bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B12: Therapeutic potential of NTRK3 in desmoplastic small round cell tumor
Authors: Spraggon Lee , Hmeljak Julija , Magnan Heather , Somwar Romel , Asher Marina , Hartono Alifiani B. , Lee Sean Bong , Ladanyi Marc 
Published: August 2018

Abstract
Desmoplastic small round cell tumor (DSRCT) is a soft-tissue sarcoma that predominantly affects adolescent and young adult males and has a dismal prognosis, despite aggressive treatment. It is characterized by the t(11;22)(p13:q12) translocation that generates the EWSR1-WT1 chimeric transcription factor, a powerful oncogene and the main molecular driver of DSRCT.
EWSR1-WT1 rewires global gene expression networks and activates aberrant expression of targets that contribute to an oncogenic expression program. It has been previously described that EWSR1-WT1 can activate neural gene expression (1), supporting the hypothesis that targeting neural differentiation markers might offer a novel therapeutic approach to treat DSRCT.
Among those markers, our analysis of DSRCT tumors demonstrated prominent expression of neurotrophic tyrosine kinase receptor 3 (NTRK3; TrkC), a druggable receptor tyrosine kinase, specifically expressed in DSRCT compared to other translocation-driven sarcomas. We show that EWSR1-WT1 directly activates its expression, and that abrogation of NTRK3 reduces growth of DSRCT cells. Conversely, we show that pharmacologic targeting of NTRK3 is effective both in in vitro and in vivo models of DSRCT, suggesting that NTRK3 is a viable therapeutic target, especially in light of the recent clinical development of highly specific and effective NTRK inhibitors.
Reference
1. Kang et al., Cancer Res 2014;15;74(16):4526-35.
Citation Format: Lee Spraggon, Julija Hmeljak, Heather Magnan, Romel Somwar, Marina Asher, Alifiani B. Hartono, Sean Bong Lee, Marc Ladanyi. Therapeutic potential of NTRK3 in desmoplastic small round cell tumor [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B12.
Baseline Cytokine Profiles of Tuberculin-Specific CD4+ T Cells in Non–Muscle-Invasive Bladder Cancer May Predict Outcomes of BCG Immunotherapy
Authors: Jallad Samer , Thomas Philip , Newport Melanie J. , Kern Florian 
Published: August 2018

Abstract
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy preserves the bladder after resection of high-risk non–muscle-invasive bladder cancer (NMIBC). About 30% of patients experience treatment failure, which cannot be predicted a priori and carries a high risk of disease progression. We examined the in vitro tuberculin responsiveness of CD4+ T cells before BCG immunotherapy in 42 patients with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing CD4+ T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation. Tuberculin-induced secreted mediators were measured by electrochemiluminescence. We correlated the results with recurrence-free patient survival 6 months after induction. A tuberculin-induced, secreted, IL2 concentration &gt; 250 pg/mL was the best predictor of recurrence-free survival, providing 79% sensitivity, 86% specificity (AUC = 0.852, P = 0.000), and overall correct classification in 78.6% of cases. In 50% of patients later experiencing recurrence, but not in any of the recurrence-free survivors, IL2 secretion was &lt; 120 pg/mL. Other parameters predicting recurrence-free survival included secreted IFNγ (AUC = 0.796, P = 0.002) and the frequencies of TNF-producing (TNF+) CD4+ T cells (AUC = 0.745, P = 0.010). “Polyfunctional” CD4+ T cells (IFNγ+/IL2+/TNF+) were significantly associated with recurrence-free survival (AUC = 0.801, P = 0.002). Thus, the amount of IL2 secretion from CD4+ T cells after overnight in vitro incubation with tuberculin predicted the outcome of BCG immunotherapy. As many as half of potential BCG failures could be identified before induction therapy is begun, enabling better choices regarding treatment. Cancer Immunol Res; 6(10); 1212–9. ©2018 AACR.
Cerebral Diffusivity Changes in Fetuses with Chiari II Malformation
Authors: Shrot Shai , Soares Bruno P. , Whitehead Matthew T. 
Published: August 2018

<b><i>Objectives:</i></b> Chiari II malformation is a congenital abnormality characterized by a small posterior fossa with downward displacement of the hindbrain into the foramen magnum. Diffusion-weighted imaging (DWI) can be used to quantitatively characterize brain injury and physiological maturation. We aim to evaluate DWI parameters of the infra- and supratentorial brain in fetuses with Chiari II malformation. <b><i>Methods:</i></b> <i>MRI and US</i> studies of 26 fetuses with Chiari II malformation and 15 controls were evaluated for the presence/severity of hydrocephalus, myelomeningocele level, and brain apparent diffusion coefficient (ADC) values. Cerebral flow impedance parameters (resistance and pulsatile indexes, resistance index [RI], and pulsatility index [PI] respectively) from concurrently preformed fetal US were also evaluated. <b><i>Results:</i></b> Of the Chiari II group, 16 fetuses had hydrocephalus. There was increasing severity of lateral ventriculomegaly in the high compared to low spinal dysraphism subgroups. There were significant lower ADC values in the frontal (<i>p</i> = 0.01) and temporal lobes (<i>p</i> = 0.05) in Chiari II group compared with normal, regardless of the presence or severity of hydrocephalus. Fetuses with Chiari II showed significantly lower RI and PI values. <b><i>Conclusions:</i></b> Abnormal ADC values indicate supratentorial microstructural changes in fetuses with Chiari II malformation. Further investigation of the role of diffusion imaging metrics in evaluating abnormal brain development, parenchymal damage and efficacy of fetal surgery is needed.
DCE-MR imaging of orbital lesions: diagnostic performance of the tumor flow residence time τ calculated by a multi-compartmental pharmacokinetic tumor model based on individual factors
Authors: Erb-Eigner Katharina , Asbach Patrick , Ro Sa-Ra , Haas Matthias , Bertelmann Eckart , Pietsch Hubertus , Schwenke Carsten , Taupitz Matthias , Denecke Timm , Hamm Bernd , Lawaczeck Rüdiger 
Published: August 2018

Background Differentiating benign from malignant orbital lesions by imaging and clinical presentation can be challenging. Purpose To differentiate benign from malignant orbital masses using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on tumor flow residence time τ calculated with the aid of a pharmacokinetic tumor model. Material and Methods Sixty patients with orbital masses were investigated by 3-T MRI including dynamic sequences. The signal intensity-time curve after i.v. contrast medium administration within lesions was approximated by Gd-concentration profiles on the basis of model calculations where the tumor is embedded in a whole-body kinetic model. One output of the model was tumor flow residence time τ, defined as the ratio of the tumor volume and the tumor blood flow rate. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of τ. The results were compared with those of Ktrans, kep, ve, iAUC, and ADC. Results Thirty-one benign and 29 malignant orbital masses were identified (reference standard: histopathology, clinical characteristics). Mean τ was significantly longer for benign masses (94 ± 48 s) than for malignant masses (21 ± 19 s, P < 0.001). ROC analysis revealed the highest area under the curve (AUC = 0.94) for τ in orbital masses compared to standard methods. Conclusion Tumor flow residence times τ of benign and malignant orbital masses are valuable in the diagnostic work-up of orbital tumors. Measures of diagnostic accuracy were superior for τ compared to ADC, Ktrans, ve, and iAUC.
Evaluation of Healing After Medial Meniscal Root Repair Using Second-Look Arthroscopy, Clinical, and Radiological Criteria
Authors: Lee Sung-Sahn , Ahn Jin Hwan , Kim Jun Ho , Kyung Bong Soo , Wang Joon Ho 
Published: August 2018

Background: Previous studies have reported various healing rates (0%-100%) as evaluated by second-look arthroscopy after repair of medial meniscal root tears (MMRTs). Such variable results might provoke suspicion of the necessity for repair. Furthermore, the effect of meniscal healing on the clinical outcomes has not been reported. Purpose: To more precisely determine the healing rate of MMRTs repaired through the transseptal portal, which could provide objective visualization of the healed meniscus, and to identify the effect of meniscal healing on the clinical and radiological outcomes. Study Design: Case series; Level of evidence, 4. Methods: Between June 2010 and April 2015, 56 patients underwent pullout suture for MMRT. Lysholm score, Hospital for Special Surgery score, International Knee Documentation Committee subjective score, medial joint space height, and Kellgren-Lawrence (K-L) grade were evaluated. Thirty-three patients underwent second-look arthroscopy and were divided into a “stable healed group” and “unhealed group” according to their healing status, as evaluated through the transseptal portal. The intraoperative, clinical, and radiological outcomes of the 2 groups were compared. Results: All other clinical outcomes improved. However, medial joint space became significantly narrower ( P < .001), and 23 patients (41%) showed K-L grade progression. On the basis of second-look arthroscopy, 23 patients (69.7%) were classified into a stable healed group and 10 (30.3%) into a unhealed group. The stable healed group showed a higher Hospital for Special Surgery score ( P = .023), International Knee Documentation Committee subjective score ( P = .031), and successful microfracture rate ( P = .023), with less progression of medial joint space narrowing ( P < .001) and K-L grade ( P < .001). Conclusion: Despite degenerative change progression, clinical outcomes were improved. The successful healing rate was 69.7% after repair of MMRTs. Compared with the unhealed group, the stable healed group showed better clinical outcomes and less degenerative change progression.
Assessing the quality, reliability and readability of online health information regarding systemic lupus erythematosus
Authors: Reynolds M , Hoi A , Buchanan R R C 
Published: August 2018

Introduction Systemic lupus erythematosus (SLE) has complex pathophysiology and treatments, and patients often use the internet to better understand their condition. This report systematically assesses the quality, reliability and readability of online information. Methods The search term ‘systemic lupus erythematosus’ was used with Google™, Bing™ and Yahoo™ search engines sequentially. The first 25 websites returned (‘hits’) for each search engine (total 75 websites) were compiled. The search terms ‘SLE’ and ‘lupus’ were used in separate Google searches to assess for commonality. After removal of excluded hits, websites were assessed using the DISCERN instrument, Journal of the American Medical Association benchmarks and Gunning Fog Index for quality, reliability and readability and presence of ‘Health on the Net Code’ (HoN) standardisation recorded. Results There was a large degree of commonality among hits from the three different search engines using the search term ‘systemic lupus erythematosus’, as well as hits returned for the three different search terms using Google. The mean DISCERN score was 47.7 (SD 13.2) for ‘systemic lupus erythematosus’, 46.4 (SD 14.2) for ‘SLE’ and 45.2 (SD 10.1) for ‘lupus’, with no statistically significant difference. The mean number of JAMA benchmarks (maximum four) present for the ‘systemic lupus erythematosus’, ‘SLE’ and ‘lupus’ searches was 1.3 (SD 1.2), 1.4 (SD 1.3) and 1.2 (SD 1.0), respectively, with no statistically significance difference. The average readability of hits for the three different search terms was 9.3 (SD 3.4), 10.0 (SD 3.1) and 11.1 (SD 2.7), with no statistically significant difference. Conclusion There was a large degree of commonality of hits among the different search engines and the utilised search terms but they are not synonymous. Regardless of search term, the overall quality of websites was fair, whilst reliability was poor. Websites appearing higher in searches did not score better. Presence of the HoN did not represent better quality. Readability was higher than recommended for near-universal understanding. There was no difference in quality, reliability or readability of websites using the search terms ‘systemic lupus erythematosus’, ‘SLE’ or ‘lupus’, with some high-scoring websites appearing in only one search term result. This study reminds clinicians to direct patients to high-quality websites rather than rely on search engines.
Functional Outcomes of Local Pedicle Graft Interpositional Arthroplasty in Adults With Severe Freiberg’s Disease
Authors: Abdul Wahid , Hickey Ben , Perera Anthony 
Published: August 2018

Background: Conservative treatment or debridement is generally sufficient for Freiberg’s disease grades I and II but operative intervention for the late stages of the disease process (III-V) is more challenging. Debridement alone is not sufficient and various forms of arthroplasty have been put forward. We have evaluated the outcomes of patients treated with an interpositional arthroplasty technique using a pedicle graft of periosteum and fat made into a “Rollmop” spacer for severe Freiberg’s disease. No results have previously been reported for this technique. Methods: Twenty-five consecutive cases (23 patients) were performed from February 2009 to September 2016 (20 females, 5 males). Mean age at surgery was 52.6 years (range 19-70.5 years) with 92% affecting the second metatarsal. Twenty-three were primary cases and 2 were revision cases. Five cases were stage III, 12 were stage IV, and 8 were stage V. All patients underwent interpositional arthroplasty using a periosteum and fat pedicle graft from the affected metatarsal shaft as described by Myerson. Patients were evaluated using Manchester-Oxford Foot Questionnaire (MOXFQ) and American Orthopaedic Foot & Ankle Society Questionnaire (AOFAS). Mean follow-up was 3.5 years (0.6-7.6 years). Paired 2-tailed Student t tests were used to assess clinical significance. Results: Surgery allowed 8 patients to return to normal footwear, 10 patients returned to fashion footwear/heels, and 5 returned to sports. Nineteen cases (17 patients) were assessed with patient-reported outcome measures and all showed a clinically and statistically significant improvement in their scores. Mean pre- and postoperative VAS pain scores were 6.2 (range 4-9) and 1.8 (range 0-6) ( P < .05). Mean perioperative AOFAS scores were 45.6 (range 15-73) and 82.7 (range 57-100) ( P < .05). Mean perioperative MOXFQ scores were 60.0 (range 23-89) and 18.1 (range 0-80) ( P < .05). Conclusion: This novel interpositional arthroplasty technique using a “rollmop” of periosteum and fat for severe Freiberg’s disease produced significant improvements in pain, functional outcome, and patient satisfaction without donor site morbidity. Furthermore, it allowed patients to return to desired footwear and sporting activities. The functional outcome and joint range of motion was superior after a K-wire was no longer placed across the joint, and we believe it is essential to avoid this to permit early range-of-motion exercises. Level of Evidence: Level IV, retrospective case series.
When can I drive? Advising patients when to drive after general surgical procedures
Authors: Dixon Steven , Woodcock Sean 
Published: August 2018

Introduction Advising patients when they are medically fit to drive following general surgical procedures is crucial to minimise risk to patients, the general public as road user’s and pedestrians and also avoid negligence claims against medical practitioners. Historically, in the UK, this advice has come from a number of sources including surgeons, general practitioners, insurers and the Driver and Vehicle Licensing Agency (DVLA). The aim of this study was to review how current surgical teams distribute this advice and what this advice is based upon. Materials and methods An online survey was devised and distributed to all consultant general surgeons and trainees in the North East of England via email. Leading vehicle insurance companies and the DVLA were contacted to assess what advice they gave for specific procedures (ventral hernia, appendicectomy, cholecystectomy, fundoplication). Results A total of 135 surveys were distributed, 56 were returned, with a response rate of 41.5%. Twenty-two (39.3%) of respondents were consultants, 30 (53.6%) were speciality trainees (ST3-8) and 4 (7.1%) were core surgical trainees (CT1-2). Some (14.2%) gave driving advice to every patient, 39.3% gave advice to most patients; 42.9% gave advice pre-operatively in clinic, 39.3% gave the advice pre-operatively on the day of surgery, and 96.4% of responders based their advice on traditional teaching. Discussion and conclusions: There is variation in the content and timing of advice regarding driving after general surgical procedures. This inconsistency will undoubtedly lead to incorrect information being distributed to patients and will impact post-operative patient safety. We suggest formulating consistent advice in a written format, standardising the process which in turn will protect patients and surgeons.
Deleterious Pulmonary Surfactant System Gene Mutations in Lung Adenocarcinomas Associated With Usual Interstitial Pneumonia
Authors: Honda Takayuki , Sakashita Hiroyuki , Masai Kyohei , Totsuka Hirohiko , Motoi Noriko , Kobayashi Masashi , Akashi Takumi , Mimaki Sachiyo , Tsuchihara Katsuya , Chiku Suenori , Shiraishi Kouya , Shimada Yoko , Otsuka Ayaka , Kanai Yae , Okubo Kenichi , Watanabe Shun-ichi , Tsuta Koji , Inase Naohiko , Kohno Takashi 
Published: August 2018

Purpose Usual interstitial pneumonia (UIP) is a risk factor for lung carcinogenesis. This study was performed to characterize mutagenesis and mutational target genes underlying lung carcinogenesis in patients with UIP. Patients and Methods A cohort of 691 Japanese patients with lung adenocarcinoma (LADC), of whom 54 had UIP and 637 did not, was studied for driver oncogene aberrations. Whole-exome analysis was performed for 296 cases, including 51 with UIP, to deduce mutagenic processes and identify commonly affected genes. Logistic regression analysis was used to detect associations of gene aberrations with clinicopathological factors. Results The EGFR mutation was markedly less prevalent in patients with LADC with UIP than in those without (1.9% [one of 54] v. 49.9% [318 of 637]; P < .001), even in heavy smokers (25.3% [38 of 150] of patients with > 40 pack-years; P < .001). Mutational signature analysis indicated that UIP-positive LADCs develop through accumulation of single-nucleotide and indel mutations caused by smoking. Pulmonary surfactant system genes (PSSGs) NKX2-1/TTF1, SFTPA1, SFTPA2, SFTPB, and SFTPC were identified as targets for mutations (preferentially indels), and mutations were specifically associated with shorter overall survival of patients with UIP-positive LADC, independent of pathologic stage (hazard ratio, 4.9; 95% CI, 1.7 to 14.4; P = .0037). Conclusion LADCs with UIP develop through mutational events caused by smoking, independently of EGFR mutation. PSSGs were identified as a mutational target and as a novel prognostic factor in UIP-positive LADC. PSSG deficiency might increase the malignancy of tumor cells by increasing the tumor-promoting effects of UIP.
Radioactive Iodine–Related Clonal Hematopoiesis in Thyroid Cancer Is Common and Associated With Decreased Survival
Authors: Boucai Laura , Falcone John , Ukena Jenny , Coombs Catherine C , Zehir Ahmet , Ptashkin Ryan , Berger Michael F , Levine Ross L , Fagin James A 
Published: August 2018

Abstract

Context
Radioactive iodine (RAI) has been epidemiologically associated with the development of hematologic malignancies. Clonal hematopoiesis (CH) is a precursor clonal state that confers increased risk of leukemia and occurs at an elevated rate in patients with thyroid cancer relative to other solid tumors.

Objective
We explore if the high prevalence of CH may be a result of RAI exposure and whether CH may be a surrogate in the association between RAI and leukemia.

Design
CH, CH-potential driver (CH-PD), and overall survival were evaluated in 279 patients with advanced thyroid carcinoma.

Results
The prevalence of CH in patients with thyroid cancer was 37%, and that of CH-PD was 5.2%. Age was the strongest predictor of CH and CH-PD. For every year increase in age, there was a 5% and 13% increase in the odds of CH and CH-PD, respectively. RAI dose was significantly associated with CH and CH-PD, even after adjustment for age, external beam radiation therapy, and chemotherapy. For every 10 mCi increase in the dose of RAI administered, there was a 2% and 4% increase in the odds of CH and CH-PD, respectively. Patients with CH-PD previously exposed to RAI had a significantly poorer survival, even when stratified by age (heart rate = 3.75, 95% CI = 1.23 to 11.5, P = 0.02).

Conclusions
RAI was associated with a high prevalence of CH, and CH is a precursor state of hematologic malignancies. The implications of this study may favor identification of CH in patients where the risks might outweigh the benefits of receiving RAI therapy for thyroid cancer.
Risk of Meningioma in European Patients Treated With Growth Hormone in Childhood: Results From the SAGhE Cohort
Authors: Swerdlow Anthony J , Cooke Rosie , Beckers Dominique , Butler Gary , Carel Jean-Claude , Cianfarani Stefano , Clayton Peter , Coste Joël , Deodati Annalisa , Ecosse Emmanuel , Hokken-Koelega Anita C S , Khan Aysha J , Kiess Wieland , Kuehni Claudia E , Flück Christa E , Pfaffle Roland , Sävendahl Lars , Sommer Grit , Thomas Muriel , Tidblad Anders , Tollerfield Sally , Zandwijken Gladys R J 
Published: August 2018

Abstract

Context
There has been concern that GH treatment of children might increase meningioma risk. Results of published studies have been inconsistent and limited.

Objective
To examine meningioma risks in relation to GH treatment.

Design
Cohort study with follow-up via cancer registries and other registers.

Setting
Population-based.

Patients
A cohort of 10,403 patients treated in childhood with recombinant GH in five European countries since this treatment was first used in 1984. Expected rates from national cancer registration statistics.

Main Outcome Measures
Risk of meningioma incidence.

Results
During follow-up, 38 meningiomas occurred. Meningioma risk was greatly raised in the cohort overall [standardized incidence ratio (SIR) = 75.4; 95% CI: 54.9 to 103.6], as a consequence of high risk in subjects who had received radiotherapy for underlying malignancy (SIR = 658.4; 95% CI: 460.4 to 941.7). Risk was not significantly raised in patients who did not receive radiotherapy. Risk in radiotherapy-treated patients was not significantly related to mean daily dose of GH, duration of GH treatment, or cumulative dose of GH.

Conclusions
Our data add to evidence of very high risk of meningioma in patients treated in childhood with GH after cranial radiotherapy, but suggest that GH may not affect radiotherapy-related risk, and that there is no material raised risk of meningioma in GH-treated patients who did not receive radiotherapy.