebitekin, Omer Yerci, Deniz Sıgırlı
AimThe aim of this study was to evaluate thymic epithelial tumors (TETs) for treatment outcomes and prognostic factors on survival.BackgroundTETs are very rare neoplasms and multidisciplinary approach is recommended according to prognostic factors.Materials and methodsBetween 1995 and 2013, 31 patients were treated with median 5400cGy (range: 1620–6596cGy) radiotherapy (RT). Eleven patients received adjuvant or concurrent chemotherapy. There were 25 thymomas, 4 thymic carcinomas and 2 thymic neuroendocrin carcinomas. According to Masaoka, staging and WHO classification, cases were divided to good (n: 10), moderate (n: 9) and poor (n: 12) prognostic risk groups. Survival was calculated from diagnosis.ResultsIn January 2016, 22 cases were alive with median 51.5 months (range: 2–170.5) follow-up. Recurrences were observed in 29% of patients in median 29.5 months (range: 6.5–105). Local control, mean overall (OS) and disease-free survival (DFS) rates were 86%, 119 and 116 months, respectively. There was a significant difference for R0 vs. R+ resection (81% vs. 43%, p=0.06, and 69% vs. 46%, p=0.05), Masaoka stage I–II vs. III–IV (75% vs. 52%, p=0.001, and 75% vs. 37%, p<0.001), and also prognostic risk groups (100% vs. 89% vs. 48%, p=0.003, and 100% vs. 87% vs. 27%, p=0.004) in terms of 5-year OS and DFS, respectively.ConclusionIn our study, prognostic risk stratification was shown to be a significant predictor of survival. There is a need to investigate subgroups that may or may not benefit from adjuvant RT.



http://ift.tt/2HHjOSS

Accuracy evaluation of distance inverse square law in determining virtual electron source location in Siemens Primus linac

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Hamid Shafaei Douk, Mahmoud Reza Aghamiri, Mahdi Ghorbani, Bagher Farhood, Mohsen Bakhshandeh, Hamid Reza Hemmati
AimThe aim of this study is to evaluate the accuracy of the inverse square law (ISL) method for determining location of virtual electron source (SVir) in Siemens Primus linac.BackgroundSo far, different experimental methods have presented for determining virtual and effective electron source location such as Full Width at Half Maximum (FWHM), Multiple Coulomb Scattering (MCS), and Multi Pinhole Camera (MPC) and Inverse Square Law (ISL) methods. Among these methods, Inverse Square Law is the most common used method.Materials and methodsFirstly, Siemens Primus linac was simulated using MCNPX Monte Carlo code. Then, by using dose profiles obtained from the Monte Carlo simulations, the location of SVir was calculated for 5, 7, 8, 10, 12 and 14MeV electron energies and 10cm×10cm, 15cm×15cm, 20cm×20cm and 25cm×25cm field sizes. Additionally, the location of SVir was obtained by the ISL method for the mentioned electron energies and field sizes. Finally, the values obtained by the ISL method were compared to the values resulted from Monte Carlo simulation.ResultsThe findings indicate that the calculated SVir values depend on beam energy and field size. For a specific energy, with increase of field size, the distance of SVir increases for most cases. Furthermore, for a special applicator, with increase of electron energy, the distance of SVir increases for most cases. The variation of SVir values versus change of field size in a certain energy is more than the variation of SVir values versus change of electron energy in a certain field size.ConclusionAccording to the results, it is concluded that the ISL method can be considered as a good method for calculation of SVir location in higher electron energies (14MeV).



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Editorial board

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2





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High accuracy dosimetry with small pieces of Gafchromic films

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Ryszard Dąbrowski, Izabela Drozdyk, Paweł Kukołowicz
AimTo investigate the influence of several factors on the accuracy of dose measurements and feasibility of application of small Gafchromic detectors for postal audit.BackgroundOur experience showed that precision of dose measurements with small pieces of Gafchromic films may be significantly improved.Materials and methodsGafchromic films with dimensions of 1×1, 2×2 and 3×3cm² were exposed to 6MV X-rays at dose levels of 50cGy-210cGy. The single- and multichannel methods (MM) were used for dose measurements. Detectors were scanned with an Epson V750PRO flatbed colour scanner. For 1×1 and larger detector sizes, separate calibration curves were established. The influence of the following factors was investigated: the heterogeneity of Gafchromic detectors group for single- and MM, ambient thermal detector conditions, the dose delivered on the measurement accuracy, application of two separate calibration curves for the smallest and larger pieces of films.ResultsThe MM improves significantly the precision of dose measurement. The uncertainty attributed to detector active layer differences and scanner instabilities was about 1cGy (1 StDev) regardless of dose and detector size. The ambient temperature of the environment in which films were stored after irradiation influenced the dose reading. Significant difference of transmission for detectors sized 1×1 and 2×2cm² was observed. The maximal difference between applied dose and dose reading performed was 1.1%.ConclusionsThe MM with a scaling protocol leads to a very high precision of dose measurements. The ambient thermal detector environment causes significant changes of measured signal. The detector size has relevant impact on dose reading.



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Assessment of the Monitor Unit Objective tool for VMAT in the Eclipse treatment planning system

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Sara Jiménez-Puertas, David Sánchez-Artuñedo, Marcelino Hermida-López
AimThis work aims to achieve the highest possible monitor units (MU) reduction using the MU Objective tool included in the Eclipse treatment planning system, while preserving the plan quality.BackgroundThe treatment planning system Eclipse (Varian Medical Systems, Palo Alto, CA) includes a control mechanism for the number of monitor units of volumetric modulated arc therapy (VMAT) plans, named the MU Objective tool.Material and methodsForty prostate plans, 20 gynecological plans and 20 head and neck plans designed with VMAT were retrospectively studied. Each plan (base plan) was optimized without using the MU Objective tool, and it was re-optimized with different values of the Maximum MU (MaxMU) parameter of the MU Objective tool. MU differences were analyzed with a paired samples t-test and changes in plan quality were assessed with a set of parameters for OARs and PTVs.ResultsThe average relative MU difference (ΔMU¯) considering all treatment sites, was the highest when MaxMU=400 (−4.2%, p<0.001). For prostate plans, the lowest ΔMU¯ was obtained (−3.7%, p<0.001). For head and neck plans ΔMU¯ was −7.3% (p<0.001) and for gynecological plans ΔMU¯ was 7.0% (p=0.002). Although similar MU reductions were observed for both sites, for some gynecological plans maximum differences were greater than 10%. All the assessed parameters for PTVs and OARs sparing showed average differences below 2%.ConclusionFor the three studied clinical sites, establishing MaxMU=400 led to the optimum MU reduction, maintaining the original dose distribution and dosimetric parameters practically unaltered.



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Extended localization and adaptive dose calculation using HU corrected cone beam CT: Phantom study

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): K Mohamathu Rafic, S Amalan, B S Timothy Peace, B Paul Ravindran
Background and aimThe practicability of computing dose calculation on cone beam CT (CBCT) has been widely investigated. In most clinical scenarios, the craniocaudal scanning length of CBCT is found to be inadequate for localization. This study aims to explore extended tomographic localization and adaptive dose calculation strategies using Hounsfield unit (HU) corrected CBCT image sets.Materials and methodsPlanning CT (pCT) images of the Rando phantom (T12-to-midthigh) were acquired with pelvic-protocol using Biograph CT-scanner. Similarly, half-fan CBCT were acquired with fixed parameters using Clinac2100C/D linear accelerator integrated with an on-board imager with 2-longitudinal positions of the table. For extended localization and dose calculation, two stitching strategies viz., one with "penumbral-overlap" (S1) and the other with "no-overlap" (S2) and a local HU-correction technique were performed using custom-developed MATLAB scripts. Fluence modulated treatment plans computed on pCT were mapped with stitched CBCT and the dosimetric analyses such as dose-profile comparison, 3D-gamma (γ) evaluation and dose-volume histogram (DVH) comparison were performed.ResultsLocalizing scanning length of CBCT was extended by up to 15cm and 16cm in S1 and S2 strategies, respectively. Treatment plan mapping resulted in minor variations in the volumes of delineated structures and the beam centre co-ordinates. While the former showed maximum variations of −1.4% and −1.6%, the latter showed maximum of 1.4mm and 2.7mm differences in anteroposterior direction in S1 and S2 protocols, respectively. Dosimetric evaluations viz., dose profile and DVH comparisons were found to be in agreement with one another. In addition, γ-evaluation results showed superior pass-rates (≥98.5%) for both 3%/3mm dose-difference (DD) and distance-to-agreement (DTA) and 2%/2mm DD/DTA criteria with desirable dosimetric accuracy.ConclusionCone beam tomographic stitching and local HU-correction strategies developed to facilitate extended localization and dose calculation enables routine adaptive re-planning while circumventing the need for repeated pCT.



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Does ITV vaginal procedure ensure dosimetric coverage during IMRT of post-operative gynaecological tumours without instructions concerning rectal filling?

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Ramona Verges, Alexandra Giraldo, Alejandro Seoane, Elisabet Toral, M. Carmen Ruiz, Ariadna Pons, Jordi Giralt
AimTo find out whether the internal target volume (ITV) vaginal procedure ensures dosimetric coverage during intensity-modulated radiation therapy (IMRT) of post-operative gynaecological tumours without instructions on rectal filling.BackgroundThe ITV vaginal procedure does not necessarily include all movements of the bladder, and does not include changes in the rectal volume. We should know if the vaginal ITV is a useful tool in maintaining CTV coverage during treatment.Materials and methodsA retrospective analysis of 24 patients treated between July 2012 and July 2014 with adjuvant IMRT for gynaecological cancer. All patients underwent empty and full bladder CT on simulation (CT-planning) and three weeks later (CT-control). ITV displacement was measured and the 3D vector was calculated. ITV coverage was then evaluated by comparing the volume covered by the prescription isodose on both CT's. Patients were asked to have full bladder but they did not follow recommendations for the rectum.ResultsThe mean 3D vector was 0.64±0.32cm (0.09–1.30). The mean ITV coverage loss was 5.8±5.7% (0–20.2). We found a significant positive correlation between the 3D vector and the loss of coverage (Pearson correlation, r=0.493, 95% CI: 0.111–0.748, p=0.0144). We did not find any significant correlation between the bladder and rectal parameters with the 3D vector and loss of dosimetric coverage. We found a trend between the maximum rectal diameter in CT-planning and 3D vector (r=0.400, 95% CI: −0.004 to 0.692, p=0.0529).ConclusionITV vaginal procedure contributed to ensuring a good dose coverage without instructions on rectal filling.



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Adenomas – Genetic factors in colorectal cancer prevention

Publication date: March–April 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 2
Author(s): Kycler Witold, Kubiak Anna, Trojanowski Maciej, Janowski Jakub
Colorectal cancer is the second most common type of cancer both in Europe and Poland. During the last 30 years more than a 3-fold increase has been observed in Poland due to environmental and genetic factors. Almost all colorectal malignancies are related to the formation and malignant transformation of colorectal dysplasia and adenoma. Efforts aiming to decrease the number of colorectal cancer deaths are focused on the disease early detection. Genetic diagnosis for hereditary syndromes predisposing to colorectal cancer has been developed and is a part of the routine treatment. Most cancers are sporadic. They often develop from polyps in the colon. In addition to the genetic events described in the 1990s, showing the adenoma transformation into carcinoma that has been a prime example of malignant transformation for a long time, there are also other possibilities of neoplastic transformation. The recognition of colorectal cancer risk factors make sense as their nature is lifestyle- and diet-related. In this review paper those risk factors are presented and the prevention of colorectal cancer is discussed taking into account genetic factors.



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Editorial board

Publication date: January–February 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 1





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Energy spectrum and dose enhancement due to the depth of the Lipiodol position using flattened and unflattened beams

Publication date: January–February 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 1
Author(s): Daisuke Kawahara, Shuichi Ozawa, Akito Saito, Tomoki Kimura, Tatsuhiko Suzuki, Masato Tsuneda, Sodai Tanaka, Kazunari Hioki, Takeo Nakashima, Yoshimi Ohno, Yuji Murakami, Yasushi Nagata
AimLipiodol was used for stereotactic body radiotherapy combining trans arterial chemoembolization. Lipiodol used for tumour seeking in trans arterial chemoembolization remains in stereotactic body radiation therapy. In our previous study, we reported the dose enhancement effect in Lipiodol with 10× flattening-filter-free (FFF). The objective of our study was to evaluate the dose enhancement and energy spectrum of photons and electrons due to the Lipiodol depth with flattened (FF) and FFF beams.MethodsFF and FFF for 6MV beams from TrueBeam were used in this study. The Lipiodol (3×3×3cm³) was located at depths of 1, 3, 5, 10, 20, and 30cm in water. The dose enhancement factor (DEF) and the energy fluence were obtained by Monte Carlo calculations of the particle and heavy ion transport code system (PHITS).ResultsThe DEFs at the centre of Lipiodol with the FF beam were 6.8, 7.3, 7.6, 7.2, 6.1, and 5.7% and those with the FFF beam were 20.6, 22.0, 21.9, 20.0, 12.3, and 12.1% at depths of 1, 3, 5, 10, 20, and 30cm, respectively, where Lipiodol was located in water. Moreover, spectrum results showed that more low-energy photons and electrons were present at shallow depth where Lipiodol was located in water. The variation in the low-energy spectrum due to the depth of the Lipiodol position was more explicit with the FFF beam than that with the FF beam.ConclusionsThe current study revealed variations in the DEF and energy spectrum due to the depth of the Lipiodol position with the FF and FFF beams. Although the FF beam could reduce the effect of energy dependence due to the depth of the Lipiodol position, the dose enhancement was overall small. To cause a large dose enhancement, the FFF beam with the distance of the patient surface to Lipiodol within 10cm should be used.



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