bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations
Authors: Tetzlaff Michael T. , Curry Jonathan L. , Ning Jing , Sagiv Oded , Kandl Thomas L. , Peng Bo , Bell Diana , Routbort Mark , Hudgens Courtney W. , Ivan Doina , Kim Tae-Boom , Chen Ken , Eterovic Agda Karina , Shaw Kenna , Prieto Victor G. , Yemelyanova Anna , Esmaeli Bita 
Published: November 2018

Abstract

Purpose:
Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies.

Experimental Design:
We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients.

Results:
We delineate two potentially distinct molecular-genetic subtypes of OA sebaceous carcinoma. The first is defined by somatic mutations impacting TP53 and/or RB1 [20/29 (70%) patients, including 10 patients whose primary tumors contained coexisting TP53 and RB1 mutations] with frequent concomitant mutations affecting NOTCH genes. These tumors arise in older patients and show frequent local recurrence. The second subtype [9/29 (31%) patients] lacks mutations affecting TP53, RB1, or NOTCH family members, but in 44% (4/9) of these tumors, RNA sequencing and in situ hybridization studies confirm transcriptionally active high-risk human papillomavirus. These tumors arise in younger patients and have not shown local recurrence.

Conclusions:
Together, our findings establish a potential molecular-genetic framework by which to understand the development and progression of OA sebaceous carcinoma and provide key molecular-genetic insights to direct the design of novel therapeutic interventions.
Whole-body Imaging of Cell Death Provides a Systemic, Minimally Invasive, Dynamic, and Near-real Time Indicator for Chemotherapeutic Drug Toxicity
Authors: Johnson Steven E. , Ugolkov Andrey , Haney Chad R. , Bondarenko Gennadiy , Li Lin , Waters Emily A. , Bergan Raymond , Tran Andy , O'Halloran Thomas V. , Mazar Andrew , Zhao Ming 
Published: November 2018

Abstract

Purpose:
Response to toxicity in chemotherapies varies considerably from tissue to tissue and from patient to patient. An ability to monitor the tissue damage done by chemotherapy may have a profound impact on treatment and prognosis allowing for a proactive management in understanding and mitigating such events. For the first time, we investigated the feasibility of using whole-body imaging to map chemotherapeutic drug–induced toxicity on an individual basis.

Experimental Design:
In a preclinical proof-of-concept, rats were treated with a single clinical dose of cyclophosphamide, methotrexate, or cisplatin. In vivo whole-body imaging data were acquired using 99mTc-duramycin, which identifies dead and dying cells as an unambiguous marker for tissue injury in susceptible organs. Imaging results were cross-validated using quantitative ex vivo measurements and histopathology and compared with standard blood and serum panels for toxicology.

Results:
The in vivo whole-body imaging data detected widespread changes, where spatially heterogeneous toxic effects were identified across different tissues, within substructures of organs, as well as among different individuals. The signal changes were consistent with established toxicity profiles of these chemotherapeutic drugs. Apart from generating a map of susceptible tissues, this in vivo imaging approach was more sensitive compared with conventional blood and serum markers used in toxicology. Also, repeated imaging during the acute period after drug treatment captured different kinetics of tissue injury among susceptible organs in males and females.

Conclusions:
This novel and highly translational imaging approach shows promise in optimizing therapeutic decisions by detecting and managing drug toxicity on a personalized basis.
Toxicity to normal tissues is a significant limitation in chemotherapies. This work demonstrated an in vivo imaging-based approach for characterizing toxicity-induced tissue injury in a systemic, dynamic, and near-real time fashion. This novel approach shows promise in optimizing therapeutic decisions by monitoring drug toxicity on a personalized basis.
Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial
Authors: Day Terry A. , Shirai Keisuke , O'Brien Paul E. , Matheus Maria Gisele , Godwin Kristina , Sood Amit J. , Kompelli Anvesh , Vick Julie A. , Martin Daniel , Vitale-Cross Lynn , Callejas-Varela Juan Luis , Wang Zhiyong , Wu Xingyu , Harismendy Olivier , Molinolo Alfredo A. , Lippman Scott M. , Van Waes Carter , Szabo Eva , Gutkind J. Silvio 
Published: November 2018

Abstract

Purpose:
We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The goals were to evaluate the mTOR pathway as a therapeutic target for patients with advanced HNSCC, and the clinical safety, antitumor, and molecular activity of rapamycin administration on HNSCC.

Patients and Methods:
Patients with untreated stage II–IVA HNSCC received rapamycin for 21 days (day 1, 15 mg; days 2–12, 5 mg) prior to definitive treatment with surgery or chemoradiation. Treatment responses were assessed clinically and radiographically with CT and FDG-PET. Pre- and posttreatment biopsies and blood were obtained for toxicity, immune monitoring, and IHC assessment of mTOR signaling, as well as exome sequencing.

Results:
Sixteen patients (eight oral cavity, eight oropharyngeal) completed rapamycin and definitive treatment. Half of patients were p16 positive. One patient had a pathologic complete response and four (25%) patients met RECIST criteria for response (1 CR, 3 PR, 12 SD). Treatment was well tolerated with no grade 4 or unexpected toxicities. No significant immune suppression was observed. Downstream mTOR signaling was downregulated in tumor tissues as measured by phosphorylation of S6 (P &lt; 0.0001), AKT (P &lt; 0.0001), and 4EBP (P = 0.0361), with a significant compensatory increase in phosphorylated ERK in most patients (P &lt; 0.001). Ki67 was reduced in tumor biopsies in all patients (P = 0.013).

Conclusions:
Rapamycin treatment was well tolerated, reduced mTOR signaling and tumor growth, and resulted in significant clinical responses despite the brief treatment duration, thus supporting the potential role of mTOR inhibitors in treatment regimens for HNSCC.
‘I would describe myself as a deformed troll’: Using interpretative phenomenological analysis to explore body image struggles among palliative care patients
Authors: Vas Szilvia , Povey Rachel , Clark-Carter David 
Published: November 2018

Background: Illness adjustment is a widely studied area in the palliative care context. However, research focussing on how altered body image can affect men and women in palliative care is limited and unclear. Aim: To explore the links between palliative care patients’ affected sense of self, altered body image and terminal illness adjustment. Design: Semi-structured interviews were conducted, and the Interpretative Phenomenological Analysis approach was used to analyse patients’ experiences. Setting/participants: English-speaking, adult palliative care outpatients were interviewed at a local community hospice in the United Kingdom. The mean age was 55 years (ranging from 35–65 years). Results: Analysis of accounts indicated three superordinate themes: (1) ‘Not being me’: self-discrepancy, (2) existing in the landscape of loss, (3) living and thriving in the landscape of loss. The most disturbing issues, such as appearance-focussed struggles and low body-confidence, were stemming from participants’ frustration over their lack of control and their attachment to their former self-image. Conclusions: The patients’ insights demonstrated that body image distress was prevalent among all respondents regardless of gender or diagnosis. A spiral model is described showing how discrepancy-based processing (i.e. ‘not being me’) and rigid attachment to former self can have harmful consequences on palliative patients’ abilities to cope. In order to facilitate adjustment to a self-identity crisis resulting from a terminal diagnosis, it is necessary for professionals to recognise and address body image changes among palliative care outpatients.
A Novel Arthroscopic Technique for Intraoperative Mobilization of Synovial Mesenchymal Stem Cells
Authors: Baboolal Thomas G. , Khalil-Khan Alam , Theodorides Anthony A. , Wall Owen , Jones Elena , McGonagle Dennis 
Published: November 2018

Background: Mesenchymal stem cells (MSCs) have emerged as a promising candidate for tissue regeneration and restoration of intra-articular structures such as cartilage, ligaments, and menisci. However, the routine use of MSCs is limited in part by their low numbers and the need for methods and procedures outside of the joint or surgical field. Purpose: To demonstrate feasibility of a technique in which minimally manipulated synovial MSCs can be mobilized during knee arthroscopy, thereby showing proof of concept for the future evaluation and clinical use of native joint resident MSCs in single-stage joint repair strategies. Study Design: Descriptive laboratory study. Methods: Patients (n = 15) undergoing knee arthroscopy who were free from synovitis or active inflammation were selected. Three samples of irrigation fluid were collected from each patient at inception of the procedure, after an initial inspection of the joint, and after agitation of the synovium. MSC numbers were evaluated by colony forming unit–fibroblastic assay. The phenotype of synovial fluid resident and synovial-mobilized MSCs was determined by flow cytometry, and their functionality was determined by trilineage differentiation. Adhesion of culture-expanded mobilized MSCs to fibrin scaffolds was also evaluated to ascertain whether mobilized MSCs might concentrate at sites of bleeding. Results: Normal irrigation during arthroscopy depleted resident synovial fluid MSCs (4-fold decrease, n = 15). Numbers of MSCs mobilized through use of a purpose-made device were significantly higher (105-fold) than those mobilized through use of a cytology brush (median of 5763 and 54 colonies, respectively; P = .001; n = 15). The mobilized cellular fraction contained viable MSCs with proliferative potential and trilineage differentiation capacity for bone, cartilage, and fat lineages, and cultured daughter cells exhibited the standard MSC phenotype. Following culture, mobilized synovial MSCs also adhered to various fibrin scaffolds in vitro. The technique was simple and convenient to use and was not associated with any complications. Conclusion: Numbers of functional MSCs can be greatly increased during arthroscopy through use of this technique to mobilize cells from the synovium. Clinical Relevance: This study highlights a novel, single-stage technique to increase joint-specific, synovial-derived MSCs and thereby increase the repair potential of the joint. This technique can be undertaken during many arthroscopic procedures, and it supports the principle of integrating mobilized MSCs into microfracture sites and sites of bleeding or targeted repair through use of fibrin-based and other scaffolds.
7-year results of primary total hip arthroplasty with the uncemented Avenir stem
Authors: Erivan Roger , Villatte Guillaume , Brientini Jean-Michel , Kreider David , Descamps Stéphane , Boisgard Stéphane 
Published: November 2018

Aims: The aim of the present study was to evaluate the 7-year functional outcome and radiographic results of primary total hip arthroplasties (THAs) performed with the uncemented Avenir stem. Patients and methods: Between January 2006 and October 2008, 100 consecutive primary hips in 92 patients were enrolled at 2 centres. The mean age at operation was 58.5 years (27–87 years). Mini-incision (50%) and standard approaches (50%) were used to implant 22 standard and 78 lateralised stems. Results: The 7-year Kaplan-Meier survival rate was 98.9% (95% CI, 92.9–99.8) with stem revision for any reason as endpoint. No stem related complications occurred. 1 stem revision was due to deep infection at 51 months post-op. We had 4 acetabular revisions. The mean Harris Hip Score (HHS) at 7 years follow-up was 93.1 points (60–100). Radiographic analysis showed 2 patients had non-progressive radiolucent lines and no patient had any signs of stem subsidence or loosening. Conclusion: The 7-year implant survival and the functional outcomes for THA performed with the study device are excellent and were in line with those documented for comparable contemporary uncemented fully HA-coated stems. Longer term follow-up of this consecutive series needs to be performed.
Cognitive-motor interference in persons with multiple sclerosis during five upper limb motor tasks with different complexity
Authors: Raats Joke , Lamers Ilse , Baert Ilse , Willekens Barbara , Veldkamp Renee , Feys Peter 
Published: November 2018

Background: Cognitive-motor interference in multiple sclerosis has been well examined during walking, but not during upper limb (UL) performance. Objectives: To examine the dual-task cost (DTC) in persons with multiple sclerosis (pwMS) and healthy controls (HC) in various type and complexity of UL motor tasks. Method: In total, 30 pwMS without major UL impairment and 30 HC performed five different UL tasks, in single condition and combined with the phonemic word list generation task. The percent change in performances was evaluated by the motor, cognitive, and combined DTC. The motor tasks consisted of four unimanual (sustained hand grip strength, box-and-block test, Purdue pegboard test, finger tapping task) and one bimanual task (Purdue pegboard test). Group and task differences were analyzed with unpaired and paired t-tests, respectively, and overall effect with a multivariate analysis of variance. Results: The motor DTC ranged between 10% (Purdue pegboard bimanual) and 35% (box-and-block test). The cognitive DTC ranged between −8% (finger tapping test) and +21% (bimanual Purdue pegboard). The magnitude of the combined DTC did not differ significantly between pwMS and HC in any task. Conclusion: DTC is influenced by the complexity of the UL task, but was not significantly different between HC and cognitive intact, but mildly motor disabled pwMS.
Persistent MOG-IgG positivity is a predictor of recurrence in MOG-IgG-associated optic neuritis, encephalitis and myelitis
Authors: Oliveira Luana Michelli , Apóstolos-Pereira Samira Luisa , Pitombeira Milena Sales , Bruel Torretta Pedro Henrique , Callegaro Dagoberto , Sato Douglas Kazutoshi 
Published: November 2018

Background: MOG-IgG-associated optic neuritis, encephalitis and myelitis (MONEM) is a recently recognized group of inflammatory central nervous system (CNS) disorders distinct from multiple sclerosis and neuromyelitis optica spectrum disorders. Limited data are available regarding the predictors of relapse in this condition. Objective: We aimed to evaluate the longitudinal serostatus of patients with MOG-IgG and to correlate serostatus with long-term clinical outcomes. Methods: Of 574 consecutive patients who presented with demyelinating inflammatory CNS disorders, we included 31 patients who were MOG-IgG-positive. Patients with MOG-IgG were followed up from 2011 to 2017 at the School of Medicine, University of São Paulo, Brazil. Results: Relapsing disease occurred in 23 out of 31 patients (74%), while 8 (26%) exhibited a monophasic course. All monophasic patients, as well as the majority of relapsing patients, became seronegative during clinical remission. Patients exhibiting disease activity in the last 2 years were more likely to remain positive, with higher medium titres than those found in patients in clinical remission. Conclusion: MOG-IgG patients usually present with a relapsing course, and the risk of relapse was associated with longitudinally persistent MOG-IgG seropositivity. In contrast, patients who experienced a single attack became spontaneously seronegative for MOG-IgG during long-term follow-up.
Impact of aortic stent-graft oversizing on outcomes of the chimney endovascular technique based on a new analysis of the PERICLES Registry
Authors: Donas Konstantinos P , Usai Marco V , Taneva Gergana T , Criado Frank J , Torsello Giovanni B , Kubilis Paul , Scali Salvatore , Veith Frank J 
Published: November 2018

Objective Chimney endovascular aortic aneurysm repair is gaining ever greater acceptance. However, persistent gutters leading to type IA endoleaks represent an unsolved issue. The aim of the current study was to analyze the impact of abdominal endograft oversizing to the occurrence of this phenomenon. Methods The PERformance of the snorkel/chImney endovascular teChnique in the treatment of compLex aortic PathologiesES registry includes the largest experience with chimney endovascular aortic aneurysm repair from 13 vascular centers in Europe and the U.S. Prospectively collected data from centers with standard use of the Endurant stent-graft and balloon-expandable covered stents as chimney grafts only were included in the present analysis. The parameter which varied was the degree of oversizing of the aortic stent-graft classifying the cohort in two groups, group A (20% and less oversizing) and group B (>20% of oversizing). The primary endpoint was the incidence of persistent type IA endoleak needed reintervention. Secondary endpoints were all-cause mortality and freedom from reintervention. Results Group A included 21 patients while group B 144. The mean preoperative pathology’s neck length and diameter was 5.8 mm (±4.4) versus 4.9 mm (±3.8) and 27.6 mm (±4.7) versus 24.9 mm (±3.7) for group A and group B, respectively. The mean length of the new sealing zone after chimney graft placement was similar for both groups (group A versus group B; 17.9 mm versus 18.3 mm, respectively, P = .21). The percentage of oversizing of the aortic stent-graft ranged between 13.8 and 20% versus 22.2 and 30%, for group A and group B, respectively. Patients of group A had more type 1A endoleaks, (14.3%) versus patients of group B (2.1%) based on the first follow-up imaging, P = .02. The incidence of persistent type IA endoleaks needing a reintervention was 14.3 and 1.4% for the group A and group B, respectively, P = .01. The mean volume of contrast medium used was greater in group A versus group B with 239 ml versus150 ml, P = .05. Additionally, 14.3% of patients of group A experienced acute renal failure compared to those in group B which was 1.0%, P = .01. Conclusions Oversizing of ideally 30% of the Endurant stent-graft is associated with significant lower incidence of type IA endoleaks requiring reintervention for patients treated by chimney endovascular aortic aneurysm repair.
Postoperative stress and pain response applying fast-track protocol in patients undergoing hepatectomy
Authors: Kapritsou Maria , Konstantinou Evangelos A , Korkolis Dimitris P , Kalafati Maria , Kaklamanos Ioannis , Giannakopoulou Margarita 
Published: November 2018

Aim To assess the clinical parameters and compare the stress and pain response between fast-track recovery protocol and conventional treatment in patients undergoing major liver resection. Methods Eighty-eight patients suffering from malignant liver tumours were surgically treated from May 2012 to March 2015. After randomisation, they were prospectively divided into two groups: group fast-track patients (n = 46) and group conventional treatment patients (n = 42). Demographic and clinical data were collected and patients were assessed with pain scale (behavioural observation scale and visual analog scale), while depression levels were evaluated with Zung self-rating depression scale and three Numeric Analog Scale self-reported questions. Peripheral blood samples were collected at time points: T1 on the admission day, T2 on the day of surgery and T3 on the day of discharge examining serum levels of adrenocorticotropic hormone and cortisol. Conclusion Fast-track recovery protocols seem to be associated with improvement in several clinical parameters, without compromising, biologic or emotional stress in patients undergoing major liver resection.
Risk stratification by means of biological age-related factors better predicts cancer-specific survival than chronological age in patients with upper tract urothelial carcinoma: a multi-institutional database study
Authors: Inamoto Teruo , Matsuyama Hideyasu , Ibuki Naokazu , Komura Kazumasa , Fujimoto Kiyohide , Shiina Hiroaki , Sakano Shigeru , Nagao Kazuhiro , Miyake Makito , Yasumoto Hiroaki , Azuma Haruhito ,   Nishinihon Uro-Oncology Collaborative Group
Published: November 2018

Background: Chronological age is an important factor in determining the treatment options and clinical response of patients with upper tract urothelial carcinoma (UTUC). Much evidence suggests that chronological age alone is an inadequate indicator to predict the clinical response to radical nephroureterectomy (RNU). Patients and methods: We retrospectively reviewed the data from 1510 patients with UTUC (Ta-4) treated by surgery. White blood cell (WBC) count, neutrophil-to-lymphocyte ratio, hemoglobin (Hb), platelets, albumin, alkaline phosphatase, lactate dehydrogenase, creatinine, and corrected calcium were tested by the Spearman correlation to indicate the direction of association with chronological age, which yielded significant, negative associations of Hb ( p < 0.001) and WBC ( p = 0.010) with chronological age. For scoring, we assigned points for these categories as follows; point ‘0’ for Hb >14 (reference) and 13–13.9 [odds ratio (OR): 1.533], point ‘1’ for 12–12.9 (OR: 2.391), point ‘2’ for 11–11.9 (OR: 3.015), and point ‘3’ for <11 (OR: 3.584). For WBC, point ‘1’ was assigned for >9200 (OR: 2.541) and ‘0’ was assigned for the rest; 9200–8500 (reference), 8499–6000 (OR: 0.873), 5999–4500 (OR: 0.772), 4499–3200 (OR: 0.486), and <3200 (OR: 1.277). Results: The 10-year cancer-specific survival (CSS) in the higher risk group with scores of 4 or higher in patients age <60 years was worse than a score of 0, or 1 in age >80 years [mean estimated survival 69.7 months, confidence interval (CI): 33.3–106 versus 103.5. CI: 91–115.9]. The concordance index between biological age scoring and chronological age was 0.704 for CSS and 0.798 for recurrence-free survival. The limitation of the present study is the retrospective nature of the cohort included. Conclusions: The biological age scoring developed for patients with UTUC undergoing RNU. It was applicable to those with localized disease and performed well in diverse age populations.