OtoRhinoLaryngology News: 01/21/18

Κυριακή 21 Ιανουαρίου 2018

Recruiting ENT and Audiology patients into pharmaceutical trials: evaluating the multi-centre experience in the UK and USA

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Influence of the oscillation frequency of different side-to-side toothbrushes on noncontact biofilm removal

Abstract

Objectives

The objective of this study was to investigate the influence of different oscillation frequencies of three powered toothbrushes with side-to-side action for noncontact biofilm removal in an artificial interdental space model.

Materials and methods

A three-species biofilm (Porphyromonas gingivalis, Fusobacterium nucleatum and Streptococcus sanguinis) was formed in vitro on protein-coated titanium disks using a flow chamber system combined with a static biofilm growth model. The oscillation frequencies of three commercial side-to-side toothbrushes were evaluated by means of a dose response. The frequency was decreased in steps (100, 85, 70, 55, and 40%). Subsequently, the biofilm-coated substrates were exposed to the side-to-side toothbrushes. The biofilm volumes were measured using volumetric analyses (Imaris 8.1.2) with confocal laser scanning microscope images (Zeiss LSM700).

Results

Compared to maximum oscillation frequency (100%), lower oscillation frequencies (up to 40%) resulted in reduced median percentages of biofilm reduction (median biofilm reduction up to 53% for maximum oscillation frequency, and up to 13% for 40% oscillation frequency) (p ≥ 0.03). In addition, decreasing the oscillation frequencies of the side-to-side toothbrushes showed an enhanced variety in the results of repeated experiments.

Conclusions

The oscillation frequency of the tested side-to-side toothbrushes affected the biofilm reduction in an interdental space model.

Clinical relevance

Within a toothbrush, higher oscillation frequencies may lead to beneficial effects on interdental biofilm removal by noncontact brushing.

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Improvement of diagnostic performance of pathologists by reducing the number of pathologists responsible for thyroid fine needle aspiration cytology: An institutional experience

Background

Various efforts have been made to improve the diagnostic accuracy of thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system by reducing the number of pathologists responsible for the thyroid FNA cytology in the routine work, and analyzed the effect on the pathologist's diagnostic performance.

Methods

Since March 1, 2015, 3 pathologists have been responsible for diagnostic thyroid FNA, previously undertaken by 9 equally. We compared the prechange period (three months, 319 nodules) and the postchange period (12 months, 1194 nodules).

Results

The turnaround time was shortened from 1.4 ± 0.7 days to 0.9 ± 0.5 days (P < .001). The utilization rate of the Bethesda system for Reporting Thyroid Cytopathology (TBSRTC) increased from 92.5% to 99.8%. Diagnostic rates of categories that are confirmative [II (benign) and VI (malignant)] increased, while the inadequate (I) or indeterminate (III) categories decreased. With category IV (follicular neoplasm), a challenging category in our country, an elevated malignancy rate was found at follow-up. Overall, the diagnostic performance was improved in terms of sensitivity (from 98.5% to 99.2%) and specificity (from 94.4% to 98.4%), with reduced false-negative rates (from 1.5% to 0.8%) and false-positive rates (from 2.9% to 1.1%). The area under the receiver operating characteristic curve increased from 0.861 to 0.958.

Conclusion

Reducing the number of pathologists responsible for diagnostic thyroid FNA cytology resulted in a higher utilization rate of TBSRTC, and more rapid and accurate diagnosis.

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Colorectal Cancer (CRC) Monitoring by Six-Monthly 18FDG-PET/CT: An Open-Label Multicentre Randomised Trial

Abstract

Background

¹⁸FDG-PET/CT has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly ¹⁸FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs.

Patients and Methods

In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1:1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly ¹⁸FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary endpoint was treatment failure defined as unresectable recurrence or death. Relative risks (RR) were estimated, and survival was analysed using the Kaplan-Meier method, Log-Rank test, and Cox models. Direct costs were compared.

Results

Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death), in the control group (RR = 1.23; 95%CI, 0.80-1.88; p=0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95%CI, 0.8-2.19; p=0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group (7 [3-20] vs. (14.3 [7.3-27], p=0.016). Mean cost/patient was higher in the intervention group (18 192±27 679 €vs. 11 131±13 254 €, p<0.033).

Conclusion

¹⁸FDG-PET/CT, when added every six months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect.

ClinicalTrials.gov identifier

NCT00624260

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Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis

Abstract

Background

Recent efforts of genome-wide gene expression profiling analyses have improved our understanding of the biological complexity and diversity of triple negative breast cancers (TNBCs) reporting, at least 6 different molecular subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). However, little is known regarding the potential driving molecular events within each subtype, their difference in survival and response to therapy. Further insight into the underlying genomic alterations is therefore needed.

Patients and Methods

This study was performed using copy-number aberrations, somatic mutations and gene expression data derived from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA). TNBC samples (n = 550) were classified according to Lehmann's molecular subtypes using the TNBCtype online subtyping tool (http://cbc.mc.vanderbilt.edu/tnbc/).

Results

Each subtype showed significant clinic-pathological characteristic differences. Using a multivariate model, IM subtype showed to be associated with a better prognosis (HR = 0.68; CI = 0.46-0.99; p = 0.043) whereas LAR subtype was associated with a worst prognosis (HR = 1.47; CI = 1.0-2.14; p = 0.046). BL1 subtype was found to be most genomically instable subtype with high TP53 mutation (92%) and copy-number deletion in genes involved in DNA repair mechanism (BRCA2, MDM2, PTEN, RB1 & TP53). LAR tumours were associated with higher mutational burden with significantly enriched mutations in PI3KCA (55%), AKT1 (13%) and CDH1 (13%) genes. M and MSL subtypes were associated with higher signature score for angiogenesis. Finally, IM showed high expression levels of immune signatures and check-point inhibitor genes such as PD1, PDL1 and CTLA4.

Conclusion

Our findings highlight for the first time the substantial genomic heterogeneity that characterize TNBC molecular subtypes, allowing for a better understanding of the disease biology as well as the identification of several candidate targets paving novel approaches for the development of anti-cancer therapeutics for TNBC.

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Next generation immunotherapies for lymphoma: one foot in the future

Abstract

Improved understanding of the interactions between cancer cells and the immune system combined with technological advances has led to the development of novel types of immunotherapies. These include checkpoint inhibitors (CPI), T cell engager antibodies (TCE), and Chimeric Antigen Receptor (CAR)-T cells which have demonstrated remarkable efficacy in B-cell malignancies, including anti-PD1 antibodies in Hodgkin lymphoma, and TCE and CAR-T cells in B-ALL, leading to their approval in these indications. Recent clinical data suggest that these immunotherapies may also benefit patients with other types of hematologic malignancies, particularly patients with Hodgkin and non-Hodgkin lymphomas. Here, we review the most recent clinical data regarding these different immunotherapies in patients with lymphoma. Ongoing and future studies should further define which immunotherapy may best apply to a given patient in order to provide a "personalized immunotherapy".

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Genetic Landscape of Ultra-Stable Chronic Lymphocytic Leukemia Patients

Abstract

Background

Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile.

Patients and Methods

Patients with absence of disease progression for over 10 years (11-30) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genomic landscape. Microarray analysis, comparing US-CLL with non US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also performed to recognize US-CLL at diagnosis.

Results

WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients.

Conclusions

The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.

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Evidence of interaction between genes in the folate/homocysteine metabolic pathway in controlling risk of nonsyndromic oral cleft

Abstract

Objective

Little consistent evidence is available for the association between the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene-gene (G×G) interaction.

Subjects and Methods

We selected markers in 18 genes from the pathway and applied the Cordell's method to test for G×G interaction using 1,908 NSCL/P case-parent trios ascertained in an international consortium where a genome-wide association study (GWAS) of oral clefts was conducted.

Results

We found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine-homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genome-wide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, P=1.45×10^-12).

Conclusions

Our study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.

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5-Chloro-2,4-dihydroxypyridine, CDHP, prevents lung metastasis of basal-like breast cancer cells by reducing nascent adhesion formation

Abstract

A drug for metastasis prevention is necessary. The orally administered anticancer drug S-1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast cancer from our previous study, the administration of S-1 inhibited lung metastasis. However, the mechanism of inhibition remains elusive. S-1 contains 5-chloro-2,4-dihydroxypyridine (CDHP), which does not have the antigrowth activity, but prevents the degradation of 5-fluorouracil, an anticancer reagent. In this study, we found that CDHP treatment shrinks cell morphology in metastatic basal-like breast cancer cell lines. Wound healing assays showed reduced cell migration in CDHP-treated cells. At the molecular level, CDHP treatment reduced the number of nascent adhesions, whereas the number of mature focal adhesions was not changed. These findings indicate that CDHP impairs focal adhesion formation, which results in a reduction in cell migration. For the in vivo metastasis assay, we used a highly lung-metastatic cell line. We xenografted them into immunodeficient mice, and administered CDHP. To determine whether CDHP prevents metastasis, we measured the weights of harvested lungs. The results showed that the lung weights of the CDHP-treated animals were not significantly different compared to the no-tumor controls, whereas the vehicle group showed a number of metastatic foci and an increase in lung weight. These observations indicate that CDHP administration prevents metastasis. This study reveals a novel effect of CDHP for lung metastasis prevention. Our findings may facilitate the establishment of future metastasis prevention therapies.

This study found a novel function of 5-chloro-2,4-dihydroxypyridine (CDHP), a component of the anti-cancer drug S-1, on cancer metastasis. CDHP-treated cells reduces cell migration and lung metastasis. Our findings may contribute to the development of metastasis prevention therapies.

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Spatial barriers impact upon appropriate delivery of radiotherapy in breast cancer patients

Abstract

Radiotherapy (RT) is the standard treatment for breast cancer patients after conserving surgery or mastectomy when patients are at high risk of relapse. Major obstacles to appropriate RT delivery are journey times. Since studies on access to RT were carried out mostly in large countries, this study investigated factors in an Italian region and the influence of RT delivery on survival. A total of 4735 female candidates for RT were included in the study. A geographic information system calculated journey times from patients' homes and surgery hospitals to RT centers. Logistic regression analyzed the influence of journey times, socioeconomic status, and other factors on RT delivery. Survival probabilities and excess mortality were assessed in 4364 propensity score-matched patients. Journey times of 40 min or less from residence and from surgery hospital to RT center played a major role in access to RT. A large survival difference emerged between treated and untreated breast cancer patients. The excess mortality for untreated patients compared with propensity score-matched women receiving RT was 3.1 (95% CI: 2.2–4.3). Expansion of RT facilities during the 11-year study period improved RT delivery and outcomes by increasing availability but mainly by shortening journey times.

This is the first European study to investigate the impact of spatial barriers upon appropriate radiotherapy (RT) in breast cancer patients. In Umbria, central Italy, journey times >40 min significantly decreased the probability of receiving RT and were consequently associated with poor outcome. New RT centers provided more patients with appropriate treatment, raising the issue of a "hub and spoke" approach. Spatial barriers to RT in Europe deserve investigation.

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SALL4 - KHDRBS3 network enhances stemness by modulating CD44 splicing in basal-like breast cancer

Abstract

Understanding the mechanism by which cancer cells enhance stemness facilitates cancer therapies. Here, we revealed that a stem cell transcription factor, SALL4, functions to enhance stemness in basal-like breast cancer cells. We used shRNA-mediated knockdown and gene overexpression systems to analyze gene functions. To evaluate stemness, we performed a sphere formation assay. In SALL4 knockdown cells, the sphere formation ability was reduced, indicating that SALL4 enhances stemness. CD44 is a membrane protein and is known as a stemness factor in cancer. CD44 splicing variants are involved in cancer stemness. We discovered that SALL4 modulates CD44 alternative splicing through the upregulation of KHDRBS3, a splicing factor for CD44. We cloned the KHDRBS3-regulated CD44 splicing isoform (CD44v), which lacks exons 8 and 9. CD44v overexpression prevented a reduction in the sphere formation ability by KHDRBS3 knockdown, indicating that CD44v is positively involved in cancer stemness. In addition, CD44v enhanced anoikis resistance under the control of the SALL4 - KHDRBS3 network. Basal-like breast cancer is an aggressive subtype among breast cancers, and there is no effective therapy so far. Our findings provide molecular targets for basal-like breast cancer therapy. In the future, this study may contribute to the establishment of drugs targeting cancer stemness.

This study revealed that the SALL4 - KHDRBS3 network augments stemness through modulation of CD44 splicing in basal-like breast cancer. This network enhances anoikis resistance for stemness. This study may contribute to the establishment of therapies targeting cancer stemness.

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Is there different risk of cancer among end-stage renal disease patients undergoing hemodialysis and peritoneal dialysis?

Abstract

Cancer is a global issue in recent decade. Despite this alarming increase in the incidence of cancer, to date, whether the risk of developing cancer differs among peritoneal dialysis (PD) and hemodialysis (HD) patients is still uncertain. In this retrospective cohort study, data were obtained from the National Health Insurance Research Database of Taiwan, which provides coverage to almost 99% of the nation's population. After matching, a total of 4491 (or 3369) incident PD patients and 8982 (or 6738) incident HD patients between 2000 and 2009 were enrolled from the database. In addition, 22,455 (or 16,845) nondialysis patients were selected as a control group. The patients were monitored for the occurrence of cancer until 2010, and their data were analyzed using several different models. In general, the results showed that the risks of hepatocellular, kidney, bladder, extra kidney/bladder urinary tract, and thyroid cancers were higher in dialysis patients. We also compared the risk of cancer between two dialysis groups by using the HD patients as the reference group. The result showed that there is no significant different for each cancer risk between two dialysis groups. In conclusion, dialysis patients had a higher risk of certain types of cancer than those in the nonuremia group. However, there was no significant difference in the cancer risk between the two dialysis groups when compared directly.

Dialysis patients had a higher risk of some cancer while comparing to nonuremia group. But there is no significant different cancer risk between two dialysis groups if comparing these two groups directly.

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CTAPIII/CXCL7: a novel biomarker for early diagnosis of lung cancer

Abstract

It is desirable to have a biomarker which can facilitate low-dose CT in diagnosis of early stage lung cancer. CTAPIII/CXCL7 is reported to be a potential biomarker for diagnosis of early lung cancer. In this study, we investigated the serum level of CTAPIII/CXCL7 in patients at different stage of lung cancer and the diagnostic efficacy of CTAPIII/CXCL7 in NSCLC. The plasma level of CTAPIII/CXCL7 was assayed by ELISA. CEA, SCCAg, and Cyfra211 were measured using a commercial chemiluminescent microparticle immunoassay. A total of 419 subjects were recruited, including 265 NSCLC patients and 154 healthy individuals. The subjects were randomly assigned to a training set and a test set. Receiver operating characteristic (ROC) and binary logistic regression analyses were conducted to evaluate the diagnostic efficacy and establish diagnostic mathematical model. Plasma CTAPIII/CXCL7 levels were significantly higher in NSCLC patients than in controls, which was independent of the stage of NSCLC. The diagnostic efficiency of CTAPIII/CXCL7 in NSCLC (training set: area under ROC curve (AUC) 0.806, 95% CI: 0.748–0.863; test set: AUC 0.773, 95% CI: 0.711–0.835) was greater than that of SCCAg, Cyfra21-1, or CEA. The model combining CTAPIII/CXCL7 with CEA, SCCAg, and Cyfra21-1 was more effective for NSCLC diagnosis than CTAPIII/CXCL7 alone. In addition, plasma level of CTAPIII/CXCL7 may contribute to the early diagnosis of NSCLC. CTAPIII/CXCL7 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly early stage lung cancer, with relatively high sensitivity and specificity.

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Bragi’s New Product Relieves Tinnitus and Enhances Hearing

Bragi has unveiled a new personal sound amplification product (PSAP), called simply as Bragi Ears, created in collaboration with Mimi Technologies that incorporates personalized hearing enhancement and a solution for hearing issues like tinnitus at this year's CES. Making use of Bragi's in-ear computing technology and Mimi's audio processing technologies, the collaboration, which is called Project Ears, aims to create the world's first intelligent sound amplifier with an embedded pure tone threshold test and give users the best sound based on their hearing profile, or Earprint. Besides optimizing hearing and easing the ringing from tinnitus, Project Ears plans to provide an innovative and chic design as well as deliver a simple user experience through its products. Those interested can help provide feedback and advice to Bragi by signing up on Project Ears' website. A release date and pricing information have not been released yet.

Published: 1/18/2018 12:34:00 PM

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Editorial Board/Aims & Scope

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Straticyte demonstrates prognostic value over oral epithelial dysplasia grade for oral potentially malignant lesion assessment

Available online <Date>

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Viable tumor in salvage neck dissections in head and neck cancer: Relation with initial treatment, change of lymph node size and human papillomavirus

Radiotherapy with or without concomitant systemic treatment is one of the main treatment strategies for patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

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Late radiation-associated dysphagia in head and neck cancer patients: evidence, research and management

In the last decades there has been a significant progress in treatment modalities of head and neck cancer (HNC) patients, especially in radiation therapy (RT) field. Globally, RT improved from three-dimensional to intensity modulated RT (IMRT) technique, which showed to be more effective in terms of target volume coverage and organs at risk (OAR) sparing [1]. Since IMRT plus concomitant chemotherapy – the standard treatment in locally advanced disease – improves survival outcomes achieved after RT alone, as well as increases side effects, great interest has been shown in the clinical evaluation of late RT-related toxicity [2].

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Reconnoitre ameloblastic carcinoma: A prognostic update

Odontogenic tumours (OTs) are rare, heterogeneous group of neoplasms, unique to oral cavity, evolving from tissue associated with tooth development or its remnants. These tumours comprise 1% of all jaw tumours and include hamartomatous, benign as well as malignant entities. Most frequent OT is odontoma considered as 'tooth hamartoma', followed by ameloblastoma [1]. Ameloblastoma is a slow growing, benign and locally invasive neoplasm which may show malignant characteristics such as metastasis with or without cytological atypia.

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Mandibular reconstruction

Since the introduction of free tissue transfer, surgical techniques for mandibular reconstruction have continued to evolve at a rapid pace, leading to improved functional and aesthetic outcomes for patients. Several large series have reported excellent results with a variety of free flap osseous donor sites, establishing microvascular free tissue transfer with bone as the gold standard for reconstruction of the mandible [1–4]. This review will cover current techniques for the reconstruction of mandibular defects, including the various plating strategies for rigid fixation, the choice of osseous donor site, and the concurrent reconstruction of associated soft tissue defects.

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Reader performance in the ultrasonographic evaluation of oropharyngeal carcinoma

Oropharyngeal carcinoma (OPC) is the most common head and neck cancer in North America [1] and is steadily increasing in incidence [2,3]. HPV-related OPC (HPV-OPC) arises primarily from the lymphoid-associated epithelia of the palatine tonsils and base of tongue (BOT) and exhibits a high rate of metastasis to cervical lymph nodes [4,5]. Patients with HPV-OPC often present with a persistently enlarged neck node, unaware of a small primary tumor present in the oropharynx [6]. HPV-OPCs are difficult to assess clinically due to their small size, and the anatomic topology of the oropharynx [6–11].

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Prediction of distant metastasis and survival in adenoid cystic carcinoma using quantitative 18F-FDG PET/CT measurements

Salivary gland cancer is a rare disease that accounts for approximately 5% of all head and neck cancers and 0.3% of all human cancers [1–3]. Salivary gland carcinoma arises in various regions of the major and minor salivary glands, presenting at least 24 different histological subtypes with different clinical features of metastasis and recurrence [4,5]. Distant metastases are relatively common in salivary gland carcinoma [6], and may be present at initial presentation or may emerge during the post-treatment period.

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59 years old male with local advanced adenoid cystic carcinoma of the hypopharynx – A case report and a review of the literature

Anatomically, the palate is the commonest site of minor salivary gland tumours, followed by paranasal sinuses, nasal cavity and the larynx [1]. Adenoid cystic carcinoma (AdCC) is the most common subtype of minor salivary gland tumours representing around 10% of all malignant salivary gland tumour [2]. The main cornerstone of treatment is the surgical resection while the role of radiotherapy and chemotherapy are still controversial [3]. Several prognostic factors have been identified such as free resection margin, nodal negativity and negative neural invasion [3].

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HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers

Recent research has found that human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies, with a reported higher incidence of both tobacco-related and virus-related cancers [1–5]. The higher incidence of tobacco-related cancers among HIV-infected individuals [6,7] has been attributed to the significantly higher prevalence of cigarette smoking among HIV-infected compared with HIV-uninfected individuals (40–60% vs. 17%) [8,9].

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Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma

Recurrent and persistent head and neck squamous cell carcinoma is becoming an increasingly important cohort for head and neck cancer providers. While curative treatment is achieved in many instances, approximately 25–50% of patients with head and neck squamous cell carcinoma will experience recurrence, and the overall median survival for those with recurrent disease who undergo treatment is less than 22 months [1]. Treatment for recurrence tends to be difficult, as these tumors are often resistant to standard therapy, complication rates are higher, and prognosis is guarded [2].

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Assessing miRNAs profile expression as a risk stratification biomarker in oral potentially malignant disorders: A systematic review

Lip, oral cavity and oropharyngeal cancer (OCC-OPC) continues to be a significant worldwide health problem. The global estimated incidence of OCC-OPC is projected to rise by 66.4% by 2030; it specifically will increase from 442,760 in 2012 to 666,432 in 2030 [1]. It is also estimated that OCC-OPC will be responsible for 368,684 deaths in 2030 from that estimated of 241,458 in 2012 [1]. Oral squamous cell carcinoma (OSCC) is the most common form and accounts 95% of all oral malignancies [2]. The prevalence of OSCC is highly related to the consumption of tobacco, smoking, alcohol drinking, betel quid chewing, the presence of human papillomavirus (HPV) and the presence of other carcinogenic stimuli [2–4].

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Sensitivity and specificity of oral HPV detection for HPV-positive head and neck cancer

Human papillomavirus (HPV) is a sexually transmitted infection that causes most oropharyngeal cancer cases in the United States [1,2]. While there are over 100 types of HPV, only 13 are considered carcinogenic, most notably HPV16 [3]. The proportion of oropharyngeal cancers in the U.S. that are caused by HPV has increased from approximately 20% in 1990 to more than 70%, and the incidence of HPV-related oropharyngeal squamous cell carcinoma (HPV-OPSCC) has increased 225% over the past 20 years [2].

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A squamous odontogenic tumor following an orthodontic micro-screw: A rare case report and review of the literature

We reported a very rare case of squamous odontogenic tumor(SOT) in a 23-year-old female. The tumor arose after an implanting operation of an orthodontic micro-screw, and was definitely diagnosed by the histopathological examination. Based on the case report and a review of the literature, we discussed about the general features, differential diagnosis and pathogenesis of SOT.

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Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre-defined institutional treatment policy in a region with a high prevalence of skin cancer

Head and neck squamous cell carcinoma of unknown primary (UKP HNSCC) comprises up to 7% of all HNSCC metastatic to regional lymph nodes in the absence of distant metastatic disease [1].

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Intraoral ultrasonography to measure tumor thickness of oral cancer: A systematic review and meta-analysis

Head and neck cancer is the sixth most common malignancy worldwide of which approximately one third consists of oral squamous cell carcinoma (OSCC) [1,2]. For early OSCC (Stage I-II), surgery is the preferred treatment choice. Its complete removal is essential for locoregional control and disease-free survival [3]. Most authors agree that adequate histopathological resection margins are crucial, although it is debated how wide surgical margins should be [4–9]. For all T-stages, free margins of at least 5 mm to the tumor invasive front are accepted as "negative" resection margins.

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Postoperative staging of the neck dissection using extracapsular spread and lymph node ratio as prognostic factors in HPV-negative head and neck squamous cell carcinoma patients

Lymph node status is one of the most important clinical predictors of survival for head and neck squamous cell carcinoma (HNSCC) patients. The standard pathological nodal staging (pN) of a neck dissection considers the number, size and location of positive lymph nodes.

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Venous thromboembolism incidence in head and neck surgery patients: Analysis of the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database

Venous thromboembolism (VTE), which consists of deep vein thrombosis (DVT) and pulmonary embolism (PE), is the most common preventable cause of mortality in hospitalized patients, accounting for approximately 10% of annual hospital deaths [1,2]. VTE is particularly common post-operatively, as surgery can increase the risk 20-fold [3]. Without prophylaxis, VTE incidence in many surgical patients is estimated to be 15–40% [2]. Certain subsets of surgical patients are known to have an even greater risk of VTE – for example, oncology patients undergoing surgical resection experience an estimated 2 times higher incidence of VTE, as well as increased associated mortality [2–6].

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Influence of tumor and microenvironment characteristics on diffusion-weighted imaging in oropharyngeal carcinoma: A pilot study

In head and neck squamous cell carcinomas (HNSCC) imaging plays a major role in staging, response evaluation and early detection of recurrent disease. Magnetic resonance imaging (MRI) is a modality which is increasingly used, since it provides excellent soft-tissue contrast. Besides conventional anatomical images, additional functional MRI sequences are applied, such as diffusion weighted MRI (DWI). DWI quantifies the restriction of random motion of water molecules in tissues as the apparent diffusion coefficient (ADC) [1,2].

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Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG 1301 study)

Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southern China and South-East Asia. The mainstay treatment is radiotherapy (RT) with or without concurrent chemotherapy (CRT). Lee et al. reported the results of NPC treated in Hong Kong (HK) from 1996 to 2000 [1]. Since then, the standard care of NPC has undergone major changes in the decades that followed, which included adopting the 7th edition of the American Joint Committee on Cancer and International Union Against Cancer (AJCC/UICC) [2,3] staging system, employing magnetic resonance imaging (MRI) as standard radiological staging of loco-regional disease, adding concurrent cisplatin chemotherapy to radiation in patients with loco-regional advanced disease, and using intensity modulated radiotherapy (IMRT) as standard radiotherapy treatment.

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Perspectives on Postmastectomy Breast Reconstruction

How can clinicians better engage their patients to improve decision-making in postmastectomy breast reconstruction?
Plastic Reconstructive Surgery-Global Open (PRS Global Open)

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Patterning of individual heterogeneity in body mass index: evidence from 57 low- and middle-income countries

Abstract

Modeling variation at population level has become increasingly valued, but no clear application exists for modeling differential variation in health between individuals within a given population. We applied Goldstein's method (in: Everrit, Howell (eds) Encyclopedia of statistics in behavioral science, Wiley, Hoboken, 2005) to model individual heterogeneity in body mass index (BMI) as a function of basic sociodemographic characteristics, each independently and jointly. Our analytic sample consisted of 643,315 non-pregnant women aged 15–49 years pooled from the latest Demographic Health Surveys (rounds V, VI, or VII; years 2005–2014) across 57 low- and middle-income countries. Individual variability in BMI ranged from 9.8 (95% CI: 9.8, 9.9) for the youngest to 23.2 (95% CI: 22.9, 23.5) for the oldest age group; 14.2 (95% CI: 14.1, 14.3) for those with no formal education to 19.7 (95% CI: 19.5, 19.9) for those who have completed higher education; and 13.6 (95% CI: 13.5, 13.7) for the poorest quintile to 20.1 (95% CI: 20.0, 20.2) for the wealthiest quintile group. Moreover, variability in BMI by age was also different for different socioeconomic groups. Empirically testing the fundamental assumption of constant variance and identifying groups with systematically large differentials in health experiences have important implications for reducing health disparity.

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Sialolith removal in the submandibular region using surgical diode laser: report of two cases and literature review

Abstract

Purpose

Sialolithiasis is defined as the presence of one or more calcified structures within the duct of a major or minor salivary gland. It occurs as a result of deposition of calcium salts around an accumulation of organic debris in the duct lumen. The main signs and symptoms are edema and bacterial infection with abscess formation.

Methods

This study aimed to report two cases of submandibular sialolithiasis treated surgically with diode laser and conduct a review of the literature by means of a systematic search. In the two cases, the calculi were located in the distal part of the submandibular duct and could be palpated intraorally. Surgery was performed in an outpatient setting under local anesthesia. A linear incision was made in the floor of the mouth, in the region of the opening of Wharton's duct, to expose and remove the calculi. Laser cutting was performed using a diode laser module coupled to a 400-μm optical fiber emitting at a wavelength of 980 nm (infrared), 2.5 W output power, and in continuous pulse mode.

Results

The use of diode laser is a safe and minimally invasive option for this type of procedure.

Conclusion

Offering advantages such as enhanced coagulation properties and high-quality incision, absence of bleeding, low risk of nerve damage, and few comorbidities.

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C11orf95-RELA fusions and upregulated NF-KB signalling characterise a subset of aggressive supratentorial ependymomas that express L1CAM and nestin

Abstract

Ependymomas (EPN) show site specific genetic alterations and a recent DNA methylation profiling study identified nine molecular subgroups. C11orf95-RELA and YAP1 fusions characterise the RELA and YAP1 molecular subgroups, respectively, of supratentorial (ST)-EPNs. Current guidelines recommend molecular subgrouping over histological grade for accurate prognostication. Clinicopathological features of ST-EPNs in correlation with C11orf95-RELA and YAP1 fusions have been assessed in only few studies. We aimed to study these fusions in EPNs, and identify diagnostic and prognostic markers. qRT-PCR and Sanger Sequencing for the detection of C11orf95-RELA, YAP1-MAMLD1 and YAP1-FAM118B fusion transcripts, gene expression analysis for NFKB1, and immunohistochemistry for p53, MIB-1, nestin, VEGF, and L1CAM were performed. 88 EPNs (10-Grade I and 78-Grade II/III) from all sites were included. RELA fusions were unique to Grade II/III ST-EPNs, detected in 81.4% (22/27) and 18.5% (5/27) of pediatric and adult ST-EPNs respectively. ST-EPNs harbouring RELA fusions showed frequent grade III histology (81.5%), clear cell morphology (70.3%), upregulated NFKB1 expression, MIB-1 labelling indices (LI) ≥ 10% (77.8%), and immunopositivity for nestin (95.7%), VEGF (72%), L1CAM (79%), and p53 (64%). Presence of RELA fusions, L1CAM immunopositivity and MIB-1 LI ≥ 10% associated with poor outcome. L1CAM showed 81% concordance with RELA fusions. YAP1-MAMLD1 fusion was identified in a single RELA fusion negative adult anaplastic ST-EPN. RELA fusions are frequent in ST-EPNs and associate with poor outcome. L1CAM is a surrogate immunohistochemical marker. RELA fusion positive ST-EPNs strongly express nestin indicating increased stemness. Further evaluation of the interactions between NFKB and stem cell pathways is warranted.

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Patterning of individual heterogeneity in body mass index: evidence from 57 low- and middle-income countries

Abstract

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Luigi Porta’s contribution to anesthesia in Europe in the 1800s

Abstract

Luigi Porta (1800–1875), an Italian physician who was well known in the field of surgery, played an important role in spreading ethereal anesthesia in Europe. Moreover, he proposed an original method to administer ethereal anesthesia, the Italian method "of the bladder of pig". This paper reminds us of the important role that this physician played in Anesthesiology.

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Depressive symptoms predict head and neck cancer survival: Examining plausible behavioral and biological pathways

BACKGROUND

Head and neck cancers are associated with high rates of depression, which may increase the risk for poorer immediate and long-term outcomes. Here it was hypothesized that greater depressive symptoms would predict earlier mortality, and behavioral (treatment interruption) and biological (treatment response) mediators were examined.

METHODS

Patients (n = 134) reported depressive symptomatology at treatment planning. Clinical data were reviewed at the 2-year follow-up.

RESULTS

Greater depressive symptoms were associated with significantly shorter survival (hazard ratio, 0.868; 95% confidence interval [CI], 0.819-0.921; P < .001), higher rates of chemoradiation interruption (odds ratio, 0.865; 95% CI, 0.774-0.966; P = .010), and poorer treatment response (odds ratio, 0.879; 95% CI, 0.803-0.963; P = .005). The poorer treatment response partially explained the depression-survival relation. Other known prognostic indicators did not challenge these results.

CONCLUSIONS

Depressive symptoms at the time of treatment planning predict overall 2-year mortality. Effects are partly influenced by the treatment response. Depression screening and intervention may be beneficial. Future studies should examine parallel biological pathways linking depression to cancer survival, including endocrine disruption and inflammation. Cancer 2018. © 2018 American Cancer Society.

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Treatment of Post Anoxic Action Myoclonus with Intrathecal Baclofen: A Case Report

A case of severe action myoclonus following pulmonary arrest is described. Although there was benefit from oral pharmacotherapy, action myoclonus remained disabling. A favorable response to baclofen during an intrathecal trial led to eventual placement of an intrathecal baclofen pump. The present case illustrates the potential utility of intrathecal baclofen for treating this condition.

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Deformable image registration–based contour propagation yields clinically acceptable plans for MRI-based cervical cancer brachytherapy planning

Publication date: Available online 10 January 2018
Source:Brachytherapy
Author(s): Christina Hunter Chapman, Daniel Polan, Karen Vineberg, Shruti Jolly, Katherine E. Maturen, Kristy K. Brock, Joann I. Prisciandaro
PurposeTo study the dosimetric impact of deformable image registration–based contour propagation on MRI-based cervical cancer brachytherapy planning.Methods and MaterialsHigh-risk clinical target volume (HRCTV) and organ-at-risk (OAR) contours were delineated on MR images of 10 patients who underwent ring and tandem brachytherapy. A second set of contours were propagated using a commercially available deformable registration algorithm. "Manual-contour" and "propagated-contour" plans were optimized to achieve a maximum dose to the most minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25 Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] + brachytherapy, respectively). Plans were compared using geometric and dosimetric (total dose [EQD2] EBRT + brachytherapy) parameters.ResultsThe differences between the manual- and propagated-contour plans with respect to the HRCTV D90 and bladder, rectum, and sigmoid D2cc were not statistically significant (per-fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the manually contoured OARs by the propagated-contour plans ranging 98–107%, 95–105%, and 92–108% of the dose delivered by the manual-contour plans (max 90.4, 70.3, and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose in the propagated-contour plans was 97–103% of the dose in the manual-contour plans (maximum difference 2.92 Gy). Increased bladder filling resulted in increased bladder dose in manual- and propagated-contour plans.ConclusionsWhen deformable image registration–propagated contours are used for cervical brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual-contour plans and the doses delivered to the OARs are clinically acceptable, suggesting that our algorithm can replace manual contouring for appropriately selected cases that lack major interfractional anatomical changes.

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Comments on “Low-dose-rate prostate brachytherapy: 4–8 week postimplant prostate-specific antigen a novel predictor of biochemical failure-free survival”

Publication date: Available online 10 January 2018
Source:Brachytherapy
Author(s): Kamyar Mansori, Erfan Ayubi, Saeid Safiri

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Validation of MRI to TRUS registration for high-dose-rate prostate brachytherapy

Publication date: Available online 10 January 2018
Source:Brachytherapy
Author(s): Eric Poulin, Karim Boudam, Csaba Pinter, Samuel Kadoury, Andras Lasso, Gabor Fichtinger, Cynthia Ménard
PurposeThe objective of this study was to develop and validate an open-source module for MRI to transrectal ultrasound (TRUS) registration to support tumor-targeted prostate brachytherapy.Methods and MaterialsIn this study, 15 patients with prostate cancer lesions visible on multiparametric MRI were selected for the validation. T2-weighted images with 1-mm isotropic voxel size and diffusion weighted images were acquired on a 1.5T Siemens imager. Three-dimensional (3D) TRUS images with 0.5-mm slice thickness were acquired. The investigated registration module was incorporated in the open-source 3D Slicer platform, which can compute rigid and deformable transformations. An extension of 3D Slicer, SlicerRT, allows import of and export to DICOM-RT formats. For validation, similarity indices, prostate volumes, and centroid positions were determined in addition to registration errors for common 3D points identified by an experienced radiation oncologist.ResultsThe average time to compute the registration was 35 ± 3 s. For the rigid and deformable registration, respectively, Dice similarity coefficients were 0.87 ± 0.05 and 0.93 ± 0.01 while the 95% Hausdorff distances were 4.2 ± 1.0 and 2.2 ± 0.3 mm. MRI volumes obtained after the rigid and deformable registration were not statistically different (p > 0.05) from reference TRUS volumes. For the rigid and deformable registration, respectively, 3D distance errors between reference and registered centroid positions were 2.1 ± 1.0 and 0.4 ± 0.1 mm while registration errors between common points were 3.5 ± 3.2 and 2.3 ± 1.1 mm. Deformable registration was found significantly better (p < 0.05) than rigid registration for all parameters.ConclusionsAn open-source MRI to TRUS registration platform was validated for integration in the brachytherapy workflow.

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A Medicare cost analysis of MRI- versus CT-based high-dose-rate brachytherapy of the cervix: Can MRI-based planning be less costly?

Publication date: Available online 10 January 2018
Source:Brachytherapy
Author(s): Amishi Bajaj, Grant Harmon, John Weaver, Brendan Martin, Michael Mysz, Murat Surucu, John C. Roeske, Andre A. Konski, William Small, Matthew M. Harkenrider
PurposeWhile some institutions deliver multiple fractions per implant for MRI-based planning, it is common for only one fraction to be delivered per implant with CT-based cervical brachytherapy. The purpose of this study was to compare physician costs, hospital costs, and overall costs for cervical cancer patients treated with either CT-based or MRI-based high-dose-rate (HDR) cervical brachytherapy to determine if MRI-based brachytherapy as described can be financially feasible.Methods and MaterialsWe identified 40 consecutive patients treated with curative intent cervical brachytherapy. Twenty patients underwent CT-based HDR brachytherapy with five fractions delivered in five implants on nonconsecutive days in an outpatient setting with the first implant placed with a Smit sleeve under general anesthesia. Twenty patients received MRI-based HDR brachytherapy with four fractions delivered in two implants, each with MRI-based planning, performed 1–2 weeks apart with an overnight hospital admission for each implant. We used Medicare reimbursements to assess physician costs, hospital costs, and overall cost.ResultsThe median cost of MRI-based brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32–$15,539.74), making it less costly than CT-based brachytherapy with conscious sedation (i.e., $18,278.85; IQR: $17,323.13–$19,863.03, p < 0.0001) and CT-based brachytherapy with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR: $26,935.14–$29,511.16, p < 0.0001). CT-based brachytherapy with conscious sedation was more costly than CT-based brachytherapy with deep sedation (p < 0.001).ConclusionsMRI-based brachytherapy using the described treatment course was less costly than both methods of CT-based brachytherapy. Cost does not need to be a barrier for MRI-based cervical brachytherapy, especially when delivering multiple fractions with the same application.

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Assessment of a source position checking tool for the quality assurance of transfer tubes used in HDR 192Ir brachytherapy treatments

Publication date: Available online 17 January 2018
Source:Brachytherapy
Author(s): O.A. Awunor
PurposeThe determination of source positions before treatment is an essential part of the quality assurance (QA) associated with high dose rate brachytherapy treatments. The purpose of this study was to design and commission a tool to allow the quantification of source positions across multiple transfer tube types.Methods and MaterialsA bespoke flexi-adapter jig, three transfer tube adapters, and a film piercing pointer were designed and built for source position QA across three transfer tube types—the standard, 6 French, and gynae transfer tubes. The jig was calibrated against a manufacturer source position check tool, and intratube and intertube source position variations investigated across a total of 40 transfer tubes, using strips of Gafchromic film irradiated at multiple positions 20 mm apart with a microSelectron V3 afterloader (Elekta, Holland). The performance of the jig in localizing the nominal dwell positions relative to the manufacturer check tool was assessed. Associated expanded uncertainties were quantified in line with the International Organization for Standardization Guidelines.ResultsThe mean expanded uncertainty associated with the use of the jig was 0.4 ± 0.0 mm (k = 1). The performance of the jig was 0.3 ± 0.0 mm, while the intratube and intertube source positional variations were observed to be within ±1.0 mm across most transfer tubes.ConclusionsA bespoke flexi-adapter jig capable of allowing source position measurements to be carried out on various transfer tube types has been designed. Measurement results highlight the need for routine QA of all transfer tubes in clinical use.

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Outcomes of Radioembolization in Patients with Chemorefractory Colorectal Cancer Liver Metastasis: a Single-Center Experience

Abstract

Purpose

We aimed to evaluate the efficacy and outcomes of radioembolization with Yttrium-90 (Y-90) microspheres in patients with unresectable and chemorefractory colorectal cancer liver metastasis (CRCLM).

Methods

This single-center study included 43 patients (34 male, 9 female) who underwent radioembolization with Y-90 for unresectable, chemorefractory CRCLM between September 2008 and July 2014. Overall survival (OS), liver progression-free survival (LPFS), overall response rate (ORR), local disease control rate (LDCR), and relations of these parameters with patient disease characteristics were evaluated. OS and LPFS rates were compared according to microspheres. Survival rates were calculated with Kaplan-Meier method, and potential prognostic variables were evaluated on univariate analyses.

Results

Post-procedural median OS was 12.8 months. LPFS was 5.6 months. ORR was 33%, LDCR was 67% on 3rd month follow-up. Low tumor burden (< 25%) was associated with higher median OS after radioembolization (< 25 vs > 25–50% p < 0.0001 and < 25 vs > 50% p = 0.005). Patients with left colon tumors exhibited significantly longer median OS after metastasis than right colon tumors (p = 0.046). Extrahepatic disease and synchronicity showed poorer survival parameters; however, the difference was not significant (p = 0.1 and p = 0.3, respectively). In subgroup analyses, the distribution of patient number and characteristics showed heterogeneity as number of patients with low tumor burden was higher in resin Y-90 group. Resin Y-90 group exhibited significantly higher median OS and LPFS compared to glass Y-90 group (16.5 vs. 7 months, p = 0.001; 6.73 vs. 3.38 months, p = 0.023, respectively).

Conclusion

Radioembolization is a safe local-regional treatment option in chemorefractory, inoperable CRCLM. Radioembolization at earlier stages may lead to more favorable results especially with lower tumor burden patients.

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Evaluating Treatment Patterns for Small Cell Carcinoma of the Colon Using the National Cancer Database (NCDB)

Abstract

Objective(s)

The objective of this study was to characterize the clinicopathological prognostic factors and treatment patterns for small cell carcinoma (SCC) of the colon, a rare disease without standard treatment guidelines.

Methods

We analyzed clinicopathological and treatment variables for 503 cases of histologically proven SCC colon entered into the National Cancer Database (NCDB) between 2004 and 2013. Survival curves were generated using Kaplan-Meier and compared by the log-rank test. Cox proportional hazard regression was used to control for covariates and evaluate the effect of different treatment modalities on overall survival.

Results

Four hundred seventy-two (93.8%) patients had complete clinical staging information and were therefore included in our analysis. Of these patients, 149 (31.5%) had limited stage disease (LD) and 323 (68.4%) had extensive stage disease (ED) at presentation. Median overall survival (OS) for patients with ED was significantly lower than for those with LD (4.04 months vs. 21.82 months; p < 0.001). Multivariate Cox regression analysis showed administration of chemotherapy was associated with improved survival in patients with LD and ED (p = 0.026, p < 0.001) while surgery was not associated with improved survival in patients with LD or ED (p = 0.943, p = 0.630). Radiation therapy was associated with improved survival in patients with ED (p = 0.044).

Conclusions

SCC of the colon carries a poor prognosis, especially in patients presenting with metastatic disease. Surgery and chemotherapy are administered more frequently than radiation, and chemotherapy is associated with improved survival, unlike surgery.

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Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma

Abstract

Background

An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB.

Methods

We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA). Landmark analysis at 6 weeks was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Cox and logistic regression models allowed for adjustment of line of therapy, number of IMDC risk factors, histology and baseline NLR.

Results

Median follow up was 16.6 months (range: 0.7–67.8). Median duration on therapy was 5.1 months (<1–61.4). IMDC risk groups were: 18% favorable, 60% intermediate, 23% poor-risk. Forty-four percent were on first-line ICB and 56% on 2nd line or more. Median NLR was 3.9 (1.3–42.4) at baseline and 4.1 (1.1–96.4) at week 6. Patients with a higher baseline NLR showed a trend toward lower ORR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was a significantly stronger predictor of all three outcomes than baseline NLR. Relative NLR change by ≥25% from baseline to 6 weeks after ICB therapy was associated with reduced ORR and an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.004), whereas a decrease in NLR by ≥25% was associated with improved outcomes.

Conclusions

Early decline and NLR at 6 weeks are associated with significantly improved outcomes in mRCC patients treated with ICB. The prognostic value of the readily-available NLR warrants larger, prospective validation.

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Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Abstract

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = −0.24 to −0.73; P < 1.49 × 10⁻⁴), and lower thickness in the precentral gyri bilaterally (d = −0.34 to −0.52; P < 4.31 × 10⁻⁶). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = −1.73 to −1.91, P < 1.4 × 10⁻¹⁹), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = −0.36 to −0.52; P < 1.49 × 10⁻⁴). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = −0.29 to −0.54; P < 1.49 × 10⁻⁴). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = −0.27 to −0.51; P < 1.49 × 10⁻⁴). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < −0.0018; P < 1.49 × 10⁻⁴). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

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Surgical treatment of enterovirus D68 brainstem encephalitis-induced dysphagia

Cluster of acute flaccid paralysis and cranial nerve dysfunction was associated with a 2014 outbreak of enterovirus D68 (EV-D68) respiratory illness in US. We describe a 33 year-old male patient of refractory dysphagia due to EV-D68-induced brainstem encephalitis successfully treated by surgery. Following acute upper respiratory tract infection, he developed dysphagia and bilateral facial paralysis. A coughing reflex was readily produced when the laryngopharyngeal fiberscope touched the epiglottis, however, water infusion induced only very weak and slow swallowing reflex, suggesting that only motor component was impaired but sensory function was preserved during swallowing.

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Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print

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Response to growth hormone treatment in very young patients with growth hormone deficiencies and mini-puberty

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print

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Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print

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Differential effects of secukinumab vs. ustekinumab for treatment of psoriasis on quality of life, work productivity and activity impairment: a structural equation modelling analysis

Abstract

Purpose

This study examined direct and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of life, work productivity, and activity impairment based on psoriasis severity and symptoms.

Methods

Analyses were based on data from the CLEAR study. Structural equation modelling (SEM) examined the effects of secukinumab vs. ustekinumab on the Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity Impairment (WPAI) questionnaire using Psoriasis Area Severity Index (PASI) severity and symptoms (pain, itching, and scaling) as potential mediators. Analyses were conducted primarily for patients achieving PASI 90 response (indicating a 90% or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and for PASI 50, 75, and 100.

Results

Results at weeks 16 and 52 showed that the effect of treatment on change in DLQI score was mediated by PASI 90 response and by improvements in itching and scaling. Achieving any PASI response as early as week 16 directly resulted in significantly better WPAI scores. At week 52, both PASI response and improvement in scaling directly resulted in significantly better WPAI scores. Pain, itching, and scaling were correlated (r = 0.51 to 0.68); improvement in any of these had a significant effect (directly or indirectly) on WPAI. All results favoured secukinumab over ustekinumab.

Conclusion

The results underscore the important role of both PASI response and reduction in symptoms on improvements in health-related quality of life and work and daily activity in favour of secukinumab vs. ustekinumab.

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How should minimally important change (MIC) scores for the Patient Oriented Eczema Measure (POEM) be interpreted? A validation using varied methods

Summary

Background

The Patient Oriented Eczema Measure (POEM), scored 0-28, is the core outcome instrument recommended for measuring patient-reported atopic eczema symptoms in clinical trials. To date, two published studies have broadly concurred that the MIC of the POEM is 3 points. Further assessment of the minimally important change (MIC) of POEM in different populations, and using a variety of methods, will improve interpretability of the POEM in research and clinical practice.

Objectives

To calculate the smallest detectable change in the POEM and estimate the MIC of the POEM using a variety of methods in a trial dataset of children with moderate to severe atopic eczema.

Methods

This study used distribution-based and anchor-based methods to calculate the MIC of the POEM in children with moderate to severe eczema.

Results

Data was collected from 300 children. The smallest detectable change was 2.12. The MIC estimates were 1.07 (0.2 SD) and 2.68 (0.5 SD) based on distribution-based methods, were 3.09 to 6.13 based on patient-reported anchor-based methods, and were 3.23 to 5.38 based on investigator-reported anchor-based methods.

Conclusions

We recommend the following thresholds are used to interpret changes in POEM scores: ≤ 2, unlikely to be a change beyond measurement error; 2.1 to 2.9, a small change detected that is likely to be beyond measurement error but may not be clinically important; 3 to 3.9, probably a clinically important change; 4+, very likely to be a clinically important change.

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In vivo dermoscopic and confocal microscopy multi-step algorithm to detect in situ melanomas

Summary

Background

Although several dermoscopic features of in situ melanoma (MIS) have been identified, data on confocal features for MIS are still lacking.

Objectives

To identify RCM (reflectance confocal microscopy) features of MIS and to develop a diagnostic score for MIS while combining dermoscopy and RCM.

Methods

120 MIS and 213 nevi (test set) were retrospectively analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral lesions have been excluded. Spearman's correlation, univariate and multivariate regression models were performed to find features significantly correlated with MIS diagnosis. Multivariate results on the test set allowed the development of a multi-step algorithm, that was tested on a validation set counting 100 lesions.

Results

Dermoscopic atypical network and regression resulted as independent predicting factors for MIS diagnosis (OR=3.437, 95%CI=1.696-6.966 and OR=4.168, 95%CI=1.930-9.002 respectively). Significant confocal predictors for malignancy were epidermal pagetoid spread (OR=2.829, 95%CI=1.324-6.043) and junctional cytological atypia (OR=3.390, 95%CI=1.383-8.305 if focal, OR=8.439, 95%CI=3.213-22.165 if widespread). A multi-step diagnostic algorithm able to predict MIS with a sensitivity of 92.5% and a specificity of 61% was developed. The validation set confirmed the high diagnostic value (sensitivity 92%, specificity 58%).

Conclusions

An easy and reproducible multi-step algorithm for MIS detection is suggested, that can be routinely used in tertiary centres.

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Expression analysis of High-mobility group box-1 (HMGB1) in histologic samples of malignant pleural mesothelioma

Abstract

Aims

High-mobility group box-1 (HMGB1) is a chromatin structural protein, ubiquitously expressed in the nuclei of mammalian cells. When transported extracellularly, it acts as tumor suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of High-mobility group box-1 (HMGB1) have been related to a poor prognosis. Conversely the significance of HMGB1 expression in malignant pleural mesothelioma (MPM) tissues is still unclear.

Methods and results

Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semi-quantitative system, that sums the intensity (0-3) and the percentage (from 0-4) of positively stained cells, in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated with ΔΔC_t method. High expression levels of HMGB1 as total (P = 0,0011) and cytoplasmic score (P = 0,0462), were related with a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathologic subgroups. No significant correlation was found between HMGB1 gene expression and DSS.

Conclusions

These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, since it is expressed also in normal and reactive mesothelial cells, HMGB1 can not be considered a diagnostic biomarker, in histologic samples of mesothelioma.

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Predicting the Hearing Outcome in Sudden Sensorineural Hearing Loss via Machine Learning Models

Abstract

Objective

Sudden sensorineural hearing loss (SSHL) is a multifactorial disorder with high heterogeneity, thus the outcomes vary widely. The present study aimed to develop predictive models based on four machine learning methods for SSHL, identifying the best performer for clinical application.

Design

Single-center retrospective study.

Setting

Chinese People's liberation army (PLA) hospital, Beijing, China.

Participants

1220 in-patient SSHL patients were enrolled between June 2008 and December 2015.

Main outcome measures

An advanced deep learning technique, deep belief network (DBN), together with the conventional logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) were developed to predict the dichotomized hearing outcome of SSHL by inputting six feature collections derived from 149 potential predictors. Accuracy, precision, recall, F-score and the area under the receiver operator characteristic curves (ROC-AUC) were exploited to compare the prediction performance of different models.

Results

Overall the best predictive ability was provided by the DBN model when tested in the raw dataset with 149 variables, achieving an accuracy of 77.58% and AUC of 0.84. Nevertheless DBN yielded inferior performance after feature pruning. In contrast, the LR, SVM and MLP models demonstrated opposite trend as the greatest individual prediction powers were obtained when included merely three variables, with the ROC-AUC ranging from 0.79 to 0.81, and then decreased with the increasing size of input features combinations.

Conclusions

With the input of enough features, DBN can be a robust prediction tool for SSHL. But LR is more practical for early prediction in routine clinical application by using three readily available variables, i.e. time elapse between symptom onset and study entry, initial hearing level and audiogram.

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Dedifferentiated Fat (DFAT) Cells: a cell source for oral and maxillofacial tissue engineering

Abstract

Tissue engineering is a promising method for the regeneration of oral and maxillofacial tissues. Proper selection of a cell source is important for the desired application. This review describes the discovery and usefulness of Dedifferentiated Fat (DFAT) cells as a cell source for tissue engineering. DFAT cells are a highly homogeneous cell population (high purity), highly proliferative, and possess a multilineage potential for differentiation into various cell types under proper in vitro inducing conditions and in vivo. Moreover, DFAT cells have a higher differentiation capability of becoming osteoblasts, chondrocytes, and adipocytes than do bone marrow-derived mesenchymal stem cells and/or adipose tissue-derived stem cells. The usefulness of DFAT cells in vivo for periodontal tissue, bone, peripheral nerve, muscle, cartilage, and fat tissue regeneration were reported. DFAT cells obtained from the human buccal fat pad (BFP) is a minimally invasive procedure with limited aesthetic complications for patients. The BFP is a convenient and accessible anatomical site to harvest DFAT cells for dentists and oral surgeons, and thus is a promising cell source for oral and maxillofacial tissue engineering.

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The role of the rehabilitation in subjects with Progressive Supranuclear Palsy: a narrative review

Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder due to the deposition of abnormal proteins in neurons of the basal ganglia that limit motor ability producing disability and reduced quality of life. So far, no pharmacologic therapy has been developed and the treatment remains symptomatic. The aim of the present study was to investigate systematically literature, and to determine the types and effects of rehabilitative interventions. A search of all studies was conducted in MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL and EMBASE.

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The oxymoron of image-guided resection in 3 T MRI-negative extratemporal epilepsy: Technique and postoperative results

Publication date: March 2018
Source:Clinical Neurology and Neurosurgery, Volume 166
Author(s): Evangelos Kogias, Petros Evangelou, Barbara Schmeiser, Peter C. Reinacher, Dirk-Matthias Altenmüller
ObjectiveWe share our experience with extratemporal MRI-negative epilepsies that received "image-guided" resection with the use of neuronavigation after invasive presurgical video-EEG monitoring. We describe and discuss our technique of image generation, navigation system registration, and surgical resection. In addition, we evaluate seizure outcome with respect to the preoperatively planned versus achieved resection.Patients and MethodsSeven patients with 3 T MRI-negative extratemporal epilepsy received navigation-guided resective surgery. The resection plan was based on electrophysiological data from intracranial EEG recordings. For each case a resection segment was created in the neuronavigation device in a systematic manner. We compared the preoperatively planned segment to the achieved resection and looked for correlation with postoperative seizure outcome according to Engel classification, at last follow-up (mean 2.4 years, range 1–4 years).ResultsMean volume of planned resections was 23.8 ± 15.3 cm³ and of achieved resections 17 ± 10.4 cm³. There was complete overlap with planned resection in 4 patients and partial overlap in 3. Postoperative seizure outcome was class I in 4 patients (57%), IIIA in 1 patient and IVB in 2 patients. Three patients reached seizure-freedom (Engel IA). Volume of planned resection, volume difference of planned versus achieved resection and level of overlap (complete versus partial) did not significantly correlate to seizure outcome.ConclusionThe use of neuronavigation for planning and executing a tailored resection in MRI-negative extratemporal epilepsy is elaborate but can be an effective procedure.

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Increased PT/SS may play an important role in the pathogenesis of lumbar spondylolisthesis with degenerative lumbar scoliosis

Publication date: March 2018
Source:Clinical Neurology and Neurosurgery, Volume 166
Author(s): Jinlei Zhang, Yong Hai, Jincai Yang, Aixing Pan, Yangpu Zhang
ObjectiveTo explore the clinical and spinopelvic features in patients with lumbar spondylolisthesis and degenerative lumbar scoliosis (LSDLS) and those with standalone lumbar spondylolisthesis (SALS).Patients and MethodsWe retrospectively analyzed 130 patients with lumbar spondylolisthesis seen between 05/2013 and 12/2016 in our hospital. Propensity score matching was used to reduce an age distribution imbalance between the two groups. Clinical and spinopelvic parameters were compared by independent samples t test and chi-square test. Nonlinear binary logistic regression analysis was used to analyze the independent factors.ResultsThere was no significant difference between groups for body mass index, level of intercrest line, level of spondylolisthesis, grade of spondylolisthesis, sagittal translation, segmental angulation, thoracic kyphosis, or sagittal vertical axis. The LSDLS group had significantly lower lumbar lordosis (LL) than the SALS group. The LSDLS group showed significantly greater pelvic tilt (PT) and ratio of PT to SS (sacral slope) (PT/SS), and lower SS. The pelvic incidence (PI) was not significantly different. The LSDLS group showed stronger significant differences in PT/SS compared to the SALS group. With each 0.1 increase in PT/SS, the risk of LSDLS increased 1.465 times.ConclusionsPatients with spondylolysis are less prone to development of DLS. Lower LL and SS, and higher PT are associated with the occurrence of LSDLS. Increased PT/SS may play an important role in the pathogenesis of LSDLS.

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The stereotactic suboccipitaltranscerebellar approach to lesions of the brainstem and the cerebellum

Publication date: March 2018
Source:Clinical Neurology and Neurosurgery, Volume 166
Author(s): Julia M. Nakagawa, Michael Trippel, Soroush Doostkam, Irina Mader, Volker A. Coenen, Peter C. Reinacher
ObjectiveThe stereotactic suboccipital-transcerebellar approach is widely regarded as technically demanding requiring substantial modifications of the standard stereotactic methods thus often making a transfrontal approach preferable.In this comprehensive series we aim to present our experience with the stereotactic suboccipital-transcerebellar approach to lesions of the brainstem or cerebellum using two standard stereotactic systems.Patients and MethodsIn the period of 2000–2015 overall 80 patients (mean age 43.95 ± 23.76 years) with lesions of the brainstem or cerebellum underwent stereotactic surgery for diagnostic or therapeutic purposes via a suboccipital approach. In 59 patients stereotactic surgery was performed using the Riechert-Mundinger Stereotactic Frame, the Leksell Stereotactic Frame was used in 21 patients. For both frames standard systems were used without modification. Retrospective analysis of intraoperative stereotactic technique, achievement of the predefined surgical objectives and perioperative complications was carried out.ResultsIn this series, the stereotactic suboccipital-transcerebellar approach proved to be feasible with two standard stereotactic systems. Using either frame the predefined surgical objective was achieved in 90.0%. A verified neuropathological diagnosis was obtained in 89.6%. Minor transient perioperative complications occurred in 8.75%. There was no surgery-related permanent morbidity or mortality.ConclusionIn this comprehensive series the stereotactic suboccipital-transcerebellar approach using a standard stereotactic system proved to be a favorable stereotactic approach with a high diagnostic success rate and no surgery-related permanent morbidity.

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Simple laryngeal suspension procedure by suturing the digastric muscle to the periosteum of the mandible in neck dissection for tongue cancer

In this article, a simple, new laryngeal suspension procedure is described. The effect of hyoid bone suspension by suturing the digastric muscle to the periosteum of the mandible is analyzed.

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Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia

Abstract

Objectives

Dental anxiety level has been previously associated with oral health status. Since general anesthesia (GA) allows dental treatments to be performed in anxious children with a high number of caries, we aimed to evaluate the dental anxiety levels of these children before and after dental treatments performed under GA.

Materials and methods

Thirty-eight children with high anxiety aged between 35 and 72 months who required multiple dental treatments to be performed under GA were included in the study. Frankl's Behavior Rating Scale, sitting patterns, Facial Image Scale, and Children's Fear Survey Schedule-Dental Subscale (completed by the children's parents) were recorded before and after the dental treatments performed under GA. Pre-treatment and post-treatment biochemical parameters, including cortisol, alpha-amylase, and chromogranin A levels, in saliva and serum samples were also evaluated.

Results

The psychometric scales showed a statistically significant reduction in the post-treatment dental anxiety levels of the children compared with the pre-treatment anxiety levels. Additionally, the biochemical parameters measured in the serum and whole saliva samples showed a decrease after treatments performed under GA.

Conclusions

Our study results suggest that performing dental treatments under GA can reduce the dental anxiety levels of children with a high number of caries.

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Industrial Symbiosis Between the Winery and Environmental Industry Through the Utilization of Grape Marc for Water Desalination Containing Copper(II)

Abstract

A bioadsorbent formulated with a secondary raw material, consisting of grape marc, subjected to a bioxidize process and entrapped in calcium alginate beads, was used for the desalination of water containing copper(II) sulfate. Experiments were established under different experimental conditions varying the concentration of contaminant, the amount of bioadsorbent, and the extraction time through response surface methodology. The most significant variable in the removal of copper(II) sulfate was the amount of bioadsorbent employed, followed by the extraction time; whereas, the adsorbent capacity was more influenced by the amount of contaminant and the amount of bioadsorbent used. At the highest concentration of copper(II) sulfate (0.15 mol/L), the equations obtained predict that the bioadsorbent has a capacity of 2785 mg/g and produces a copper(II) removal about 43% using low adsorbent/water ratios, 1:10 (v/v), and maximum extraction times; whereas, it would remove 97.2% of copper(II) sulfate in 5 min, using adsorbent/water ratios close to 1:2 (v/v), with capacity values, in this case, around 1800 mg/g. The encapsulation of the bioxidize adsorbent increased its capacity to 30% and allowed the precipitation of sulfate ions as calcium sulfate. The results obtained in this work could presume advances for promoting the industrial symbiosis between winery and environmental industries. Graphical abstract

Utilization of secondary raw material, consisting of bioxidize grape marc from winery industry, as bioadsorbent encapsulated in calcium alginate beads, for the removal of copper(II) sulfate from water

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Quantitative evaluation of dental anxiety indicators in the serum and saliva samples of children treated under general anesthesia

Abstract

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Materials and methods

Results

Conclusions

Our study results suggest that performing dental treatments under GA can reduce the dental anxiety levels of children with a high number of caries.

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Αρχειοθήκη ιστολογίου

Κυριακή 21 Ιανουαρίου 2018

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