The involvement of E6, p53, p16, MDM2 and Gal-3 in the clinical outcome of patients with cervical cancer.

The involvement of E6, p53, p16, MDM2 and Gal-3 in the clinical outcome of patients with cervical cancer.

Oncol Lett. 2017 Oct;14(4):4467-4476

Authors: Stiasny A, Freier CP, Kuhn C, Schulze S, Mayr D, Alexiou C, Janko C, Wiest I, Dannecker C, Jeschke U, Kost BP

Abstract
High-risk human papilloma virus (HPV) is the leading cause of cervical cancer. HPV oncogenes are responsible for the development of malignancy, and the E6 oncoprotein that HPV expresses induces the degradation of tumour suppressor protein p53 (p53). This degradation leads to the upregulation of p16; however, unidentified proteins may also serve a role in the development and progression of cervical cancer. Therefore, the aim of the present study was to analyse the expression levels of E6, p53, p16, MDM2 proto-oncogene (MDM2) and galectin-3 (gal-3) in cervical cancer specimens. A total of 250 cervical cancer tissue slides were used. The expression of E6, p53, p16, MDM2 and gal-3 was analysed with immunohistochemical methods and a semi-quantitative scoring. SPSS software was used for the statistical evaluation of staining results and survival analysis of patients with cervical cancer. Cervical cancer specimens demonstrated significantly increased E6 staining with advanced T-status and increased International Federation of Gynecology and Obstetrics classification. E6, p53 and p16 demonstrated significantly different expression levels in squamous epithelial tissue compared with adenocarcinomas. MDM2 and gal-3 demonstrated positively correlated expression levels in cervical cancer. In addition, gal-3 expression was correlated with poor prognosis in p16-negative cases. A negative correlation between the expression of E6 and a mutated form of p53 was also identified in cervical cancer. p53 mutation was demonstrated to be common in cervical cancer, and gal-3 and MDM2 appeared to act in a combined manner in this type of tumour. As gal-3 is overexpressed in the cervical cancer tissue of patients with poor prognosis, the use of gal-3 inhibitors should be investigated in future studies.

PMID: 29085443 [PubMed]

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Peripheral Leukocytosis Is Inversely Correlated with Intratumoral CD8+ T-Cell Infiltration and Associated with Worse Outcome after Chemoradiotherapy in Anal Cancer.

Peripheral Leukocytosis Is Inversely Correlated with Intratumoral CD8+ T-Cell Infiltration and Associated with Worse Outcome after Chemoradiotherapy in Anal Cancer.

Front Immunol. 2017;8:1225

Authors: Martin D, Rödel F, Winkelmann R, Balermpas P, Rödel C, Fokas E

Abstract
Peripheral blood leukocytosis has been implicated in promoting tumor progression leading to worse survival, but the mechanisms behind this phenomenon remain unexplored. Here, we examined the prognostic role of pretreatment white blood cell (WBC) count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL) and myeloperoxidase+ tumor-associated neutrophils (TANs) in patients with anal squamous cell carcinoma (ASCC) treated with definitive chemoradiotherapy (CRT). After a median follow-up of 26 months, leukocytosis correlated with advanced T-stage (p < 0.001) and N-stage (p < 0.001), and predicted for worse distant-metastasis-free survival (p = 0.006), disease-free-survival (DFS, p = 0.029), and overall survival (p = 0.013). Importantly, leukocytosis was associated with a lower intraepithelial CD8+ TIL density (p = 0.014), whereas low CD8+ TIL expression in the intraepithelial compartment was associated with worse DFS (p = 0.028). Additionally, high TAN expression in the peritumoral compartment was associated with a significantly lower density of CD8+ TIL (p = 0.039), albeit, TAN expression lacked prognostic value. In conclusion, leukocytosis constitutes an important prognostic marker in ASCC patients treated with CRT. In conjunction with intratumoral TIL and TAN, these data provide for the first time important insight on the correlation of peripheral blood leukocytosis with the intratumoral immune contexture and could be relevant for future patient stratification using immunotherapies in ASCC.

PMID: 29085358 [PubMed]

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Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions.

Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions.

Nat Commun. 2017 Oct 30;8(1):1197

Authors: Dalin MG, Katabi N, Persson M, Lee KW, Makarov V, Desrichard A, Walsh LA, West L, Nadeem Z, Ramaswami D, Havel JJ, Kuo F, Chadalavada K, Nanjangud GJ, Ganly I, Riaz N, Ho AL, Antonescu CR, Ghossein R, Stenman G, Chan TA, Morris LGT

Abstract
Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer.

PMID: 29084941 [PubMed - in process]

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Cord Blood Banking for Potential Future Transplantation.

Cord Blood Banking for Potential Future Transplantation.

Pediatrics. 2017 Oct 30;:

Authors: Shearer WT, Lubin BH, Cairo MS, Notarangelo LD, SECTION ON HEMATOLOGY/ONCOLOGY, SECTION ON ALLERGY AND IMMUNOLOGY

Abstract
This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that operate or have a relationship with cord blood banking programs. The information on all aspects of cord blood banking gathered in this policy statement will facilitate parental choice for public or private cord blood banking.

PMID: 29084832 [PubMed - as supplied by publisher]

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Long-Term Natural Course of Small Nonfunctional Pancreatic Neuroendocrine Tumors in MEN1-Results From the Dutch MEN1 Study Group.

Related Articles

Long-Term Natural Course of Small Nonfunctional Pancreatic Neuroendocrine Tumors in MEN1-Results From the Dutch MEN1 Study Group.

J Clin Endocrinol Metab. 2017 Oct 01;102(10):3795-3805

Authors: Pieterman CRC, de Laat JM, Twisk JWR, van Leeuwaarde RS, de Herder WW, Dreijerink KMA, Hermus ARMM, Dekkers OM, van der Horst-Schrivers ANA, Drent ML, Bisschop PH, Havekes B, Borel Rinkes IHM, Vriens MR, Valk GD

Abstract
Background: Pancreatic neuroendocrine tumors (pNETs) are highly prevalent in patients with multiple endocrine neoplasia type 1 (MEN1), and metastatic disease is an important cause of MEN1-related mortality. Especially small nonfunctional (NF) pNETs pose a challenge to the treating physician and more information is needed regarding their natural course. We assessed long-term natural history of small NF-pNETs and its modifiers in the Dutch MEN1 population.
Patients and Methods: Retrospective longitudinal observational cohort study of patients with small (<2 cm) NF-pNETs from the Dutch national MEN1 database, which includes >90% of the Dutch MEN1 population. Modifiers of long-term natural course were analyzed using linear mixed-models analysis.
Results: Growth rate of the 115 included small NF-pNETs from 99 patients was slow (0.4 mm/y; 95% confidence interval, 0.15 to 0.59). Seventy percent of the tumors was stable and a subgroup of 30% of the tumors was growing (1.6 mm/y; 95% confidence interval, 1.1 to 2.0). No differences in clinical characteristics were identified between growing and stable tumors. Within the subgroup of growing tumors, germline missense mutations were significantly associated with accelerated growth compared with nonsense and frameshift mutations.
Conclusion: The majority of small NF-pNETs are stable at long-term follow-up, irrespective of the underlying MEN1 genotype. A subgroup of tumors is slowly growing but cannot be identified on clinical grounds. In this subgroup, tumors with missense mutations exhibited faster growth. Additional events appear necessary for pNETs to progress. Future studies should be aimed at identifying these molecular driving events, which could be used as potential biomarkers.

PMID: 28938468 [PubMed - indexed for MEDLINE]

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Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

Brain. 2017 Nov 01;140(11):2838-2850

Authors: Wang H, Salter CG, Refai O, Hardy H, Barwick KES, Akpulat U, Kvarnung M, Chioza BA, Harlalka G, Taylan F, Sejersen T, Wright J, Zimmerman HH, Karakaya M, Stüve B, Weis J, Schara U, Russell MA, Abdul-Rahman OA, Chilton J, Blakely RD, Baple EL, Cirak S, Crosby AH

Abstract
The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection.

PMID: 29088354 [PubMed - in process]

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Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

Related Articles

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

Cancer Cell. 2017 Oct 09;32(4):520-537.e5

Authors: Mackay A, Burford A, Carvalho D, Izquierdo E, Fazal-Salom J, Taylor KR, Bjerke L, Clarke M, Vinci M, Nandhabalan M, Temelso S, Popov S, Molinari V, Raman P, Waanders AJ, Han HJ, Gupta S, Marshall L, Zacharoulis S, Vaidya S, Mandeville HC, Bridges LR, Martin AJ, Al-Sarraj S, Chandler C, Ng HK, Li X, Mu K, Trabelsi S, Brahim DH, Kisljakov AN, Konovalov DM, Moore AS, Carcaboso AM, Sunol M, de Torres C, Cruz O, Mora J, Shats LI, Stavale JN, Bidinotto LT, Reis RM, Entz-Werle N, Farrell M, Cryan J, Crimmins D, Caird J, Pears J, Monje M, Debily MA, Castel D, Grill J, Hawkins C, Nikbakht H, Jabado N, Baker SJ, Pfister SM, Jones DTW, Fouladi M, von Bueren AO, Baudis M, Resnick A, Jones C

Abstract
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

PMID: 28966033 [PubMed - indexed for MEDLINE]

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Development and evaluation of finasteride loaded ethosomes for targeting to the pilosebaceous unit.

Development and evaluation of finasteride loaded ethosomes for targeting to the pilosebaceous unit.

Artif Cells Nanomed Biotechnol. 2017 Oct 31;:1-10

Authors: Wilson V, Siram K, Rajendran S, Sankar V

Abstract
Androgenetic alopecia, a major cause for baldness, is caused by the deposition of dihydrotestosterone (DHT) at the androgen receptors present in the pilosebaceous unit (PSU). Finasteride (FIN) is a potent 5α-reductase inhibitor capable of preventing the conversion of testosterone to DHT. But, its oral administration in males causes infertility. An attempt was made to prepare ethosomes of FIN with a size range 100-300 nm to enhance its delivery to the PSU. Finasteride loaded ethosomes (FES) were prepared using an ultra-probe sonicator and characterized for its size, morphology, surface charge and entrapment efficiency. The ability of FES to permeate across rat skin and frontal scalp skin of human cadaver was also evaluated. The spherical shaped ethosomes of different batches were in the size range of 107.8 ± 2.50 to 220.4 ± 6.92 nm and showed good permeation across rat skin and frontal scalp skin of human cadaver when compared to the unencapsulated FIN. The results portrayed the ability of FES to permeate across the stratum corneum to reach the PSU of the hair follicle. Although additional use of permeation enhancer increases the permeation of FIN across the skin, its addition may not be a favourable option for the deposition of ethosomes in the PSU.

PMID: 29087225 [PubMed - as supplied by publisher]

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Design, characterization and antimalarial efficacy of PEGylated galactosylated nano lipid carriers of primaquine phosphate.

Design, characterization and antimalarial efficacy of PEGylated galactosylated nano lipid carriers of primaquine phosphate.

Artif Cells Nanomed Biotechnol. 2017 Oct 31;:1-21

Authors: Baruah UK, Gowthamarajan K, Ravisankar V, Karri VVSR, Simhadri PK, Singh V, Babu PP

Abstract
This study was aimed to design and optimize primaquine phosphate (PQ) loaded nanostructured lipid carriers (NLCs) using response surface methodology. The optimized NLCs were evaluated for various physical and morphological characterizations. The in vitro studies for drug release showed that PQ loaded NLCs had a sustained release up to 72 h and the stability studies confirmed that the PQ-NLCs were stable for 90 d at 4 °C and 25 °C. In vitro erythrocyte toxicity revealed that PQ-NLCs were less toxic than the pure drug. In vitro parasite growth inhibition assay showed an IC50 value of 71.11 ± 6.47 ng/ml for the 3D7 Plasmodium falciparum (CQ sensitive) strain and 263.86 ± 5.68 ng/ml for RKL9 P. falciparum (CQ resistant) strain for the PQ-NLCs. Enhanced parasitaemia suppression of 99.46% at 2 mg/kg/d, a better suppression of parasitaemia of about 28% more than pure drug and a higher survivality rate of 66.66% even after the 35th day was observed for the PQ loaded NLCs. Also from the comparative fluorescent imaging study, it was clearly observed that accumulation of PQ-NLCs in the liver was more that of the pure drug. These results clearly indicated that the limitations of antimalarial drug PQ can be overcomed by loading it into the NLCs.

PMID: 29087218 [PubMed - as supplied by publisher]

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Impact of Close and Positive Margins in Transoral Laser Microsurgery for Tis-T2 Glottic Cancer.

Impact of Close and Positive Margins in Transoral Laser Microsurgery for Tis-T2 Glottic Cancer.

Front Oncol. 2017;7:245

Authors: Fiz I, Mazzola F, Fiz F, Marchi F, Filauro M, Paderno A, Parrinello G, Piazza C, Peretti G

Abstract
INTRODUCTION: Transoral laser microsurgery (TLM) represents one of the most effective treatment strategies for Tis-T2 glottic squamous cell carcinomas (SCC). The prognostic influence of close/positive margins is still debated, and the role of narrow band imaging (NBI) in their intraoperative definition is still to be validated on large cohort of patients. This study analyzed the influence of margin status on recurrence-free survival (RFS) and disease-specific survival (DSS).
METHODS: We retrospectively studied 507 cases of pTis-T1b (Group A) and 127 cases of pT2 (Group B) glottic SCC. We identified the following margin status: negative (n = 232), close superficial (n = 79), close deep (CD) (n = 35), positive single superficial (n = 146), positive multiple superficial (n = 94), and positive deep (n = 48) and analyzed their impact on RFS and DSS. Close margins were defined by tumor-margin distance <1 mm. Pre-TLM margins were defined by white light in 323 patients, whereas NBI was employed in 311 patients.
RESULTS: In Group A, DSS and RFS were reduced in positive multiple superficial and positive deep margins (DSS = 96.1 and 97%, both p < 0.05; RFS = 72%, p < 0.001 and 75.8%, p < 0.01). In Group B, DSS was reduced in positive multiple superficial margins (82.4%, p < 0.05). RFS was reduced in positive single superficial, positive multiple superficial, and positive deep margins (62.5, 41.2, and 53.3%, p < 0.01). In the entire population, RFS was reduced in CD margins (77.1%, p < 0.05). Use of NBI led to improvement in RFS and DSS.
CONCLUSION: The study indicates that close and positive single superficial margins do not affect DSS. By contrast, all types of margin positivity predict the occurrence of relapses, albeit with different likelihood, depending on stage/margin type. CD margins should be considered as a single risk factor. Use of NBI granted better intraoperative margins definition.

PMID: 29085805 [PubMed]

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Utilization of Patient-Reported Outcomes to Guide Symptom Management during Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer.

Utilization of Patient-Reported Outcomes to Guide Symptom Management during Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer.

Front Oncol. 2017;7:227

Authors: Danner M, Hung MY, Yung TM, Ayoob M, Lei S, Collins BT, Suy S, Collins SP

Abstract
INTRODUCTION: Utilization of patient-reported outcomes (PROs) to guide symptom management during radiation therapy is increasing. This study focuses on the use of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) as a tool to assess urinary and bowel bother during stereotactic body radiation therapy (SBRT) and its utility in guiding medical management.
METHODS: Between September 2015 and January 2017, 107 patients with clinically localized prostate cancer were treated with 35-36.25 Gy via SBRT in five fractions. PROs were assessed using EPIC-CP 1 h prior to the first fraction and after each subsequent fraction. Symptom management medications were prescribed based on the physician clinical judgment or if patients reported a moderate to big problem. Clinical significance was assessed using a minimally important difference of 1/2 SD from baseline score.
RESULTS: A median baseline EPIC-CP urinary symptom score of 1.5 significantly increased to 3.7 on the day of the final treatment (p < 0.0001). Prior to treatment, 9.3% of men felt that their overall urinary function was a moderate to big problem that increased to 28% by the end of the fifth treatment. A median baseline EPIC-CP bowel symptom score of 0.3 significantly increased to 1.4 on the day of the final treatment (p < 0.0001). Prior to treatment, 1.9% of men felt that their overall bowel function was a moderate to big problem that increased to 3.7% by the end of the fifth treatment. The percentage of patients requiring an increased dose of alpha-antagonist increased to 47% by the end of treatment, and an additional 28% of patients required a short steroid taper to manage moderate to big urinary problems. Similarly, the percentage of patients requiring antidiarrheals reached 12% by the fifth treatment.
CONCLUSION: During the course of SBRT, an increasing percentage of patients experienced clinically significant symptoms many of which required medical management. Monitoring patient symptoms during treatment allowed for prompt detection and management of acute urinary and bowel symptoms. The usage of symptom management medications was high in this study compared to historical controls and may be due to increased physician awareness of moderate to big patient problems.

PMID: 29085804 [PubMed]

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AEROSOL SIZE DISTRIBUTION IN URANIUM PROCESSING FACILITY FOR APPLICATION IN THE ASSESSMENT OF INTERNAL EXPOSURE.

AEROSOL SIZE DISTRIBUTION IN URANIUM PROCESSING FACILITY FOR APPLICATION IN THE ASSESSMENT OF INTERNAL EXPOSURE.

Radiat Prot Dosimetry. 2017 Oct 27;:1-6

Authors: Shailesh M, Das T, Prabhat M, Kolekar RV, Gopalakrishnan RK

Abstract
In circumstances of inhalation exposure the radiotoxicity of radionuclide depends on the fractional deposition of inhaled activity, which is governed by the aerodynamic characteristics of the particles. Although International Commission on Radiological Protection (ICRP) provides default size distribution parameters for work place aerosols, inhaled aerosol characteristics may be different depending on the physical and chemical conditions of aerosol generation process. The present study is undertaken to determine the particle activity-size distribution during operation of various significant processes of uranium metal production facility of Bhabha Atomic Research Centre (BARC). Activity median aerodynamic diameter (AMAD) and its geometric standard deviation (GSD) were estimated for these process areas for uranium aerosol particles. The AMAD varied from 3.2 to 10.06 µm and GSD ranged from 1.5 to 3.0. Also, the obtained size distribution was tested by Pearson's chi-squared distribution test method to ascertain the assumption that the particle size distribution is best described by log-normal relationship.

PMID: 29088460 [PubMed - as supplied by publisher]

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DESIGN IMPROVEMENT OF A LIQUID-MODERATOR-BASED NEUTRON SPECTROMETER FOR BNCT.

DESIGN IMPROVEMENT OF A LIQUID-MODERATOR-BASED NEUTRON SPECTROMETER FOR BNCT.

Radiat Prot Dosimetry. 2017 Oct 27;:1-4

Authors: Tamaki S, Kusaka S, Sato F, Murata I

Abstract
Boron neutron capture therapy is known to be an effective radiation cancer therapy that requires neutron irradiation. A neutron field generated by an accelerator-based neutron source has various energy spectra, and it is necessary to evaluate the neutron spectrum in the treatment field. However, the method used to measure the neutron spectrum in the treatment field is not well established. Many researchers are making efforts to improve the spectrometers. To solve this problem, we are developing a liquid-moderator-based neutron spectrometer that is based on the same theory as that of the Bonner sphere spectrometer. The spectrometer uses a liquid moderator and absorber. In the present study, we performed a design study to improve the previously developed liquid-moderator-based neutron spectrometer. By carrying out a numerical simulation of the designed new spectrometer, we finally assessed and confirmed the validity of this spectrometer numerically.

PMID: 29088420 [PubMed - as supplied by publisher]

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Evaluation of Additional Track Parameters from Fluorescent Nuclear Track Detectors to Determine the LET of Individual Ions.

Evaluation of Additional Track Parameters from Fluorescent Nuclear Track Detectors to Determine the LET of Individual Ions.

Radiat Prot Dosimetry. 2017 Oct 27;:1-4

Authors: Greilich S, Jansen J, Neuholz A, Stadler A, Mescher H, Klimpki G

Abstract
The measurement of single-track intensity in fluorescence nuclear track detectors can yield relative linear energy transfer (LET)-spectra with small line-width. The absolute determination of LET is, however, currently hampered by the inter-detector variability of crystal coloration and hence detector sensitivity. We therefore investigated the LET response of three additional quantities (average width and the variation of intensity and width along single tracks) using detectors irradiated with mono-energetic ion beams with LETs from 1.5 to 150 keV/μm in alumina. All quantities showed in fact smaller inter-detector variability, but at the same time larger line-width and limited dynamic range as the average intensity along a track. The additional quantities might therefore serve as a helpful complement, but not as a replacement for the current approach.

PMID: 29088413 [PubMed - as supplied by publisher]

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MICRODOSIMETRIC STUDY AT THE CNAO ACTIVE-SCANNING CARBON-ION BEAM.

MICRODOSIMETRIC STUDY AT THE CNAO ACTIVE-SCANNING CARBON-ION BEAM.

Radiat Prot Dosimetry. 2017 Oct 26;:1-5

Authors: Colautti P, Conte V, Selva A, Chiriotti S, Pola A, Bortot D, Fazzi A, Agosteo S, Ciocca M

Abstract
The Italian National Centre for Oncological Hadrontherapy (CNAO) has been treating patients since 2011 with carbon-ion beams using the active-scanning modality. In such irradiation modality, the beam spot, which scans the treatment area, is characterised by very high particle-fluence rates (more than 105 s-1 mm-2). Moreover, the Bragg-peak is only ~1 mm-FWHM. Commercial tissue-equivalent proportional counters (TEPC), like the Far West Technologies LET-½, are large, hence they have limited capability to measure at high counting fluence rates. In this study we have used two home-made detectors, a mini-TEPC 0.81 mm2 in sensitive area and a silicon telescope 0.125 mm2 in sensitive area, to perform microdosimetric measurements in the therapeutic carbon-ion beam of CNAO. A monoenergetic carbon-ion beam of 189.5 ± 0.3 MeV/u scanning a 3 × 3 cm2 area has been used. Spectral differences are visible in the low y-value region, but the mean microdosimetric values, measured with the two detectors, result to be pretty consistent, as well as the microdosimetric spectra in the high y-value region.

PMID: 29087524 [PubMed - as supplied by publisher]

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NEUTRON RADIATION DAMAGE IN CCD CAMERAS AT JOINT EUROPEAN TORUS (JET).

NEUTRON RADIATION DAMAGE IN CCD CAMERAS AT JOINT EUROPEAN TORUS (JET).

Radiat Prot Dosimetry. 2017 Oct 26;:1-6

Authors: Milocco A, Conroy S, Popovichev S, Sergienko G, Huber A

Abstract
The neutron and gamma radiations in large fusion reactors are responsible for damage to charged couple device (CCD) cameras deployed for applied diagnostics. Based on the ASTM guide E722-09, the 'equivalent 1 MeV neutron fluence in silicon' was calculated for a set of CCD cameras at the Joint European Torus. Such evaluations would be useful to good practice in the operation of the video systems.

PMID: 29087509 [PubMed - as supplied by publisher]

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DEVELOPMENT OF A MULTIMODAL MONTE CARLO BASED TREATMENT PLANNING SYSTEM.

DEVELOPMENT OF A MULTIMODAL MONTE CARLO BASED TREATMENT PLANNING SYSTEM.

Radiat Prot Dosimetry. 2017 Oct 26;:1-5

Authors: Kumada H, Takada K, Sakurai Y, Suzuki M, Takata T, Sakurai H, Matsumura A, Sakae T

Abstract
To establish boron neutron capture therapy (BNCT), the University of Tsukuba is developing a treatment device and peripheral devices required in BNCT, such as a treatment planning system. We are developing a new multimodal Monte Carlo based treatment planning system (developing code: Tsukuba Plan). Tsukuba Plan allows for dose estimation in proton therapy, X-ray therapy and heavy ion therapy in addition to BNCT because the system employs PHITS as the Monte Carlo dose calculation engine. Regarding BNCT, several verifications of the system are being carried out for its practical usage. The verification results demonstrate that Tsukuba Plan allows for accurate estimation of thermal neutron flux and gamma-ray dose as fundamental radiations of dosimetry in BNCT. In addition to the practical use of Tsukuba Plan in BNCT, we are investigating its application to other radiation therapies.

PMID: 29087501 [PubMed - as supplied by publisher]

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A scoping review of the working alliance in acquired brain injury rehabilitation.

A scoping review of the working alliance in acquired brain injury rehabilitation.

Disabil Rehabil. 2017 Oct 31;:1-9

Authors: Stagg K, Douglas J, Iacono T

Abstract
PURPOSE: The aim was to review the empirical literature to determine the nature and breadth of research into the working alliance in acquired brain injury (ABI) rehabilitation.
METHODS: A scoping review was conducted, beginning with a systematic search of relevant databases using key search terms. Studies with a focus on the role of the working alliance in shaping rehabilitation outcomes, and factors influencing perceptions of the working alliance were included and key information extracted.
RESULTS: A total of 10 quantitative studies met inclusion criteria. In most studies, ratings of the working alliance were compared with other process variables or outcome measures. The working alliance was linked to positive activity and participation outcomes, including return to work, school, and driving. Client related factors such as age, level of education and approach to rehabilitation tasks were associated with client and therapist perceptions of the working alliance.
CONCLUSIONS: The working alliance emerged as a complex process that interacts with many factors and processes at play in the rehabilitation environment. Notwithstanding the limitations of the research base, findings indicate that enhancement of the working alliance may indeed influence rehabilitation outcomes. Allowing time for the development of the working alliance, and consideration of factors such as therapist skill, may support therapists to strengthen their alliances in ABI rehabilitation. Implications for Rehabilitation Allowing time for the development of the working alliance has the potential to enhance the alliance and thereby influence rehabilitation outcomes. Factors such as the client's age and level of education may influence the strength of the working alliance, and hence, awareness of these factors may assist clinicians in maintaining strong alliances with all clients. A strong working alliance is possible in the presence of client cognitive impairment, however, the skill of the therapist may be important in managing the potential impact of cognitive impairment on the working alliance.

PMID: 29084474 [PubMed - as supplied by publisher]

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Development of the assisting hand assessment for adults following stroke: a Rasch-built bimanual performance measure.

Development of the assisting hand assessment for adults following stroke: a Rasch-built bimanual performance measure.

Disabil Rehabil. 2017 Oct 31;:1-9

Authors: Krumlinde-Sundholm L, Lindkvist B, Plantin J, Hoare B

Abstract
AIMS: To describe the development of a new test of bimanual performance for adults following Stroke, the Adult-Assisting Hand Assessment Stroke, and to report the evidence of internal and external validity.
METHODS: Scale development included: (i) establishing the test situation; (ii) constructing test items; (iii) evaluating internal construct validity by use of Rasch measurement analysis on 144 assessments of adults with hemiparesis, mean age 53 years (SD11.45); and (iv) investigating external validity by correlation to the Jebsen and Taylor Test of Hand Function and the ABILHAND Stroke.
RESULTS: The Adult-Assisting Hand Assessment Stroke scale, scored on 19 items using a four-point rating scale, provided a valid measure of bimanual performance. The rating scale structure, goodness of fit, and principal component analysis demonstrated evidence of a unidimensional construct. The strong reliability and high person separation ratio indicated high probability for the scale to be responsive to change. Correlation to outcomes of the Jebsen and Taylor Test of Hand Function and the ABILHAND Stroke indicated strong external validity.
CONCLUSION: Using two hands together is a critical aspect for performance of most daily life tasks. However, assessments of hand function commonly focus on measuring aspects of unimanual function. The Adult-Assisting Hand Assessment Stroke has the potential to contribute new and clinically important knowledge to stroke rehabilitation by providing an observation-based valid functional measure of bimanual performance. Implications for rehabilitation Hand function assessments commonly focus on unimanual aspects, although the use of two hands together is critical to perform most daily life tasks. The Adult-Assisting Hand Assessment Stroke measures how effectively a patient with a hemiparesis uses his/her affected hand together with the unaffected hand to perform bimanual tasks. The Adult-Assisting Hand Assessment Stroke contributes a new and clinically important aspect to stroke rehabilitation by providing a valid bimanual observation-based measure to guide intervention and measure change over time.

PMID: 29084457 [PubMed - as supplied by publisher]

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Endoscopic Urinary Diversion As Initial Management of Symptomatic Obstructive Ectopic Ureter in Infants.

Endoscopic Urinary Diversion As Initial Management of Symptomatic Obstructive Ectopic Ureter in Infants.

Front Pediatr. 2017;5:208

Authors: Ortiz R, Parente A, Burgos L, Angulo JM

Abstract
AIM: Definitive surgery of ectopic ureter in infants is challenging. We propose an endoscopic urinary diversion (EUD) as a novel surgical technique in the initial management of symptomatic obstructive ectopic ureter.
PATIENTS AND METHODS: Sixteen obstructive ectopic ureters (14 patients) were initially treated by EUD between 2006 and 2015. All patients had urinary tract dilatation worsening at preoperative US scans and at least two febrile urinary tract infection (UTI) or urinary sepsis despite antibiotic prophylaxis. Ectopic ureter was confirmed by cystoscopy. When ectopic meatus was not found, EUD consisted in the creation of a transurethral neo-orifice (TUNO) performed by needle puncturing of the ureterovesical wall, under fluoroscopic and ultrasound control. If ectopic meatus was identified in the posterior urethra, "intravesicalization procedure" was done opening the urethral-ureteral wall to create a new ureteral outlet into the bladder.
RESULTS: EUD was done at a median age of 3.5 months (0.5-7) with median follow-up of 48 months (24-136). TUNO was performed in six patients and "intravesicalization" in eight patients. Significant differences were observed in ureteral diameter and anteroposterior pelvis diameter before and after endoscopic treatment (p < 0.005). Initial renal function was preserved in all cases. Postoperative complications were UTI in four patients and TUNO stenosis in one patient, treated by endoscopic balloon dilation. Definitive treatment was further individualized in each patient after 1 year of life.
CONCLUSION: EUD is a feasible and safe less-invasive technique in the initial management of symptomatic obstructive ectopic ureter. It allows an adequate ureteral drainage preserving renal function until definitive repair if necessary and does not invalidate other surgical options in case of failure or future definitive treatments.

PMID: 29085813 [PubMed]

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Results after implementation of a protocol on the incidence of urinary tract infection in an intensive care unit.

Related Articles

Results after implementation of a protocol on the incidence of urinary tract infection in an intensive care unit.

Rev Lat Am Enfermagem. 2016 Sep 09;24(0):e2804

Authors: Miranda AL, Oliveira AL, Nacer DT, Aguiar CA

Abstract
OBJECTIVE: to compare the results of urinary tract infection incidence, by means of the rate of indwelling urethral catheter use, and to identify microorganisms in urine cultures and surveillance cultures before and after the implementation of a clinical protocol for intensive care unit patients .
METHOD: urinary tract infection is defined as a positive urine culture > 105 CFU/mL, notified by the hospital infection control service, six months before and after the implementation of the protocol. The sample consisted of 47 patients, 28 reported before and 19 after implementation. The protocol established in the institution is based on the Ministry of Health manual to prevent healthcare-related infections; the goal is patient safety and improving the quality of health services.
RESULTS: a negative linear correlation was observed between the later months of implementation and the reduction of reported cases of urinary tract infection, using the Spearman rank order coefficient (p = 0.045), and a reduction in the number of urine culture microorganisms (p = 0.026) using the Fisher exact test.
CONCLUSION: educational interventions with implementation protocols in health institutions favor the standardization of maintenance of the invasive devices, which may reduce colonization and subsequent infections.
OBJETIVO: comparar os resultados da incidência de infecção do trato urinário, por meio da taxa de utilização do cateter vesical de demora e identificar os micro-organismos na urocultura e cultura de vigilância antes e após a implementação de um protocolo assistencial em pacientes internados em unidade de terapia intensiva.
M?TODO: definiu-se infecção do trato urinário pacientes com urocultura positiva >105 UFC/mL, notificados pelo Serviço de Controle de Infecção Hospitalar, seis meses antes e após a implementação do protocolo. A amostra foi constituída por 47 pacientes, sendo 28 notificados antes e 19 após. O protocolo, criado na instituição, é baseado no manual do Ministério da Saúde na prevenção de infecções relacionadas à assistência a saúde, como meta a segurança do paciente e o aperfeiçoamento na qualidade dos serviços de saúde.
RESULTADOS: foi possível observar uma correlação linear negativa entre os meses posteriores da implementação e a redução dos casos notificados de infecção do trato urinário, pelo teste de Spearman (p=0,045) e redução do número de micro-organismos na urocultura (p=0,026) pelo teste de Fisher.
CONCLUS?O: intervenções educativas com implementação de protocolos nas instituições de saúde favorece a padronização da manutenção com dispositivos invasivos podendo reduzir a colonização e posterior casos de infecção.
OBJETIVO: comparar los resultados de la incidencia de infección del tracto urinario, por medio de la tasa de utilización del catéter vesical de demora e identificar los microorganismos en el urocultivo y cultura de vigilancia antes y después de la implementación de un protocolo asistencial, en pacientes internados en unidad de terapia intensiva.
M?TODO: se definió la infección del tracto urinario de pacientes con urocultivo positivo >105 UFC/mL, notificados por el Servicio de Control de Infección Hospitalario, seis meses antes y después de la implementación del protocolo. La muestra estuvo constituida por 47 pacientes, siendo 28 notificados antes y 19 después. El protocolo, creado en la institución, está basado en el manual del Ministerio de la Salud para la prevención de infecciones relacionadas a la asistencia la salud, siendo la meta la seguridad del paciente y el perfeccionamiento de la calidad de los servicios de la salud.
RESULTADOS: fue posible observar una correlación linear negativa entre los meses posteriores a la implementación y la reducción de los casos notificados de infección del tracto urinario, por el test de Spearman (p=0,045) y reducción del número de microorganismos en el urocultivo (p=0,026) por el test de Fisher.
CONCLUSI?N: las intervenciones educativas con implementación de protocolos en las instituciones de la salud favorecen la estandarización de la manutención de dispositivos invasivos, lo que podría reducir la colonización y posterior aparecimiento de casos de infección.

PMID: 27627125 [PubMed - indexed for MEDLINE]

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One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin.

Related Articles

One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin.

Diabetes Obes Metab. 2016 Nov;18(11):1128-1133

Authors: Matthaei S, Aggarwal N, Garcia-Hernandez P, Iqbal N, Chen H, Johnsson E, Chin A, Hansen L

Abstract
AIMS: Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis.
MATERIALS AND METHODS: Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on.
RESULTS: The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (≤1.5 kg) occurred in both groups. Similar proportions of patients reported ≥1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (≤2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on.
CONCLUSIONS: Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia.

PMID: 27403645 [PubMed - indexed for MEDLINE]

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Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes.

Related Articles

Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes.

Diabetes Obes Metab. 2016 Nov;18(11):1134-1137

Authors: Mathieu C, Herrera Marmolejo M, González González JG, Hansen L, Chen H, Johnsson E, Garcia-Sanchez R, Iqbal N

Abstract
We previously reported that dapagliflozin versus placebo as add-on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D). Here we report results after 52 weeks of treatment. Patients stabilized on open-label metformin and saxagliptin 5 mg/day for 8-16 weeks were randomized to placebo or dapagliflozin 10 mg/day plus open-label saxagliptin plus metformin for 52 weeks. Changes from baseline to week 52 were greater with dapagliflozin versus placebo in A1C (-0.74% vs. 0.07%), FPG (-27 vs. 10 mg/dL) and BW (-2.1 vs. -0.4 kg). More patients achieved A1C <7% with dapagliflozin (29.4%) versus placebo (12.6%). Adverse events were similar with dapagliflozin (66%) and placebo (71%), and hypoglycaemia was rare (≤2%). Genital infections occurred more often with dapagliflozin (6%) than with placebo (1%); frequency of urinary tract infections was similar between the two groups (9% vs. 10%). Triple therapy with dapagliflozin add-on to saxagliptin plus metformin is a durable, effective and well-tolerated intervention for the treatment of T2D.

PMID: 27385192 [PubMed - indexed for MEDLINE]

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Switching from sulphonylurea to a sodium-glucose cotransporter2 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia.

Related Articles

Switching from sulphonylurea to a sodium-glucose cotransporter2 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia.

Diabetes Obes Metab. 2016 Jun;18(6):628-32

Authors: Wan Seman WJ, Kori N, Rajoo S, Othman H, Mohd Noor N, Wahab NA, Sukor N, Mustafa N, Kamaruddin NA

Abstract
The aim of the present study was to assess the hypoglycaemia risk and safety of dapagliflozin compared with sulphonylurea during the fasting month of Ramadan. In this 12-week, randomized, open-label, two-arm parallel group study, 110 patients with type 2 diabetes who were receiving sulphonylurea and metformin were randomized either to receive 10 mg (n = 58) of dapagliflozin daily or to continue receiving sulphonylurea (n = 52). The primary outcome was to compare the effects of dapagliflozin and sulphonylurea on the proportions of patients with at least one episode of hypoglycaemia during Ramadan, as well as to assess the safety of dapagliflozin when used to treat patients observing Ramadan. A lower proportion of patients had reported or documented hypoglycaemia in the dapagliflozin group than in the sulphonylurea group: 4 (6.9%) versus 15 (28.8%); p = 0.002. The relative risk of any reported or documented hypoglycaemia in the 4th week of Ramadan was significantly lower in the dapagliflozin group: RR=0.24, 95%CI: 0.09, 0.68; p=0.002. No significance differences were observed between the two groups regarding postural hypotension (13.8 vs 3.8%; p = 0.210) or urinary tract infections (10.3 vs 3.8%; p = 0.277). In conclusion, fewer patients exhibited hypoglycaemia in the dapagliflozin group than in the sulphonylurea group.

PMID: 26889911 [PubMed - indexed for MEDLINE]

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A relapsed lower lip squamous cell carcinoma treated with curative electrochemotherapy in elderly patient.

A relapsed lower lip squamous cell carcinoma treated with curative electrochemotherapy in elderly patient.

Minerva Stomatol. 2017 Oct 31;:

Authors: Gargiulo M, Cortese A, Pantaleo G, Parascandalo S, Amato M

Abstract
INTRODUCTION: ECT is normally used in the treatment of basal cell carcinoma, cutaneous and subcutaneous tumours, metastases of melanoma, Kaposi sarcoma, because of its high power, safety and low toxicity. The ECT treatment efficacy depends on the drug concentration during the use, patient characteristics, the distribution of the electric field inside the tumour and the tumour characteristics.
AIM: The aim of this study was to evaluate the effect of ECT in a patient affected by relapsed lower lip squamous cell carcinoma, not candidate for traditional surgery but treated for persistent pain with swallowing and breathing difficulties.
MATERIALS AND METHODS: A 58-year-old caucasian man was referred with a relapsed lower lip squamous cell carcinoma. The patient showed a TNM staging system of T2N0M0. The patient was treated with ECT with midazolam, remifentanil and intravenous bleomycin therapy.
RESULTS: The results of the treatment performed on the patient in the study showed good subjective tolerance. The patient had no postoperative bleeding or swelling of the treated area. The 2 years follow up showed no local or regional relapse, echography was negative.
CONCLUSIONS: This study demonstrates that ECT is an effective therapeutic solution for relapsed lower lip squamous cell carcinoma. ECT treatment is a conservative surgery option with a reduced postoperative damage.

PMID: 29087094 [PubMed - as supplied by publisher]

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Adjunctive use of an Ethyl Lauroyl Arginate (LAE)-containing mouthwash in the nonsurgical therapy of periodontitis: a randomized clinical trial.

Adjunctive use of an Ethyl Lauroyl Arginate (LAE)-containing mouthwash in the nonsurgical therapy of periodontitis: a randomized clinical trial.

Minerva Stomatol. 2017 Oct 31;:

Authors: Pilloni A, Carere M, Orrù G, Scano A, Trezza C, Rojas MA, Zeza B

Abstract
BACKGROUND: This randomized clinical trial evaluated the clinical and microbiological effects of 0.147% ethyl lauroyl arginate (LAE)-containing mouthwash compared to 0.12% chlorhexidine (CHX) mouthwash in the treatment of periodontitis.
MATERIALS AND METHODS: Subjects were randomized to use 0.147% LAE and 0.12% CHX mouthwash after professional mechanical plaque removal (PMPR) twice daily 1 hour after brushing for 4 weeks. Periodontal pocket depth (PPD), bleeding on probing (FMBS) and dental plaque (FMPS) were measured at baseline, 4 weeks and 3 months. Microbiological samples were taken at baseline, at 4 weeks and 3 months after plaque recording and prior to PPD and BoP measurements.
RESULTS: Forty subjects were randomized to treatment. Both therapies resulted in reduced FMPS, FMBS and residual pockets at 4 weeks and 3 months. The differences were not statistically significant. There were no treatment-related adverse events. Total bacterial count and the specific pathogens were reduced at 4 weeks and 3 months by both mouthwashes with no statistical differences between them at neither periods of time.
CONCLUSIONS: 0.147% LAE-containing mouthwash could be an alternative to the use of 0.12% CHX in the non surgical therapy of periodontitis considering the similar clinical effects, more stable microbiological improvement and absence of adverse effects.

PMID: 29087093 [PubMed - as supplied by publisher]

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Death by suicide in Graves' disease and Graves' orbitopathy. A nationwide Danish register study.

Death by suicide in Graves' disease and Graves' orbitopathy. A nationwide Danish register study.

Thyroid. 2017 Oct 30;:

Authors: Ferløv-Schwensen C, Brix TH, Hegedus L

Abstract
BACKGROUND: Graves' disease is associated with excess morbidity and mortality, but little is known about unnatural manners of death and the potential relation with Graves' orbitopathy. Here we investigate the risk of unnatural death in Graves' patients with orbitopathy (GO) and without (GD), compared to matched control populations.
METHODS: Cohort study covering all adult Danes (≥18 years) diagnosed with GD or GO during 1995-2012. Median follow-up time was 7.9 years (range, 0-17.5). Utilizing the Danish Register of Causes of Death and the Danish National Patient Registry, 28,461 subjects with GD, and 3,965 with GO were identified and matched for age and gender with four subjects from the background population. Manner of death was identified and hazard ratios (HR) for mortality due to unnatural deaths (accident, suicide, violence/homicide, and unknown) were calculated using Cox regression analyses, adjusted for pre-existing somatic and psychiatric morbidity.
RESULTS: In Graves' disease overall there was an increased risk of death from unknown unnatural manners [HR: 2.01 (95% confidence interval: 1.17-3.45); P=0.012] and of suicide, although the latter difference was not with certainty statistically significant [HR 1.43 (1.00-2.04); P=0.053]. There was no significant difference in risk of death from suicide in GD subjects compared to their controls [HR 1.27 (0.85-1.89); P=0.253]. However, GO patients had a significantly higher risk of death from suicide [HR 2.71 (1.16-6.32); p=0.022].
CONCLUSIONS: Mortality by suicide was increased in Graves' disease, most significantly in patients with Graves' orbitopathy, also after adjustment for pre-existing somatic and psychiatric disease. These findings indicate that Graves' disease and Graves' orbitopathy may have a significant role in the pathophysiological mechanisms of suicidal behavior. Beyond independent confirmation, reasons for this need to be explored in order to introduce preventive measures.

PMID: 29084476 [PubMed - as supplied by publisher]

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Use of HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells as a Potential Therapeutic for Progressive HER2-Positive Glioblastoma.

Use of HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells as a Potential Therapeutic for Progressive HER2-Positive Glioblastoma.

Neurosurgery. 2017 Nov 01;81(5):N42-N43

Authors: Schneider JR, Kwan K, Boockvar JA

PMID: 29088463 [PubMed - in process]

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Prevalence and Patterns of Injury Sustained During Military Hand-to-Hand Combat Training (Krav-Maga).

Prevalence and Patterns of Injury Sustained During Military Hand-to-Hand Combat Training (Krav-Maga).

Mil Med. 2017 Nov;182(11):e2005-e2009

Authors: Farkash U, Dreyfuss D, Funk S, Dreyfuss U

Abstract
BACKGROUND: Krav-Maga (KM) is a unique Israeli hand-to-hand combat system, designed to teach soldiers self-defense in true-to-life situations. With the increase in military Israel Defense Force (IDF) units participating in KM training in recent years, the number of injuries incurred in KM has also increased. The purpose of our report is to describe the prevalence and pattern of these injuries.
METHODS: Instances of KM injury were taken from IDF patients' computerized clinical records over a 1-year period. Data pertaining to the type, location, and severity of the injury, as well as data relating to soldier's gender and age were collected from the charts. "Moderate" injury was defined as injury necessitating absence from military activity for more than 1 week; "major" injury was defined as injury necessitating surgical intervention.
FINDINGS: During the year 2014, 916 soldiers complaining of 946 traumatic injuries sustained during KM training were evaluated in IDF clinics. The vast majority of injuries (95%) occurred in male soldiers, and most injured soldiers (92%) were between the ages of 18 and 22. The upper limbs were the most frequently injured body parts, with the fingers, hands, and wrists being the most involved regions (31%) followed by the shoulder (16%). Injury severity was mild in most cases. However, 64 soldiers (6.7%) were moderately injured and major injuries necessitating surgical treatment occurred in 33 cases (3.5%).
DISCUSSION: KM involves both striking and grappling elements, and we assume that injuries result from both fighting forms. With striking styles, such as boxing and kickboxing, hand and wrist are the prevalent injury locations; with grappling styles such as wrestling, strain and sprain injuries of large joints are most prevalent. Head and neck injuries, a major concern in martial arts sports, were not identified as significant problems in KM. To minimize participant injury, preventative measures should focus on improving protective equipment, especially of the hand, as well as warm up and training technique modifications, and shoulder strengthening exercises.

PMID: 29087872 [PubMed - in process]

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3-Dimensional Metrics of Proximal Femoral Shape Deformities in Legg-Calvé-Perthes Disease and Slipped Capital Femoral Epiphysis.

3-Dimensional Metrics of Proximal Femoral Shape Deformities in Legg-Calvé-Perthes Disease and Slipped Capital Femoral Epiphysis.

J Orthop Res. 2017 Oct 31;:

Authors: Chan EF, Farnsworth CL, Klisch SM, Hosalkar HS, Sah RL

Abstract
Legg-Calvé-Perthes disease (LCPD) and slipped capital femoral epiphysis (SCFE) are two common pediatric hip disorders that affect the 3-dimensional shape and function of the proximal femur. This study applied the principles of continuum mechanics to statistical shape modeling (SSM) and determined 3-D metrics for the evaluation of shape deformations in normal growth, LCPD, and SCFE. CT scans were obtained from 32 patients with asymptomatic, LCPD, and SCFE hips ((0.5-0.9mm)(2) in-plane resolution, 0.63mm slice thickness). SSM was performed on segmented proximal femoral surfaces, and shape deformations were described by surface displacement, strain, and growth plate angle metrics. Asymptomatic normal femurs underwent coordinated, growth-associated surface displacements and anisotropic strains that were site-specific and highest at the greater trochanter. After size- and age-based shape adjustment, LCPD femurs exhibited large displacements and surface strains in the femoral head and neck, with associated changes in femoral head growth plate angles. Mild SCFE femurs had contracted femoral neck surfaces, and surface displacements in all regions tended to increase with severity of slip. The results of this paper provide new 3-D metrics for characterizing the shape and biomechanics of the proximal femur. Statement of Clinical Significance: Quantitative 3-D metrics of shape may be useful for understanding and monitoring disease progression, identifying target regions for shape modulation therapies, and objectively evaluating the success of such therapies. This article is protected by copyright. All rights reserved.

PMID: 29087625 [PubMed - as supplied by publisher]

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Anterior palatoplasty in the treatment of obstructive sleep apnoea - a systemic review.

Anterior palatoplasty in the treatment of obstructive sleep apnoea - a systemic review.

Acta Otorhinolaryngol Ital. 2017 Oct 31;:

Authors: Pang KP, Pang EB, Pang KA, Rotenberg B

Abstract
This study seeks to determine the objective and subjective success rates of anterior palatoplasty and its variants for the treatment of obstructive sleep apnoea (OSA). A systematic review with two independent searches of Medline, PubMed, Cochrane Library and Evidence Based Medicine Reviews was performed to identify publications relevant to OSA and anterior palatoplasty. All relevant studies published before 30 June 2015 were included. Six studies were included in the systematic review. The numbers of patients in each paper ranged from 13 to 77 (total=240), and mean age ranged from 21 to 51 years. Substantial and consistent improvement in polysomnography (PSG) outcomes were observed in patients after the anterior palatoplasty, with or without multilevel surgery. The results showed that the anterior palatoplasty technique provides significantly improvement in the post-operative AHI. The mean pre-operative AHI (in the 6 papers) improved from 16.3 to 7.1, the snore visual analogue scale improved from 7.5 to 3.1 and the Epworth score reduced from 11.3 to 7.3 post-operatively. The overall pro-rated pooled success rate for all the patients was 72.5%, with a mean follow-up of 17.3 months. Anterior palatoplasty is an effective option in the management of patients with mild to moderate OSA.

PMID: 29087404 [PubMed - as supplied by publisher]

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Folliculotropic mycosis fungoides presenting with a solitary lesion: clinicopathological features and long-term follow-up data in a series of nine cases.

Folliculotropic mycosis fungoides presenting with a solitary lesion: clinicopathological features and long-term follow-up data in a series of nine cases.

J Cutan Pathol. 2017 Oct 31;:

Authors: van Santen S, Jansen PM, Vermeer MH, Willemze R

Abstract
Folliculotropic mycosis fungoides (FMF) is a rare but distinct variant of mycosis fungoides (MF), histologically characterized by the presence of folliculotropic infiltrates, often with sparing of the epidermis, and clinically by the preferential involvement of the head and neck region.(1).

PMID: 29086994 [PubMed - as supplied by publisher]

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Objective and subjective voice outcomes after total laryngectomy: a systematic review.

Objective and subjective voice outcomes after total laryngectomy: a systematic review.

Eur Arch Otorhinolaryngol. 2017 Oct 31;:

Authors: van Sluis KE, van der Molen L, van Son RJJH, Hilgers FJM, Bhairosing PA, van den Brekel MWM

Abstract
BACKGROUND: Esophageal speech (ES), tracheoesophageal speech (TES) and/or electrolarynx speech (ELS) are three speech rehabilitation methods which are commonly provided after total laryngectomy (TL).
METHODS: A systematic review of the literature was conducted to evaluate comparative acoustic, perceptual, and patient-reported outcomes for ES, TES, ELS and healthy speakers.
RESULTS: Twenty-six articles could be included. In most studies, methodological quality was low. It is likely that an inclusion bias exists, many studies only included exceptional speakers. Significant better outcomes are reported for TES compared to ES for the acoustic parameters, fundamental frequency, maximum phonation time and intensity. Perceptually, TES is rated with a significant better voice quality and intelligibility than ES and ELS. None of the speech rehabilitation groups reported clearly better outcomes in patient-reported outcomes.
CONCLUSIONS: Studies on speech outcomes after TL are flawed in design and represent weak levels of evidence. There is an urge for standardized measurement tools for evaluations of substitute voice speakers. TES is the favorable speech rehabilitation method according to acoustic and perceptual outcomes. All speaker groups after TL report a degree of voice handicap. Knowledge of caretakers and differences in health care and insurance systems play a role in the speech rehabilitation options that can be offered.

PMID: 29086803 [PubMed - as supplied by publisher]

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Anterior Palatoplasty for Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.

Anterior Palatoplasty for Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.

Otolaryngol Head Neck Surg. 2017 Oct 01;:194599817739857

Authors: Binar M, Karakoc O

Abstract
Objective The aim of this study was to determine the general outcomes and surgical success rates of anterior palatoplasty (AP) in patients with obstructive sleep apnea (OSA). Data Sources A systematic review of the literature and meta-analysis of published data were performed by searching the Cochrane, SAGE, MEDLINE, and Google Scholar databases, from January 1, 2007, to March 27, 2017, using relevant keywords. Review Methods The search scanned for studies with patients who had undergone AP (with or without tonsillectomy) as a single-stage, single-level surgical intervention for treatment of OSA. Two independent reviewers (M.B. and O.K.) inspected titles and abstracts of the studies according to established criteria. The full texts were then reviewed to extract the clinical and polysomnographic data. The primary outcome was the surgical success rate, defined as a reduction in the apnea-hypopnea index (AHI) of 50% or greater and an AHI of less than 20 postoperatively. The PRISMA statement was followed. Results After systematic evaluation of potentially relevant articles, 14 studies were downloaded, and 6 studies, consisting of 170 patients, met the study criteria. A fixed effects model was used to analyze the data. The surgical success rate of AP was 60.6%. No serious complications were reported in the literature. Conclusion The results of the present meta-analysis support AP as a moderately effective surgical method for the treatment of OSA. Comparative and randomized controlled prospective studies showing long-term results, with pre- and postoperative data, should be conducted to demonstrate the exact outcomes and reliability of this surgical technique.

PMID: 29086603 [PubMed - as supplied by publisher]

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[Maxillary sinusitis as a diagnostical adverse finding of the dental cone-beam computed tomography study].

[Maxillary sinusitis as a diagnostical adverse finding of the dental cone-beam computed tomography study].

Orv Hetil. 2017 Nov;158(44):1747-1753

Authors: Schreindorfer K, Kiss Á, Marada G

Abstract
INTRODUCTION: Cone-beam computed tomography is a frequently used diagnostical method in the head and neck region. The thickening of the maxillary sinus mucosa is often observed in these images.
AIM: Determining the prevalence of teeth and roots that can be identified as cause of maxillary odontogenic sinusitis, and recording the average observed mucosa thickening on these images.
METHOD: The scans that give the base of the study have been performed by the Department of Dentistry of Medical University of Pécs between 2015-2016. The size of the voxels had been varied between 0.25 and 0.4 mm and the size of the image had been set up to 15×12 cm. The acquisition time had been set up to 27 seconds.
RESULTS: 170 cases of the 260 revised records fulfilled the initial criterion conditions. The average mucosa thickness was 8.8 mm. During the present study, the upper first molars palatal and the second molars mesiobuccal roots were mainly associated with maxillary odontogenic sinusitis.
CONCLUSION: Whether in the case of chronic maxillary sinusitis that is not or only temporarily responsive to conventional therapy, may it be justifiable to provide dental consultation and cone-beam computed tomography to exclude the dental origin of sinusitis. Orv Hetil. 2017; 158(44): 1747-1753.

PMID: 29086594 [PubMed - in process]

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Oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States, 1973-2013.

Oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States, 1973-2013.

Laryngoscope. 2017 Oct 31;:

Authors: Megwalu UC, Sirjani D, Devine EE

Abstract
OBJECTIVE: To analyze oropharyngeal squamous cell carcinoma incidence and mortality trends in the United States for the years 1973 through 2013.
STUDY DESIGN: Cross-sectional study using a large population-based cancer database.
METHODS: Data on incidence and mortality rates were extracted from the Surveillance, Epidemiology, and End Results (SEER) 9 Database. Annual percentage change in rates was calculated using Joinpoint regression analysis (National Cancer Institute, Bethesda, MD).
RESULTS: Incidence rates increased (annual percent change [APC]; 1.52, 95% confidence interval [CI] 0.17 to 2.88) from 1973 to 1983, remained stable (APC -0.52, 95% CI -1.30 to 0.26) from 1983 to 1997, and increased (APC 1.32, 95% CI 0.83 to 1.81) from 1997 to 2013. Overall, incidence rates increased for males (APC 0.73, 95% CI 0.22 to 1.25) but not females (APC -0.77, 95% CI -0.68 to 0.82). Incidence rates increased in the white population (APC 0.79, 95% CI 0.33 to 1.25) but decreased in the black population (APC -0.72, 95% CI -1.41 to -0.02). The incidence rates increased for tongue-base tumors (APC 1.17, 95% CI 0.42 to 1.92) and tonsil tumors (APC 0.47, 95% CI 1.10 to 4.96) but decreased for other sites. Incidence-based mortality decreased (APC -0.78, 95% CI -1.13 to -0.42) from 1993 to 2013.
CONCLUSION: Oropharyngeal squamous cell carcinoma incidence rates increased in a nonlinear fashion from 1973 to 2013, whereas mortality rates declined. This, along with variation in trends by demographic and tumor factors, suggest that human papilloma virus is the main driver of the recent rise in incidence.
LEVEL OF EVIDENCE: 2b. Laryngoscope, 2017.

PMID: 29086431 [PubMed - as supplied by publisher]

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Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

Laryngoscope. 2017 Oct 31;:

Authors: Suzuki R, Katsuno T, Kishimoto Y, Nakamura R, Mizuta M, Suehiro A, Yamashita M, Nakamura T, Tateya I, Omori K

Abstract
OBJECTIVES/HYPOTHESIS: The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury.
STUDY DESIGN: Animal experiments with controls.
METHODS: Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin.
RESULTS: TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury.
CONCLUSIONS: It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer.
LEVEL OF EVIDENCE: NA Laryngoscope, 2017.

PMID: 29086429 [PubMed - as supplied by publisher]

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Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

Laryngoscope. 2017 Oct 31;:

Authors: Haidar YM, Sahyouni R, Moshtaghi O, Wang BY, Djalilian HR, Middlebrooks JC, Verma SP, Lin HW

Abstract
OBJECTIVES/HYPOTHESIS: Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses.
STUDY DESIGN: Acute experiments in cats.
METHODS: The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement.
RESULTS: Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments.
CONCLUSIONS: We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management.
LEVEL OF EVIDENCE: NA Laryngoscope, 2017.

PMID: 29086427 [PubMed - as supplied by publisher]

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MRSA chronic bacterial laryngitis: A growing problem.

MRSA chronic bacterial laryngitis: A growing problem.

Laryngoscope. 2017 Oct 31;:

Authors: Carpenter PS, Kendall KA

Abstract
OBJECTIVES: Chronic bacterial infection of the larynx is characterized by long-standing hoarseness and exudative laryngitis. Prolonged antibiotic therapy is required to clear the infection, and methicillin-resistant staphylococcus aureus (MRSA) may be the responsible pathogen. The objective of this study was to describe the presentation, comorbidities, treatment response, and underlying etiology- including the incidence of MRSA-in our patient population with chronic bacterial laryngitis.
METHODS: A review of patients with a diagnosis of chronic bacterial laryngitis from 2012 to 2016 was performed. Diagnosis of chronic bacterial laryngitis was based on clinical history and findings on flexible laryngoscopy. In selected cases, the diagnosis of bacterial laryngitis was confirmed by operative biopsy. Information regarding clinical presentation and course was collected.
RESULTS: Twenty-eight patients were included in the study. Twenty-three were treated empirically with Amoxicillin-clavulonic acid for a minimum of 21 days. Twelve of the 23 (52%) had recurrence or nonresolution of infection. Seven of the 12 nonresponders (58%) were found to have MRSA by laryngeal tissue culture. Five patients were treated initially with Sulfamethoxazole and trimethoprim, and all resolved the infection without the need for further treatment. There was a nonstatistically significant increase in smoking and reflux in the MRSA population compared to the non-MRSA group.
CONCLUSION: MRSA infection was documented in 30% of patients overall with chronic bacterial laryngitis. Based on the results of the study, a treatment algorithm for management of this unusual patient population is suggested.
LEVEL OF EVIDENCE: 4. Laryngoscope, 2017.

PMID: 29086424 [PubMed - as supplied by publisher]

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Feasibility of preservation of chorda tympani nerve during noninflammatory ear surgery: A systematic review.

Feasibility of preservation of chorda tympani nerve during noninflammatory ear surgery: A systematic review.

Laryngoscope. 2017 Oct 31;:

Authors: Ziylan F, Smeeing DPJ, Bezdjian A, Stegeman I, Thomeer HGXM

Abstract
OBJECTIVE: The objective of our systematic review is to investigate the postoperative gustatory function of the chorda tympani nerve following noninflammatory ear surgery for which the chorda tympani is at risk for iatrogenic injury (stretching, handling, or sacrificing).
DATA SOURCES: PubMed and EMBASE.
REVIEW METHODS: A PubMed and EMBASE databases search was conducted on November 15, 2016. Study inclusion criteria included: 1) ear surgery performed for noninflammatory ear diseases, and 2) gustatory function of the chorda tympani reported as an outcome. The quality of eligible studies was assessed using the risk of bias assessment tool for nonrandomized studies. Study characteristics and outcome data of the included studies were extracted.
RESULTS: In total 1,094 articles were retrieved. Fourteen studies encompassing 1,062 operated ears were included after quality assessment. Stapedectomy was the most frequent surgical procedure performed in 398 ears. The follow-up time varied between 6 weeks and 99 months. Patients with a preserved chorda tympani were less symptomatic (24% was symptomatic) compared to patients with a stretched (53% was symptomatic) or sacrificed chorda tympani (47% was symptomatic). The recovery rate varied from 61% to 79%. The results of the electrogustometry and strip test showed a discrepancy with the subjective complaints of the patients.
CONCLUSION: Patients with a stretched chorda tympani were slightly more symptomatic compared to patients with a sacrificed chorda tympani. Therefore, in cases for which the chorda tympani greatly hinders a proper view of the surgical field, sacrificing the nerve could be considered to maximize surgical performance and have a satisfactory postoperative result. Laryngoscope, 2017.

PMID: 29086423 [PubMed - as supplied by publisher]

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Ribeye protein is intrinsically dynamic but is stabilized in the context of the ribbon synapse.

Ribeye protein is intrinsically dynamic but is stabilized in the context of the ribbon synapse.

J Physiol. 2017 Oct 31;:

Authors: Chen Z, Chou SW, McDermott BM

Abstract
Ribeye protein is a major constituent of the synaptic ribbon, an organelle that coordinates rapid and sustained vesicle release to enable hearing and balance. The ribbon is considered to be a stable structure. However, under certain physiological conditions such as acoustic overexposure that results in temporary noise-induced hearing loss or perturbations of ion channels, ribbons may change shape or vanish altogether, suggesting greater plasticity than previously appreciated. The dynamic properties of ribeye proteins are unknown. Here we use transgenesis and imaging to explore the behaviours of ribeye proteins within the ribbon and also their intrinsic properties outside the context of the ribbon synapse in a control cell type, the skin cell. By fluorescence recovery after photobleaching (FRAP) on transgenic zebrafish larvae, we test whether ribeye proteins are dynamic in vivo in real time. In the skin, a cell type devoid of synaptic contacts, Ribeye a-mCherry exchanges with ribbon-like structures on a minute timescale (t1/2  = 3.2 min). In contrast, Ribeye a of the ear and lateral line and Ribeye b of the lateral line each exchange at ribbons of hair cells an order of magnitude slower (t1/2 of 125.6 min, 107.0 min, and 95.3 min, respectively) than Ribeye a of the skin. These basal exchange rates suggest that long-term ribbon presence may require ribeye renewal. Our studies demonstrate that ribeye proteins are inherently dynamic but are stabilized at the ribbons of sensory cells in vivo. This article is protected by copyright. All rights reserved.

PMID: 29086422 [PubMed - as supplied by publisher]

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Utility of intraoperative imaging in cochlear implantation: A systematic review.

Utility of intraoperative imaging in cochlear implantation: A systematic review.

Laryngoscope. 2017 Oct 31;:

Authors: Appachi S, Schwartz S, Ishman S, Anne S

Abstract
BACKGROUND: Many institutions routinely perform intraoperative imaging during cochlear implant (CI) surgery to determine accurate electrode placement. Different modalities exist; however, there remains some controversy regarding the usefulness of intraoperative imaging.
OBJECTIVE: Systematically review the utility of intraoperative imaging in CI surgery and implications for management.
METHODS: PubMed, EMBASE, Medline, CINAHL, and Cochrane library were searched from inception to April 2017. Studies analyzing the use of intraoperative imaging during CI surgery were included. Outcome measures included unsatisfactory placement and change in management. Two independent evaluators reviewed each abstract and article.
RESULTS: Two hundred and sixty-seven articles were identified. Of those, 17 met inclusion criteria. There were no randomized controlled trials. Intraoperative X-rays were performed in 917 CIs in eight studies. Placement was unsatisfactory on radiograph in 19 implants (3.5%), and management was changed in 18 of 19 (94.7%). Intraoperative computed tomography (CT) was performed in 69 CIs in seven studies. Placement was unsatisfactory on CT in two implants (3.0%), and management was changed in both (100%). Intraoperative real-time fluoroscopy was performed in 20 CIs in two studies to help guide correct placement. Twenty-two of these patients had abnormal cochleas. Fifteen out of 17 studies concluded that intraoperative imaging is useful, especially with challenging anatomy or when the surgeon questions placement.
CONCLUSION: Intraoperative imaging detects unsatisfactory placement of electrodes during CI surgery at a low, but not negligible, rate. The current literature is not conclusive regarding the utility of routine imaging, but it appears to be most useful with abnormal cochlear anatomy or when the surgeon questions placement.
LEVEL OF EVIDENCE: NA. Laryngoscope, 2017.

PMID: 29086418 [PubMed - as supplied by publisher]

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Upper airway stimulation therapy and prior airway surgery for obstructive sleep apnea.

Upper airway stimulation therapy and prior airway surgery for obstructive sleep apnea.

Laryngoscope. 2017 Oct 31;:

Authors: Mahmoud AF, Thaler ER

Abstract
OBJECTIVE: To determine if patients with prior airway surgery for obstructive sleep apnea (OSA) had increased benefit following implantation with hypoglossal nerve stimulator.
STUDY DESIGN: Retrospective chart review at a single institution tertiary academic care center.
METHODS: Following implantation with hypoglossal nerve stimulator device, the outcomes of patients who underwent prior airway surgery for OSA were compared with those who did not. Primary outcome measures included apnea-hypopnea index (AHI) and nadir oxyhemoglobin saturation (NOS) as measured by polysomnography. Secondary outcome measures included Epworth Sleepiness Scale.
RESULTS: Forty-seven patients underwent implantation with hypoglossal nerve stimulator. Of these, 30 patients had undergone prior airway surgery for OSA, whereas 16 did not. Mean preoperative AHI and NOS were 39.3 ± 2.8 and 78% ± 1.8% for all patients, 39.4 ± 3.7 and 79% ± 14% for patients with prior airway surgery, and 39.1 ± 4.0 and 77% ± 2.6% for patients without prior surgery. Mean postoperative AHI and NOS were 3.9 ± 1.2 and 91% ± 0.4% for all patients, 4.2 ± 1.7 and 91% ± 0.5% for patients with prior surgery, and 3.4 ± 1.5 and 93% ± 0.6% for patients without prior surgery (P = 0.756 and 0.053, respectively).
CONCLUSION: Overall, patients had significant improvement following implantation with hypoglossal nerve stimulator. Prior airway surgery had no statistically significant effect on postoperative AHI or NOS.
LEVEL OF EVIDENCE: 4. Laryngoscope, 2017.

PMID: 29086415 [PubMed - as supplied by publisher]

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A matched comparison of human papillomavirus-induced squamous cancer of unknown primary with early oropharynx cancer.

A matched comparison of human papillomavirus-induced squamous cancer of unknown primary with early oropharynx cancer.

Laryngoscope. 2017 Oct 31;:

Authors: Ross RB, Koyfman SA, Reddy CA, Houston N, Geiger JL, Woody NM, Joshi NP, Greskovich JF, Burkey BB, Scharpf J, Lamarre ED, Prendes B, Lorenz RR, Adelstein DJ, Ward MC

Abstract
OBJECTIVES/HYPOTHESIS: Patients with human papillomavirus (HPV)-induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched-pair analysis to compare outcomes between T0N1-3M0 HPV+ CUP and T1-2N1-3M0 HPV+ oropharynx known primary (OPX).
STUDY DESIGN: Retrospective cohort study at a single institution.
METHODS: Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis.
RESULTS: Of 298 patients with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow-up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3-year DFS (89% vs. 85%, P = .44), and 3-year OS (91% vs. 91%, P = .11), respectively.
CONCLUSIONS: Patients with T0N+M0 HPV-induced CUP have similar survival outcomes to matched patients with T1-2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early-stage known primary OPX cancer.
LEVEL OF EVIDENCE: 4. Laryngoscope, 2017.

PMID: 29086413 [PubMed - as supplied by publisher]

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Identification of E6/E7-Dependent MicroRNAs in HPV-Positive Cancer Cells.

Identification of E6/E7-Dependent MicroRNAs in HPV-Positive Cancer Cells.

Methods Mol Biol. 2018;1699:119-134

Authors: Honegger A, Schilling D, Sültmann H, Hoppe-Seyler K, Hoppe-Seyler F

Abstract
Oncogenic types of human papillomaviruses (HPVs) are closely linked to the development of anogenital and head and neck cancers . The expression of the viral E6 and E7 genes is crucial for the transforming activities of HPVs. There is accumulating evidence that the HPV E6/E7 oncogenes can profoundly affect the cellular microRNA (miRNA) composition. Since alterations of miRNA expression levels can contribute to cancer development and maintenance, it will be important to understand in depth the crosstalk between the HPV oncogenes and the cellular miRNA network . Here, we describe a method to identify E6/E7-dependent intracellular miRNAs by small RNA deep sequencing , upon silencing of endogenous E6/E7 expression in HPV-positive cancer cells in vitro. In addition, we provide a protocol to identify E6/E7-dependent miRNA alterations in exosomes that are secreted by HPV-positive cancer cells in vitro.

PMID: 29086374 [PubMed - in process]

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A Clinical Trial of Combination Neoadjuvant Chemotherapy and Transoral Robotic Surgery in Patients with T3 and T4 Laryngo-Hypopharyngeal Cancer.

A Clinical Trial of Combination Neoadjuvant Chemotherapy and Transoral Robotic Surgery in Patients with T3 and T4 Laryngo-Hypopharyngeal Cancer.

Ann Surg Oncol. 2017 Oct 30;:

Authors: Park YM, Keum KC, Kim HR, Cho BC, Kim DH, Cho NH, Kim SH

Abstract
BACKGROUND: We conducted a prospective clinical trial of combination neoadjuvant chemotherapy, transoral robotic surgery (TORS), and customized adjuvant therapy in patients with locally advanced laryngo-hypopharyngeal cancer.
METHODS: Between September 2008 and August 2016, 35 patients were enrolled in this clinical trial.
RESULTS: Twenty patients had hypopharyngeal cancer and 15 had laryngeal cancer. Twenty-nine patients (82.9%) had T3 disease and six patients (17.1%) had T4 disease, while 12 patients (34.3%) had stage III disease and 23 patients (65.7%) had stage IV disease. The 3-year disease-specific survival rate was 82.4% and the 3-year disease-free survival rate was 69.48%. Decannulation was successful in 31 of 34 patients at an average of 18 days postoperatively. Among all patients, 83% exhibited a favorable subjective swallowing status, while five patients (14.4%) became dependent on feeding tubes.
CONCLUSIONS: Neoadjuvant chemotherapy combined with TORS and customized adjuvant therapy, based on detailed pathological information, afforded favorable oncological outcomes and preserved organ functionalities in T3-T4 laryngo-hypopharyngeal cancer.

PMID: 29086129 [PubMed - as supplied by publisher]

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Diagnostic and prognostic value of 18F-FDG PET, CT, and MRI in perineural spread of head and neck malignancies.

Diagnostic and prognostic value of 18F-FDG PET, CT, and MRI in perineural spread of head and neck malignancies.

Eur Radiol. 2017 Oct 30;:

Authors: Dercle L, Hartl D, Rozenblum-Beddok L, Mokrane FZ, Seban RD, Yeh R, Bidault F, Ammari S

Abstract
OBJECTIVES: We assessed whether quantitative imaging biomarkers derived from fluorodeoxyglucose-positron emission tomography (18F-FDG PET) could be extracted from perineural spread (PNS) in head and neck malignancies (HNM) to improve patient risk stratification.
METHODS: A case-control exploratory study (1:2 ratio) enrolled 81 patients with FDG-avid HNM. The case-group comprised 28 patients with documented PNS (reference: expert consensus), including 14 squamous cell carcinomas (SCC). Imaging biomarkers were extracted from the PNS on 18F-FDG PET, CT-scan, and MRI. The control-group enrolled 53 SCCs. The Cox proportional-hazards regression model explored the association with overall survival by univariate and multivariate analyses.
RESULTS: The rate of PNS detection by 18F-FDG PET was 100% in the case-group. Quantitative imaging biomarkers were not associated with the presence of sensory (p>0.20) or motor (p>0.10) symptoms. In SCC patients (case: 14; control: 53), PNS was associated with a hazard ratio of death of 5.5 (95%CI: 1.4:20.9) by multivariate analysis. Increased cranial nerve SUVmax was significantly associated with poorer overall survival by univariate analysis (p=0.001).
CONCLUSIONS: Our pilot study showed the feasibility of extracting 18F-FDG PET biomarkers from PNS in FDG-avid HNM. Our results encourage the development of new PET/CT- or PET/MRI-guided management strategies in further prospective studies.
KEY POINTS: • 18F-FDG PET/CT detects PNS in FDG-avid HNM. • PNS metabolism is more heterogeneous than healthy tissue. • PNS diagnosis is crucial: most patients were asymptomatic, N0 and M0. • PNS diagnosis is associated with poorer overall survival in SCC. • PET/CT- or PET/MRI-guided management strategies should be evaluated.

PMID: 29086023 [PubMed - as supplied by publisher]

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Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets.

Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets.

PLoS One. 2017;12(10):e0186364

Authors: Mogire RM, Akala HM, Macharia RW, Juma DW, Cheruiyot AC, Andagalu B, Brown ML, El-Shemy HA, Nyanjom SG

Abstract
Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens.

PMID: 29088219 [PubMed - in process]

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Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission.

Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission.

Proc Natl Acad Sci U S A. 2017 Oct 30;:

Authors: Yarwood RE, Imlach WL, Lieu T, Veldhuis NA, Jensen DD, Klein Herenbrink C, Aurelio L, Cai Z, Christie MJ, Poole DP, Porter CJH, McLean P, Hicks GA, Geppetti P, Halls ML, Canals M, Bunnett NW

Abstract
G protein-coupled receptors (GPCRs) are considered to function primarily at the plasma membrane, where they interact with extracellular ligands and couple to G proteins that transmit intracellular signals. Consequently, therapeutic drugs are designed to target GPCRs at the plasma membrane. Activated GPCRs undergo clathrin-dependent endocytosis. Whether GPCRs in endosomes control pathophysiological processes in vivo and are therapeutic targets remains uncertain. We investigated the contribution of endosomal signaling of the calcitonin receptor-like receptor (CLR) to pain transmission. Calcitonin gene-related peptide (CGRP) stimulated CLR endocytosis and activated protein kinase C (PKC) in the cytosol and extracellular signal regulated kinase (ERK) in the cytosol and nucleus. Inhibitors of clathrin and dynamin prevented CLR endocytosis and activation of cytosolic PKC and nuclear ERK, which derive from endosomal CLR. A cholestanol-conjugated antagonist, CGRP8-37, accumulated in CLR-containing endosomes and selectively inhibited CLR signaling in endosomes. CGRP caused sustained excitation of neurons in slices of rat spinal cord. Inhibitors of dynamin, ERK, and PKC suppressed persistent neuronal excitation. CGRP8-37-cholestanol, but not unconjugated CGRP8-37, prevented sustained neuronal excitation. When injected intrathecally to mice, CGRP8-37-cholestanol inhibited nociceptive responses to intraplantar injection of capsaicin, formalin, or complete Freund's adjuvant more effectively than unconjugated CGRP8-37 Our results show that CLR signals from endosomes to control pain transmission and identify CLR in endosomes as a therapeutic target for pain. Thus, GPCRs function not only at the plasma membrane but also in endosomes to control complex processes in vivo. Endosomal GPCRs are a drug target that deserve further attention.

PMID: 29087309 [PubMed - as supplied by publisher]

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