bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-Class, First-in-Human Study Evaluating LV305, a Dendritic-Cell Tropic Lentiviral Vector, in Sarcoma and Other Solid Tumors Expressing NY-ESO-1
Authors: Somaiah Neeta , Block Matthew S. , Kim Joseph W. , Shapiro Geoffrey I. , Do Khanh T. , Hwu Patrick , Eder Joseph P. , Jones Robin L. , Lu Hailing , ter Meulen Jan H. , Bohac Chet , Chen Michael , Hsu Frank J. , Gnjatic Sacha , Pollack Seth M. 
Published: June 2019

Abstract

Purpose:
LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo. LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1–expressing tumors. This phase I study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors.

Patients and Methods:
Adults with previously treated, advanced, NY-ESO-1–positive solid tumors and limited tumor burden were eligible. LV305 was administered every 3 weeks by intradermal injection in four dose cohorts (Cohort 1: 108 vector genomes (vg) x 3 doses; Cohorts 1A, 2, and 3: 108 vg, 109 vg, 1010 vg x 4 doses).

Results:
Thirty-nine patients were enrolled: 3 patients each in Cohorts 1, 1A, and 2, and 30 patients in Cohort 3. No dose-limiting toxicities were observed. Tumor types included sarcoma (n = 24), ovarian (n = 8), melanoma (n = 6), and lung cancer (n = 1). All treatment-related adverse events were grade 1 or 2. Common treatment-related adverse events were fatigue (49%), injection site reactions (46%), and myalgia (21%). The disease control rate was 56.4% in all patients and 62.5% in sarcoma patients. One patient with synovial sarcoma achieved a partial response lasting &gt;36 months. Anti–NY-ESO-1-specific CD4+ and/or CD8+ T cells were induced in 57% of evaluable sarcoma patients. Induction of an anti–NY-ESO-1 immune response was associated with improved 1-year survival in an exploratory analysis.

Conclusions:
This first-in-class, first-in-human study of LV305 demonstrated a favorable safety profile, induction of antigen-specific responses, and potential clinical activity in patients with advanced cancer.
Evolutionary Routes in Metastatic Uveal Melanomas Depend on MBD4 Alterations
Authors: Rodrigues Manuel , Mobuchon Lenha , Houy Alexandre , Alsafadi Samar , Baulande Sylvain , Mariani Odette , Marande Benjamin , Ait Rais Khadija , Van der Kooij Monique K. , Kapiteijn Ellen , Gassama Sieta , Gardrat Sophie , Barnhill Raymond L. , Servois Vincent , Dendale Rémi , Putterman Marc , Tick Sarah , Piperno-Neumann Sophie , Cassoux Nathalie , Pierron Gaëlle , Waterfall Joshua J. , Roman-Roman Sergio , Mariani Pascale , Stern Marc-Henri 
Published: June 2019

Abstract

Purpose:
Uveal melanomas (UM) are genetically simple tumors carrying few copy number alterations (CNA) and a low mutation burden, except in rare MBD4-deficient, hypermutated cases. The genomics of uveal melanoma metastatic progression has not been described. We assessed the genetic heterogeneity of primary and metastatic MBD4-proficient and -deficient uveal melanomas.
Experimental Design: We prospectively collected 75 metastatic and 16 primary samples from 25 consecutive uveal melanoma patients, and performed whole-exome sequencing.

Results:
MBD4-proficient uveal melanomas contained stable genomes at the nucleotide level, acquiring few new single nucleotide variants (SNVs; 16 vs. 13 in metastases and primary tumors, respectively), and no new driver mutation. Five CNAs were recurrently acquired in metastases (losses of 1p, 6q, gains of 1q, 8q, and isodisomy 3). In contrast, MBD4-deficient uveal melanomas carried more than 266 SNVs per sample, with high genetic heterogeneity and TP53, SMARCA4, and GNAS new driver mutations. SNVs in MBD4-deficient contexts were exploited to unveil the timeline of oncogenic events, revealing that metastatic clones arose early after tumor onset. Surprisingly, metastases were not enriched in monosomy 3, a previously defined metastatic risk genomic feature. Monosomy 3 was associated with shorter metastatic-free interval compared with disomy 3 rather than higher rate of relapse.

Conclusions:
MBD4-proficient uveal melanomas are stable at the nucleotide level, without new actionable alterations when metastatic. In contrast, MBD4 deficiency is associated with high genetic heterogeneity and acquisition of new driver mutations. Monosomy 3 is associated with time to relapse rather than rate of relapse, thus opening avenues for a new genetic prognostic classification of uveal melanomas.
When Cancer Vaccines Go Viral
Authors: Repáraz David , Llopiz Diana , Sarobe Pablo 
Published: June 2019

Abstract
Induction of antitumor responses by vaccines requires strong immunogens. Heterologous viral prime/boost immunization with the BN-CV301 vaccine promotes activation of immune responses that provide a clinical benefit to patients with cancer. This viral platform may be used to harbor different antigens and prime tumor immunity potentially useful for combinatorial strategies.
See related article by Gatti-Mays et al., p. 4933
Longitudinal evaluation of the Teen Outreach Programme: Impacts of a health promotion programme on risky sexual behaviours
Authors: Daley Ellen M , Marhefka Stephanie L , Wang Wei , Noble Charlotte A , Mahony Helen , Arzola Saba , Singleton Ashley , Malmi Markku , Ziemba Robert , Turner DeAnne , Marwah Elizabeth , Walsh-Buhi Eric R 
Published: June 2019

Objective: This study evaluated the longitudinal impact of the Teen Outreach Programme (TOP) on adolescent pregnancy, sexual behaviour, risky sex and sexual intentions in non-metropolitan high schools. Design: Pair-matched, cluster randomised controlled trial. Setting: Non-metropolitan public high schools in Florida, USA. Methods: TOP was evaluated against the standard school health curriculum content. Young people ( N = 3,836) enrolled in 26 schools were surveyed at baseline (2012), immediate post-programme (2013) and at 1-year follow-up (2014). Most youth were 14 years old and in ninth grade at baseline. Missing data were imputed using a sequential imputation procedure and analysis took place using generalised linear mixed-effects models with logit link function. Results: Post-programme, young people in the treatment group were less likely to report ever having sex, recent sex, recent sex without a condom or intention to have sex in the next year. At 1-year follow-up, programme participants were less likely to report ever having been pregnant or having got someone pregnant. When examining treatment effects by gender, statistically significant differences were found only for female programme participants. Conclusion: Although many protective factors dissipated by second follow-up and were primarily found among female programme participants, TOP has the potential to decrease risky sexual behaviour.
Unexpected serious aplastic anemia from PD-1 inhibitors: beyond what we know
Authors: Filetti Marco , Giusti Raffaele , Di Napoli Arianna , Iacono Daniela , Marchetti Paolo 
Published: June 2019

Introduction: The recent introduction of checkpoint inhibitor–based immunotherapy has revolutionized the treatment of advanced lung cancers, becoming standard of care in both first- and second-line treatment. New types of toxicity are emerging with the increasingly widespread use of these inhibitors. Case presentation: We describe a case of aplastic anemia in a patient with stage IV non-small cell lung cancer after a single administration of nivolumab. Conclusions: Several similar case reports reported in literature show an increasing rate of toxicities from immunotherapy in this setting. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.
Increased blood pressure visit-to-visit variability in patients with systemic lupus erythematosus: association with inflammation and comorbidity burden
Authors: Reese T , Dickson A L , Shuey M M , Gandelman J S , Barnado A , Barker K A , Neal J E , Khan O A , Dupont W D , Stein C M , Chung C P 
Published: June 2019

Background Blood pressure visit-to-visit variability is a novel risk factor for deleterious long-term cardiac and renal outcomes in the general population. We hypothesized that patients with systemic lupus erythematosus (SLE) have greater blood pressure visit-to-visit variability than control subjects and that blood pressure visit-to-visit variability is associated with a higher comorbidity burden. Methods We studied 899 patients with SLE and 4172 matched controls using de-identified electronic health records from an academic medical center. We compared blood pressure visit-to-visit variability measures in patients with SLE and control subjects and examined the association between blood pressure visit-to-visit variability and patients’ characteristics. Results Patients with SLE had higher systolic blood pressure visit-to-visit variability 9.7% (7.8–11.8%) than the control group 9.2% (7.4–11.2%), P < 0.001 by coefficient of variation. Additional measures of systolic blood pressure visit-to-visit variability (i.e. standard deviation, average real variation, successive variation and maximum measure-to-measure change) were also significantly higher in patients with SLE than in control subjects. In patients with SLE, blood pressure visit-to-visit variability correlated significantly with age, creatinine, CRP, triglyceride concentrations and the Charlson comorbidity score (all P < 0.05). Hydroxychloroquine use was associated with reduced blood pressure visit-to-visit variability ( P < 0.001), whereas the use of antihypertensives, cyclophosphamide, mycophenolate mofetil and corticosteroids was associated with increased blood pressure visit-to-visit variability ( P < 0.05). Conclusion Patients with SLE had higher blood pressure visit-to-visit variability than controls, and this increased blood pressure visit-to-visit variability was associated with greater Charlson comorbidity scores, several clinical characteristics and immunosuppressant medications. In particular, hydroxychloroquine prescription was associated with lower blood pressure visit-to-visit variability.
Telecare management of pain and mood symptoms: Adherence, utility, and patient satisfaction
Authors: Bushey Michael A , Kroenke Kurt , Weiner Julia , Porter Brian , Evans Erica , Baye Fitsum , Lourens Spencer , Weitlauf Sharon 
Published: June 2019

Introduction Pain, depression, and anxiety are prominent symptoms that frequently co-occur, causing significant debilitation and frequent primary care visits. This paper examines the acceptability of telecare and self-management modules in managing these conditions in a randomized trial. Methods The Comprehensive Management of Mood and Physical Symptoms (CAMMPS) trial compared an automated symptom management (ASM) plus self-management intervention with a comprehensive symptom management (CSM) intervention that added telecare facilitation of enhanced services. Data from the CAMMPS trial were analysed to compare the acceptability of these two interventions as indicated by utilization and patient satisfaction surveys. Results The mean number of automated reports completed was similar between the CSM and ASM groups (14.5 vs 14.0). Responses designated with clinically relevant “red alerts” (i.e. patient reports warranting an expedited nurse contact) were more frequent in the CSM group (10.2 vs 8.3). The CSM and ASM groups completed a similar number of the nine self-management modules (6.3 vs 5.8). The mean helpfulness score across all modules was higher in the CSM group than in the ASM group (1.8 vs 1.5; p = .003). The most common feedback suggestion from the ASM group was to have more personal interaction, while participants from both groups commonly suggested technical improvements or requests for more flexible timing of calls. Discussion Participants generally found both interventions satisfactory, with a trend in satisfaction data suggesting that patients tended to find the CSM intervention more helpful.
A Transfer Learning Approach for Malignant Prostate Lesion Detection on Multiparametric MRI
Authors: Chen Quan , Hu Shiliang , Long Peiran , Lu Fang , Shi Yujie , Li Yunpeng 
Published: June 2019

Purpose: In prostate focal therapy, it is important to accurately localize malignant lesions in order to increase biological effect of the tumor region while achieving a reduction in dose to noncancerous tissue. In this work, we proposed a transfer learning–based deep learning approach, for classification of prostate lesions in multiparametric magnetic resonance imaging images. Methods: Magnetic resonance imaging images were preprocessed to remove bias artifact and normalize the data. Two state-of-the-art deep convolutional neural network models, InceptionV3 and VGG-16, were pretrained on ImageNet data set and retuned on the multiparametric magnetic resonance imaging data set. As lesion appearances differ by the prostate zone that it resides in, separate models were trained. Ensembling was performed on each prostate zone to improve area under the curve. In addition, the predictions from lesions on each prostate zone were scaled separately to increase the area under the curve for all lesions combined. Results: The models were tuned to produce the highest area under the curve on validation data set. When it was applied to the unseen test data set, the transferred InceptionV3 model achieved an area under the curve of 0.81 and the transferred VGG-16 model achieved an area under the curve of 0.83. This was the third best score among the 72 methods from 33 participating groups in ProstateX competition. Conclusion: The transfer learning approach is a promising method for prostate cancer detection on multiparametric magnetic resonance imaging images. Features learned from ImageNet data set can be useful for medical images.
Validating Autoclave Cycles for Carcass Disposal in Animal Biosafety Level 2/3 Containment Laboratories
Authors: McGirr Rebecca , Sample Christopher , Arwood Leslee , Burch James , Alderman Scott 
Published: June 2019

Introduction:Animal carcasses differ in composition from other types of solid waste, and through prior testing it was determined that cycle parameters applied to general, solid biohazardous waste did not ensure proper sterilization of ferret carcasses.Objectives:The goals of this study were to develop and validate an autoclave cycle that would ensure the decontamination of infectious animal carcasses before removal from an animal biosafety level 2/3 containment suite for downstream disposal and to test different ways to prepare and package animal carcasses for autoclaving.Methods:Intact ferret carcasses were implanted with biological indicators, and the carcasses were placed in biohazard bags, then into metal pans. To test the efficacy of the autoclave cycle on larger biomasses, 1, 2, or 4 ferret carcasses were placed in a biohazard bag. A total of 4 carcasses were placed in each pan. An autoclave cycle was created to begin the study. After initial tests, minor modifications to the initial test cycle parameters were made, and a new cycle was validated for ferret carcasses up to 2 kg each. Parameters for the validated cycle were as follows: sterilization time 240 minutes, temperature 125°C, 5 prevacuum pulses, and chamber pressure 15 psi.Results:The results of this study indicate that an extended sterilization time is required to successfully decontaminate animal carcasses compared with regular, solid, and biohazardous waste.Conclusions:This study demonstrates that it is possible to sterilize multiple intact ferret carcasses per load under validated autoclave cycle conditions.
Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study
Authors: van der Louw Elles J. T. M. , Olieman Joanne F. , van den Bemt Patricia M. L. A. , Bromberg Jacoline E. C. , Oomen-de Hoop Esther , Neuteboom Rinze F. , Catsman-Berrevoets Coriene E. , Vincent Arnaud J. P. E. 
Published: June 2019

Background: High-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme. Methods: A full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates. Results: Eleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months. Conclusion: KD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival. Clinical trial registration: Netherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp
Prescription Of analgesia in Emergency Medicine (POEM): a multicentre observational survey of pain relief in patients presenting with an isolated limb fracture and/or dislocation
Authors: Sheehan James Robert , Wilson Sarah , Quinlan Jane , Beer Sally , Darwent Melanie , Dainty Jack R , Ezra Martyn , Keating Liza 
Published: June 2019

Background: Acute pain is one of the most commonly cited reasons for attendance to the emergency department (ED), and the Royal College of Emergency Medicine (RCEM) Best Practice Guideline (2014) acknowledged that the current management of acute pain in UK EDs is inadequate and has a poor evidence base. Methods: The Prescription Of analgesia in Emergency Medicine (POEM) survey is a cross-sectional observational survey of consecutive patients presenting to 12 National Health Service (NHS) EDs with limb fracture and/or dislocation in England and Scotland and was carried out between 2015 and 2017. The primary outcome was to assess the adequacy of pain management in the ED against the recommendations in the RCEM Best Practice Guidelines. Results: In all, 8346 patients were identified as attending the ED with a limb fracture and/or dislocation but adherence to RCEM guidelines could only be evaluated for the 4160 (49.8%) patients with a recorded pain score. Of these, 2409/4160 (57.9%) patients received appropriate pain relief, but only 1347 patients were also assessed within 20 minutes of their arrival in the ED. Therefore, according to the RCEM guidelines, only 16.1% (1347/8346) of all patients were assessed and had satisfactory pain management in the ED. Conclusions: The POEM survey has identified that pain relief for patients with an isolated limb fracture remains inadequate when strictly compared to the RCEM Best Practice Guidelines. However, we have found that some patients receive analgesia despite having no pain score recorded, while other analgesic modalities are provided that are not currently encompassed by the Best Practice Guidelines. Future iterations of these guidelines may wish to encompass the breadth of available modalities of pain relief and the whole patient journey. In addition, more work is needed to improve timely and repeated assessment of pain and its recording, which has been better achieved in some EDs than others.
Preoperative lymphocyte count in relation to sarcoma prognosis
Authors: Teck Seo Soon , Singh Vivek Ajit , Yasin Nor Faissal 
Published: June 2019

Purpose: Inflammation plays a major role in tumour development, progression and metastasis. Multiple inflammatory markers such as absolute lymphocyte count, neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR) and platelet–lymphocyte ratio have been discovered as prognostic markers for various malignancies. We investigate preoperative lymphocyte count and other cell count ratios and their relation to survival and prognosis of sarcoma patients after surgery. Methods: A total of 142 patients from the Orthopaedics Oncology Database were included into this retrospective study. Kaplan–Meier curve and multivariate Cox proportional models were used to calculate the overall survival of patients with sarcoma who underwent radical excision surgery. Results: High preoperative LMR is significantly associated with better overall survival and prognosis in sarcoma patients, whereas high preoperative NLR is significantly associated with shorter overall survival and poorer prognosis. Multivariate analysis shows that LMR and NLR are good predictors for overall survival at 3 and 5 years after surgery, respectively. Patients with high preoperative lymphocytes count are associated with longer overall survival, but this association is not statistically significant. Our findings suggest that preoperative NLR and LMR are good predictive markers for survival of sarcoma patients. Conclusion: LMR and NLR can be used to identify patients at risk for poor clinical outcome, so that a more aggressive course of treatment can be applied to improve outcome. These are cost-effective prognostic tools as they are calculated from routine preoperative peripheral blood counts. In conclusion, preoperative NLR and LMR are good prognostic markers for predicting the clinical outcome of patients with sarcoma.
Barbed sutures versus staples for closure in total hip arthroplasty using wound ooze as a primary outcome measure: A prospective study
Authors: Knapper Thomas D , Dahill Mark , Eastaugh-Waring Stephen , Baker Richard P , Webb Jason CJ , Blom Ashley W , Whitehouse Michael R 
Published: June 2019

Background: Prosthetic joint infection is a rare, but devastating complication of primary total hip arthroplasty (THA). Postoperative wound discharge and deep infection are related. We examined whether barbed sutures were associated with a decrease in the incidence of postoperative wound discharge when compared with skin closure using metal staples. Methods: Prospective nonrandomized comparison between two groups (35 barbed suture closures vs. 49 staple closures). Wounds were assessed daily for postoperative wound discharge until dry. Hemoglobin and hematocrit were recorded at the preoperative assessment and on day 3 postoperative. Results: There were no significant differences between the groups with regard to age, body mass index, gender, preoperative hemoglobin, preoperative hematocrit, or estimated blood volume. The number of days elapsed until the wound was dry was significantly lower in the barbed suture group than the staples group ( p < 0.0001). In the staples cohort, ongoing wound ooze resulted in delayed hospital discharge in three (6%) patients, six bed days total. Conclusion: Barbed sutures reliably reduce the period of postoperative wound ooze following primary THA compared to staple closure. The use of barbed sutures may prevent delayed patient discharge from hospital, decreasing the bed burden.